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1. Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

Author: Femke Rutters, Amber A van der Heijden, Manfred Wuhrer, Mandy van Hoek, Eric J G Sijbrands, Aloysius G Lieverse, Viktoria Dotz, Emma Schoep, Elham Memarian, Roderick C Slieker, Leen M 't Hart, Giel Nijpels, and Roosmarijn F L Lemmers
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Published: 2021
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2. Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: comparison between American Diabetes Association and World Health Organization diagnostic criteria

Author: Maarten J G Leening, M Arfan Ikram, Abbas Dehghan, Maryam Kavousi, Mandy van Hoek, Eric J G Sijbrands, Aloysius G Lieverse, Thijs T W van Herpt, and Symen Ligthart
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Introduction Pre-diabetes, a status conferring high risk of overt diabetes, is defined differently by the American Diabetes Association (ADA) and the WHO. We investigated the impact of applying definitions of pre-diabetes on lifetime risk of diabetes in women and men from the general population.Research design and methods We used data from 8844 women without diabetes and men aged ≥45 years from the prospective population-based Rotterdam Study in the Netherlands. In both gender groups, we calculated pre-diabetes prevalence according to ADA and WHO criteria and estimated the 10-year and lifetime risk to progress to overt diabetes with adjustment for competing risk of death.Results Out of 8844 individuals, pre-diabetes was identified in 3492 individuals (prevalence 40%, 95% CI 38% to 41%) according to ADA and 1382 individuals (prevalence 16%, 95% CI 15% to 16%) according to WHO criteria. In both women and men and each age category, ADA prevalence estimates doubled WHO-defined pre-diabetes. For women and men aged 45 years having ADA-defined pre-diabetes, the 10-year risk of diabetes was 14.2% (95% CI 6.0% to 22.5%) and 9.2% (95% CI 3.4% to 15.0%) compared with 23.2% (95% CI 6.8% to 39.6%) and 24.6% (95% CI 8.4% to 40.8%) in women and men with WHO-defined pre-diabetes. At age 45 years, the remaining lifetime risk to progress to overt diabetes was 57.5% (95% CI 51.8% to 63.2%) vs 80.2% (95% CI 74.1% to 86.3%) in women and 46.1% (95% CI 40.8% to 51.4%) vs 68.4% (95% CI 58.3% to 78.5%) in men with pre-diabetes according to ADA and WHO definitions, respectively.Conclusion Prevalence of pre-diabetes differed considerably in both women and men when applying ADA and WHO pre-diabetes definitions. Women with pre-diabetes had higher lifetime risk to progress to diabetes. The lifetime risk of diabetes was lower in women and men with ADA-defined pre-diabetes as compared with WHO. Improvement of pre-diabetes definition considering appropriate sex-specific and age-specific glycemic thresholds may lead to better identification of individuals at high risk of diabetes.
Published: 2020
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3. Introduction of the DiaGene study: clinical characteristics, pathophysiology and determinants of vascular complications of type 2 diabetes

Author: Thijs T. W. van Herpt, Roosmarijn F. H. Lemmers, Mandy van Hoek, Janneke G. Langendonk, Ronald J. Erdtsieck, Bert Bravenboer, Annelies Lucas, Monique T. Mulder, Harm R. Haak, Aloysius G. Lieverse, and Eric J. G. Sijbrands
Subjects: Type 2 diabetes mellitus, Cardiovascular disease, Prospective follow-up, Complications, Genetics, Case–control, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Abstract Background Type 2 diabetes is a major healthcare problem. Glucose-, lipid-, and blood pressure-lowering strategies decrease the risk of micro- and macrovascular complications. However, a substantial residual risk remains. To unravel the etiology of type 2 diabetes and its complications, large-scale, well-phenotyped studies with prospective follow-up are needed. This is the goal of the DiaGene study. In this manuscript, we describe the design and baseline characteristics of the study. Methods The DiaGene study is a multi-centre, prospective, extensively phenotyped type 2 diabetes cohort study with concurrent inclusion of diabetes-free individuals at baseline as controls in the city of Eindhoven, The Netherlands. We collected anthropometry, laboratory measurements, DNA material, and detailed information on medication usage, family history, lifestyle and past medical history. Furthermore, we assessed the prevalence and incidence of retinopathy, nephropathy, neuropathy, and diabetic feet in cases. Using logistic regression models, we analyzed the association of 11 well known genetic risk variants with type 2 diabetes in our study. Results In total, 1886 patients with type 2 diabetes and 854 controls were included. Cases had worse anthropometric and metabolic profiles than controls. Patients in outpatient clinics had higher prevalence of macrovascular (41.9% vs. 34.8%; P = 0.002) and microvascular disease (63.8% vs. 20.7%) compared to patients from primary care. With the exception of the genetic variant in KCNJ11, all type 2 diabetes susceptibility variants had higher allele frequencies in subjects with type 2 diabetes than in controls. Conclusions In our study population, considerable rates of macrovascular and microvascular complications are present despite treatment. These prevalence rates are comparable to other type 2 diabetes populations. While planning genomics, we describe that 11 well-known type 2 diabetes genetic risk variants (in TCF7L2, PPARG-P12A, KCNJ11, FTO, IGF2BP2, DUSP9, CENTD2, THADA, HHEX, CDKAL1, KCNQ1) showed similar associations compared to literature. This study is well-suited for multiple omics analyses to further elucidate disease pathophysiology. Our overall goal is to increase the understanding of the underlying mechanisms of type 2 diabetes and its complications for developing new prediction, prevention, and treatment strategies.
Published: 2017
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4. The effect of guideline revisions on vascular complications of type 2 diabetes

Author: Ralph Heijmans, Sunny S. Singh, Aloysius G. Lieverse, Eric J.G. Sijbrands, and Mandy van Hoek
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study ( n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend
Published: 2019
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5. Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus

Author: Willem A. Dik, Monique T. Mulder, Nikita Martens, Roosmarijn F.H. Lemmers, Adrie J.M. Verhoeven, L. C. van Vark-van der Zee, M. van Hoek, Aloysius G Lieverse, Frank P.J. Leijten, Harm R. Haak, Eric J.G. Sijbrands, A.H. Maas, Pieter J. M. Leenen, C.M. Groot-van Ruijven, Internal Medicine, and Immunology
Subjects: medicine.medical_specialty, medicine.drug_class, High density, Anti-inflammatory, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, Internal medicine, Type 2 diabetes mellitus, Internal Medicine, Medicine, Diseases of the circulatory (Cardiovascular) system, Peg precipitation, Endothelium, Breakfast, VCAM-1, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Retinal, Iodixanol, High-density lipoprotein function, Endocrinology, medicine.anatomical_structure, chemistry, RC666-701, Density gradient ultracentrifugation, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, Density gradient centrifugation, medicine.drug, Artery
Abstract: Background and aims: High-density lipoproteins (HDL) of patients with type 2 diabetes mellitus (T2DM) have impaired anti-inflammatory activities. The anti-inflammatory activity of HDL has been determined ex vivo after isolation by different methods from blood mostly obtained after overnight fasting. We first determined the effect of the HDL isolation method, and subsequently the effect of food intake on the anti-inflammatory function of HDL from T2DM patients. Methods: Blood was collected from healthy controls and T2DM patients after an overnight fast, and from T2DM patients 3 h after breakfast (n = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDLDGUC2), by sequential salt density flotation (HDLSEQ) or by PEG precipitation (HDLPEG). The anti-inflammatory function of HDL was determined by the reduction of the TNFα-induced expression of VCAM-1 in human coronary artery endothelial cells (HCAEC) and retinal endothelial cells (REC). Results: HDL isolated by the three different methods from healthy controls inhibited TNFα-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 μM, HDLDGUC2 and HDLSEQ were similarly effective (16% versus 14% reduction; n = 3; p > 0.05) but less effective than HDLPEG (28%, p < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDLDGUC2 for further experiments. With apoA-I at 3.2 μM, HDL from fasting healthy controls and T2DM patients reduced TNFα-induced VCAM-1 expression in HCAEC by 58 ± 13% and 51 ± 20%, respectively (p = 0.35), and in REC by 42 ± 13% and 25 ± 18%, respectively (p < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 ± 16% (paired test: p < 0.001) in HCAEC and by 34 ± 13% (paired test: p < 0.05) in REC. Conclusions: The ex vivo anti-inflammatory activity of HDL is affected by the HDL isolation method. Two-step ultracentrifugation in an iodixanol gradient is a suitable method for HDL isolation when testing HDL anti-inflammatory function. The anti-inflammatory activity of HDL from overnight fasted T2DM patients is significantly impaired in REC but not in HCAEC. The anti-inflammatory function of HDL is partly restored by food intake.
Published: 2021

6. Sex difference in the incidence of microvascular complications in patients with type 2 diabetes mellitus: a prospective cohort study

Author: Eric J.G. Sijbrands, Roosmarijn F.H. Lemmers, Jeanine E. Roeters-van Lennep, Aloysius G Lieverse, Thijs T. W. van Herpt, Sunny S Singh, Mandy van Hoek, and Internal Medicine
Subjects: Male, medicine.medical_specialty, Microvascular complications, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Cohort Studies, Endocrinology, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Diabetes mellitus, Sex differences, Internal Medicine, medicine, Albuminuria, Humans, Prospective Studies, Retinopathy, Prospective cohort study, Aged, Dyslipidemias, Netherlands, Cause of death, Sex Characteristics, business.industry, Incidence, Microcirculation, Incidence (epidemiology), Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Neuropathy, Diabetes Mellitus, Type 2, Hypertension, Original Article, Female, Microalbuminuria, business, Diabetic Angiopathies, Dyslipidemia, Follow-Up Studies
Abstract: Aims Type 2 diabetes mellitus is a major cause of death and disability due to its long-term macro- and microvascular diseases. Although women with type 2 diabetes have more macrovascular diseases, it is unclear whether there are sex differences in the occurrence of microvascular disease. The aim of our study was to investigate sex differences in the incidence of microvascular complications in type 2 diabetes. Methods Analyses were performed in the DiaGene study, a prospective cohort study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886, mean follow-up time = 6.93 years). Cox proportional hazard models adjusted for risk factors for complications (age, smoking, hypertension, dyslipidemia, HbA1c and duration of type 2 diabetes) were used to analyze the incidence of microvascular complications in men and women. Results The incidence of microalbuminuria was significantly higher in men (HR microalbuminuria 1.64 [CI 1.21–2.24], p = 0.002). Additionally, men are more likely to develop two or three microvascular complications compared to women (OR 2.42 [CI 1.69–3.45], p Conclusions This study shows that men with type 2 diabetes are more likely to develop microvascular complications, especially microalbuminuria. Furthermore, men seem to have a higher chance of developing multiple microvascular complications. Our results highlight that men and women may not benefit to a similar extent from current treatment approaches to prevent diabetes-related microvascular diseases.
Published: 2020

7. Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus

Author: Mandy van Hoek, Yolanda B. de Rijke, M. Rashid, Florian Kronenberg, Sunny S Singh, Monique T. Mulder, Aloysius G Lieverse, Eric J.G. Sijbrands, Claudia Lamina, Internal Medicine, and Clinical Chemistry
Subjects: Male, medicine.medical_specialty, Microvascular complications, Endocrinology, Diabetes and Metabolism, Population, SNP, Type 2 diabetes, rs3798220, Gastroenterology, Polymorphism, Single Nucleotide, Article, Nephropathy, Lp(a), SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, rs10455872, Prospective Studies, Risk factor, education, Prospective cohort study, Retinopathy, Macrovascular disease, Aged, education.field_of_study, biology, business.industry, Type 2 Diabetes Mellitus, Lipoprotein(a), Middle Aged, medicine.disease, Spline, Neuropathy, LPA, Diabetes Mellitus, Type 2, biology.protein, Female, business
Abstract: Aims/hypothesis Microvascular disease in type 2 diabetes is a significant cause of end-stage renal disease, blindness and peripheral neuropathy. The strict control of known risk factors, e.g. lifestyle, hyperglycaemia, hypertension and dyslipidaemia, reduces the incidence of microvascular complications, but a residual risk remains. Lipoprotein (a) [Lp(a)] is a strong risk factor for macrovascular disease in the general population. We hypothesised that plasma Lp(a) levels and the LPA gene SNPs rs10455872 and rs3798220 are associated with the incident development of microvascular complications in type 2 diabetes. Methods Analyses were performed of data from the DiaGene study, a prospective study for complications of type 2 diabetes, collected in the city of Eindhoven, the Netherlands (n = 1886 individuals with type 2 diabetes, mean follow-up time = 6.97 years). To assess the relationship between plasma Lp(a) levels and the LPA SNPs with each newly developed microvascular complication (retinopathy n = 223, nephropathy n = 246, neuropathy n = 236), Cox proportional hazards models were applied and adjusted for risk factors for microvascular complications (age, sex, mean arterial pressure, non-HDL-cholesterol, HDL-cholesterol, BMI, duration of type 2 diabetes, HbA1c and smoking). Results No significant associations of Lp(a) plasma levels and the LPA SNPs rs10455872 and rs3798220 with prevalent or incident microvascular complications in type 2 diabetes were found. In line with previous observations the LPA SNPs rs10455872 and rs3798220 did influence the plasma Lp(a) levels. Conclusions/interpretation Our data show no association between Lp(a) plasma levels and the LPA SNPs with known effect on Lp(a) plasma levels with the development of microvascular complications in type 2 diabetes. This indicates that Lp(a) does not play a major role in the development of microvascular complications. However, larger studies are needed to exclude minimal effects of Lp(a) on the development of microvascular complications.
Published: 2020

8. Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

Author: Amber A. van der Heijden, Manfred Wuhrer, Giel Nijpels, Leen M 't Hart, Elham Memarian, Viktoria Dotz, Aloysius G Lieverse, Mandy van Hoek, Emma Schoep, Roosmarijn F L Lemmers, Eric J.G. Sijbrands, Femke Rutters, Roderick C. Slieker, Internal Medicine, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, APH - Aging & Later Life, General practice, APH - Methodology, and ACS - Diabetes & metabolism
Subjects: medicine.medical_specialty, Glycosylation, glycosylation, Endocrinology, Diabetes and Metabolism, Disease, Type 2 diabetes, Gastroenterology, Diseases of the endocrine glands. Clinical endocrinology, Nephropathy, Plasma, chemistry.chemical_compound, Retinal Diseases, N-linked glycosylation, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, medicine, Humans, Fucosylation, business.industry, Proportional hazards model, biomarkers, diabetes complications, Genetics/Genomes/Proteomics/Metabolomics, Blood Proteins, RC648-665, medicine.disease, Diabetes Mellitus, Type 2, chemistry, Cardiovascular Diseases, business
Abstract: IntroductionAlthough associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality. Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).Research design and methodsBlood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner. Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation. After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation. Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.ResultsOur results demonstrated similarities between incident and prevalent complications. The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10−11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10−6). Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.ConclusionsThese findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
Published: 2021

9. Metformin and statin use associate with plasma protein

Author: Sunny S, Singh, Annemieke, Naber, Viktoria, Dotz, Emma, Schoep, Elham, Memarian, Roderick C, Slieker, Petra J M, Elders, Gerda, Vreeker, Simone, Nicolardi, Manfred, Wuhrer, Eric J G, Sijbrands, Aloysius G, Lieverse, Leen M, 't Hart, and Mandy, van Hoek
Subjects: carbohydrates (lipids), Angiotensin Receptor Antagonists, Glycosylation, Diabetes Mellitus, Type 2, Humans, Angiotensin-Converting Enzyme Inhibitors, Blood Proteins, Emerging Technologies, Pharmacology and Therapeutics, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Metformin, glycosylated proteins, lipid medication
Abstract: Introduction Recent studies revealed N-glycosylation signatures of type 2 diabetes, inflammation and cardiovascular risk factors. Most people with diabetes use medication to reduce cardiovascular risk. The association of these medications with the plasma N-glycome is largely unknown. We investigated the associations of metformin, statin, ACE inhibitor/angiotensin II receptor blocker (ARB), sulfonylurea (SU) derivatives and insulin use with the total plasma N-glycome in type 2 diabetes. Research design and methods After enzymatic release from glycoproteins, N-glycans were measured by matrix-assisted laser desorption/ionization mass spectrometry in the DiaGene (n=1815) and Hoorn Diabetes Care System (n=1518) cohorts. Multiple linear regression was used to investigate associations with medication, adjusted for clinical characteristics. Results were meta-analyzed and corrected for multiple comparisons. Results Metformin and statins were associated with decreased fucosylation and increased galactosylation and sialylation in glycans unrelated to immunoglobulin G. Bisection was increased within diantennary fucosylated non-sialylated glycans, but decreased within diantennary fucosylated sialylated glycans. Only few glycans were associated with ACE inhibitor/ARBs, while none associated with insulin and SU derivative use. Conclusions We conclude that metformin and statins associate with a total plasma N-glycome signature in type 2 diabetes. Further studies are needed to determine the causality of these relations, and future N-glycomic research should consider medication a potential confounder.
Published: 2020

10. Association of the IgG N-glycome with the course of kidney function in type 2 diabetes

Author: Ralph Heijmans, Gordan Lauc, Sunny S Singh, Aloysius G Lieverse, Olga Gornik, Claudia K E Meulen, Mandy van Hoek, Eric J.G. Sijbrands, and Internal Medicine
Subjects: Glycosylation, Endocrinology, Diabetes and Metabolism, Renal function, Type 2 diabetes, N-glycosylation, 030204 cardiovascular system & hematology, Kidney, Diseases of the endocrine glands. Clinical endocrinology, Immunoglobulin G, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Humans, Prospective Studies, Pathophysiology/Complications, kidney function, Fucosylation, 030304 developmental biology, 0303 health sciences, biology, diabetes type 2, business.industry, RC648-665, medicine.disease, Glycome, chemistry, Diabetes Mellitus, Type 2, IgG N-glycans, nephropathy, Case-Control Studies, Immunology, biology.protein, business
Abstract: IntroductionInflammatory processes are thought to be involved in kidney function decline in individuals with type 2 diabetes. Glycosylation of immunoglobulin G (IgG) is an important post-translation process affecting the inflammatory potential of IgG. We investigated the prospective relationship between IgG N-glycosylation patterns and kidney function in type 2 diabetes.Research design and methodsIn the DiaGene study, an all-lines-of-care case–control study (n=1886) with mean prospective follow-up of 7.0 years, the association between 58 IgG N-glycan profiles and estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) per year and during total follow-up was analyzed. Models were adjusted for clinical variables and multiple comparisons.ResultsEleven traits were significantly associated with eGFR change per year. Bisecting GlcNAc in fucosylated and fucosylated disialylated structures and monosialylation of fucosylated digalactosylated structures were associated with a faster decrease of eGFR. Fucosylation of neutral and monogalactosylated structures was associated with less eGFR decline per year. No significant associations between IgG glycans and ACR were found.ConclusionsIn type 2 diabetes, we found IgG N-glycosylation patterns associated with a faster decline of kidney function, reflecting a pro-inflammatory state of IgG. eGFR, but not ACR, was associated with IgG glycans, which suggests these associations may represent renal macroangiopathy rather than microvascular disease.
Published: 2020

11. Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: Comparison between American Diabetes Association and World Health Organization diagnostic criteria

Author: Symen Ligthart, Abbas Dehghan, Thijs T. W. van Herpt, Eric J.G. Sijbrands, Maryam Kavousi, Aloysius G Lieverse, Mandy van Hoek, Maarten J.G. Leening, M. Arfan Ikram, Epidemiology, Internal Medicine, Cardiology, Neurology, and Radiology & Nuclear Medicine
Subjects: Research design, pre-diabetic state, Male, diagnosis, Endocrinology, Diabetes and Metabolism, Population, Type 2 diabetes, World Health Organization, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Prediabetic State, Rotterdam Study, SDG 3 - Good Health and Well-being, Diabetes mellitus, medicine, Humans, Prospective Studies, education, Glycemic, Netherlands, education.field_of_study, lcsh:RC648-665, business.industry, risk assessment, Glucose Tolerance Test, Middle Aged, medicine.disease, United States, type 2, Diabetes Mellitus, Type 2, diabetes mellitus, Lifetime risk, Female, Clinical care/Education/Nutrition, business, Risk assessment, Demography
Abstract: IntroductionPre-diabetes, a status conferring high risk of overt diabetes, is defined differently by the American Diabetes Association (ADA) and the WHO. We investigated the impact of applying definitions of pre-diabetes on lifetime risk of diabetes in women and men from the general population.Research design and methodsWe used data from 8844 women without diabetes and men aged ≥45 years from the prospective population-based Rotterdam Study in the Netherlands. In both gender groups, we calculated pre-diabetes prevalence according to ADA and WHO criteria and estimated the 10-year and lifetime risk to progress to overt diabetes with adjustment for competing risk of death.ResultsOut of 8844 individuals, pre-diabetes was identified in 3492 individuals (prevalence 40%, 95% CI 38% to 41%) according to ADA and 1382 individuals (prevalence 16%, 95% CI 15% to 16%) according to WHO criteria. In both women and men and each age category, ADA prevalence estimates doubled WHO-defined pre-diabetes. For women and men aged 45 years having ADA-defined pre-diabetes, the 10-year risk of diabetes was 14.2% (95% CI 6.0% to 22.5%) and 9.2% (95% CI 3.4% to 15.0%) compared with 23.2% (95% CI 6.8% to 39.6%) and 24.6% (95% CI 8.4% to 40.8%) in women and men with WHO-defined pre-diabetes. At age 45 years, the remaining lifetime risk to progress to overt diabetes was 57.5% (95% CI 51.8% to 63.2%) vs 80.2% (95% CI 74.1% to 86.3%) in women and 46.1% (95% CI 40.8% to 51.4%) vs 68.4% (95% CI 58.3% to 78.5%) in men with pre-diabetes according to ADA and WHO definitions, respectively.ConclusionPrevalence of pre-diabetes differed considerably in both women and men when applying ADA and WHO pre-diabetes definitions. Women with pre-diabetes had higher lifetime risk to progress to diabetes. The lifetime risk of diabetes was lower in women and men with ADA-defined pre-diabetes as compared with WHO. Improvement of pre-diabetes definition considering appropriate sex-specific and age-specific glycemic thresholds may lead to better identification of individuals at high risk of diabetes.
Published: 2020

12. IgG glycan patterns are associated with type 2 diabetes in independent European populations

Author: Caroline Hayward, Mirna Šimurina, Felix Agakov, Harry Campbell, James F. Wilson, Olga Gornik, Eric J.G. Sijbrands, Igor Rudan, Marija Vilaj, Roosmarijn F.H. Lemmers, Aloysius G Lieverse, Lucija Klaric, Daniel Urda, Mandy van Hoek, Gordan Lauc, and Internal Medicine
Subjects: 0301 basic medicine, Male, Glycan, Glycosylation, IgG Glycosylation Type 2 diabetes Prediction Inflammation Ageing, Population, Biophysics, Type 2 diabetes, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, education, Molecular Biology, Aged, education.field_of_study, biology, Galactose, Middle Aged, medicine.disease, Pathophysiology, N-Acetylneuraminic Acid, 030104 developmental biology, Bonferroni correction, chemistry, Diabetes Mellitus, Type 2, Ageing, 030220 oncology & carcinogenesis, Area Under Curve, Immunoglobulin G, Immunology, biology.protein, symbols, Biomarker (medicine), Female
Abstract: BACKGROUND: Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.METHODS: In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.RESULTS: After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.CONCLUSIONS: Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.GENERAL SIGNIFICANCE: This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.
Published: 2017

13. The effect of guideline revisions on vascular complications of type 2 diabetes

Author: Aloysius G Lieverse, Sunny S Singh, Mandy van Hoek, Eric J.G. Sijbrands, Ralph Heijmans, and Internal Medicine
Subjects: microvascular complications, medicine.medical_specialty, lcsh:RC648-665, business.industry, Endocrinology, Diabetes and Metabolism, Incidence (epidemiology), Type 2 diabetes, Guideline, Diabetic retinopathy, Odds ratio, medicine.disease, Lower risk, lcsh:Diseases of the endocrine glands. Clinical endocrinology, diabetic retinopathy, macrovascular complications, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, Medicine, type 2 diabetes, business, guideline, diabetes care, Original Research, Retinopathy
Abstract: Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study ( n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend Conclusions: The introduction of the first diabetes guideline and subsequent revisions have reduced the risk of macrovascular and microvascular complications of type 2 diabetes, most strongly in diabetic retinopathy. This indicates that real-time diabetes care has improved over time.
Published: 2019

14. 04 - THE ASSOCIATION OF THE IGG N-GLYCOME WITH THE COURSE OF KIDNEY FUNCTION IN TYPE 2 DIABETES MELLITUS

Author: Mandy van Hoek, prof.dr. Eric Sijbrands, Aloysius G. Lieverse, Sunny Singh, and Claudia Meulen
Published: 2019

15. Plasma protein N-glycan signatures of type 2 diabetes

Author: Agnes L. Hipgrave Ederveen, Mandy van Hoek, Monique T. Mulder, Aloysius G Lieverse, Manfred Wuhrer, Roosmarijn F.H. Lemmers, Karli R. Reiding, Viktoria Dotz, Eric J.G. Sijbrands, and Internal Medicine
Subjects: Male, 0301 basic medicine, Glycan, Glycosylation, Biophysics, Type 2 diabetes, N-glycosylation, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, N-linked glycosylation, SDG 3 - Good Health and Well-being, Diabetes complications, Polysaccharides, Diabetes mellitus, medicine, Humans, Molecular Biology, Fucosylation, Aged, 030102 biochemistry & molecular biology, biology, business.industry, Blood Proteins, Odds ratio, Middle Aged, medicine.disease, MALDI-TOF-MS, Sialic acid, carbohydrates (lipids), 030104 developmental biology, Diabetes Mellitus, Type 2, chemistry, inflammation, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Immunology, diabetes mellitus, biology.protein, Female, business, Protein Processing, Post-Translational, Body mass index
Abstract: Background Little is known about enzymatic N-glycosylation in type 2 diabetes, a common posttranslational modification of proteins influencing their function and integrating genetic and environmental influences. We sought to gain insights into N-glycosylation to uncover yet unexplored pathophysiological mechanisms in type 2 diabetes. Methods Using a high-throughput MALDI-TOF mass spectrometry method, we measured N-glycans in plasma samples of the DiaGene case-control study (1583 cases and 728 controls). Associations were investigated with logistic regression and adjusted for age, sex, body mass index, high-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol, and smoking. Findings were replicated in a nested replication cohort of 232 cases and 108 controls. Results Eighteen glycosylation features were significantly associated with type 2 diabetes. Fucosylation and bisection of diantennary glycans were decreased in diabetes (odds ratio (OR) = 0.81, p = 1.26E-03, and OR = 0.87, p = 2.84E-02, respectively), whereas total and, specifically, alpha2,6-linked sialylation were increased (OR = 1.38, p = 9.92E-07, and OR = 1.40, p = 5.48E-07). Alpha2,3-linked sialylation of triantennary glycans was decreased (OR = 0.60, p = 6.38E-11). Conclusions While some glycosylation changes were reflective of inflammation, such as increased alpha2,6-linked sialylation, our finding of decreased alpha2,3-linked sialylation in type 2 diabetes patients is contradictory to reports on acute and chronic inflammation. Thus, it might have previously unreported immunological implications in type 2 diabetes. General significance This study provides new insights into N-glycosylation patterns in type 2 diabetes, which can fuel studies on causal mechanisms and consequences of this complex disease.
Published: 2018

16. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Author: Adrian F Hernandez, Jennifer B Green, Salim Janmohamed, Ralph B D'Agostino, Christopher B Granger, Nigel P Jones, Lawrence A Leiter, Anne E Rosenberg, Kristina N Sigmon, Matthew C Somerville, Karl M Thorpe, John J V McMurray, Stefano Del Prato, John J.V. McMurray, Ralph B. D'Agostino, Christopher B. Granger, Adrian F. Hernandez, Lawrence A. Leiter, Robert M Califf, Rury Holman, David DeMets, Matthew Riddle, Shaun Goodman, Darren McGuire, Karen Alexander, Adam Devore, Chiara Melloni, Chetan Patel, David Kong, Gerald Bloomfield, Matthew Roe, Pierluigi Tricoci, Rob Harrison, Renato Lopes, Robin Mathews, Rajendra Mehta, William Schuyler Jones, Sreekanth Vemulapalli, Thomas Povsic, Zubin Eapen, Keith Dombrowski, Brad Kolls, Dedrick Jordan, Andrew Ambrosy, Stephen Greene, Aditya Mandawat, Jay Shavadia, Lauren Cooper, Abhinav Sharma, Patricia Guimaraes, Daniel Friedman, Matt Wilson, Patricia Endsley, Tracy Gentry, Jeannie Collier, Kathleen Perez, Kourtnei James, Jennifer Roush, Connie Pope, Christina Howell, Megan Johnson, Matt Bailey, Joanna Cole, Teresa Akers, Beth Vandyne, Betsy Thomas, Jenny Rich, Susan Bartone, Gail Beaulieu, Kim Brown, Tuan Chau, Tamra Christian, Rebecca Coker, Deb Greene, Trevorlyn Haddock, Wendy Jenkins, Ghazala Haque, Marsha Marquess, Jean Pesarchick, Renee Rethaford, Allegra Stone, Firas Al Kawas, Michelle Anderson, Robert Enns, Isaac Sinay, Chantal Mathieu, Victor Yordanov, Irene Hramiak, Martin Haluzik, Søren Galatius, Bruno Guerci, Michael Nauck, Ilias Migdalis, Choon Beng Kathryn Tan, Gyozo Kocsis, Andrea Giaccari, Moon Kyu Lee, Ernesto German Cardona Muñoz, Jan Cornel, Kare Birkeland, Miguel Pinto, Louie Tirador, Martyna Olesinska-Mader, Marina Shestakova, Larry Distiller, Jose Lopez-Sendon, Bjorn Eliasson, Chern-En Chiang, Suphot Srimahachota, Boris Mankovsky, M Angelyn Bethel, Kathleen Dungan, Mikhail Kosiborod, Andres Alvarisqueta, Jorge Baldovino, Diego Besada, Pedro Calella, Maria Cecilia Cantero, Patricia Castaño, Alejandro Chertkoff, Jesus Cuadrado, Luis De Loredo, Andrea Dominguez, Maria Vanesa Español, Hernan Finkelstein, Gustavo Frechtel, Jose Fretes, Natalia Garrido Santos, Joaquin Gonzalez, Marcos Litvak, Juan Loureyro, Laura Maffei, Natacha Maldonado, Diego Mohr Gasparini, Silvia Orio, Federico Perez Manghi, Nelson Rodriguez Papini, Jorgelina Sala, Pablo Schygiel, Georgina Sposetti, Maria Ulla, Fernando Verra, Silvina Zabalua, Cesar Zaidman, Laurent Crenier, Corinne Debroye, Francis Duyck, André Scheen, Luc Van Gaal, Chris Vercammen, Velichka Damyanova, Stefan Dimitrov, Snezhina Kovacheva, Lachezar Lozanov, Viktor Margaritov, Rositsa Mihaylova-Shumkova, Antoaneta Nikolaeva, Zhasmina Stoyanova, Ronald Akhras, Yves Beaudry, Jacques Bedard, Joseph Berlingieri, Raja Chehayeb, Stephen Cheung, James Conway, Jean Cusson, Anthony Della Siega, Richard Dumas, Peter Dzongowski, Murdo Ferguson, Daniel Gaudet, Francois Grondin, Anil Gupta, Milan Gupta, Frank Halperin, Pierre-Alain Houle, Michael Jones, Simon Kouz, Christopher Kovacs, Daniel Landry, Eva Lonn, William O'Mahony, Sean Peterson, Dennis Reich, Alan Rosenbloom, Francois St-Maurice, Barna Tugwell, Saul Vizel, Vincent Woo, Tomas Brychta, Vladimir Cech, Eva Dvorakova, Tomas Edelsberger, Katarina Halciakova, Jarmila Krizova, Jiri Lastuvka, Martin Piperek, Vera Prymkova, Lea Raclavska, Elena Silhova, Robin Urbanek, Jan Vrkoc, Ulla Andersen, Jens Brønnum-Schou, Jens Hove, Jan Skov Jensen, Lars Kober, Ole Peter Kristiansen, Per Lund, Thomas Melchior, Ole Nyvad, Morten Schou, Alain Boye, Didier Cadinot, Didier Gouet, Patrick Henry, Laurence Kessler, Jean-Daniel Lalau, Catherine Petit, Jean-Francois Thuan, Christel Voinot, Julien Vouillarmet, Christoph Axthelm, Dirk Berger, Tasso Bieler, Andreas Birkenfeld, Jochen Bott, Klaus Busch, Karel Caca, Julia Chevts, Torsten Donaubauer, Rudolf Erlinger, Klaus Funke, Josef Grosskopf, Andreas Hagenow, Monika Hamann, Manfred Hartard, Peter Heymer, Wolfgang Huppertz, Gabriele Illies, Stephan Jacob, Thomas Jung, Gerd Kahrmann, Petra Kast, Monika Kellerer, Hans-Peter Kempe, Andrei Khariouzov, Gerhard Klausmann, Christiane Klein, Uwe Kleinecke-Pohl, Klaus Kleinertz, Thorsten Koch, Christine Kosch, Babette Lorra, Joerg Luedemann, Matthias Luttermann, Stephan Maxeiner, Karsten Milek, Andrea Moelle, Gerhard Neumann, Ruth Nischik, Edith Oehrig-Pohl, Georg Plassmann, Lars Pohlmeier, Felix Proepper, Stefan Regner, Werner Rieker, Ludger Rose, Holger Samer, Joachim Sauter, Frank Schaper, Clemens Schiffer, Juergen Schmidt, Bernd-M. Scholz, Joerg Schulze, Alexander Segner, Jochen Seufert, Helena Sigal, Joerg Steindorf, Juergen Stockhausen, Petra Stuebler, Heidrun Taeschner, Dietrich Tews, Diethelm Tschoepe, Karl Wilhelm, Helga Zeller-Stefan, Iakovos Avramidis, Stavros Bousboulas, Magdalini Bristianou, Georgios Dimitriadis, Moses Elisaf, Kalliopi Kotsa, Andreas Melidonis, Asimina Mitrakou, Emmanouil Pagkalos, Nikolaos Papanas, Angelos Pappas, Christos Sampanis, Nikolaos Tentolouris, Apostolos Tsapas, Glykeria Tzatzagou, Risa Ozaki, Csaba Hajdú, Eleonóra Harcsa, Laszlo Konyves, János Mucsi, Zsolt Pauker, Gizella Petró, Zsolt Plés, Katalin Revesz, Vangel Sándor, Viktor Vass, Angelo Avogaro, Massimo Boemi, Riccardo Bonadonna, Agostino Consoli, Salvatore De Cosmo, Paolo Di Bartolo, Francesco Dotta, Simona Frontoni, Marianna Galetta, Alessandra Gambineri, Carmine Gazzaruso, Francesco Giorgino, Davide Lauro, Emanuela Orsi, Giuseppe Paolisso, Gabriele Perriello, Piermarco Piatti, Antonio Pontiroli, Paola Ponzani, Angela Albarosa Rivellese, Giorgio Sesti, Giancarlo Tonolo, Roberto Trevisan, Chul Woo Ahn, Sei-Hyun Baik, Bong-Soo Cha, Choon-Hee Chung, Hak Chul Jang, Chong-Jin Kim, Hye Soon Kim, In Joo Kim, Eun Young Lee, Hyoung Woo Lee, Kwan-Woo Lee, Keon-Woong Moon, June Namgung, Kyong Soo Park, Soon Jib Yoo, Jaemyung Yu, Edmundo-Alfredo Bayram Llamas, Jose-Luis Cervantes-Escárcega, Luis Fernando Flota-Cervera, José Gerardo González-González, Sara Pascoe-Gonzalez, Emilia Susana Pelayo-Orozco, Santiago-Paulino Ramirez-Diaz, Arturo Saldana-Mendoza, Carlos Sánchez Jerjes-Díaz, Jose Juan Torres-Colores, Maricela Vidrio-Velázquez, Juan Villagordoa-Mesa, Hugo Peter Beijerbacht, Reginald G.E.J. Groutars, Boudewijn A Hoek, Pieter A.M. Hoogslag, Adriaan Kooy, Johannes A. Kragten, Aloysius G. Lieverse, Hendrik P. Swart, Eric P. Viergever, Jørn Ahlqvist, John Cooper, Hanne Gulseth, Gaute Guttormsen, Cecilie Wium, Hugo Arbañil, Jorge Calderon, Luis Camacho, Augusto Dextre Espinoza, Elizabeth Garrido, Alejandro Luna, Helard Manrique, Frederick Massucco Revoredo, Rolando Vargas Gonzales, Luis Zapata Rincon, Carlos Zubiate, Geraldine Ebo, Ellen Morales-Palomares, Malgorzata Arciszewska, Marek Banach, Renata Bijata-Bronisz, Tadeusz Derezinski, Waldemar Gadzinski, Jacek Gajek, Katarzyna Klodawska, Ewa Krzyzagorska, Andrzej Madej, Pawel Miekus, Jaroslaw Opiela, Piotr Romanczuk, Anna Siegel, Ewa Skokowska, Andrzej Stankiewicz, Teresa Stasinska, Iwona Trznadel-Morawska, Robert Witek, Sergey Aksentyev, Irina Bondar, Irina Demidova, Alexander Dreval, Olga Ershova, Gagik Galstyan, Alla Garganeeva, Nadezhda Izmozherova, Victoria Karetnikova, Marina Kharakhulakh, Aleksandr Khokhlov, Zhanna Kobalava, Olga Koshelskaya, Elena Kosmacheva, Vladimir Kostin, Natalia Koziolova, Anatoly Kuzin, Victor Lesnov, Tatyana Lysenko, Valentin Markov, Alexander Mayorov, Sergey Moiseev, Svetlana Myasoedova, Nina Petunina, Andrey Rebrov, Ludmila Ruyatkina, Julia Samoylova, Olga Sazonova, Natalia Shilkina, Nadezhda Sokolova, Olga Vasilevskaya, Nelli Verbovaya, Elena Vishneva, Sergey Vorobyev, Natalya Vorokhobina, Olga Zanozina, Elena Zhdanova, Tatyana Zykova, Lesley Burgess, Kathleen Coetzee, Saleem Dawood, Landman Lombard, Ellen Makotoko, Rajendran Moodley, Wessels Oosthuysen, Mohamed Sarvan, Carlos Calvo Gómez, Isidoro Cano Rodríguez, Almudena Castro Conde, Angel Cequier Fillat, Guillem Cuatrecasas Cambra, Fernando de Álvaro Moreno, Luis De Teresa Parreño, Javier Delgado Lista, José Ramón Domínguez Escribano, Santiago Durán García, Javier Elvira González, José María Fernández Rodríguez, Alberto Goday Arno, Ricardo Gomez Huelgas, José Ramón González Juanatey, Antonio Hernandez Mijares, Víctor Alfonso Jiménez Díaz, Esteban Jodar Gimeno, Tomás Lucas Morante, Monica Marazuela, Nieves Martell Claros, Didac Mauricio Puente, Elena Mena Ribas, Juan Francisco Merino Torres, Pedro Mezquita Raya, Andreu Nubiola Calonge, Xavier Ordoñez Sánchez, Jose Maria Pascual Izuel, Verónica Perea Castilla, Antonio Pérez Pérez, Isabel Perez Soto, Miguel Quesada Charneco, Angustias Quesada Simón, Josep Redón Mas, Antonia Rego Iraeta, Maria Rodriguez Alvarez, Irene Rodríguez Rodríguez, José Sabán Ruiz, Alfonso Soto González, Francisco Tinahones Madueno, Carlos Trescoli Serrano, Angels Ulied Armiñana, Erasmus Bachus, Katarina Berndtsson Blom, Ken Eliasson, Pekka Koskinen, Hans Larnefeldt, Cornelia Lif-Tiberg, Carina Linderfalk, Gustav Lund, Pia Lundman, Linda Moris, Åke Olsson, Staffan Salmonsson, Johan Sanmartin Berglund, Folke Sjöberg, Stefan Söderberg, Ingemar Torstensson, Jung-Fu Chen, Kai Jen Tien, Shih-Ting Tseng, Shih-Te Tu, Chih-Yuan Wang, Ji-Hung Wang, Arintaya Phrommintikul, Sukit Yamwong, Woravut Jintapakorn, Pisit Hutayanon, Nakarin Sansanayudh, Larysa Bazhan, Ivan Fushtey, Mariya Grachova, Vitaliy Katerenchuk, Vadym Korpachev, Nonna Kravchun, Oleksandr Larin, Galyna Mykhalchyshyn, Halyna Myshanych, Olga Oleksyk, Valeriia Orlenko, Nataliia Pashkovska, Nataliia Pertseva, Olena Petrosyan, Ivan Smirnov, Maryna Vlasenko, Tetiana Zlova, Myint Aye, Arun Baksi, Mathangi Balasubramani, Ronnie Beboso, Mark Blagden, Charles Bundy, Tobias Cookson, Allan Copland, Alistair Emslie-Smith, Fiona Green, Anthony Gunstone, Basil Issa, Ewart Jackson-Voyzey, Andrew Johnson, Malcolm Maclean, John McKnight, Solomon Muzulu, Ian O'Connell, Babatunde Oyesile, Catherine Patterson, Ewan Pearson, Sam Philip, Paul Smith, Usha Sukumaran, Jalal Abbas, Gaurav Aggarwala, Faiq Akhter, James Andersen, Moise Anglade, Georges Argoud, Mehrdad Ariani, Reswan Ashdji, Ladan Bakhtari, Subhash Banerjee, Andrew Bartlett, Howard Baum, Harold Bays, Richard Beasley, Renata Belfort de Aguiar, Sabrina Benjamin, Ravi Bhagwat, Anuj Bhargava, Bruce Bode, Christina Bratcher, Toby Briskin, Andrew Brockmyre, Raymond Broughton, Judith Brown, Madhusudan Budhraja, Kevin Cannon, Jewell Carr, Harold Cathcart, Arvind Cavale, Louis Chaykin, Deanna Cheung, Richard Childress, Allan Cohen, Jonathan Condit, Erin Cooksey, George Mitchell Cornett, Ira Dauber, William Davila, Luis De Armas, Julius Dean, Robert Detweiler, Ernesto Diaz, Michael Di Giovanna, Isaac Dor, Waymon Drummond, Donald Eagerton, John Earl, Charles Eaton, Howard Ellison, Neil Farris, Thomas Fiel, Anthony Firek, Brian First, Les Forgosh, William French, Winston Gandy, Ronald Garcia, Santosh Gill, Murray Gordon, Michael Guice, Siva Gummadi, Jonathan Hackenyos, Kristen Hairston, Lenita Hanson, Lindsay Harrison, Israel Hartman, John Heitner, Srini Hejeebu, Paul Hermany, Carlos Hernandez-Cassis, Horacio Hidalgo, Alexander Higgins, Hassan Ibrahim, Shahram Jacobs, David Johnson, Parag Joshi, Steven Kaster, Daniel Kellum, Christopher Kim, Ellen Kim, William Kirby, Albert Knouse, Steven Kulback, Mariananda Kumar, Tulsidas Kuruvanka, Ajay Labroo, William Lasswell, John Lentz, Thomas Lenzmeier, David Lewis, Zhaoping Li, Michael Lillestol, Raymond Little, Richard Lorraine, Cecilia McKeown-Biagas, Robert McNeill, Anand Mehta, Alan Miller, Joseph Moran, Emily Morawski, Venkatesh Nadar, Thomas O'Connor, Alberto Odio, Reginald Parker, Rajesh Patel, Lawrence Phillips, George Raad, Aref Rahman, Marina Raikhel, Ajit Raisinghani, Raj Rajan, Neda Rasouli, Frank Rauzi, Kathryn Rohr, Hal Roseman, Sergio Rovner, Fadi Saba, Richard Sachson, Alex Schabauer, Ricky Schneider, Timothy Schuchard, John Sensenbrenner, Yshay Shlesinger, Narendra Singh, Kanagaratnam Sivalingam, Larry Stonesifer, Daniel Storey, David Suh, Mohammed Tahir, Anjanette Tan, Marilyn Tan, Alain Taylon, Maitreya Thakkar, Devjit Tripathy, Gabriel Uwaifo, Amarnath Vedere, Chandra Venugopal, Anthony Vo, Michelle Welch, James Welker, Alexander White, John Willis, Alan Wynne, Shahram Yazdani, Anne Rosenberg, Lauren Price, Kristina Sigmon, Yuliya Lokhngina, Weibing Xing, Robert Overton, Murray Stewart, Janet Stead, Alistair Lindsay, Vickas Patel, Jorge Ross, Joseph Soffer, Shruti Daga, Margaret Sowell, Prashant Patel, Louisa Garvey, Jessica Ackert, Sybil Abraham, Mary Beth Sabol, Desma Altobelli, JuYoung Ha, Mangesh Kulkarni, Matthew Somerville, Drusilla Noronha, Ed Casson, Eddie Zang, Chamandeep Sandhu, Rakesh Kumar, David Chen, Lin Taft, Rajivkumar Patel, June Ye, Jennifer Shannon, Tim Wilson, Charleen Babi, Diane Miller, Karl Thorpe, Rachael Russell, Georgina Bull, Belinda Hereghty, Eva Fernandez-Salazar, Troy Longley, Jill Donaldson, Marie Jarosz, Karen Murphy, Patricia Adams, Peter Smith, Rachel James, Jackie Richards, Sangeeta Sedani, Denise Althouse, David Watson, Jamie Lorimer, Steven Lauder, Ron Schultheis, Terese Womer, Ella Wraight, Wenyan Li, Emma Price-Olsen, Anthony Watson, Aoife Kelly, Patricia McLaughlin, John Fleming, Jessica Schubert, Debra Schleiden, Tara Harris, Rahul Prakash, Jody Breneman, Sameer Deshpande, Aarti Saswadkar, Aditi Kumari, Aditi Shitut, Amruta Raorane, Anisha Karmalkar, Ankita Mhambrey, Archana Bhosale, Ashok Vaphare, Ashwini P Patil, Chaitali Khandelwal, Fayaz Shaik, Madhumitha Nadar, Mounika Karka, Neha Kadgaonkar, Nikita Gupta, Nutan Aher, Omkar Potnis, Pallavi Naicker, Rakesh Shinde, Richa Sharma, Rupali Godse, Sheetal Solanki, Shruti Sahu, Snehal Dumbre, Somesh Kumar, Suradnya Patil, Trisha Mandal, Hernandez, Adrian F, Green, Jennifer B, Janmohamed, Salim, D'Agostino, Ralph B, Granger, Christopher B, Jones, Nigel P, Leiter, Lawrence A, Rosenberg, Anne E, Sigmon, Kristina N, Somerville, Matthew C, Thorpe, Karl M, Mcmurray, John J V, Del Prato, Stefano, Mcmurray, John J. V., D'Agostino, Ralph B., Granger, Christopher B., Hernandez, Adrian F., Leiter, Lawrence A., Califf, Robert M, Holman, Rury, Demets, David, Riddle, Matthew, Goodman, Shaun, Mcguire, Darren, Alexander, Karen, Devore, Adam, Melloni, Chiara, Patel, Chetan, Kong, David, Bloomfield, Gerald, Roe, Matthew, Tricoci, Pierluigi, Harrison, Rob, Lopes, Renato, Mathews, Robin, Mehta, Rajendra, Schuyler Jones, William, Vemulapalli, Sreekanth, Povsic, Thoma, Eapen, Zubin, Dombrowski, Keith, Kolls, Brad, Jordan, Dedrick, Ambrosy, Andrew, Greene, Stephen, Mandawat, Aditya, Shavadia, Jay, Cooper, Lauren, Sharma, Abhinav, Guimaraes, Patricia, Friedman, Daniel, Wilson, Matt, Endsley, Patricia, Gentry, Tracy, Collier, Jeannie, Perez, Kathleen, James, Kourtnei, Roush, Jennifer, Pope, Connie, Howell, Christina, Johnson, Megan, Bailey, Matt, Cole, Joanna, Akers, Teresa, Vandyne, Beth, Thomas, Betsy, Rich, Jenny, Bartone, Susan, Beaulieu, Gail, Brown, Kim, Chau, Tuan, Christian, Tamra, Coker, Rebecca, Greene, Deb, Haddock, Trevorlyn, Jenkins, Wendy, Haque, Ghazala, Marquess, Marsha, Pesarchick, Jean, Rethaford, Renee, Stone, Allegra, Al Kawas, Fira, Anderson, Michelle, Enns, Robert, Sinay, Isaac, Mathieu, Chantal, Yordanov, Victor, Hramiak, Irene, Haluzik, Martin, Galatius, Søren, Guerci, Bruno, Nauck, Michael, Migdalis, Ilia, Tan, Choon Beng Kathryn, Kocsis, Gyozo, Giaccari, Andrea, Lee, Moon Kyu, Muñoz, Ernesto German Cardona, Cornel, Jan, Birkeland, Kare, Pinto, Miguel, Tirador, Louie, Olesinska-Mader, Martyna, Shestakova, Marina, Distiller, Larry, Lopez-Sendon, Jose, Eliasson, Bjorn, Chiang, Chern-En, Srimahachota, Suphot, Mankovsky, Bori, Bethel, M Angelyn, Dungan, Kathleen, Kosiborod, Mikhail, Alvarisqueta, Andre, Baldovino, Jorge, Besada, Diego, Calella, Pedro, Cantero, Maria Cecilia, Castaño, Patricia, Chertkoff, Alejandro, Cuadrado, Jesu, De Loredo, Lui, Dominguez, Andrea, Español, Maria Vanesa, Finkelstein, Hernan, Frechtel, Gustavo, Fretes, Jose, Garrido Santos, Natalia, Gonzalez, Joaquin, Litvak, Marco, Loureyro, Juan, Maffei, Laura, Maldonado, Natacha, Mohr Gasparini, Diego, Orio, Silvia, Perez Manghi, Federico, Rodriguez Papini, Nelson, Sala, Jorgelina, Schygiel, Pablo, Sposetti, Georgina, Ulla, Maria, Verra, Fernando, Zabalua, Silvina, Zaidman, Cesar, Crenier, Laurent, Debroye, Corinne, Duyck, Franci, Scheen, André, Van Gaal, Luc, Vercammen, Chri, Damyanova, Velichka, Dimitrov, Stefan, Kovacheva, Snezhina, Lozanov, Lachezar, Margaritov, Viktor, Mihaylova-Shumkova, Rositsa, Nikolaeva, Antoaneta, Stoyanova, Zhasmina, Akhras, Ronald, Beaudry, Yve, Bedard, Jacque, Berlingieri, Joseph, Chehayeb, Raja, Cheung, Stephen, Conway, Jame, Cusson, Jean, Della Siega, Anthony, Dumas, Richard, Dzongowski, Peter, Ferguson, Murdo, Gaudet, Daniel, Grondin, Francoi, Gupta, Anil, Gupta, Milan, Halperin, Frank, Houle, Pierre-Alain, Jones, Michael, Kouz, Simon, Kovacs, Christopher, Landry, Daniel, Lonn, Eva, O'Mahony, William, Peterson, Sean, Reich, Denni, Rosenbloom, Alan, St-Maurice, Francoi, Tugwell, Barna, Vizel, Saul, Woo, Vincent, Brychta, Toma, Cech, Vladimir, Dvorakova, Eva, Edelsberger, Toma, Halciakova, Katarina, Krizova, Jarmila, Lastuvka, Jiri, Piperek, Martin, Prymkova, Vera, Raclavska, Lea, Silhova, Elena, Urbanek, Robin, Vrkoc, Jan, Andersen, Ulla, Brønnum-Schou, Jen, Hove, Jen, Jensen, Jan Skov, Kober, Lar, Kristiansen, Ole Peter, Lund, Per, Melchior, Thoma, Nyvad, Ole, Schou, Morten, Boye, Alain, Cadinot, Didier, Gouet, Didier, Henry, Patrick, Kessler, Laurence, Lalau, Jean-Daniel, Petit, Catherine, Thuan, Jean-Francoi, Voinot, Christel, Vouillarmet, Julien, Axthelm, Christoph, Berger, Dirk, Bieler, Tasso, Birkenfeld, Andrea, Bott, Jochen, Busch, Klau, Caca, Karel, Chevts, Julia, Donaubauer, Torsten, Erlinger, Rudolf, Funke, Klau, Grosskopf, Josef, Hagenow, Andrea, Hamann, Monika, Hartard, Manfred, Heymer, Peter, Huppertz, Wolfgang, Illies, Gabriele, Jacob, Stephan, Jung, Thoma, Kahrmann, Gerd, Kast, Petra, Kellerer, Monika, Kempe, Hans-Peter, Khariouzov, Andrei, Klausmann, Gerhard, Klein, Christiane, Kleinecke-Pohl, Uwe, Kleinertz, Klau, Koch, Thorsten, Kosch, Christine, Lorra, Babette, Luedemann, Joerg, Luttermann, Matthia, Maxeiner, Stephan, Milek, Karsten, Moelle, Andrea, Neumann, Gerhard, Nischik, Ruth, Oehrig-Pohl, Edith, Plassmann, Georg, Pohlmeier, Lar, Proepper, Felix, Regner, Stefan, Rieker, Werner, Rose, Ludger, Samer, Holger, Sauter, Joachim, Schaper, Frank, Schiffer, Clemen, Schmidt, Juergen, Scholz, Bernd-M., Schulze, Joerg, Segner, Alexander, Seufert, Jochen, Sigal, Helena, Steindorf, Joerg, Stockhausen, Juergen, Stuebler, Petra, Taeschner, Heidrun, Tews, Dietrich, Tschoepe, Diethelm, Wilhelm, Karl, Zeller-Stefan, Helga, Avramidis, Iakovo, Bousboulas, Stavro, Bristianou, Magdalini, Dimitriadis, Georgio, Elisaf, Mose, Kotsa, Kalliopi, Melidonis, Andrea, Mitrakou, Asimina, Pagkalos, Emmanouil, Papanas, Nikolao, Pappas, Angelo, Sampanis, Christo, Tentolouris, Nikolao, Tsapas, Apostolo, Tzatzagou, Glykeria, Ozaki, Risa, Hajdú, Csaba, Harcsa, Eleonóra, Konyves, Laszlo, Mucsi, Jáno, Pauker, Zsolt, Petró, Gizella, Plés, Zsolt, Revesz, Katalin, Sándor, Vangel, Vass, Viktor, Avogaro, Angelo, Boemi, Massimo, Bonadonna, Riccardo, Consoli, Agostino, De Cosmo, Salvatore, Di Bartolo, Paolo, Dotta, Francesco, Frontoni, Simona, Galetta, Marianna, Gambineri, Alessandra, Gazzaruso, Carmine, Giorgino, Francesco, Lauro, Davide, Orsi, Emanuela, Paolisso, Giuseppe, Perriello, Gabriele, Piatti, Piermarco, Pontiroli, Antonio, Ponzani, Paola, Rivellese, Angela Albarosa, Sesti, Giorgio, Tonolo, Giancarlo, Trevisan, Roberto, Ahn, Chul Woo, Baik, Sei-Hyun, Cha, Bong-Soo, Chung, Choon-Hee, Jang, Hak Chul, Kim, Chong-Jin, Kim, Hye Soon, Kim, In Joo, Lee, Eun Young, Lee, Hyoung Woo, Lee, Kwan-Woo, Moon, Keon-Woong, Namgung, June, Park, Kyong Soo, Yoo, Soon Jib, Yu, Jaemyung, Llamas, Edmundo-Alfredo Bayram, Cervantes-Escárcega, Jose-Lui, Flota-Cervera, Luis Fernando, González-González, José Gerardo, Pascoe-Gonzalez, Sara, Pelayo-Orozco, Emilia Susana, Ramirez-Diaz, Santiago-Paulino, Saldana-Mendoza, Arturo, Jerjes-Díaz, Carlos Sánchez, Torres-Colores, Jose Juan, Vidrio-Velázquez, Maricela, Villagordoa-Mesa, Juan, Beijerbacht, Hugo Peter, Groutars, Reginald G. E. J., Hoek, Boudewijn A, Hoogslag, Pieter A. M., Kooy, Adriaan, Kragten, Johannes A., Lieverse, Aloysius G., Swart, Hendrik P., Viergever, Eric P., Ahlqvist, Jørn, Cooper, John, Gulseth, Hanne, Guttormsen, Gaute, Wium, Cecilie, Arbañil, Hugo, Calderon, Jorge, Camacho, Lui, Espinoza, Augusto Dextre, Garrido, Elizabeth, Luna, Alejandro, Manrique, Helard, Revoredo, Frederick Massucco, Gonzales, Rolando Varga, Rincon, Luis Zapata, Zubiate, Carlo, Ebo, Geraldine, Morales-Palomares, Ellen, Arciszewska, Malgorzata, Banach, Marek, Bijata-Bronisz, Renata, Derezinski, Tadeusz, Gadzinski, Waldemar, Gajek, Jacek, Klodawska, Katarzyna, Krzyzagorska, Ewa, Madej, Andrzej, Miekus, Pawel, Opiela, Jaroslaw, Romanczuk, Piotr, Siegel, Anna, Skokowska, Ewa, Stankiewicz, Andrzej, Stasinska, Teresa, Trznadel-Morawska, Iwona, Witek, Robert, Aksentyev, Sergey, Bondar, Irina, Demidova, Irina, Dreval, Alexander, Ershova, Olga, Galstyan, Gagik, Garganeeva, Alla, Izmozherova, Nadezhda, Karetnikova, Victoria, Kharakhulakh, Marina, Khokhlov, Aleksandr, Kobalava, Zhanna, Koshelskaya, Olga, Kosmacheva, Elena, Kostin, Vladimir, Koziolova, Natalia, Kuzin, Anatoly, Lesnov, Victor, Lysenko, Tatyana, Markov, Valentin, Mayorov, Alexander, Moiseev, Sergey, Myasoedova, Svetlana, Petunina, Nina, Rebrov, Andrey, Ruyatkina, Ludmila, Samoylova, Julia, Sazonova, Olga, Shilkina, Natalia, Sokolova, Nadezhda, Vasilevskaya, Olga, Verbovaya, Nelli, Vishneva, Elena, Vorobyev, Sergey, Vorokhobina, Natalya, Zanozina, Olga, Zhdanova, Elena, Zykova, Tatyana, Burgess, Lesley, Coetzee, Kathleen, Dawood, Saleem, Lombard, Landman, Makotoko, Ellen, Moodley, Rajendran, Oosthuysen, Wessel, Sarvan, Mohamed, Calvo Gómez, Carlo, Cano Rodríguez, Isidoro, Castro Conde, Almudena, Cequier Fillat, Angel, Cuatrecasas Cambra, Guillem, de Álvaro Moreno, Fernando, De Teresa Parreño, Lui, Delgado Lista, Javier, Domínguez Escribano, José Ramón, Durán García, Santiago, Elvira González, Javier, Fernández Rodríguez, José María, Goday Arno, Alberto, Gomez Huelgas, Ricardo, González Juanatey, José Ramón, Hernandez Mijares, Antonio, Jiménez Díaz, Víctor Alfonso, Jodar Gimeno, Esteban, Lucas Morante, Tomá, Marazuela, Monica, Martell Claros, Nieve, Mauricio Puente, Didac, Mena Ribas, Elena, Merino Torres, Juan Francisco, Mezquita Raya, Pedro, Nubiola Calonge, Andreu, Ordoñez Sánchez, Xavier, Pascual Izuel, Jose Maria, Perea Castilla, Verónica, Pérez Pérez, Antonio, Perez Soto, Isabel, Quesada Charneco, Miguel, Quesada Simón, Angustia, Redón Mas, Josep, Rego Iraeta, Antonia, Rodriguez Alvarez, Maria, Rodríguez Rodríguez, Irene, Sabán Ruiz, José, Soto González, Alfonso, Tinahones Madueno, Francisco, Trescoli Serrano, Carlo, Ulied Armiñana, Angel, Bachus, Erasmu, Berndtsson Blom, Katarina, Eliasson, Ken, Koskinen, Pekka, Larnefeldt, Han, Lif-Tiberg, Cornelia, Linderfalk, Carina, Lund, Gustav, Lundman, Pia, Moris, Linda, Olsson, Åke, Salmonsson, Staffan, Sanmartin Berglund, Johan, Sjöberg, Folke, Söderberg, Stefan, Torstensson, Ingemar, Chen, Jung-Fu, Tien, Kai Jen, Tseng, Shih-Ting, Tu, Shih-Te, Wang, Chih-Yuan, Wang, Ji-Hung, Phrommintikul, Arintaya, Yamwong, Sukit, Jintapakorn, Woravut, Hutayanon, Pisit, Sansanayudh, Nakarin, Bazhan, Larysa, Fushtey, Ivan, Grachova, Mariya, Katerenchuk, Vitaliy, Korpachev, Vadym, Kravchun, Nonna, Larin, Oleksandr, Mykhalchyshyn, Galyna, Myshanych, Halyna, Oleksyk, Olga, Orlenko, Valeriia, Pashkovska, Nataliia, Pertseva, Nataliia, Petrosyan, Olena, Smirnov, Ivan, Vlasenko, Maryna, Zlova, Tetiana, Aye, Myint, Baksi, Arun, Balasubramani, Mathangi, Beboso, Ronnie, Blagden, Mark, Bundy, Charle, Cookson, Tobia, Copland, Allan, Emslie-Smith, Alistair, Green, Fiona, Gunstone, Anthony, Issa, Basil, Jackson-Voyzey, Ewart, Johnson, Andrew, Maclean, Malcolm, Mcknight, John, Muzulu, Solomon, O'Connell, Ian, Oyesile, Babatunde, Patterson, Catherine, Pearson, Ewan, Philip, Sam, Smith, Paul, Sukumaran, Usha, Abbas, Jalal, Aggarwala, Gaurav, Akhter, Faiq, Andersen, Jame, Anglade, Moise, Argoud, George, Ariani, Mehrdad, Ashdji, Reswan, Bakhtari, Ladan, Banerjee, Subhash, Bartlett, Andrew, Baum, Howard, Bays, Harold, Beasley, Richard, Belfort de Aguiar, Renata, Benjamin, Sabrina, Bhagwat, Ravi, Bhargava, Anuj, Bode, Bruce, Bratcher, Christina, Briskin, Toby, Brockmyre, Andrew, Broughton, Raymond, Brown, Judith, Budhraja, Madhusudan, Cannon, Kevin, Carr, Jewell, Cathcart, Harold, Cavale, Arvind, Chaykin, Loui, Cheung, Deanna, Childress, Richard, Cohen, Allan, Condit, Jonathan, Cooksey, Erin, Cornett, George Mitchell, Dauber, Ira, Davila, William, De Armas, Lui, Dean, Juliu, Detweiler, Robert, Diaz, Ernesto, Di Giovanna, Michael, Dor, Isaac, Drummond, Waymon, Eagerton, Donald, Earl, John, Eaton, Charle, Ellison, Howard, Farris, Neil, Fiel, Thoma, Firek, Anthony, First, Brian, Forgosh, Le, French, William, Gandy, Winston, Garcia, Ronald, Gill, Santosh, Gordon, Murray, Guice, Michael, Gummadi, Siva, Hackenyos, Jonathan, Hairston, Kristen, Hanson, Lenita, Harrison, Lindsay, Hartman, Israel, Heitner, John, Hejeebu, Srini, Hermany, Paul, Hernandez-Cassis, Carlo, Hidalgo, Horacio, Higgins, Alexander, Ibrahim, Hassan, Jacobs, Shahram, Johnson, David, Joshi, Parag, Kaster, Steven, Kellum, Daniel, Kim, Christopher, Kim, Ellen, Kirby, William, Knouse, Albert, Kulback, Steven, Kumar, Mariananda, Kuruvanka, Tulsida, Labroo, Ajay, Lasswell, William, Lentz, John, Lenzmeier, Thoma, Lewis, David, Li, Zhaoping, Lillestol, Michael, Little, Raymond, Lorraine, Richard, McKeown-Biagas, Cecilia, Mcneill, Robert, Mehta, Anand, Miller, Alan, Moran, Joseph, Morawski, Emily, Nadar, Venkatesh, O'Connor, Thoma, Odio, Alberto, Parker, Reginald, Patel, Rajesh, Phillips, Lawrence, Raad, George, Rahman, Aref, Raikhel, Marina, Raisinghani, Ajit, Rajan, Raj, Rasouli, Neda, Rauzi, Frank, Rohr, Kathryn, Roseman, Hal, Rovner, Sergio, Saba, Fadi, Sachson, Richard, Schabauer, Alex, Schneider, Ricky, Schuchard, Timothy, Sensenbrenner, John, Shlesinger, Yshay, Singh, Narendra, Sivalingam, Kanagaratnam, Stonesifer, Larry, Storey, Daniel, Suh, David, Tahir, Mohammed, Tan, Anjanette, Tan, Marilyn, Taylon, Alain, Thakkar, Maitreya, Tripathy, Devjit, Uwaifo, Gabriel, Vedere, Amarnath, Venugopal, Chandra, Vo, Anthony, Welch, Michelle, Welker, Jame, White, Alexander, Willis, John, Wynne, Alan, Yazdani, Shahram, Rosenberg, Anne, Price, Lauren, Sigmon, Kristina, Lokhngina, Yuliya, Xing, Weibing, Overton, Robert, Stewart, Murray, Stead, Janet, Lindsay, Alistair, Patel, Vicka, Ross, Jorge, Soffer, Joseph, Daga, Shruti, Sowell, Margaret, Patel, Prashant, Garvey, Louisa, Ackert, Jessica, Abraham, Sybil, Sabol, Mary Beth, Altobelli, Desma, Ha, Juyoung, Kulkarni, Mangesh, Somerville, Matthew, Noronha, Drusilla, Casson, Ed, Zang, Eddie, Sandhu, Chamandeep, Kumar, Rakesh, Chen, David, Taft, Lin, Patel, Rajivkumar, Ye, June, Shannon, Jennifer, Wilson, Tim, Babi, Charleen, Miller, Diane, Thorpe, Karl, Russell, Rachael, Bull, Georgina, Hereghty, Belinda, Fernandez-Salazar, Eva, Longley, Troy, Donaldson, Jill, Jarosz, Marie, Murphy, Karen, Adams, Patricia, Smith, Peter, James, Rachel, Richards, Jackie, Sedani, Sangeeta, Althouse, Denise, Watson, David, Lorimer, Jamie, Lauder, Steven, Schultheis, Ron, Womer, Terese, Wraight, Ella, Li, Wenyan, Price-Olsen, Emma, Watson, Anthony, Kelly, Aoife, Mclaughlin, Patricia, Fleming, John, Schubert, Jessica, Schleiden, Debra, Harris, Tara, Prakash, Rahul, Breneman, Jody, Deshpande, Sameer, Saswadkar, Aarti, Kumari, Aditi, Shitut, Aditi, Raorane, Amruta, Karmalkar, Anisha, Mhambrey, Ankita, Bhosale, Archana, Vaphare, Ashok, Patil, Ashwini P, Khandelwal, Chaitali, Shaik, Fayaz, Nadar, Madhumitha, Karka, Mounika, Kadgaonkar, Neha, Gupta, Nikita, Aher, Nutan, Potnis, Omkar, Naicker, Pallavi, Shinde, Rakesh, Sharma, Richa, Godse, Rupali, Solanki, Sheetal, Sahu, Shruti, Dumbre, Snehal, Kumar, Somesh, Patil, Suradnya, Mandal, Trisha, McMurray, John J V, McMurray, John J.V., DeMets, David, McGuire, Darren, Groutars, Reginald G.E.J., Hoogslag, Pieter A.M., McKnight, John, McNeill, Robert, Ha, JuYoung, McLaughlin, Patricia, Hernandez, A. 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M., Dauber, I., Davila, W., De Armas, L., Dean, J., Detweiler, R., Diaz, E., Di Giovanna, M., Dor, I., Drummond, W., Eagerton, D., Earl, J., Eaton, C., Ellison, H., Farris, N., Fiel, T., Firek, A., First, B., Forgosh, L., French, W., Gandy, W., Garcia, R., Gill, S., Gordon, M., Guice, M., Gummadi, S., Hackenyos, J., Hairston, K., Hanson, L., Harrison, L., Hartman, I., Heitner, J., Hejeebu, S., Hermany, P., Hernandez-Cassis, C., Hidalgo, H., Higgins, A., Ibrahim, H., Jacobs, S., Johnson, D., Joshi, P., Kaster, S., Kellum, D., Kim, C., Kim, E., Kirby, W., Knouse, A., Kulback, S., Kumar, M., Kuruvanka, T., Labroo, A., Lasswell, W., Lentz, J., Lenzmeier, T., Lewis, D., Li, Z., Lillestol, M., Little, R., Lorraine, R., McKeown-Biagas, C., Mcneill, R., Mehta, A., Miller, A., Moran, J., Morawski, E., Nadar, V., O'Connor, T., Odio, A., Parker, R., Patel, R., Phillips, L., Raad, G., Rahman, A., Raikhel, M., Raisinghani, A., Rajan, R., Rasouli, N., Rauzi, F., Rohr, K., Roseman, H., Rovner, S., Saba, F., Sachson, R., Schabauer, A., Schneider, R., Schuchard, T., Sensenbrenner, J., Shlesinger, Y., Singh, N., Sivalingam, K., Stonesifer, L., Storey, D., Suh, D., Tahir, M., Tan, A., Tan, M., Taylon, A., Thakkar, M., Tripathy, D., Uwaifo, G., Vedere, A., Venugopal, C., Vo, A., Welch, M., Welker, J., White, A., Willis, J., Wynne, A., Yazdani, S., Price, L., Lokhngina, Y., Xing, W., Overton, R., Stewart, M., Stead, J., Lindsay, A., Patel, V., Ross, J., Soffer, J., Daga, S., Sowell, M., Patel, P., Garvey, L., Ackert, J., Abraham, S., Sabol, M. B., Altobelli, D., Ha, J., Kulkarni, M., Noronha, D., Casson, E., Zang, E., Sandhu, C., Kumar, R., Chen, D., Taft, L., Ye, J., Shannon, J., Wilson, T., Babi, C., Miller, D., Russell, R., Bull, G., Hereghty, B., Fernandez-Salazar, E., Longley, T., Donaldson, J., Jarosz, M., Murphy, K., Adams, P., James, R., Richards, J., Sedani, S., Althouse, D., Watson, D., Lorimer, J., Lauder, S., Schultheis, R., Womer, T., Wraight, E., Li, W., Price-Olsen, E., Watson, A., Kelly, A., Mclaughlin, P., Fleming, J., Schubert, J., Schleiden, D., Harris, T., Prakash, R., Breneman, J., Deshpande, S., Saswadkar, A., Kumari, A., Shitut, A., Raorane, A., Karmalkar, A., Mhambrey, A., Bhosale, A., Vaphare, A., Patil, A. P., Khandelwal, C., Shaik, F., Nadar, M., Karka, M., Kadgaonkar, N., Gupta, N., Aher, N., Potnis, O., Naicker, P., Shinde, R., Sharma, R., Godse, R., Solanki, S., Sahu, S., Dumbre, S., Kumar, S., Patil, S., Mandal, T., Skin function and permeability, Dermatology, Hernandez, A, Green, J, Janmohamed, S, D'Agostino, R, Granger, C, Jones, N, Leiter, L, Rosenberg, A, Sigmon, K, Somerville, M, Thorpe, K, Mcmurray, J, Del Prato, S, Califf, R, Holman, R, Demets, D, Riddle, M, Goodman, S, Mcguire, D, Alexander, K, Devore, A, Melloni, C, Patel, C, Kong, D, Bloomfield, G, Roe, M, Tricoci, P, Harrison, R, Lopes, R, Mathews, R, Mehta, R, Schuyler Jones, W, Vemulapalli, S, Povsic, T, Eapen, Z, Dombrowski, K, Kolls, B, Jordan, D, Ambrosy, A, Greene, S, Mandawat, A, Shavadia, J, Cooper, L, Sharma, A, Guimaraes, P, Friedman, D, Wilson, M, Endsley, P, Gentry, T, Collier, J, Perez, K, James, K, Roush, J, Pope, C, Howell, C, Johnson, M, Bailey, M, Cole, J, Akers, T, Vandyne, B, Thomas, B, Rich, J, Bartone, S, Beaulieu, G, Brown, K, Chau, T, Christian, T, Coker, R, Greene, D, Haddock, T, Jenkins, W, Haque, G, Marquess, M, Pesarchick, J, Rethaford, R, Stone, A, Al Kawas, F, Anderson, M, Enns, R, Sinay, I, Mathieu, C, Yordanov, V, Hramiak, I, Haluzik, M, Galatius, S, Guerci, B, Nauck, M, Migdalis, I, Tan, C, Kocsis, G, Giaccari, A, Lee, M, Munoz, E, Cornel, J, Birkeland, K, Pinto, M, Tirador, L, Olesinska-Mader, M, Shestakova, M, Distiller, L, Lopez-Sendon, J, Eliasson, B, Chiang, C, Srimahachota, S, Mankovsky, B, Bethel, M, Dungan, K, Kosiborod, M, Alvarisqueta, A, Baldovino, J, Besada, D, Calella, P, Cantero, M, Castano, P, Chertkoff, A, Cuadrado, J, De Loredo, L, Dominguez, A, Espanol, M, Finkelstein, H, Frechtel, G, Fretes, J, Garrido Santos, N, Gonzalez, J, Litvak, M, Loureyro, J, Maffei, L, Maldonado, N, Mohr Gasparini, D, Orio, S, Perez Manghi, F, Rodriguez Papini, N, Sala, J, Schygiel, P, Sposetti, G, Ulla, M, Verra, F, Zabalua, S, Zaidman, C, Crenier, L, Debroye, C, Duyck, F, Scheen, A, Van Gaal, L, Vercammen, C, Damyanova, V, Dimitrov, S, Kovacheva, S, Lozanov, L, Margaritov, V, Mihaylova-Shumkova, R, Nikolaeva, A, Stoyanova, Z, Akhras, R, Beaudry, Y, Bedard, J, Berlingieri, J, Chehayeb, R, Cheung, S, Conway, J, Cusson, J, Della Siega, A, Dumas, R, Dzongowski, P, Ferguson, M, Gaudet, D, Grondin, F, Gupta, A, Gupta, M, Halperin, F, Houle, P, Jones, M, Kouz, S, Kovacs, C, Landry, D, Lonn, E, O'Mahony, W, Peterson, S, Reich, D, Rosenbloom, A, St-Maurice, F, Tugwell, B, Vizel, S, Woo, V, Brychta, T, Cech, V, Dvorakova, E, Edelsberger, T, Halciakova, K, Krizova, J, Lastuvka, J, Piperek, M, Prymkova, V, Raclavska, L, Silhova, E, Urbanek, R, Vrkoc, J, Andersen, U, Bronnum-Schou, J, Hove, J, Jensen, J, Kober, L, Kristiansen, O, Lund, P, Melchior, T, Nyvad, O, Schou, M, Boye, A, Cadinot, D, Gouet, D, Henry, P, Kessler, L, Lalau, J, Petit, C, Thuan, J, Voinot, C, Vouillarmet, J, Axthelm, C, Berger, D, Bieler, T, Birkenfeld, A, Bott, J, Busch, K, Caca, K, Chevts, J, Donaubauer, T, Erlinger, R, Funke, K, Grosskopf, J, Hagenow, A, Hamann, M, Hartard, M, Heymer, P, Huppertz, W, Illies, G, Jacob, S, Jung, T, Kahrmann, G, Kast, P, Kellerer, M, Kempe, H, Khariouzov, A, Klausmann, G, Klein, C, Kleinecke-Pohl, U, Kleinertz, K, Koch, T, Kosch, C, Lorra, B, Luedemann, J, Luttermann, M, Maxeiner, S, Milek, K, Moelle, A, Neumann, G, Nischik, R, Oehrig-Pohl, E, Plassmann, G, Pohlmeier, L, Proepper, F, Regner, S, Rieker, W, Rose, L, Samer, H, Sauter, J, Schaper, F, Schiffer, C, Schmidt, J, Scholz, B, Schulze, J, Segner, A, Seufert, J, Sigal, H, Steindorf, J, Stockhausen, J, Stuebler, P, Taeschner, H, Tews, D, Tschoepe, D, Wilhelm, K, Zeller-Stefan, H, Avramidis, I, Bousboulas, S, Bristianou, M, Dimitriadis, G, Elisaf, M, Kotsa, K, Melidonis, A, Mitrakou, A, Pagkalos, E, Papanas, N, Pappas, A, Sampanis, C, Tentolouris, N, Tsapas, A, Tzatzagou, G, Ozaki, R, Hajdu, C, Harcsa, E, Konyves, L, Mucsi, J, Pauker, Z, Petro, G, Ples, Z, Revesz, K, Sandor, V, Vass, V, Avogaro, A, Boemi, M, Bonadonna, R, Consoli, A, De Cosmo, S, Di Bartolo, P, Dotta, F, Frontoni, S, Galetta, M, Gambineri, A, Gazzaruso, C, Giorgino, F, Lauro, D, Orsi, E, Paolisso, G, Perriello, G, Piatti, P, Pontiroli, A, Ponzani, P, Rivellese, A, Sesti, G, Tonolo, G, Trevisan, R, Ahn, C, Baik, S, Cha, B, Chung, C, Jang, H, Kim, C, Kim, H, Kim, I, Lee, E, Lee, H, Lee, K, Moon, K, Namgung, J, Park, K, Yoo, S, Yu, J, Llamas, E, Cervantes-Escarcega, J, Flota-Cervera, L, Gonzalez-Gonzalez, J, Pascoe-Gonzalez, S, Pelayo-Orozco, E, Ramirez-Diaz, S, Saldana-Mendoza, A, Jerjes-Diaz, C, Torres-Colores, J, Vidrio-Velazquez, M, Villagordoa-Mesa, J, Beijerbacht, H, Groutars, R, Hoek, B, Hoogslag, P, Kooy, A, Kragten, J, Lieverse, A, Swart, H, Viergever, E, Ahlqvist, J, Cooper, J, Gulseth, H, Guttormsen, G, Wium, C, Arbanil, H, Calderon, J, Camacho, L, Espinoza, A, Garrido, E, Luna, A, Manrique, H, Revoredo, F, Gonzales, R, Rincon, L, Zubiate, C, Ebo, G, Morales-Palomares, E, Arciszewska, M, Banach, M, Bijata-Bronisz, R, Derezinski, T, Gadzinski, W, Gajek, J, Klodawska, K, Krzyzagorska, E, Madej, A, Miekus, P, Opiela, J, Romanczuk, P, Siegel, A, Skokowska, E, Stankiewicz, A, Stasinska, T, Trznadel-Morawska, I, Witek, R, Aksentyev, S, Bondar, I, Demidova, I, Dreval, A, Ershova, O, Galstyan, G, Garganeeva, A, Izmozherova, N, Karetnikova, V, Kharakhulakh, M, Khokhlov, A, Kobalava, Z, Koshelskaya, O, Kosmacheva, E, Kostin, V, Koziolova, N, Kuzin, A, Lesnov, V, Lysenko, T, Markov, V, Mayorov, A, Moiseev, S, Myasoedova, S, Petunina, N, Rebrov, A, Ruyatkina, L, Samoylova, J, Sazonova, O, Shilkina, N, Sokolova, N, Vasilevskaya, O, Verbovaya, N, Vishneva, E, Vorobyev, S, Vorokhobina, N, Zanozina, O, Zhdanova, E, Zykova, T, Burgess, L, Coetzee, K, Dawood, S, Lombard, L, Makotoko, E, Moodley, R, Oosthuysen, W, Sarvan, M, Calvo Gomez, C, Cano Rodriguez, I, Castro Conde, A, Cequier Fillat, A, Cuatrecasas Cambra, G, de Alvaro Moreno, F, De Teresa Parreno, L, Delgado Lista, J, Dominguez Escribano, J, Duran Garcia, S, Elvira Gonzalez, J, Fernandez Rodriguez, J, Goday Arno, A, Gomez Huelgas, R, Gonzalez Juanatey, J, Hernandez Mijares, A, Jimenez Diaz, V, Jodar Gimeno, E, Lucas Morante, T, Marazuela, M, Martell Claros, N, Mauricio Puente, D, Mena Ribas, E, Merino Torres, J, Mezquita Raya, P, Nubiola Calonge, A, Ordonez Sanchez, X, Pascual Izuel, J, Perea Castilla, V, Perez Perez, A, Perez Soto, I, Quesada Charneco, M, Quesada Simon, A, Redon Mas, J, Rego Iraeta, A, Rodriguez Alvarez, M, Rodriguez Rodriguez, I, Saban Ruiz, J, Soto Gonzalez, A, Tinahones Madueno, F, Trescoli Serrano, C, Ulied Arminana, A, Bachus, E, Berndtsson Blom, K, Eliasson, K, Koskinen, P, Larnefeldt, H, Lif-Tiberg, C, Linderfalk, C, Lund, G, Lundman, P, Moris, L, Olsson, A, Salmonsson, S, Sanmartin Berglund, J, Sjoberg, F, Soderberg, S, Torstensson, I, Chen, J, Tien, K, Tseng, S, Tu, S, Wang, C, Wang, J, Phrommintikul, A, Yamwong, S, Jintapakorn, W, Hutayanon, P, Sansanayudh, N, Bazhan, L, Fushtey, I, Grachova, M, Katerenchuk, V, Korpachev, V, Kravchun, N, Larin, O, Mykhalchyshyn, G, Myshanych, H, Oleksyk, O, Orlenko, V, Pashkovska, N, Pertseva, N, Petrosyan, O, Smirnov, I, Vlasenko, M, Zlova, T, Aye, M, Baksi, A, Balasubramani, M, Beboso, R, Blagden, M, Bundy, C, Cookson, T, Copland, A, Emslie-Smith, A, Green, F, Gunstone, A, Issa, B, Jackson-Voyzey, E, Johnson, A, Maclean, M, Mcknight, J, Muzulu, S, O'Connell, I, Oyesile, B, Patterson, C, Pearson, E, Philip, S, Smith, P, Sukumaran, U, Abbas, J, Aggarwala, G, Akhter, F, Andersen, J, Anglade, M, Argoud, G, Ariani, M, Ashdji, R, Bakhtari, L, Banerjee, S, Bartlett, A, Baum, H, Bays, H, Beasley, R, Belfort de Aguiar, R, Benjamin, S, Bhagwat, R, Bhargava, A, Bode, B, Bratcher, C, Briskin, T, Brockmyre, A, Broughton, R, Brown, J, Budhraja, M, Cannon, K, Carr, J, Cathcart, H, Cavale, A, Chaykin, L, Cheung, D, Childress, R, Cohen, A, Condit, J, Cooksey, E, Cornett, G, Dauber, I, Davila, W, De Armas, L, Dean, J, Detweiler, R, Diaz, E, Di Giovanna, M, Dor, I, Drummond, W, Eagerton, D, Earl, J, Eaton, C, Ellison, H, Farris, N, Fiel, T, Firek, A, First, B, Forgosh, L, French, W, Gandy, W, Garcia, R, Gill, S, Gordon, M, Guice, M, Gummadi, S, Hackenyos, J, Hairston, K, Hanson, L, Harrison, L, Hartman, I, Heitner, J, Hejeebu, S, Hermany, P, Hernandez-Cassis, C, Hidalgo, H, Higgins, A, Ibrahim, H, Jacobs, S, Johnson, D, Joshi, P, Kaster, S, Kellum, D, Kim, E, Kirby, W, Knouse, A, Kulback, S, Kumar, M, Kuruvanka, T, Labroo, A, Lasswell, W, Lentz, J, Lenzmeier, T, Lewis, D, Li, Z, Lillestol, M, Little, R, Lorraine, R, McKeown-Biagas, C, Mcneill, R, Mehta, A, Miller, A, Moran, J, Morawski, E, Nadar, V, O'Connor, T, Odio, A, Parker, R, Patel, R, Phillips, L, Raad, G, Rahman, A, Raikhel, M, Raisinghani, A, Rajan, R, Rasouli, N, Rauzi, F, Rohr, K, Roseman, H, Rovner, S, Saba, F, Sachson, R, Schabauer, A, Schneider, R, Schuchard, T, Sensenbrenner, J, Shlesinger, Y, Singh, N, Sivalingam, K, Stonesifer, L, Storey, D, Suh, D, Tahir, M, Tan, A, Tan, M, Taylon, A, Thakkar, M, Tripathy, D, Uwaifo, G, Vedere, A, Venugopal, C, Vo, A, Welch, M, Welker, J, White, A, Willis, J, Wynne, A, Yazdani, S, Price, L, Lokhngina, Y, Xing, W, Overton, R, Stewart, M, Stead, J, Lindsay, A, Patel, V, Ross, J, Soffer, J, Daga, S, Sowell, M, Patel, P, Garvey, L, Ackert, J, Abraham, S, Sabol, M, Altobelli, D, Ha, J, Kulkarni, M, Noronha, D, Casson, E, Zang, E, Sandhu, C, Kumar, R, Chen, D, Taft, L, Ye, J, Shannon, J, Wilson, T, Babi, C, Miller, D, Russell, R, Bull, G, Hereghty, B, Fernandez-Salazar, E, Longley, T, Donaldson, J, Jarosz, M, Murphy, K, Adams, P, James, R, Richards, J, Sedani, S, Althouse, D, Watson, D, Lorimer, J, Lauder, S, Schultheis, R, Womer, T, Wraight, E, Li, W, Price-Olsen, E, Watson, A, Kelly, A, Mclaughlin, P, Fleming, J, Schubert, J, Schleiden, D, Harris, T, Prakash, R, Breneman, J, Deshpande, S, Saswadkar, A, Kumari, A, Shitut, A, Raorane, A, Karmalkar, A, Mhambrey, A, Bhosale, A, Vaphare, A, Patil, A, Khandelwal, C, Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, N, Aher, N, Potnis, O, Naicker, P, Shinde, R, Sharma, R, Godse, R, Solanki, S, Sahu, S, Dumbre, S, Kumar, S, Patil, S, and Mandal, T
Subjects: Male, Placebo-controlled study, Myocardial Infarction, alanine aminotransferase, albiglutide, bilirubin, placebo, antidiabetic agent, glucagon like peptide 1, rGLP-1 protein, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Glucagon-Like Peptide 1, Cardiovascular Disease, Medicine(all), education.field_of_study, Subcutaneous, Medicine (all), albigutide, Hazard ratio, General Medicine, Middle Aged, Albiglutide, Stroke, Treatment Outcome, Tolerability, Cardiovascular Diseases, Female, type 2 diabetes, Type 2, Human, Adult, medicine.medical_specialty, Injections, Subcutaneous, Population, 030209 endocrinology & metabolism, Placebo, Injections, Subcutaneou, Drug Administration Schedule, Injections, 03 medical and health sciences, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, education, Aged, Diabetes Mellitus, Type 2, Hypoglycemic Agent, business.industry, Semaglutide, Settore MED/13 - ENDOCRINOLOGIA, Harmony, business
Abstract: Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p
Published: 2018

17. Igg N-Glycan Patterns Are Associated With Ischemic Heart Disease In Type 2 Diabetes

Author: M. van Hoek, Olga Gornik, Ralph Heijmans, Sunny S Singh, Gordan Lauc, Aloysius G Lieverse, and Eric J.G. Sijbrands
Subjects: Glycan, biology, business.industry, Immunology, medicine, biology.protein, Type 2 diabetes, Disease, Cardiology and Cardiovascular Medicine, medicine.disease, business, Ischemic heart
Published: 2019

18. Introduction of the DiaGene study: clinical characteristics, pathophysiology and determinants of vascular complications of type 2 diabetes

Author: Monique T. Mulder, Eric J.G. Sijbrands, Bert Bravenboer, Harm R. Haak, Janneke G. Langendonk, Aloysius G Lieverse, Annelies Lucas, Ronald J. Erdtsieck, Mandy van Hoek, Roosmarijn F.H. Lemmers, Thijs T. W. van Herpt, Huisartsgeneeskunde, Psychiatrie & Neuropsychologie, RS: CAPHRI - R1 - Ageing and Long-Term Care, Interne Geneeskunde, Clinical sciences, and Internal Medicine
Subjects: medicine.medical_specialty, Complications, SUSCEPTIBILITY LOCI, Endocrinology, Diabetes and Metabolism, Prospective follow-up, Disease, Type 2 diabetes, 030204 cardiovascular system & hematology, GENETIC ARCHITECTURE, 03 medical and health sciences, MELLITUS, 0302 clinical medicine, SDG 3 - Good Health and Well-being, US ADULTS, Internal medicine, Diabetes mellitus, Type 2 diabetes mellitus, GENERAL-PRACTICE, Internal Medicine, medicine, Journal Article, Genetics, Outpatient clinic, 030212 general & internal medicine, GENOME-WIDE ASSOCIATION, CDKAL1, lcsh:RC620-627, business.industry, Research, Type 2 Diabetes Mellitus, Case-control, medicine.disease, Cardiovascular disease, Surgery, lcsh:Nutritional diseases. Deficiency diseases, MYOCARDIAL-INFARCTION, RISK-FACTORS, business, Case–control, FOLLOW-UP, TCF7L2, PERIPHERAL NEUROPATHY, Cohort study
Abstract: Background Type 2 diabetes is a major healthcare problem. Glucose-, lipid-, and blood pressure-lowering strategies decrease the risk of micro- and macrovascular complications. However, a substantial residual risk remains. To unravel the etiology of type 2 diabetes and its complications, large-scale, well-phenotyped studies with prospective follow-up are needed. This is the goal of the DiaGene study. In this manuscript, we describe the design and baseline characteristics of the study. Methods The DiaGene study is a multi-centre, prospective, extensively phenotyped type 2 diabetes cohort study with concurrent inclusion of diabetes-free individuals at baseline as controls in the city of Eindhoven, The Netherlands. We collected anthropometry, laboratory measurements, DNA material, and detailed information on medication usage, family history, lifestyle and past medical history. Furthermore, we assessed the prevalence and incidence of retinopathy, nephropathy, neuropathy, and diabetic feet in cases. Using logistic regression models, we analyzed the association of 11 well known genetic risk variants with type 2 diabetes in our study. Results In total, 1886 patients with type 2 diabetes and 854 controls were included. Cases had worse anthropometric and metabolic profiles than controls. Patients in outpatient clinics had higher prevalence of macrovascular (41.9% vs. 34.8%; P = 0.002) and microvascular disease (63.8% vs. 20.7%) compared to patients from primary care. With the exception of the genetic variant in KCNJ11, all type 2 diabetes susceptibility variants had higher allele frequencies in subjects with type 2 diabetes than in controls. Conclusions In our study population, considerable rates of macrovascular and microvascular complications are present despite treatment. These prevalence rates are comparable to other type 2 diabetes populations. While planning genomics, we describe that 11 well-known type 2 diabetes genetic risk variants (in TCF7L2, PPARG-P12A, KCNJ11, FTO, IGF2BP2, DUSP9, CENTD2, THADA, HHEX, CDKAL1, KCNQ1) showed similar associations compared to literature. This study is well-suited for multiple omics analyses to further elucidate disease pathophysiology. Our overall goal is to increase the understanding of the underlying mechanisms of type 2 diabetes and its complications for developing new prediction, prevention, and treatment strategies. Electronic supplementary material The online version of this article (doi:10.1186/s13098-017-0245-x) contains supplementary material, which is available to authorized users.
Published: 2017

19. Strength Training Affects Lower Extremity Gait Kinematics, Not Kinetics, in People With Diabetic Polyneuropathy

Author: Paul Willems, Ton L.H. de Lange, Kenneth Meijer, T. Herman IJzerman, Nicolaas C. Schaper, Aloysius G. Lieverse, Hans H.C.M. Savelberg, Tom Melai, Nutrition and Movement Sciences, Interne Geneeskunde, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CAPHRI School for Public Health and Primary Care, RS: NUTRIM - HB/BW section B, RS: CARIM - R3 - Vascular biology, and RS: CAPHRI - Redesigning Health Care
Subjects: Male, medicine.medical_specialty, Strength training, Biophysics, STRIDE, Kinematics, gait, FOOT ULCERATION, plantar loading, MELLITUS, Gait (human), Physical medicine and rehabilitation, Diabetic Neuropathies, medicine, Humans, Orthopedics and Sports Medicine, physical therapy, stride length, Aged, Leg, business.industry, Forefoot, Rehabilitation, NEUROPATHY, TAI-CHI, Resistance Training, RANDOMIZED CONTROLLED-TRIAL, medicine.disease, Extremity Gait, Biomechanical Phenomena, Kinetics, medicine.anatomical_structure, PHYSICAL-ACTIVITY, MOBILITY, Case-Control Studies, Physical therapy, Female, JOINT MOMENTS, Ankle, business, Polyneuropathy, human activities, PLANTAR PRESSURE, WALKING
Abstract: Increased forefoot loading in diabetic polyneuropathy plays an important role in the development of plantar foot ulcers and can originate from alterations in muscle strength, joint moments and gait pattern. The current study evaluated whether strength training can improve lower extremity joint moments and spatiotemporal gait characteristics in patients with diabetic polyneuropathy. An intervention group receiving strength training during 24 weeks and a control group receiving no intervention. Measurements were performed in both groups at t = 0, t = 12, t = 24 and t = 52 weeks at an individually preferred and standardized imposed gait velocity. The strength training did not affect the maximal amplitude of hip, knee and ankle joint moments, but did result in an increase in stance phase duration, stride time and stride length of approximately 5%, during the imposed gait velocity. In addition, both groups increased their preferred gait velocity over one year. Future longitudinal studies should further explore the possible effects of strength training on spatiotemporal gait characteristics. The current study provides valuable information on changes in gait velocities and the progressive lower extremity problems in patients with polyneuropathy.
Published: 2014

20. Lp(A) Plasma Levels Are Not Associated With Microvascular Complications In T2d A Prospective Cohort Study

Author: Monique T. Mulder, M. Licona, T van Herpt, Y.B. de Rijke, M. van Hoek, Eric J.G. Sijbrands, Aloysius G Lieverse, Sunny S Singh, and Roosmarijn F.H. Lemmers
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Medicine, Plasma levels, Cardiology and Cardiovascular Medicine, business, Prospective cohort study
Published: 2019

21. The Association Of The Igg N-Glycome With The Course Of Kidney Function In Type 2 Diabetes Mellitus

Author: M. van Hoek, Sunny S Singh, C. Meulen, Gordan Lauc, Aloysius G Lieverse, Eric J.G. Sijbrands, and Olga Gornik
Subjects: medicine.medical_specialty, business.industry, Internal medicine, medicine, Type 2 Diabetes Mellitus, Renal function, Cardiology and Cardiovascular Medicine, business, Gastroenterology, Glycome
Published: 2019

22. Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality

Author: Kim van Dijk, Ernst J. Kuipers, Aria Sana, Aloysius G Lieverse, Eric J.G. Sijbrands, Désirée van Noord, Janneke G. Langendonk, Peter Mensink, Bert Bravenboer, Stephanie Kooij, Clinical sciences, Gastroenterology & Hepatology, and Internal Medicine
Subjects: Male, medicine.medical_specialty, Disease, SDG 3 - Good Health and Well-being, Ischemia, Risk Factors, Interquartile range, health services administration, Internal medicine, Diabetes mellitus, mental disorders, medicine, Humans, Myocardial infarction, Mortality, Family history, Stroke, Chronic gastrointestinal ischemia, Aged, Netherlands, business.industry, Middle Aged, Atherosclerosis, Cardiovascular disease, medicine.disease, humanities, Gastrointestinal Tract, Standardized mortality ratio, Cardiovascular Diseases, Case-Control Studies, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract: Objectives: We determined the prevalence of classical risk factors for atherosclerosis and mortality risk in patients with CGI. Methods: A case-control study was conducted. Patients referred with suspected CGI underwent a standard work-up including risk factors for atherosclerosis, radiological imaging of abdominal vessels and tonometry. Cases were patients with confirmed atherosclerotic CGI. Controls were healthy subjects previously not known with CGI. The mortality risk was calculated as standardized mortality ratio derived from observed mortality, and was estimated with ten-year risk of death using SCORE and PREDICT. Results: Between 2006 and 2009, 195 patients were evaluated for suspected CGI. After a median follow-up of 19 months, atherosclerotic CGI was diagnosed in 68 patients. Controls consisted of 132 subjects. Female gender, diabetes, hypercholesterolemia, a personal and family history of cardiovascular disease (CVD), and current smoking are highly associated with CGI. After adjustment, female gender (OR 2.14 95% CI 1.05-4.36), diabetes (OR 5.59, 95% CI 1.95-16.01), current smoking (OR 5.78, 95% CI 2.27-14.72), and history of CVD (OR 21.61, 95% CI 8.40-55.55) remained significant. CGI patients >55 years had a higher median ten-year risk of death (15% vs. 5%, P = 0.001) compared to controls. During follow-up of 116 person-years, standardized mortality rate was higher in CGI patients (3.55; 95% CI 1.70-6.52). Conclusions: Patients with atherosclerotic CGI have an increased estimated CVD risk, and severe excess mortality. Secondary cardiovascular prevention therapy should be advocated in patients with CGI. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Published: 2012

23. The Cockcroft-Gault

Author: Aloysius G. Lieverse, Nanne Kleefstra, Henk J. G. Bilo, Susan J. J. Logtenberg, Klaas H. Groenier, Liane Santing, I. Drion, Hanneke Joosten, and Lifestyle Medicine (LM)
Subjects: Male, Health (social science), Overweight, Kidney, urologic and male genital diseases, GLOMERULAR-FILTRATION-RATE, DISEASE, Body Mass Index, Diabetes mellitus, Epidemiology, EQUATION, Diabetic Nephropathies, Estimated glomerular filtration rate, reproductive and urinary physiology, education.field_of_study, Middle Aged, female genital diseases and pregnancy complications, Creatinine, Female, Original Article, medicine.symptom, medicine.medical_specialty, ALBUMINURIA, Population, Renal function, AGE, Bias, Physiology (medical), Internal medicine, medicine, Humans, Obesity, education, METAANALYSIS, Aged, Retrospective Studies, SERUM CREATININE, business.industry, Reproducibility of Results, PERFORMANCE, medicine.disease, BODY-MASS INDEX, Creatinine clearance, Endocrinology, Albuminuria, Kidney Failure, Chronic, WEIGHT, business, Body mass index, Mathematics, Kidney disease
Abstract: Background: The performance of the Cockcroft-Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) formula, and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) was evaluated in body mass index (BMI) categories. Material and Methods: In this retrospective cohort study in diabetic patients, creatinine clearance was measured by collecting 24-hour urines. Renal function was estimated using the CG, MDRD, and CKD-EPI. The performance of the equations was evaluated using correlation, Krippendorff's coefficient, bias, precision, and accuracy. Results: The bias of the MDRD and CKD-EPI increased from -13.9 ml/min/1.73 m(2) and -14.0 ml/min/1.73 m(2) (BMI 30 kg/m(2)), respectively. Bias of the CG decreased from -13.4 ml/min (BMI 30 kg/m(2)). With an accepted 30% dispersion, CG had the largest accuracy in the overweight and obese group (76.9 and 76.8%, respectively). The MDRD and CKD-EPI had an accuracy of 45.8 and 34.0% (overweight group), respectively,and 51.9 and 37.3% (obese group), respectively. Conclusions: All renal function prediction equations are biased when used in overweight or obese diabetic populations with preserved renal function. The CG provides the best estimate of kidney function. The limitations of renal function prediction equations should be kept in mind when making clinical decisions.
Published: 2011

24. Calculation of plantar pressure time integral, an alternative approach

Author: Kenneth Meijer, Nicolaas C. Schaper, Aloysius G. Lieverse, T. Herman IJzerman, Hans H.C.M. Savelberg, Ton L.H. de Lange, Tom Melai, Paul Willems, Nutrition and Movement Sciences, Interne Geneeskunde, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, and RS: CAPHRI School for Public Health and Primary Care
Subjects: Peak pressure, Biophysics, Walking, Force time integral, Models, Biological, Foot loading, Diabetic Neuropathies, Diabetic polyneuropathy, Polyneuropathy, Pressure time integral, Pressure, Humans, In patient, Orthopedics and Sports Medicine, Simulation, Aged, Mathematics, Alternative methods, Foot, Plantar pressure, Diabetes, Mathematical analysis, Rehabilitation, Healthy subjects, Middle Aged, Diabetes Mellitus, Type 2, Case-Control Studies, Time integral, Software
Abstract: In plantar pressure measurement, both peak pressure and pressure time integral are used as variables to assess plantar loading. However, pressure time integral shows a high concordance with peak pressure. Many researchers and clinicians use Novel software (Novel GmbH Inc., Munich, Germany) that calculates this variable as the summation of the products of peak pressure and duration per time sample, which is not a genuine integral of pressure over time. Therefore, an alternative calculation method was introduced. The aim of this study was to explore the relevance of this alternative method, in different populations. Plantar pressure variables were measured in 76 people with diabetic polyneuropathy, 33 diabetic controls without polyneuropathy and 19 healthy subjects. Peak pressure and pressure time integral were obtained using Novel software. The quotient of the genuine force time integral over contact area was obtained as the alternative pressure time integral calculation. This new alternative method correlated less with peak pressure than the pressure time integral as calculated by Novel. The two methods differed significantly and these differences varied between the foot sole areas and between groups. The largest differences were found under the metatarsal heads in the group with diabetic polyneuropathy. From a theoretical perspective, the alternative approach provides a more valid calculation of the pressure time integral. In addition, this study showed that the alternative calculation is of added value, along peak pressure calculation, to interpret adapted plantar pressures patterns in particular in patients at risk for foot ulceration.
Published: 2011
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25. The anti-inflammatory function of high-density lipoprotein in type II diabetes: A systematic review

Author: Roosmarijn F.H. Lemmers, Monique T. Mulder, Eric J.G. Sijbrands, Aloysius G Lieverse, Adrie J.M. Verhoeven, Mandy van Hoek, and Internal Medicine
Subjects: 0301 basic medicine, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Inflammation, Disease, 030204 cardiovascular system & hematology, Bioinformatics, Anti-inflammatory, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal Medicine, medicine, Humans, Nutrition and Dietetics, business.industry, Cholesterol, nutritional and metabolic diseases, medicine.disease, Pathophysiology, 030104 developmental biology, Diabetes Mellitus, Type 2, chemistry, Immunology, lipids (amino acids, peptides, and proteins), medicine.symptom, Lipoproteins, HDL, Cardiology and Cardiovascular Medicine, business, Lipoprotein
Abstract: Background Inflammation is a pathophysiological factor in diabetes and its cardiovascular complications. High-density lipoprotein (HDL) suppresses inflammation in healthy individuals. The relationship of HDL with diabetes and cardiovascular disease may be explained by HDL function rather than by HDL cholesterol level. In diabetes, HDL seems to become dysfunctional. Objective We performed a systematic review to answer the following research questions: Is the anti-inflammatory function of HDL diminished in individuals with diabetes and if so, what causes this? Methods We systematically searched Medline and Embase and included original research articles on the anti-inflammatory effects of HDL or HDL-based interventions in diabetes or diabetes models. We assessed the risk of bias of all included studies. Results Fourteen studies were included. These showed great heterogeneity in methodology, study populations, and diabetes models. Overall, HDL from subjects with type II diabetes displayed a reduced ability to suppress inflammatory processes and inflammation markers. However, the mechanisms and the in vivo effects remain largely unknown. No studies reported on HDL from individuals with other types of diabetes. In most studies, the risk of bias was high or could not be assessed. Conclusions HDL isolated from individuals with type II diabetes showed a decreased ability to suppress inflammation. However, the direction of causality and the underlying mechanisms are unknown and should be investigated. For development of treatments directed at restoring HDL anti-inflammatory function in diabetes, a standardized method for assessing HDL anti-inflammatory function needs to be developed and in vivo biomarkers must be identified.
Published: 2017

26. Lower leg muscle strengthening does not redistribute plantar load in diabetic polyneuropathy: a randomised controlled trial

Author: Aloysius G. Lieverse, Valéria Lima Passos, Ton L.H. de Lange, T. Herman IJzerman, Nicolaas C. Schaper, Paul Willems, Hans H.C.M. Savelberg, Tom Melai, Kenneth Meijer, Nutrition and Movement Sciences, Interne Geneeskunde, Bewegingswetenschappen, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, and RS: CAPHRI School for Public Health and Primary Care
Subjects: medicine.medical_specialty, Strength training, PRESSURE, FOOT ULCERATION, law.invention, Leg muscle, MELLITUS, Randomized controlled trial, law, Diabetic polyneuropathy, Diabetes mellitus, PROGRAM, Medicine, Orthopedics and Sports Medicine, Exercise, business.industry, Foot, Forefoot, Research, Diabetes, NEUROPATHY, medicine.disease, PREVENTION, body regions, Kinetics, PHYSICAL-ACTIVITY, MOBILITY, Orthopedic surgery, Physical therapy, business, WALKING, INTERVENTIONS
Abstract: Background Higher plantar pressures play an important role in the development of plantar foot ulceration in diabetic polyneuropathy and earlier studies suggest that higher pressures under the forefoot may be related to a decrease in lower leg muscle strength. Therefore, in this randomised controlled trial we evaluated whether lower-extremity strength training can reduce plantar pressures in diabetic polyneuropathy. Methods This study was embedded in an unblinded randomised controlled trial. Participants had diabetes and polyneuropathy and were randomly assigned to the intervention group (n = 48) receiving strength training during 24 weeks, or the control group (n = 46) receiving no intervention. Plantar pressures were measured in both groups at 0, 12, 24 and 52 weeks. A random intercept model was applied to evaluate the effects of the intervention on peak pressures and pressure–time-integrals, displacement of center-of-pressure and the forefoot to rearfoot pressure–time-integral-ratio. Results Plantar pressure patterns were not affected by the strength training. In both the intervention and control groups the peak pressure and the pressure–time-integral under the forefoot increased by 55.7 kPa (95% CI: 14.7, 96.8) and 2.0 kPa.s (95% CI: 0.9, 3.2) over 52 weeks, respectively. Both groups experienced a high number of drop-outs, mainly due to deterioration of health status and lower-extremity disabilities. Conclusions Plantar pressures under the forefoot increase progressively over time in people with diabetic polyneuropathy, but in this study were not affected by strength training. Future intervention studies should take this increase of plantar pressure into account and alternative interventions should be developed to reduce the progressive lower extremity problems in these patients. Trial registration This study was embedded in a clinical trial with trial number NCT00759265.
Published: 2013

27. A genetic variant in SLC6A20 is associated with Type 2 diabetes in white-European and Chinese populations

Author: A.G. Uitterlinden, T van Herpt, Bert Bravenboer, C M van Duijn, D. Lu, Albert Hofman, M. van Hoek, X. Gao, Y. Ling, Eric J.G. Sijbrands, Abbas Dehghan, S. Jiang, Aloysius G Lieverse, Clinical sciences, Internal Medicine, Epidemiology, and Public Health
Subjects: Adult, Male, medicine.medical_specialty, China, Endocrinology, Diabetes and Metabolism, Population, Type 2 diabetes, Polymorphism, Single Nucleotide, White People, Cohort Studies, Rotterdam Study, Endocrinology, SDG 3 - Good Health and Well-being, Asian People, Gene Frequency, Internal medicine, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, SLC6A20, education, Allele frequency, Alleles, Genetic Association Studies, Aged, Netherlands, education.field_of_study, business.industry, Hazard ratio, Case-control study, Membrane Transport Proteins, Odds ratio, Middle Aged, medicine.disease, Introns, Minor allele frequency, Diabetes Mellitus, Type 2, Case-Control Studies, Female, type 2 diabetes, business, Follow-Up Studies
Abstract: Aims To investigate whether polymorphisms in SLC6A20 are associated with susceptibility to Type 2 diabetes. Methods In the Rotterdam Study, a prospective, population-based cohort (n = 5974), 22 tagging polymorphisms with minor allele frequencies>0.05 across SLC6A20 were studied. Replication studies were performed in an independent Dutch case–control study (DiaGene-Rotterdam Study 2 n = 3133), and in a Chinese Han case–control population (n = 2279). A meta-analysis of the results was performed. Results In the Rotterdam study, the minor alleles of rs13062383, rs10461016 and rs2286489 increased the risk of Type 2 diabetes (hazard ratio 1.37, 95% CI 1.15–1.63, hazard ratio 1.30 95% CI 1.09–1.54 and hazard ratio 1.20, 95% CI 1.07–1.35, respectively). In the DiaGene/Rotterdam Study 2, the A allele of rs13062383 increased the risk of Type 2 diabetes (odds ratio 1.45, 95% CI 1.19–1.76). In the Chinese Han study, the rs13062383 A allele also increased the risk of Type 2 diabetes (odds ratio 1.21, 95% CI 1.03–1.42). Meta-analysis showed a highly significant association of rs13062383 with Type 2 diabetes (odds ratio 1.35, 95% CI 1.21–1.47; P = 3.3 × 10-8). Conclusions In conclusion, rs13062383 in SLC6A20 increased the susceptibility to Type 2 diabetes in populations with different genetic backgrounds.
Published: 2013

28. Increased forefoot loading is associated with an increased plantar flexion moment

Author: Kenneth Meijer, Nicolaas C. Schaper, Ton L.H. de Lange, Paul Willems, Tom Melai, T. Herman IJzerman, Hans H.C.M. Savelberg, Aloysius G. Lieverse, Nutrition and Movement Sciences, Interne Geneeskunde, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, and RS: CAPHRI School for Public Health and Primary Care
Subjects: Male, Walking, Plantar flexion, Weight-Bearing, Center of pressure (terrestrial locomotion), Diabetic Neuropathies, Reference Values, Orthopedics and Sports Medicine, Plantar pressure, Range of Motion, Articular, PREDICTORS, Gait, Postural Balance, Diabetes, Age Factors, General Medicine, Middle Aged, Biomechanical Phenomena, medicine.anatomical_structure, DIABETIC-NEUROPATHY, Gait analysis, Female, medicine.symptom, Polyneuropathy, medicine.medical_specialty, GAIT CHARACTERISTICS, Pressure time integral, Acceleration, Biophysics, Experimental and Cognitive Psychology, PRESSURE, FOOT ULCERATION, Physical medicine and rehabilitation, medicine, Reaction Time, Humans, Aged, Lower extremity, business.industry, Forefoot, Muscle weakness, Forefoot, Human, medicine.disease, body regions, Physical therapy, MUSCLE WEAKNESS, Ankle, business, human activities, PERIPHERAL NEUROPATHY, Ankle Joint
Abstract: The aim of this study was to identify the cascade of effects leading from alterations in force generation around the ankle joint to increased plantar pressures under the forefoot. Gait analysis including plantar pressure measurement was performed at an individually preferred and a standardized, imposed gait velocity in diabetic subjects with polyneuropathy (n=94), without polyneuropathy (n=39) and healthy elderly (n=19). The plantar flexion moment at 40% of the stance phase was negatively correlated with the displacement rate of center of pressure (r=-.749, p
Published: 2012

29. Abdominal Aortic Aneurysm Is Associated with a Variant in Low-Density Lipoprotein Receptor-Related Protein 1

Author: Wolfgang Lieb, Bruna Gigante, Thodur M. Vasudevan, Georg Homuth, Joseph B. Muhlestein, Mark J. Daly, Andrew P. Morris, Jacqueline de Graaf, Peter Kraft, Ann-Kristin Petersen, André G. Uitterlinden, Jaqueline C M Witteman, Valgerdur Steinthorsdottir, Jutta Palmen, Amanda L. Elliott, Cecilia M. Lindgren, Richard N. Bergman, Benjamin D. Horne, Tony R. Merriman, Robert W. Davies, Jaspal S. Kooner, Gavin Lucas, Carl G. P. Platou, Diederick E. Grobbee, Ruth J. F. Loos, Fulvio Ricceri, Karin Leander, Wen H. L. Kao, Torsten Lauritzen, Qi Sun, Narisu Narisu, Stephan B. Felix, N. William Rayner, Aaron R. Folsom, Robert D. Sayers, Ross D. Blair, John F. Carlquist, Jing Hua Zhao, L. Vicky Phillips, Gabe Crawford, Anne Johnson, Chris Wallace, Paul F. O'Reilly, Jose C. Florez, Andreas Ziegler, Salvatore Panico, Neil R. Robertson, Ruth Frikke-Schmidt, Leif Groop, Pier Mannuccio Mannucci, Stanley L. Hazen, Gerjan Navis, Peter P. Pramstaller, Laura J. Scott, Niels Grarup, Klaus Berger, Christian Gieger, Stephen E. Epstein, Cornelia Huth, Stephanie Tennstedt, Morris J. Brown, Timothy A. Barnes, Naomi Hammond, Ulf de Faire, Vilmundur Gudnason, Marcus Fischer, Nita G. Forouhi, Paolo Vineis, Thomas Quertermous, Christopher Patterson, W.H. Wilson Tang, Konstantinos A. Papadakis, Lincoln Stein, Maciej Tomaszewski, Suthesh Sivapalaratnam, M. S. Sandhu, Feng Zhang, Christa Meisinger, David R. Lewis, Norman Klopp, Roza Blagieva, Gonçalo R. Abecasis, Jeffrey L. Anderson, Lu Qi, Amy J. Swift, Albert Hofman, George Dedoussis, Robert Luben, Daniel J. Rader, Thomas Münzel, Bert Bravenboer, Christopher J. O'Donnell, Elin Org, Veikko Salomaa, Philipp S. Wild, Stephen G. Ellis, Dawn M. Waterworth, Vesela Gateva, Loukianos S. Rallidis, Joseph M. Devaney, kevin Burnand, Robert Clarke, George A. Wells, Harold Snieder, Kay-Tee Khaw, Panos Deloukas, Jaakko Tuomilehto, Louise V. Wain, Eric Boerwinkle, Inke R. König, Amanda J. Bennett, Uwe Völker, Florian Ernst, Markus M. Nöthen, Thomas Sparsø, Jean Tichet, Inga Prokopenko, Paul Johnson, Jaume Marrugat, Marju Orho-Melander, Aloysius G Lieverse, Ian Thomson, Vincent Mooser, Teresa Ferreira, Man Li, Benjamin J. Wright, Ryan P. Welch, Alessandra Allione, Stefan Blankenberg, Veryan Codd, Philippe Froguel, James C. Engert, Pekka Jousilahti, Klaus Stark, Toby Johnson, Cornelia M. van Duijn, Ivo Gut, John J.P. Kastelein, Thomas M. Morgan, Noël P. Burtt, Laura J. McCulloch, Tim D. Spector, Peter S. Chines, Timo T. Valle, Peter Shrader, Christian Dina, Diana Zelenika, Monika Stoll, Peter S. Braund, Harry Campbell, Rainer Rettig, Joep A.W. Teijink, Thomas Illig, Anne Tybjærg-Hansen, Peter Vollenweider, Guangju Zhai, Frits R. Rosendaal, Pau Navarro, James B. Meigs, Ghislain Rocheleau, Li Chen, Pilar Galan, Giuseppe Matullo, Henry Völzke, Samer S. Najjar, Christina Loley, N. Charlotte Onland-Moret, Alison H. Goodall, Riyaz S. Patel, S. Matthijs Boekholdt, Pim van der Harst, John R. B. Perry, Angela Doering, James S. Pankow, Gudmundur Thorgeirsson, Xin Yuan, Patricia B. Munroe, Abbas Dehghan, Tamara B. Smith, Valeriya Lyssenko, Mark I. McCarthy, Andrew T. Hattersley, Simon Futers, Barbara Thorand, Andre G. Uitterlinden, Simon J. Griffin, Winfried März, Nilesh J. Samani, Frank B. Hu, Valeria Romanazzi, Michael N. Weedon, Zouhair Aherrahrou, Ruth McPherson, Benjamin F. Voight, Wolfgang Rathmann, Markus Perola, Stefania Bandinelli, Kathy Stirrups, Hilma Holm, Maja Barbalić, Kiran Musunuru, David Couper, David S. Siscovick, Guillaume Charpentier, Alexandre F.R. Stewart, Patrick Diemert, Leena Peltonen, Serge Hercberg, Robert Roberts, Michael Roden, Rhian Gwilliam, Guillaume Lettre, Eric J.G. Sijbrands, Lambertus A. Kiemeney, Martha Ganser, Silvia Polidoro, Kristin G. Ardlie, Stephen G. Ball, Kristina Bengtsson Boström, Katharine R. Owen, Paul E. de Jong, Felicity Payne, Wendy L. McArdle, Frances M K Williams, Paul Elliott, Roberto Elosua, Devin Absher, Kristian Midthjell, Jan D. Blankensteijn, Nelson B. Freimer, John C. Chambers, G. Kolovou, Karl Andersen, John Webster, Nicholas J. Wareham, Eric E. Schadt, Simon Heath, Diana Rubin, Solveig Gretarsdottir, Willem H. Ouwehand, Oluf Pedersen, Liming Qu, Sandra Eifert, Mary Susan Burnett, Paul Burton, Frank M. van Bockxmeer, Eleftheria Zeggini, Stephen M. Schwartz, Simon C. Potter, Tiinamaija Tuomi, Jeffrey R. Gulcher, David Altshuler, Harald Grallert, Hooman Allayee, Kari Stefansson, Anne H. Child, Sekar Kathiresan, Torben Hansen, Unnur Thorsteinsdottir, Isaac Subirana, Serena Sanna, Muredach P. Reilly, J. Wouter Jukema, H.-Erich Wichmann, François Cambien, Pier Angelica Merlini, Wiek H. van Gilst, Caroline S. Fox, Andrew Smith, Oliviero Olivieri, S Sohrabi, James F. Wilson, Gillian W. Cockerill, Guanming Wu, Andrew D. Morris, Carlos Iribarren, Joshua W. Knowles, Angelo Scuteri, Göran Berglund, Marilyn C. Cornelis, Pascal P. McKeown, Thorsten Reffelmann, Gérard Waeber, Les McNoe, Maris Laan, Dilip K. Naik, Karen L. Mohlke, Matthew Waltham, Rachel E. Clough, Claudia Langenberg, Seamus C. Harrison, Hany Hafez, Timon W. van Haeften, Carlotta Sacerdote, Robert Sladek, Nicola Martinelli, Declan Bradley, Cristen J. Willer, Sarah E. Hunt, Sven Cichon, Udo Seedorf, Winston Hide, Arne Schillert, Cuno S.P.M. Uiterwaal, Steve E. Humphries, Andre A van Rij, Stéphane Cauchi, Michael Boehnke, Beverley M. Shields, Suzannah Bumpstead, Diane M. Becker, Ron Do, Heribert Schunkert, Jacques S. Beckmann, Alistair S. Hall, Mike Sampson, Christine Proença, Lachlan J. M. Coin, Rob M. van Dam, Mohan U. Sivananthan, Martin Farrall, B. Gerry Hill, Simonetta Guarrera, Thijs T. W. van Herpt, Sonia S. Anand, Peter M. Nilsson, Arne Pfeufer, Rafn Benediktsson, Candace Guiducci, Lee M. Kaplan, Michel Marre, Thomas Meitinger, Annette F. Baas, Graham A. Hitman, Roberto Lorbeer, Flora Peyvandi, David J. Hunter, Seraya Maouche, G. Mark Lathrop, Michael R. Erdos, Thomas W. Mühleisen, L. Adrienne Cupples, Anne E. Hughes, Ayellet V. Segrè, Igor Rudan, Kijoung Song, Reijo Laaksonen, G. Bragi Walters, Christopher P. Nelson, Christopher S. Franklin, Richard M. Watanabe, Mattijs E. Numans, Christina Willenborg, Jeanette Erdmann, Alessandra Di Gregorio, John M. C. Connell, Soumya Raychaudhuri, Jian'an Luan, Anthony J. Balmforth, Yurii S. Aulchenko, Arne Schäfer, Catherine M. Rice, Tanja Zeller, Grace Yu, Augustine Kong, Matthew M Thompson, Diego Ardissino, Oliver Hofmann, John R. Thompson, J.B. Wild, Alexander Teumer, Ulf Gyllensten, David P. Strachan, Martin D. Tobin, Michael A. Kaiser, Steve McCarroll, Beverley Balkau, Stephen J. Newhouse, Michael Preuss, John A. Spertus, Janja Nahrstaedt, Neelam Hassanali, Gunnar Sigurdsson, Jaapjan D. Snoep, Angela Döring, Todd Green, D. Julian A. Scott, Christian Herder, Bo Isomaa, Anne U. Jackson, David Hadley, Domenico Girelli, Jes S. Lindholt, Toshiko Tanaka, Ruth Topless, Bernhard O. Boehm, Jana V. van Vliet-Ostaptchouk, Anna-Liisa Hartikainen, Anneli Pouta, Anuj Goel, Stefan Schreiber, Kristian Hveem, Gabriel Crawford, Pierre Meneton, Jürgen Schrezenmeir, Andre M. van Rij, Markku Laakso, Richa Saxena, Joshua C. Bis, Samy Hadjadj, Anders Franco-Cereceda, Noha Lim, Christopher J. Groves, Klaus Strassburger, Stefan E Matthiasson, M. Lourdes Sampietro, Josée Dupuis, Morris J. Bown, Cisca Wijmenga, Shu Ye, Jennifer Freyer, Anders Hamsten, Christian Hengstenberg, Olle Melander, Sarah Edkins, Alberto Smith, Luigi Ferrucci, Murielle Bochud, Lori L. Bonnycastle, Gregory T. Jones, Manuela Uda, Lasse Folkersen, Timothy M. Frayling, Giovanni Tognoni, Torben Jørgensen, Anna F. Dominiczak, Michiel L. Bots, Mario A. Morken, Ian Buysschaert, Colin N. A. Palmer, Andrew Hill, Mark J. Caulfield, Nicolas Sylvius, Nicole Soranzo, Susana Eyheramendy, Christopher Newton-Cheh, Eran Halperin, Mandy van Hoek, Stephen A. Badger, Paul Scheet, Gudmar Thorleifsson, Themistocles L. Assimes, Inês Barroso, Sheila Bingham, Nour Eddine El Mokhtari, Yvonne T. van der Schouw, Andrew J. Lotery, Heather M. Stringham, Marcus Dörr, Per Eriksson, Mark Walker, Mette Refstrup, Anna L. Gloyn, Ann-Christine Syvänen, John F. Peden, Diether Lambrechts, Arshed A. Quyyumi, Katherine S. Elliott, Jonathan Golledge, Edward G. Lakatta, Serkalem Demissie, Lewis C. Becker, Alex S. F. Doney, Najaf Amin, Hugh Watkins, Johanna Kuusisto, Paul Norman, Marjo-Riitta Järvelin, Annette Peters, David Schlessinger, Janet T. Powell, Surgery, ICaR - Ischemia and repair, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Male, VASCULAR WALL, Genome-wide association study, 030204 cardiovascular system & hematology, Bioinformatics, Aortic aneurysm, 0302 clinical medicine, Risk Factors, Odds Ratio, Genetics(clinical), Genetics (clinical), Aorta, 0303 health sciences, Cardiovascular diseases [NCEBP 14], Homozygote, Abdominal aortic aneurysm, Organ Specificity, Data Interpretation, Statistical, CORONARY-ARTERY-DISEASE, Female, METALLOPROTEINASE, Sterol Regulatory Element Binding Protein 1, Low Density Lipoprotein Receptor-Related Protein-1, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Locus (genetics), Biology, Polymorphism, Single Nucleotide, DISSECTIONS, Article, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genome-wide associaton, Coronary-artery-disease, Susceptibility loci, Sequence variant, Vascular wall, Metalloproteinase, Atherosclerosis, Identification, Metaanalysis, Dissections, medicine.artery, Internal medicine, Cell Line, Tumor, medicine, Genetics, Humans, Genetic Predisposition to Disease, ddc:610, GENOME-WIDE ASSOCIATION, METAANALYSIS, 030304 developmental biology, Genetic association, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], Aged, IDENTIFICATION, Case-control study, Odds ratio, medicine.disease, Endocrinology, ATHEROSCLEROSIS, SEQUENCE VARIANT, Genetic Loci, Case-Control Studies, Aortic Aneurysm, Abdominal, Follow-Up Studies, Genome-Wide Association Study
Abstract: Contains fulltext : 97601.pdf (Publisher’s version ) (Closed access) Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 x 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 x 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 x 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression. 9 p.
Published: 2011

30. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Author: Unnur Thorsteinsdottir, Carl G. P. Platou, Albert Hofman, Qi Sun, Narisu Narisu, Oliver Hofmann, Jean Tichet, Lu Qi, Jose C. Florez, H-Erich Wichmann, Peter Kraft, Leif Groop, Benjamin F. Voight, Wolfgang Rathmann, Francis S. Collins, Wen H. L. Kao, André G. Uitterlinden, Torben Hansen, James F. Wilson, Guanming Wu, Valgerdur Steinthorsdottir, Robert Sladek, Cornelia M. van Duijn, James B. Meigs, Philippe Froguel, Cristen J. Willer, Andrew D. Morris, Harry Campbell, Cecilia M. Lindgren, Igor Rudan, Josée Dupuis, Richard N. Bergman, Andrew T. Hattersley, Suzannah Bumpstead, Kristian Midthjell, Richard M. Watanabe, Kristina Bengtsson Boström, Eric J.G. Sijbrands, Mike Sampson, Thomas Meitinger, Graham A. Hitman, Amanda J. Bennett, Anna L. Gloyn, Ayellet V. Segrè, Mark I. McCarthy, Simon J. Griffin, Frank B. Hu, Kari Stefansson, Soumya Raychaudhuri, G. Bragi Walters, David Altshuler, Karen L. Mohlke, Michel Marre, Harald Grallert, Yurii S. Aulchenko, Bernhard O. Boehm, Aloysius G Lieverse, Christian Gieger, Samy Hadjadj, Kristin Ardlie, Man Li, Winston Hide, Caroline S. Fox, N P Burtt, Gonçalo R. Abecasis, Katharine R. Owen, Inês Barroso, Neil R. Robertson, Beverley M. Shields, Ulf Gyllensten, Torsten Lauritzen, Gabe Crawford, Claudia Langenberg, Martha Ganser, Bo Isomaa, Anne U. Jackson, Eleftheria Zeggini, Timon W. van Haeften, Jana V. van Vliet-Ostaptchouk, Rob M. van Dam, Richa Saxena, Ghislain Rocheleau, Mandy van Hoek, Niels Grarup, Cornelia Huth, Roza Blagieva, Christian Dina, Katherine S. Elliott, Rafn Benediktsson, Candace Guiducci, Barbara Thorand, Alex S. F. Doney, Najaf Amin, Christopher J. Groves, Gudmar Thorleifsson, Todd Green, Amy J. Swift, Klaus Strassburger, Paul Johnson, Johanna Kuusisto, Mark J. Daly, Jaakko Tuomilehto, Andrew P. Morris, David J. Hunter, Thomas Sparsø, N. William Rayner, Ann-Kristin Petersen, Pau Navarro, Norman Klopp, Jacqueline C. M. Witteman, Torben Jørgensen, Mark Walker, Eric Boerwinkle, Inga Prokopenko, Teresa Ferreira, Kristian Hveem, John R. B. Perry, Peter P. Pramstaller, James S. Pankow, Valeriya Lyssenko, Cisca Wijmenga, Lori L. Bonnycastle, Michael Roden, Felicity Payne, Timothy M. Frayling, Nicholas J. Wareham, Tiinamaija Tuomi, Heather M. Stringham, Mario A. Morken, Colin N. A. Palmer, Laura J. Scott, Thomas Illig, Guillaume Charpentier, Christian Herder, Lincoln Stein, Michael N. Weedon, Markku Laakso, Michael R. Erdos, Beverley Balkau, Augustine Kong, Neelam Hassanali, Steve McCarroll, Stéphane Cauchi, Michael Boehnke, David Couper, Peter M. Nilsson, Christopher S. Franklin, Marilyn C. Cornelis, Peter Shrader, Laura J. McCulloch, Oluf Pedersen, Peter S. Chines, Christine Proença, Thijs T. W. van Herpt, Amanda F. Elliott, Gunnar Sigurdsson, Bert Bravenboer, Ryan P. Welch, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Epidemiology, Internal Medicine, Dermatology, Erasmus MC other, and Ophthalmology
Subjects: Blood Glucose, QT INTERVAL DURATION, COMPLEX DISEASES, endocrine system diseases, Gene Dosage, Locus (genetics), KLF14, Genome-wide association study, Type 2 diabetes, Biology, Polymorphism, Single Nucleotide, Article, HNF1-ALPHA GENE, 03 medical and health sciences, Genetic Heterogeneity, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Meta-Analysis as Topic, genome wide association study, glucose, diabetes type 2, Genetics, medicine, Humans, Genetic Predisposition to Disease, Hepatocyte Nuclear Factor 1-alpha, GENOME-WIDE ASSOCIATION, CDKAL1, 030304 developmental biology, Genetic association, GENE-EXPRESSION, 0303 health sciences, INSULIN-RESISTANCE, Genetic heterogeneity, Genome, Human, Gene Expression Profiling, COMMON VARIANTS, nutritional and metabolic diseases, Fasting, medicine.disease, C-REACTIVE PROTEIN, CROHNS-DISEASE, HNF1A, FASTING PLASMA-GLUCOSE, Diabetes Mellitus, Type 2, KCNQ1 Potassium Channel, Dual-Specificity Phosphatases, Mitogen-Activated Protein Kinase Phosphatases, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P 5 × 10 8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. © 2010 Nature America, Inc. All rights reserved.
Published: 2010

31. PS10 - 54. Adverse plantar pressures are associated with increased plantar flexion moments at the first part of the stance phase

Author: Hans H.C.M. Savelberg, Herman IJzerman, Nicolaas C. Schaper, Kenneth Meijer, Paul C. Willems, Tom Melai, Aloysius G. Lieverse, and Ton L.H. de Lange
Subjects: medicine.medical_specialty, Momentum (technical analysis), Stance phase, business.industry, Forefoot, Centre of pressure, Muscle weakness, medicine.disease, Plantar flexion, Physical medicine and rehabilitation, Diabetic polyneuropathy, medicine, Physical therapy, medicine.symptom, business, Polyneuropathy
Abstract: A previous study by Savelberg et al. indicated higher plantar flexion moments at 40% of the stance phase and simultaneously an increase in plantar loading in people with diabetic polyneuropathy. It was hypothesised that muscle weakness in the lower extremity caused by polyneuropathy can affect the ability to generate enough momentum during the first part of the stance phase to counter the forward momentum of the body and the roll off of the foot. This could lead to a faster forward transfer of the centre of pressure of the foot (COP) and consequently a higher forefoot loading. The current study sought to test this hypothetical cascade.
Published: 2011

32. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

Author: Seppo Koskinen, Christian Herder, Daniel I. Chasman, Andrew R. Wood, Jonna L. Grimsby, J.F. Wilson, Day Inm., Massimo Mangino, Gonneke Willemsen, Robert W. Mahley, Cristian Pattaro, Nicole L. Glazer, T.B. Harris, Irene Pichler, M S Sandhu, D. van Heemst, Christine Proença, Martha Ganser, Robert A. Hegele, Richa Saxena, Eleftheria Zeggini, Markku Laakso, Peter Kraft, Judith B. Borja, Karen L. Mohlke, J B Richards, de Geus Ejc., Robert Sladek, Cristen J. Willer, Samy Hadjadj, S.M. Boekholdt, Gina M. Peloso, Kijoung Song, Sutapa Mukherjee, Gudmar Thorleifsson, Winston Hide, Mark I. McCarthy, Ruth E. Pakyz, Marian Beekman, Ayellet V. Segrè, Inga Prokopenko, Ping An, George Dedoussis, Danielle Posthuma, Jeanette Erdmann, Simon J. Griffin, Nilesh J. Samani, Inke R. König, Frank B. Hu, Lokki M-L., David M. Evans, Xiaohui Li, Valgerdur Steinthorsdottir, Aimo Ruokonen, A Pouta, Kerrin S. Small, Cecilia M. Lindgren, O Le Bacquer, Xijing Han, Florian Kronenberg, E Katsareli, Christian Dina, S. Gabriel, Jochen Spranger, James S. Pankow, M. Kloppenburg, Penninx Bwjh., Torben Hansen, Josh Smith, Jennie Hui, Gordon H. Williams, Mark Seielstad, Ingrid B. Borecki, Weihua Zhang, Peter P. Pramstaller, Stephen J. Sharp, Neil R. Robertson, Zee Ryl., Mike Sampson, Angela Silveira, C.M. van Duijn, Anders Hamsten, Peter Shrader, Denis Rybin, Chen Y-Di., Gunnar Sigurdsson, Michael Stumvoll, Russel Tracy, Mark O. Goodarzi, Göran Hallmans, Michael R. Erdos, Valeriya Lyssenko, Juha Saharinen, Sven Bergmann, Jeffrey R. O'Connell, Debbie A Lawlor, Thomas Meitinger, Yvonne Böttcher, Jérôme Delplanque, Sarah G. Buxbaum, Silvia Naitza, Shah Ebrahim, Graham A. Hitman, Angelo Scuteri, Aroon D. Hingorani, Heribert Schunkert, François Pattou, Claudia Lamina, A L Elliott, Sekar Kathiresan, Dawn M. Waterworth, Jennifer A. Brody, Thomas Quertermous, Leena Peltonen, Josephine M. Egan, Daniel J. Rader, J F Peden, Yarnell Jwg., Daniel S. Pearson, Pfeiffer Afh., P S Chines, N Vogelzangs, Susan Redline, Alka M. Kanaya, T B Harris, J. V. van Vliet-Ostaptchouk, Ghislain Rocheleau, Rune R. Frants, Olga D. Carlson, James G. Wilson, Melissa Garcia, Ong Rt-H., Mark J. Caulfield, Tanya M. Teslovich, Loo B-M., Beatrice Knight, Andreas Ziegler, Claudia Langenberg, Yoon Shin Cho, Paul M. Ridker, Mark J. Rieder, Praveen Sethupathy, Bert Bravenboer, J. Viikari, Matt Neville, Ioannis M. Stylianou, Andrew Walley, Jarvelin M-R., Jarred B. McAteer, Ronald M. Krauss, Augustine Kong, Oluf Pedersen, Mark J. Daly, Andrew P. Morris, Anna F. Dominiczak, Stéphane Cauchi, Michael Boehnke, Christopher J. O'Donnell, Barbara Thorand, Peter M. Nilsson, Aaron Isaacs, Deborah A. Nickerson, Roza Blagieva, Mary F. Feitosa, Nicholas J. Wareham, Robert Roberts, J S Kooner, K W van Dijk, Tiinamaija Tuomi, Paul Scheet, Lynda M. Rose, Albert V. Smith, Rafn Benediktsson, Chiara Sabatti, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Toby Johnson, Samuli Ripatti, Erik Ingelsson, Mario A. Morken, Carl G. P. Platou, Anke Tönjes, Qi Sun, Narisu Narisu, S J Bumpstead, Jose M. Ordovas, Alan B. Feranil, L Groop, P Chines, Sara M. Willems, Perry Jrb., Matthew A. Allison, Jan Scott, Cécile Lecoeur, Kastelein Jjp., Herman A. Taylor, Anyuan Cao, Christopher J. Groves, Lincoln D. Stein, Laura J. Scott, John Beilby, Kristin G. Ardlie, Christopher S. Franklin, Yoav Ben-Shlomo, B M Shields, N J Timpson, Marco Orrù, Amélie Bonnefond, Kiran Musunuru, Murielle Bochud, Udo Seedorf, Yongmei Liu, Guillaume Lettre, Lee J-Y., Alan R. Shuldiner, Ryan P. Welch, David J. Hunter, John Whitfield, Klaus Strassburger, Khaw K-T., Hartikainen A-L., Gunnar Sigurðsson, Lu Qi, Richard N. Bergman, G M Lathrop, Sigrid W. Fouchier, T van Herpt, David S. Siscovick, Igor Rudan, Richard M. Watanabe, Themistocles L. Assimes, Nicholas G. Martin, Ozren Polasek, Dhiraj Varma, K Kim, Oliver Hofmann, Nicholas D. Hastie, S Bumpstead, Jose C. Florez, Fernando Rivadeneira, Katharine R. Owen, Braxton D. Mitchell, Alisa K. Manning, Abbas Dehghan, Bruce Bartholow Duncan, Cisca Wijmenga, Timo T. Valle, Jaakko Kaprio, Mika Kivimäki, B Shields, Laila Simpson, Tim D. Spector, Paul W. Franks, Guangju Zhai, María Teresa Martínez-Larrad, Janssens Acjw., Kim L. Ward, Inês Barroso, Xiuqing Guo, Rosa Maria Roccasecca, Zari Dastani, Reijo Laaksonen, Wilmar Igl, Vincent Mooser, Niels Grarup, Cornelia Huth, Christian Gieger, Fabio Marroni, Jaakko Tuomilehto, Doney Asf., Andrew C. Edmondson, Christian Fuchsberger, Meena Kumari, David M. Nathan, Reedik Mägi, Solomon K. Musani, U de Faire, Knut Borch-Johnsen, Masahiro Koseki, Giuseppe Paolisso, Norman Klopp, Caroline S. Fox, Nelson B. Freimer, Mika Kähönen, Peter Henneman, Diana Zelenika, K Willems-Vandijk, Steven A. McCarroll, Paul Elliott, Wichmann H-E., J. C. Bis, Nita G. Forouhi, Antti Jula, Witteman Jcm., Fredrik Karpe, Joseph Hung, Antje Fischer-Rosinsky, Eric J. Brunner, Elena Gonzalez, Soumya Raychaudhuri, Jian'an Luan, Josée Dupuis, Joshua C. Randall, Taesung Park, Francis S. Collins, Lori L. Bonnycastle, Andrew A. Hicks, Peter Kovacs, Thomas Illig, Maja Barbalić, David Couper, Jaspal S. Kooner, Damien C. Croteau-Chonka, Gavin Lucas, P J Wagner, Young-Jin Kim, Yurii S. Aulchenko, Aurelian Bidulescu, Ingrid Meulenbelt, Pilar Galan, Iris M. Heid, Michael N. Weedon, Serena Sanna, Sarah H. Wild, Hivert M-F., Patricia B. Munroe, Johan G. Eriksson, Teresa Ferreira, Robert A. Scott, A. Sandbaek, Kenneth Rice, Veronique Vitart, Xin Yuan, Leslie A. Lange, Hilma Holm, Jorge R. Kizer, Timothy M. Frayling, Marika Kaakinen, Liu C-T., Petersen A-K., Peter Schwarz, G B Walters, Palmer Cna., Jean Tichet, Bernhard Paulweber, Ying Wu, Alyson Hall, Christopher T. Johansen, David Masson, Martin Ladouceur, Christie M. Ballantyne, Tai E-S., Robert Luben, Guillaume Charpentier, Angela Döring, Philip J. Barter, Ruth McPherson, Benjamin F. Voight, Wolfgang Rathmann, Mark Walker, Markus Perola, M. A. Province, Veikko Salomaa, James B. Meigs, George Davey Smith, Robert Clarke, Gerard Waeber, Stefania Bandinelli, Sally L. Ricketts, Kaisa Silander, Loos Rjf., Amanda J. Bennett, John C. Chambers, Marilyn C. Cornelis, L A Cupples, Andrew T. Hattersley, M Sandhu, Marju Orho-Melander, C M van Duijn, Olli T. Raitakari, David Meyre, Ida Surakka, Jouke-Jan Hottenga, Uh H-W., Kari Stefansson, David Melzer, P E Slagboom, Kristian Midthjell, Robert K. Semple, James P. Pirruccello, Aloysius G Lieverse, Åsa Johansson, Michael Roden, Felicity Payne, Eric J.G. Sijbrands, N P Burtt, David R. Hillman, Michael Marmot, Todd Green, Eric E. Schadt, Sijbrands Ejg., Tien Yin Wong, Coin Ljm., K B Boström, Olov Rolandsson, A D Morris, David Altshuler, Harald Grallert, L C Groop, Alan F. Wright, Karen Kapur, Xueling Sim, Philippe Froguel, K O Kyvik, T. Lauritzen, Linda S. Adair, Yavuz Ariyurek, Talin Haritunians, Toshiko Tanaka, Albert Hofman, MariaGrazia Franzosi, Nicholas L. Smith, Laura Crisponi, Andrew B. Singleton, A Uitterlinden, Bo Isomaa, Y A Kesaniemi, Anne U. Jackson, Christa Meisinger, Holly E. Syddall, Dorret I. Boomsma, Harry Campbell, Gonçalo R. Abecasis, Lyudmyla Kedenko, Christine Cavalcanti-Proença, G Crawford, Scott M. Grundy, Johnson Prv., Nuotio M-L., I Chen, J.H. Smit, Anuj Goel, M Li, David P. Strachan, Kenechi Ejebe, Beverley Balkau, Neelam Hassanali, Kristian Hveem, Pierre Meneton, R. Gwilliam, A J Swift, Caroline Hayward, J. Graessler, Carina Zabena, B. St Pourcain, Michel Marre, Margot Haun, Lyytikäinen L-P., Ben A. Oostra, Stefan Coassin, M. van Hoek, Nigel W. Rayner, John R. Thompson, Kurt Lohman, Ulla Sovio, Unnur Thorsteinsdottir, Naveed Sattar, Lyle J. Palmer, Ulf Gyllensten, A Elliott, Muredach P. Reilly, A Swift, Luigi Ferrucci, Syvänen A-C., Simon C. Potter, T.W. van Haeften, G Wu, Stefan Böhringer, Grant W. Montgomery, Edward G. Lakatta, Serkalem Demissie, Alex S. F. Doney, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Lars Lind, Stefan R. Bornstein, Laura J. Rasmussen-Torvik, Terho Lehtimäki, Guillaume Paré, Sophie Visvikis-Siest, S C Heath, David Schlessinger, Juha Sinisalo, Kao Whl., Mark E. Cooper, Kati Kristiansson, Thomas W. Winkler, Thomas Sparsø, Laura J. McCulloch, Taina K. Lajunen, Alex N. Parker, Nabila Bouatia-Naji, Markku S. Nieminen, Peter Vollenweider, Wendy L. McArdle, G K Hovingh, Thomas A. Buchanan, Avan Aihie Sayer, M C Zillikens, Jing Hua Zhao, Naomi Hammond, Vilmundur Gudnason, Björn Zethelius, Panos Deloukas, Jacqueline C. M. Witteman, Eric Boerwinkle, Manuel Serrano-Ríos, Anna L. Gloyn, Katherine S. Elliott, A C Fedson, Torben Jørgensen, Nicole Soranzo, Heather M. Stringham, Bruce M. 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Boehm, Eleanor Wheeler, Epidemiology, Medical Microbiology & Infectious Diseases, Clinical Genetics, Dastani, Z, Hivert, Mf, Timpson, N, Perry, Jr, Yuan, X, Scott, Ra, Henneman, P, Heid, Im, Kizer, Jr, Lyytikäinen, Lp, Fuchsberger, C, Tanaka, T, Morris, Ap, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, J, Uh, Hw, Wu, Y, Bidulescu, A, Rasmussen Torvik, Lj, Greenwood, Cm, Ladouceur, M, Grimsby, J, Manning, Ak, Liu, Ct, Kooner, J, Mooser, Ve, Vollenweider, P, Kapur, Ka, Chambers, J, Wareham, Nj, Langenberg, C, Frants, R, Willems Vandijk, K, Oostra, Ba, Willems, Sm, Lamina, C, Winkler, Tw, Psaty, Bm, Tracy, Rp, Brody, J, Chen, I, Viikari, J, Kähönen, M, Pramstaller, Pp, Evans, Dm, St Pourcain, B, Sattar, N, Wood, Ar, Bandinelli, S, Carlson, Od, Egan, Jm, Böhringer, S, van Heemst, D, Kedenko, L, Kristiansson, K, Nuotio, Ml, Loo, Bm, Harris, T, Garcia, M, Kanaya, A, Haun, M, Klopp, N, Wichmann, He, Deloukas, P, Katsareli, E, Couper, Dj, Duncan, Bb, Kloppenburg, M, Adair, L, Borja, Jb, DIAGRAM+, Consortium, Magic, Consortium, Glgc, Investigator, Muther, Consortium, Wilson, Jg, Musani, S, Guo, X, Johnson, T, Semple, R, Teslovich, Tm, Allison, Ma, Redline, S, Buxbaum, Sg, Mohlke, Kl, Meulenbelt, I, Ballantyne, Cm, Dedoussis, Gv, Hu, Fb, Liu, Y, Paulweber, B, Spector, Td, Slagboom, Pe, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, Jc, Salomaa, V, Eriksson, Jg, Frayling, Tm, Hicks, Aa, Lehtimäki, T, Smith, Gd, Siscovick, D, Kronenberg, F, van Duijn, C, Loos, Rj, Waterworth, Dm, Meigs, Jb, Dupuis, J, Richards, Jb, Voight, Bf, Scott, Lj, Steinthorsdottir, V, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, 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Hveem, K, Laakso, M, Morris, Ad, Palmer, Cn, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Pedersen, O, Barroso, I, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Elliott, P, Rybin, D, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Lajunen, T, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Diagram, Consortium, Giant, Consortium, Global B., Pgen Consortium, Borecki, Ib, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Serrano Ríos, M, Lind, L, Palmer, Lj, Hu FB, 1st, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Procardis, Consortium, Buchanan, Ta, Valle, Tt, Rotter, Ji, Penninx, Bw, Boomsma, Di, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Peltonen, L, Mooser, V, Magic, Investigator, Glgc, Consortium, Musunuru, K, Smith, Av, Edmondson, Ac, Stylianou, Im, Koseki, M, Pirruccello, Jp, Chasman, Di, Johansen, Ct, Fouchier, Sw, Peloso, Gm, Barbalic, M, Ricketts, Sl, Bis, Jc, Feitosa, Mf, Orho Melander, M, Melander, O, Li, X, Cho, Y, Go, Mj, Kim, Yj, Lee, Jy, Park, T, Kim, K, Sim, X, Ong, Rt, Croteau Chonka, Dc, Lange, La, Smith, Jd, Ziegler, A, Zhang, W, Zee, Ry, Whitfield, Jb, Thompson, Jr, Surakka, I, Smit, Jh, Sinisalo, J, Scott, J, Saharinen, J, Sabatti, C, Rose, Lm, Roberts, R, Rieder, M, Parker, An, Pare, G, O'Donnell, Cj, Nieminen, M, Nickerson, Da, Montgomery, Gw, Mcardle, W, Masson, D, Martin, Ng, Marroni, F, Lucas, G, Luben, R, Lokki, Ml, Lettre, G, Launer, Lj, Lakatta, Eg, Laaksonen, R, König, Ir, Khaw, Kt, Kaplan, Lm, Johansson, Å, Janssens, Ac, Igl, W, Hovingh, Gk, Hengstenberg, C, Havulinna, A, Hastie, Nd, Harris, Tb, Haritunians, T, Hall, A, Groop, Lc, Gonzalez, E, Freimer, Nb, Erdmann, J, Ejebe, Kg, Döring, A, Dominiczak, Af, Demissie, S, de Faire, U, Caulfield, Mj, Boekholdt, Sm, Assimes, Tl, Quertermous, T, Seielstad, M, Wong, Ty, Tai, E, Feranil, Ab, Kuzawa, Cw, Taylor HA, Jr, Gabriel, Sb, Holm, H, Gudnason, V, Krauss, Rm, Ordovas, Jm, Munroe, Pb, Tall, Ar, Hegele, Ra, Kastelein, Jj, Schadt, Ee, Strachan, Dp, Reilly, Mp, Samani, Nj, Schunkert, H, Cupples, La, Ridker, Pm, Rader, Dj, Kathiresan, S., Medical Research Council (MRC), Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Semple, Robert [0000-0001-6539-3069], Griffin, Simon [0000-0002-2157-4797], Barroso, Ines [0000-0001-5800-4520], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Zhao, Jing Hua [0000-0003-4930-3582], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Sandhu, Manjinder [0000-0002-2725-142X], Apollo - University of Cambridge Repository, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Other departments, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Lääketieteen yksikkö - School of Medicine, University of Tampere, Institute for Molecular Medicine Finland, Hjelt Institute (-2014), Clinicum, Department of General Practice and Primary Health Care, Department of Public Health, Haartman Institute (-2014), Transplantation Laboratory, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., and O'Leary, DH.
Subjects: Netherlands Twin Register (NTR), Male, Insulin Resistance/genetics, VARIANTS, 0302 clinical medicine, POPULATION, African Americans, blood/genetics, 0303 health sciences, education.field_of_study, Adiponectin/blood, Adiponectin/genetics, Asian Continental Ancestry Group, Cholesterol, HDL/genetics, Diabetes Mellitus, Type 2/genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Global B Pgen Consortium, MAGIC investigators, 3. Good health, Cholesterol, Medicine, Adiponectin, Type 2, medicine.medical_specialty, HDL, Biolääketieteet - Biomedicine, Single-nucleotide polymorphism, DIAGRAM Consortium, White People, Molecular Genetics, GLGC Consortium, 03 medical and health sciences, Asian People, SDG 3 - Good Health and Well-being, GIANT Consortium, Diabetes Mellitus, Genetics, DIAGRAM+ Consortium, GENOME-WIDE ASSOCIATION, Polymorphism, education, Biology, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, Science & Technology, GLGC Investigators, nutritional and metabolic diseases, ta3121, medicine.disease, Obesity, Black or African American, blood/genetics, African Americans, Asian Continental Ancestry Group, Cholesterol, genetics, Diabetes Mellitus, genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, genetics, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Endocrinology, Diabetes Mellitus, Type 2, Developmental Biology, Type 2/genetics, Cancer Research, Type 2 diabetes, QH426-470, 030204 cardiovascular system & hematology, LIPID CONCENTRATIONS, GENETICS & HEREDITY, Genetics (clinical), RISK, 2. Zero hunger, INSULIN-RESISTANCE, Glucose tolerance test, medicine.diagnostic_test, MAGIC Consortium, Single Nucleotide, ADIPOSE-TISSUE, CORONARY-ARTERY-DISEASE, Life Sciences & Biomedicine, Research Article, Clinical Research Design, GENETIC-BASIS, Population, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, ddc:610, 030304 developmental biology, RECEPTOR, Cholesterol, HDL, Human Genetics, HDL/genetics, 3121 General medicine, internal medicine and other clinical medicine, MuTHER Consortium, 3111 Biomedicine, Procardis Consortium, Insulin Resistance
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p, Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.
Published: 2012

33. Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons

Author: T van Herpt, Albert Hofman, Abbas Dehghan, Aloysius G Lieverse, Eric J.G. Sijbrands, M. van Hoek, Jacqueline C. M. Witteman, C.M. van Duijn, Internal Medicine, and Epidemiology
Subjects: APOC3, Male, medicine.medical_treatment, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Cohort Studies, Risk Factors, Polymorphism (computer science), Prevalence, Insulin, Prospective Studies, Promoter Regions, Genetic, Netherlands, Aged, 80 and over, education.field_of_study, Middle Aged, Type 1 diabetes, Female, medicine.medical_specialty, Population, Polymorphism, Single Nucleotide, Article, BMI, Thinness, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Internal Medicine, Humans, Hypoglycemic Agents, Genetic Predisposition to Disease, Polymorphism, Risk factor, education, Alleles, Aged, Apolipoprotein C-III, business.industry, Haplotype, Case-control study, medicine.disease, Logistic Models, Endocrinology, Diabetes Mellitus, Type 2, Haplotypes, Case-Control Studies, business
Abstract: Aims/hypothesis An APOC3 promoter haplotype has been previously associated with type 1 diabetes. In this population-based study, we investigated whether APOC3 polymorphisms increase type 2 diabetes risk and need for insulin treatment in lean participants. Methods In the Rotterdam Study, a population-based prospective cohort (n = 7,983), Cox and logistic regression models were used to analyse the associations and interactive effects of APOC3 promoter variants (−482C > T, −455T > C) and BMI on type 2 diabetes risk and insulin treatment. Analyses were followed by replication in an independent case–control sample (1,817 cases, 2,292 controls) and meta-analysis. Results In lean participants, the −482T allele was associated with increased risk of prevalent and incident type 2 diabetes: OR −482CT 1.47 (95% CI 1.13–1.92), −482TT 1.40 (95% CI 0.83–2.35), p = 0.009 for trend; HR −482CT 1.35 (95% CI 0.96–1.89), −482TT 1.68 (95% CI 0.91–3.1), p = 0.03 for trend, respectively. These results were confirmed by replication. Meta-analysis was highly significant (−482T meta-analysis p = 1.1 × 10-4). A borderline significant interaction was observed for insulin use among participants with type 2 diabetes (−482CT*BMI p = 0.06, −455TC*BMI p = 0.02). Conclusions/interpretation At a population-based level, the influence of APOC3 promoter variants on type 2 diabetes risk varies with the level of adiposity. Lean carriers of the −482T allele had increased type 2 diabetes risk, while such an effect was not observed in overweight participants. Conversely, in overweight participants the −455C allele seemed protective against type 2 diabetes. The interaction of the variants with need for insulin treatment may indicate beta cell involvement in lean participants. Our findings suggest overlap in the genetic backgrounds of type 1 diabetes and type 2 diabetes in lean patients.
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33 results on '"Aloysius G Lieverse"'

1. Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

2. Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: comparison between American Diabetes Association and World Health Organization diagnostic criteria

3. Introduction of the DiaGene study: clinical characteristics, pathophysiology and determinants of vascular complications of type 2 diabetes

4. The effect of guideline revisions on vascular complications of type 2 diabetes

5. Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus

6. Sex difference in the incidence of microvascular complications in patients with type 2 diabetes mellitus: a prospective cohort study

7. Lipoprotein(a) plasma levels are not associated with incident microvascular complications in type 2 diabetes mellitus

8. Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

9. Metformin and statin use associate with plasma protein

10. Association of the IgG N-glycome with the course of kidney function in type 2 diabetes

11. Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: Comparison between American Diabetes Association and World Health Organization diagnostic criteria

12. IgG glycan patterns are associated with type 2 diabetes in independent European populations

13. The effect of guideline revisions on vascular complications of type 2 diabetes

14. 04 - THE ASSOCIATION OF THE IGG N-GLYCOME WITH THE COURSE OF KIDNEY FUNCTION IN TYPE 2 DIABETES MELLITUS

15. Plasma protein N-glycan signatures of type 2 diabetes

16. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

17. Igg N-Glycan Patterns Are Associated With Ischemic Heart Disease In Type 2 Diabetes

18. Introduction of the DiaGene study: clinical characteristics, pathophysiology and determinants of vascular complications of type 2 diabetes

19. Strength Training Affects Lower Extremity Gait Kinematics, Not Kinetics, in People With Diabetic Polyneuropathy

20. Lp(A) Plasma Levels Are Not Associated With Microvascular Complications In T2d A Prospective Cohort Study

21. The Association Of The Igg N-Glycome With The Course Of Kidney Function In Type 2 Diabetes Mellitus

22. Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality

23. The Cockcroft-Gault

24. Calculation of plantar pressure time integral, an alternative approach

25. The anti-inflammatory function of high-density lipoprotein in type II diabetes: A systematic review

26. Lower leg muscle strengthening does not redistribute plantar load in diabetic polyneuropathy: a randomised controlled trial

27. A genetic variant in SLC6A20 is associated with Type 2 diabetes in white-European and Chinese populations

28. Increased forefoot loading is associated with an increased plantar flexion moment

29. Abdominal Aortic Aneurysm Is Associated with a Variant in Low-Density Lipoprotein Receptor-Related Protein 1

30. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

31. PS10 - 54. Adverse plantar pressures are associated with increased plantar flexion moments at the first part of the stance phase

32. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

33. Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons

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