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1. Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events

Author

Fowkes, FGR, Murray, GD, Butcher, I, Folsom, AR, Hirsch, AT, Couper, DJ, DeBacker, G, Kornitzer, M, Newman, Sutton-Tyrrell, KC, Cushman, M, Lee, AJ, Price, JF, D'Agostino, RB, Murabito, JM, Norman, PE, Masaki, KH, Bouter, LM, Heine, RJ, Stehouwer, CDA, McDermott, MM, Stoffers, HEJH, Knottnerus, JA, Ogren, M, Hedblad, B, Koenig, W, Meisinger, C, Cauley, JA, Franco, OH, Hunink, MGM, Hofman, A, Witteman, JC, Criqui, MH, Langer, RD, Hiatt, WR, and Hamman, RF

Subjects
Cardiovascular, Prevention, Clinical Research, Heart Disease, Adult, Aged, Aged, 80 and over, Ankle Brachial Index, Cardiovascular Diseases, Europe, Female, Humans, Male, Middle Aged, Models, Statistical, Predictive Value of Tests, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States, White People, Young Adult, Ankle Brachial Index Collaboration, Ankle brachial index, cardiovascular diseases, risk assessment, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

BackgroundThe ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.DesignAn analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events.MethodsSubjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events.ResultsIn predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p

Published
2014

2. One hour post-load plasma glucose and 3 year risk of worsening fasting and 2 hour glucose tolerance in the RISC cohort

Author

Manco, Melania, Mari, Andrea, Petrie, John, Mingrone, Geltrude, Balkau, Beverley, Amsterdam, for the EGIR-RISC study group., Heine, Rj, Dekker, J, S de Rooij, Nijpels, G, W Boorsma Athens, Greece:, A Mitrakou, Tournis, S, Kyriakopoulou, K, P Thomakos Belgrade, Serbia:, N Lalic, Lalic, K, Jotic, A, Lukic, L, M Civcic Dublin, Ireland:, J Nolan, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, M Hatunic Frankfurt, Germany:, T Konrad, Böhles, H, Fuellert, S, Baer, F, H Zuchhold Geneva, Switzerland:, A Golay, E Harsch Bobbioni, Barthassat, V, Makoundou, V, Tno, Lehmann, T Merminod Glasgow, Scotland, UK: JR Petrie, Perry, C, Neary, F, Macdougall, C, Shields, K, L Malcolm Kuopio, Finland:, M Laakso, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, H Saloranta London, England, UK: SW Coppack, Mcintosh, N, Ross, J, Pettersson, L, P Khadobaksh Lyon, France:, M Laville, F Bonnet (now Rennes), A Brac de la Perriere, Louche-Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, A Serusclat Madrid, Spain:, R Gabriel, Sánchez, Em, Carraro, R, Friera, A, B Novella Malmö, Sweden (1):, P Nilsson, Persson, M, G Östling (2):, O Melander, P Burri Milan, Italy: PM Piatti, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, A Colleluori Newcastle-upon-Tyne, Uk:, M Walker, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, D Richardson Odense, Denmark:, H Beck-Nielsen, Staehr, P, Højlund, K, Vestergaard, V, Olsen, C, L Hansen Perugia, Italy: GB Bolli, Porcellati, F, Fanelli, C, Lucidi, P, Calcinaro, F, A Saturni Pisa, Italy:, E Ferrannini, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, BD Astiarraga Rome, Italy:, G Mingrone, Guidone, C, Favuzzi, A, P Di Rocco Vienna, Austria:, C Anderwald, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, and Roden, M

Subjects
Post-load glucose, Adult, Male, Blood Glucose, 0301 basic medicine, Diagnostic criteria, Endocrinology, Diabetes and Metabolism, Physiology, 030209 endocrinology & metabolism, Prediabetic State, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Research Letter, Internal Medicine, medicine, Humans, Prediabetes, Plasma glucose, Glucose tolerance test, Post-challenge glucose, Prediabetes phenotype, Progression, medicine.diagnostic_test, business.industry, Fasting, Female, Glucose Tolerance Test, Middle Aged, Settore MED/13 - ENDOCRINOLOGIA, Human physiology, medicine.disease, Diabetes and Metabolism, 030104 developmental biology, Cohort, business
Abstract

The affiliation details for Geltrude Mingrone are corrected below.

Published
2018

3. Unequal Access to Newly Registered Cancer Drugs Leads to Potential Loss of Life-Years in Europe

Author

Uyl - de Groot, Carin, Heine, RJ, Krol, HM, Verweij, Jaap, Uyl - de Groot, Carin, Heine, RJ, Krol, HM, and Verweij, Jaap

Abstract

Background. Many new cancer medicines have been developed that can improve patients’ outcomes. However, access to these agents comes later in Europe than in the United States (US). The aim of this study is to assess the access in Europe to newly registered cancer drugs and to get more insight in the implications of these variations for patients. Methods. A retrospective database study was conducted. Analyses involved 12 cancer drugs and 28 European countries in the period 2011–2018. Time to patient access, speed of drug uptake, and the potential loss of life years due to a delayinaccesshavebeenstudied. Results. Marketingapprovalforthecancerdrugscameonaverage 242 days later in Europe than in the US, and actual patient access varied extensively across Europe. The average time to market in Europe was 403 days (range 17–1187 days). The delay in patient access of ipilimumab and abiraterone may have led to a potential loss of more than 30,000 life years. Conclusion. It takes a long time for patients to get access to newly registered cancer drugs and there is great variation in access. The health outcomes can be substantially improved by faster processes.

Published
2020

4. NHG-Standaard Diabetes mellitus type 2

Author

Rutten, GEHM, primary, De Grauw, WJC, additional, Nijpels, G, additional, Goudswaard, AN, additional, Uitewaal, PJM, additional, Van der Does, FEE, additional, Heine, RJ, additional, Van Ballegooie, E, additional, Verduijn, MM, additional, and Bouma, M, additional

Published
2011
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6. Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis

Author

Trico, D, Mengozzi, A, Nesti, L, Hatunic, M, Sanchez, Rg, Konrad, T, Lalic, K, Lalic, Nm, Mari, A, Natali, A, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Bohles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, Eh, Barthassat, V, Makoundou, V, Lehmann, Tno, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere, Ab, Louche-Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sanchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, I, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck-Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, F, Fanelli, C, Lucidi, P, Calcinaro, F, Saturni, A, Ferrannini, E, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhausl, W, Roden, M, Balkau, B, Dekker, Jm, Petrie, J, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Tura, A, Hills, Sa, and Mota, L.

Subjects
Adult, Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Subcutaneous adipose tissue, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030209 endocrinology & metabolism, Carbohydrate metabolism, Palmitate, NEFA, Fatty Acids, Monounsaturated, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Insulin-Secreting Cells, Internal medicine, Adipokine, Internal Medicine, medicine, Humans, Palmitoleic acid, Longitudinal Studies, Monounsaturated fatty acid, Lipokine, Beta cell function, Glucose tolerance, Metabolism, Glucose Tolerance Test, Middle Aged, medicine.disease, Insulin sensitivity, Cross-Sectional Studies, 030104 developmental biology, Endocrinology, chemistry, Body Composition, Female, Insulin Resistance, Hormone
Abstract

Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or ‘lipokine’) to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic–euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = −0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = −0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.

Published
2019

9. Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study

Author

Kozakova, M, Natali, A, Dekker, J, Beck Nielsen, H, Laakso, M, Nilsson, P, Balkau, B, Ferrannini, E, Heine, Rj, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie Dundee JR, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, Filippo, Saturni, A, Muscelli, E, Pinnola, S, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, Dekker, Ferrannini, Mari, A, Natali, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, Mota, L., Epidemiology and Data Science, and EMGO - Lifestyle, overweight and diabetes

Subjects
Adult, Blood Glucose, Carotid Artery Diseases, Male, medicine.medical_specialty, Adipokine, Carotid Intima-Media Thickness, Risk Assessment, Sensitivity and Specificity, Cohort Studies, Insulin resistance, Age Distribution, Adipokines, Diabetes mellitus, Internal medicine, medicine.artery, medicine, Humans, Common carotid artery, cardiovascular diseases, Sex Distribution, Retrospective Studies, business.industry, Incidence, Fatty Acids, Insulin sensitivity, Cholesterol, LDL, Glucose Tolerance Test, Middle Aged, medicine.disease, Prognosis, Endocrinology, Intima-media thickness, Cardiovascular Diseases, Cohort, Glucose Clamp Technique, cardiovascular system, Female, Insulin Resistance, Cardiology and Cardiovascular Medicine, business, Dyslipidemia
Abstract

Objective— Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. Approach and Results— We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated after 3 years. In men, baseline intima-media thickness in the common carotid artery (CCA-IMT) was significantly higher ( P P Conclusions— In young-to-middle aged apparently healthy people, the association of CCA-IMT with insulin sensitivity and its metabolic correlates differs between men and women. Lower insulin sensitivity is associated with higher IMT only in men; this association seems to be mediated by circulating free fatty acids and adipocytokines. In women, CCA-IMT is independently associated with fasting plasma glucose.

Published
2013

10. Does Glucose Variability Influence the Relationship Between Mean Plasma Glucose and HbA1c Levels in Type 1 and Type 2 Diabetic Patients?

Author

Kuenen, Jc, Borg, R, Kuik, Dj, Zheng, H, Schoenfeld, D, Diamant, M, Nathan, Dm, Heine, Rj, Sartore, Giovanni, Lapolla, Annunziata, Internal medicine, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, and ICaR - Ischemia and repair

Subjects
Research design, Adult, Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Adolescent, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Young Adult, Glycation, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Pathophysiology/Complications, Glycemic, Original Research, Aged, Advanced and Specialized Nursing, Glycated Hemoglobin, Type 1 diabetes, Plasma glucose, business.industry, Confounding, nutritional and metabolic diseases, Middle Aged, medicine.disease, Endocrinology, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, business
Abstract

OBJECTIVE The A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between HbA1c and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability indices and the MPG-HbA1c relationship. RESEARCH DESIGN AND METHODS Analyses included 268 patients with type 1 diabetes and 159 with type 2 diabetes. MPG during 3 months was calculated from 7-point self-monitored plasma glucose and continuous glucose monitoring. We calculated three different measures of GV and used a multiple-step regression model to determine the contribution of the respective GV measures to the MPG-HbA1c relationship. RESULTS GV, as reflected by SD and continuous overlapping net glycemic action, had a significant effect on the MPG-HbA1c relationship in type 1 diabetic patients so that high GV led to a higher HbA1c level for the same MPG. In type 1 diabetes, the impact of confounding and effect modification of a low versus high SD at an MPG level of 160 mg/dL on the HbA1c level is 7.02 vs. 7.43 and 6.96 vs. 7.41. All GV measures showed the same tendency. CONCLUSIONS In only type 1 diabetic patients, GV shows a significant interaction with MPG in the association with HbA1c. This effect is more pronounced at higher HbA1c levels. However, the impact of GV on the HbA1c level in type 1 diabetes is modest, particularly when HbA1c is close to the treatment target of 7%.

Published
2011

11. Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events

Author

Stoffers, HEJH, Ogren, M, Fowkes, FGR, Cushman, M, Cauley, JA, Price, JF, Kornitzer, M, Murabito, JM, Lee, AJ, Meisinger, C, Hirsch, AT, Witteman, JC, Knottnerus, JA, D'Agostino, RB, McDermott, MM, Heine, RJ, Masaki, KH, Folsom, AR, Hunink, MGM, Sutton-Tyrrell, KC, Stehouwer, CDA, Norman, PE, DeBacker, G, Couper, DJ, Murray, GD, Bouter, LM, Butcher, I, Franco, OH, Newman, AB, Hofman, A, Koenig, W, and Hedblad, B

Subjects
body regions, animal structures, cardiovascular system, cardiovascular diseases, human activities
Abstract

The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.

Published
2014
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12. The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases

Author

Danesh, J, Erqou, S, Walker, M, Thompson, Sg, Tipping, R, Ford, C, Pressel, S, Walldius, G, Jungner, I, Folsom, Ar, Chambless, Le, Knuiman, M, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Willeit, J, Kiechl, S, Santer, P, Mayr, A, Wald, N, Ebrahim, S, Lawlor, Da, Yarnell, Jw, Gallacher, J, Casiglia, Edoardo, Tikhonoff, Valerie, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, Cushman, M, Psaty, Bm, Tracy, Rp, Tybjaerg Hansen, A, Nordestgaard, Bg, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, S, Vanuzzo, D, Pilotto, L, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Smith, Fb, Taylor, J, Guralnik, J, Phillips, C, Wallace, R, Blazer, D, Khaw, Kt, Jansson, Jh, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, Rs, Pencina, Mj, Bladbjerg, Em, Jorgensen, T, Moller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Bjorkelund, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, T, Rodriguez, B, Bouter, Lm, Heine, Rj, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, J, Sato, S, Iso, H, Kitamura, A, Noda, H, Goldbourt, U, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Deeg, D, Poppelaars, Jl, Meade, T, Cooper, J, Hedblad, B, Berglund, G, Engstrom, G, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Kuller, L, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Hankinson, S, Manson, J, De Stavola, B, Knottenbelt, C, Cooper, Ja, Bauer, Ka, Rosenberg, Rd, Naito, Y, Holme, I, Nakagawa, H, Miura, H, Ducimetiere, P, Jouven, X, Crespo, C, Garcia Palmieri, M, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, C, Sattar, N, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, D, Bettencourt, R, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Witteman, J, Kardys, I, Breteler, M, Hofman, A, Tunstall Pedoe, H, Tavendale, R, Lowe, Gd, Ben Shlomo, Y, Howard, Bv, Zhang, Y, Best, L, Umans, J, Onat, A, Meade, Tw, Njolstad, I, Mathiesen, E, Lochen, Ml, Wilsgaard, T, Gaziano, Jm, Stampfer, M, Ridker, P, Ulmer, H, Diem, G, Concin, H, Rodeghiero, F, Tosetto, A, Brunner, E, Shipley, M, Buring, J, Cobbe, Sm, Ford, I, Robertson, M, He, Y, Ibanez, Am, Feskens, Ej, Kromhout, D, Collins, R, Di Angelantonio, E, Kaptoge, S, Lewington, S, Orfei, L, Pennells, L, Perry, P, Ray, K, Sarwar, N, Scherman, M, Thompson, A, Watson, S, Wensley, F, White, Ir, Wood, Am, Emerging Risk Factors Collaboration, Interne Geneeskunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: CARIM School for Cardiovascular Diseases, Movement Behavior, Executive board Vrije Universiteit, Clinical Child and Family Studies, Sociology and Social Gerontology, Earth and Climate, Environmental Policy Analysis, Developmental Genetics, Danesh, J, Erqou, S, Walker, M, Thompson, Sg, Tipping, R, Ford, C, Pressel, S, Walldius, G, Jungner, I, Folsom, Ar, Chambless, Le, Knuiman, M, Whincup, Ph, Wannamethee, Sg, Morris, Rw, Willeit, J, Kiechl, S, Santer, P, Mayr, A, Wald, N, Ebrahim, S, Lawlor, Da, Yarnell, Jw, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, Pj, Sutherland, Se, Bachman, Dl, Keil, Je, Cushman, M, Psaty, Bm, Tracy, Rp, Tybjaerg Hansen, A, Nordestgaard, Bg, Frikke Schmidt, R, Giampaoli, S, Palmieri, L, Panico, Salvatore, Vanuzzo, D, Pilotto, L, Simons, L, Mccallum, J, Friedlander, Y, Fowkes, Fg, Lee, Aj, Smith, Fb, Taylor, J, Guralnik, J, Phillips, C, Wallace, R, Blazer, D, Khaw, Kt, Jansson, Jh, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D'Agostino, Rb, Wolf, Pa, Vasan, R, Pencina, Mj, Bladbjerg, Em, Jorgensen, T, Moller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Bjorkelund, C, Cremer, P, Nagel, D, Tilvis, R, Strandberg, T, Rodriguez, B, Bouter, Lm, Heine, Rj, Dekker, Jm, Nijpels, G, Stehouwer, Cd, Rimm, E, Pai, J, Sato, S, Iso, H, Kitamura, A, Noda, H, Goldbourt, U, Salonen, Jt, Nyyssönen, K, Tuomainen, Tp, Deeg, D, Poppelaars, Jl, Meade, T, Cooper, J, Hedblad, B, Berglund, G, Engstrom, G, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Kuller, L, Selmer, R, Tverdal, A, Nystad, W, Gillum, R, Mussolino, M, Hankinson, S, Manson, J, De Stavola, B, Knottenbelt, C, Cooper, Ja, Bauer, Ka, Rosenberg, Rd, Naito, Y, Holme, I, Nakagawa, H, Miura, H, Ducimetiere, P, Jouven, X, Crespo, C, Garcia Palmieri, M, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, C, Sattar, N, Cantin, B, Lamarche, B, Després, Jp, Dagenais, Gr, Barrett Connor, E, Wingard, D, Bettencourt, R, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Witteman, J, Kardys, I, Breteler, M, Hofman, A, Tunstall Pedoe, H, Tavendale, R, Lowe, Gd, Ben Shlomo, Y, Howard, Bv, Zhang, Y, Best, L, Umans, J, Onat, A, Meade, Tw, Njolstad, I, Mathiesen, E, Lochen, Ml, Wilsgaard, T, Gaziano, Jm, Stampfer, M, Ridker, P, Ulmer, H, Diem, G, Concin, H, Rodeghiero, F, Tosetto, A, Brunner, E, Shipley, M, Buring, J, Cobbe, Sm, Ford, I, Robertson, M, He, Y, Ibanez, Am, Feskens, Ej, Kromhout, D, Collins, R, Di Angelantonio, E, Kaptoge, S, Lewington, S, Orfei, L, Pennells, L, Perry, P, Ray, K, Sarwar, N, Scherman, M, Thompson, A, Watson, S, Wensley, F, White, Ir, and Wood, A. M.

Subjects
Databases, Factual, Nutrition and Disease, Epidemiology, Inflammatory markers, middle-aged men, Disease, Leukocyte Count, c-reactive protein, Risk Factors, Voeding en Ziekte, adult-treatment-panel, Prospective Studies, Myocardial infarction, Prospective cohort study, education.field_of_study, biology, plasma-fibrinogen, Asia, Eastern, Confounding, density-lipoprotein cholesterol, Cardiovascular disease, Lipids, myocardial-infarction, Coronary heart disease, Cardiovascular Diseases, Meta-analysis, Lipoproteins, HDL, high blood cholesterol, medicine.medical_specialty, low-dose aspirin, Population, 10-year follow-up, SDG 3 - Good Health and Well-being, Albumins, medicine, Humans, education, Triglycerides, VLAG, Inflammation, Estimation, business.industry, C-reactive protein, medicine.disease, Surgery, Emergency medicine, biology.protein, business, coronary-heart-disease, Biomarkers
Abstract

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age-and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily,with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Published
2007

13. Influence of Apolipoproteins on the Association Between Lipids and Insulin Sensitivity: A cross-sectional analysis of the RISC Study

Author

Baldi, S., Bonnet, F., Laville, M., Morgantini, C., Monti, L., Hojlund, K., Ferrannini, E., Natali, A., Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, Filippo, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Gaffney, P, Boran, G, Baldi, S, Balkau, B, Mhamdi, L, Mari, A, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Tura, A, Hills, Sa, Dekker, Jm, and Walker, M.

Published
2013

14. From metabolic normality to cardiometabolic risk factors in subjects with obesity

Author

Elisabetta Bobbioni Harsch, Zoltan, Pataky, Vincent, Makoundou, Martine, Laville, Emmanuel, Disse, Christian, Anderwald, Thomas, Konrad, Alain, Golay, Heine, Rj, Dekker, J, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Pataky, Z, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, and Mota, L.

Subjects
Adult, Male, medicine.medical_specialty, Obesity, cardiometabolic risk factors, Carotid Artery, Common, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Blood Pressure, Overweight, Carotid Intima-Media Thickness, Body Mass Index, Impaired glucose tolerance, Young Adult, Endocrinology, Insulin resistance, Reference Values, Risk Factors, Internal medicine, Glucose Intolerance, medicine, Humans, Obesity, ddc:613, Nutrition and Dietetics, business.industry, Body Weight, Fasting, Middle Aged, medicine.disease, Impaired fasting glucose, Blood pressure, Cardiovascular Diseases, lipids (amino acids, peptides, and proteins), Female, medicine.symptom, Insulin Resistance, business, Lipoproteins, HDL, Body mass index, Weight gain
Abstract

The aim of the study was to evaluate the 3 years incidence of cardiometabolic risk factors, such as impaired fasting glucose, reduced high-density lipoprotein (HDL)-cholesterol, increased plasma triglycerides or blood pressure as well as impaired glucose tolerance in overweight or obese (ow/ob) and normal body weight (nbw) subjects metabolically normal at baseline. Subjects from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study were analyzed. We analyzed 284 nbw and 152 ow/ob subjects who, at baseline, did not show any of the above-mentioned cardiometabolic risk factors. At 3 years, these parameters were re-evaluated. Intima-media thickness (IMT) of the common carotid artery (CCA) was echographically measured. At follow-up, the incidence of one or more cardiometabolic risk factors was 57.2% in ow/ob vs. 31.7% in nbw (P < 0.0001). After adjustment for age, sex, menopause status, lifestyle parameters, insulin sensitivity, and fasting insulinemia, BMI remained significantly linked to the development of one or more cardiometabolic risk factors (P = 0.02). An increased BMI at follow-up was significantly associated with the development of cardiometabolic alterations, in both nbw and ow/ob groups (P = 0.04). Ow/ob subjects who, at 3 years follow-up, remained metabolically normal, showed a less favourable cardiometabolic profile, when compared to nbw counterparts. In ow/ob metabolically normal males and females, intima-media of the common carotid at follow-up was thicker than in nbw (P = 0.03 for males, P = 0.04 for females). In conclusion, metabolically normal obese subjects show a higher incidence of cardiometabolic risk factors, in a short follow-up period. Weight gain is significantly associated with the development of these factors, in both nbw and ow/ob subjects.

Published
2012

15. Fatty liver index, gamma-glutamyltransferase, and early carotid plaques

Author

Kozakova, M, Palombo, C, Eng, Mp, Dekker, J, Flyvbjerg, A, Mitrakou, A, Gastaldelli, A, Ferrannini, E, Heine, Rj, Dekker, Jm, de Rooij, S, Nijpels, G, Boorsma, W, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni Harsch, E, Barthassat, V, Makoundou, V, Lehmann, T, Merminod, T, Petrie, J, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere AB, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Me, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Natali, A, Muscelli, E, Pinnola, S, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Mari, A, Gaffney, P, Boran, G, Beck Nielsen, H, Kok, A, Patel, S, Ciociaro, D, Guillanneuf, Mt, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, Mota, L., Epidemiology and Data Science, and EMGO - Lifestyle, overweight and diabetes

Subjects
Carotid Artery Diseases, Male, SMOOTH-MUSCLE-CELLS, Comorbidity, INTIMA-MEDIA THICKNESS, Severity of Illness Index, ADIPONECTIN, AMERICAN-HEART-ASSOCIATION, Prevalence, Gamma-glutamyltransferase, Ultrasonography, RISK, biology, INSULIN SENSITIVITY, Fatty liver, gamma-Glutamyltransferase, Middle Aged, Prognosis, Plaque, Atherosclerotic, Survival Rate, CARDIOVASCULAR-DISEASE, Hypertension, Female, Waist Circumference, Adult, medicine.medical_specialty, HEPATIC STEATOSIS, PLASMA-PROTEIN, ATHEROSCLEROSIS, Risk Assessment, Insulin resistance, Age Distribution, Internal medicine, Diabetes mellitus, medicine, Humans, Sex Distribution, Proportional Hazards Models, Hepatology, Adiponectin, business.industry, medicine.disease, Fatty Liver, Endocrinology, Cross-Sectional Studies, Logistic Models, Intima-media thickness, Multivariate Analysis, biology.protein, Metabolic syndrome, Insulin Resistance, business, Dyslipidemia
Abstract

An association between fatty liver and carotid atherosclerosis has been established; however, it is not clear whether this relationship is a consequence of shared conventional risk factors or whether it is determined by specific circulating factors originating from liver or adipose tissue. To identify the factors possibly linking fatty liver and atherosclerosis, we assessed, in 1,012 subjects free of confounding diseases (e.g., hypertension, diabetes, cardiovascular diseases, and dyslipidemia) and metabolic syndrome, the relationship between the presence of early plaques at carotid bifurcation and fatty liver index (FLI; a validated surrogate marker of fatty liver), as well as the associations between carotid plaque presence and established atherosclerotic risk factors, family history of cardiovascular disease (FH-CVD) or diabetes, insulin sensitivity, serum liver enzymes, adipokines, fatty free acids, and high-sensitivity C-reactive protein (hsCRP). A total of 55 of 1,012 subjects (5.4%) had small plaque at carotid bifurcation. Subjects with plaque were older and had higher prevalence of FLI ≥60 and FH-CVD, higher blood pressure, plasma low-density lipoprotein cholesterol, glucose, gamma-glutamyltransferase (GGT), and hsCRP, as compared to subjects without plaques (P < 0.05). In a logistic regression model, adjusted for sex, liver transaminase, and alcohol consumption, the independent predictors of plaque presence were age (P < 0.0005), FLI ≥60 (P < 0.0005), and current smoking (P < 0.05). When FLI in the model was replaced by variables used in its equation (e.g., body mass index, waist circumference, plasma triglycerides, and GGT), the independent determinants of plaque presence were age (P < 0.001), GGT (P = 0.001), and current smoking (P < 0.05). Conclusions: Our cross-sectional study suggests that subjects with FLI ≥60 are at higher risk of atherosclerotic lesions, independently of established risk factors, and that serum GGT may represent a link between fatty liver and the development of early atherosclerosis. (HEPATOLOGY 2012)

Published
2012

16. Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population

Author

Handberg, A, Højlund, K, Gastaldelli, A, Flyvbjerg, A, Dekker, Jm, Petrie, J, Piatti, P, Beck Nielsen, H, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, Eh, Barthassat, V, Makoundou, V, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, de la Perriere AB, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Dirocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Ciociaro, D, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, and Mota, L.

Subjects
Adult, CD36 Antigens, Male, Enzyme-Linked Immunosorbent Assay, Middle Aged, Atherosclerosis, Body Mass Index, Cohort Studies, Europe, Fatty Liver, Cross-Sectional Studies, Predictive Value of Tests, Diabetes Mellitus, Humans, Female, Prospective Studies, Insulin Resistance, Algorithms, Biomarkers
Abstract

Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid atherosclerosis in nondiabetic subjects.In 1296 healthy subjects without diabetes or hypertension recruited from 19 centres in 14 European countries (RISC study), we determined the levels of sCD36, adiponectin, lipids and liver enzymes, insulin sensitivity (M/I) by euglycaemic-hyperinsulinaemic clamp, carotid atherosclerosis as intima-media thickness (IMT) and two estimates of fatty liver, the fatty liver index (FLI) and liver fat percentage (LF%).IMT, FLI, LF%, presence of the metabolic syndrome, impaired glucose regulation, insulin and triglycerides increased across sCD36 quartiles (Q2-Q4), whereas adiponectin and M/I decreased (P ≤ 0.01). sCD36 was lower in women than in men (P = 0.045). Log sCD36 showed a bimodal distribution, and amongst subjects with sCD36 within the log-normal distribution (log-normal population, n = 1029), sCD36 was increased in subjects with impaired glucose regulation (P = 0.045), metabolic syndrome (P = 0.006) or increased likelihood of fatty liver (P0.001). sCD36 correlated significantly with insulin, triglycerides, M/I and FLI (P0.05) after adjustment for study centre, gender, age, glucose tolerance status, smoking habits and alcohol consumption. In the log-normal population, these relationships were stronger than in the total study population and, additionally, sCD36 was significantly associated with LF% and IMT (P0.05).In this cross-sectional study of nondiabetic subjects, sCD36 was significantly associated with indices of insulin resistance, carotid atherosclerosis and fatty liver. Prospective studies are needed to further evaluate the role of sCD36 in the inter-relationship between atherosclerosis, fatty liver and insulin resistance.

Published
2011

17. A novel surrogate index for hepatic insulin resistance

Author

Vangipurapu, J, Stančáková, A, Kuulasmaa, T, Paananen, J, Kuusisto, J, EGIR RISC Study Group, Ferrannini, E, Laakso, M, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perrier, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Pacini, G, Cavaggion, C, Hills, Sa, and Mota

Published
2011

18. Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women

Author

Bonnet, F, Ducluzeau, Ph, Gastaldelli, A, Laville, M, Anderwald, Ch, Konrad, T, Mari, A, Balkau, B, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Böhles, H, Fuellert, S, Ber, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Östling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Stehr, P, Hojlund, K, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Casolaro, A, Astiarraga, Bd, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Dekker, Jm, Petrie, J, Gaffney, P, Boran, G, Kok, A, Patel, S, Ciociaro, D, Flyvbjerg, A, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, Tura, A, Hills, Sa, and Mot

Published
2011

19. Effect of sedentary behaviour and vigorous physical activity on segment-specific carotid wall thickness and its progression in a healthy population

Author

Kozàkovà, M, Palombo, C, Morizzo, C, Nolan, Jj, Konrad, T, Balkau, B, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sanchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhausl, W, Roden, M, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Mota, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, and Mota, L.

Published
2010

20. Impact of family history on relations between insulin resistance, LDL cholesterol and carotid IMT in healthy adults

Author

Anderwald, C, Stadler, M, Golay, A, Krebs, M, Petrie, J, Luger, A, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Bönles, H, Franke, S, Baer, F, Zuchhold, H, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm Kuopio, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Bischof, M, Promintzer, M, Mandl, M, Hofer, A, Waldhäusl, W, Roden, M, Balkau, B, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, and Mota, L.

Published
2010

24. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women

Author

Muscelli, E, Kozàkovà, M, Flyvbjerg, A, Kyriakopoulou, K, Astiarraga, Bd, Glintborg, D, Konrad, T, Favuzzi, A, Petrie, J, Heine, Rj, Dekker, J, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Balkau, B, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, and Mota, L.

Published
2009

25. Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population

Author

Gastaldelli, A, Kozakova, M, Højlund, K, Flyvbjerg, A, Favuzzi, A, Mitrakou, A, Balkau, B, Heine, Rj, Dekker, J, Nijpels, G, Boorsma, W, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Bohles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Harsch Bobbioni, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Mingrone, G, Guidone, C, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Patel, S, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Pacini, G, Cavaggion, C, Hills, Sa, Landucci, L, and Mota, L.

Published
2009

26. Body composition and common carotid artery remodeling in a healthy population

Author

Kozakova, M, Palombo, C, Paterni, M, Anderwald, Ch, Konrad, T, Colgan, Mp, Flyvbjerg, A, Dekker, J, Heine, Rj, de Rooij, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, N, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Hatunic, M, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, Bobbioni, Eh, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Petrie, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Laville, M, Bonnet, F, Brac de la Perriere, A, Louche Pelissier, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Monti, Ld, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Walker, M, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, Beck Nielsen, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Gb, Porcellati, Francesca, Fanelli, Carmine Giuseppe, Lucidi, Paola, Calcinaro, F, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Mingrone, G, Guidone, C, Favuzzi, A, Di Rocco, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, and Roden, M.

Published
2008

27. Translating the A1C assay into estimated average glucose values

Author

Nathan, Dm, Kuenen, J, Borg, R, Zheng, H, Schoenfeld, D, Heine, Rj, Kerner, Gs, VAN IPEREN, A, Horton, E, Cohen, A, HERZLINGER BOTEIN, S, Paradis, J, Saudek, C, Moore, K, Greene, A, Islas, M, Nerup, J, Glumer, C, Mosca, A, Lapolla, Annunziata, Fedele, Domenico, and Sartore, Giovanni

Published
2008

28. Influence of the ACE gene insertion/deletion polymorphism on insulin sensitivity and impaired glucose tolerance in healthy subjects

Author

Bonnet, F, Patel, S, Laville, M, Balkau, B, Favuzzi, A, Monti, Ld, Lalic, N, Walker, M, Heine, Rj, Dekker, J, DE ROOIJ, S, Nijpels, G, Boorsma, W, Mitrakou, A, Tournis, S, Kyriakopoulou, K, Thomakos, P, Lalic, K, Jotic, A, Lukic, L, Civcic, M, Nolan, J, Yeow, Tp, Murphy, M, Delong, C, Neary, G, Colgan, Mp, Hatunic, M, Konrad, T, Böhles, H, Fuellert, S, Baer, F, Zuchhold, H, Golay, A, HARSCH BOBBIONI, E, Barthassat, V, Makoundou, V, Lehmann, Tn, Merminod, T, Dundee, Jr, Perry, C, Neary, F, Macdougall, C, Shields, K, Malcolm, L, Laakso, M, Salmenniemi, U, Aura, A, Raisanen, R, Ruotsalainen, U, Sistonen, T, Laitinen, M, Saloranta, H, Coppack, Sw, Mcintosh, N, Ross, J, Pettersson, L, Khadobaksh, P, Rennes, F, BRAC DE LA PERRIERE, A, LOUCHE PELISSIER, C, Maitrepierre, C, Peyrat, J, Beltran, S, Serusclat, A, Gabriel, R, Sánchez, Em, Carraro, R, Friera, A, Novella, B, Nilsson, P, Persson, M, Ostling, G, Melander, O, Burri, P, Piatti, Pm, Setola, E, Galluccio, E, Minicucci, F, Colleluori, A, Ibrahim, Im, Jayapaul, M, Carman, D, Ryan, C, Short, K, Mcgrady, Y, Richardson, D, BECK NIELSEN, H, Staehr, P, Hojlund, K, Vestergaard, V, Olsen, C, Hansen, L, Bolli, Geremia Brunetto, Porcellati, F, Fanelli, Carmine Giuseppe, Lucidi, P, Calcinaro, Filippo, Saturni, A, Ferrannini, E, Natali, A, Muscelli, E, Pinnola, S, Kozakova, M, Mingrone, G, Guidone, C, DI ROCCO, P, Anderwald, C, Bischof, M, Promintzer, M, Krebs, M, Mandl, M, Hofer, A, Luger, A, Waldhäusl, W, Roden, M, Dekker, Jm, Mari, A, Gaffney, P, Boran, G, Kok, A, Gastaldelli, A, Ciociaro, D, Guillanneuf, Mt, Mhamdi, L, Landucci, L, Hills, S, Mota, L, Pacini, G, Cavaggion, C, and Hills, Sa

Published
2008

32. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial

Author

Dormandy, Ja, Charbonnel, B, Eckland, Dj, Erdmann, E, Massi Benedetti, M, Moules, Ik, Skene, Am, Tan, Mh, Lefèbvre, Pj, Murray, Gd, Standl, E, Wilcox, Rg, Wilhelmsen, L, Betteridge, J, Birkeland, K, Golay, A, Heine, Rj, Korányi, L, Laakso, M, Mokán, M, Norkus, A, Pirags, V, Podar, T, Scheen, A, Scherbaum, W, Schernthaner, G, Schmitz, O, Skrha, J, Smith, U, Taton, J, Squatrito, Sebastiano, and Proactive, Investigators

Published
2005

33. What does postprandial hyperglycaemia mean?

Author

Heine, Rj, Balkau, B, Ceriello, A, DEL PRATO, Stefano, Horton, Es, and Taskinen, Mr

Subjects
Blood Glucose, Glycated Hemoglobin, Metabolic Syndrome, Diabetes Mellitus, Type 2, Risk Factors, Hyperglycemia, Humans, Insulin Resistance, Postprandial Period, Diabetic Angiopathies, Triglycerides
Abstract

The potential importance of postprandial glucose (PPG) control in the development of complications in Type 2 diabetes is much debated. The recent American Diabetes Association (ADA) consensus statement discussed the role of postprandial hyperglycaemia in the pathogenesis of diabetic complications and concluded that the relationship between PPG excursions and the well-established risk factors for cardiovascular disease (CVD) should be further examined. Using the ADA statement as a starting point and including the more recent American College of Endocrinology guidelines on glycaemic control, a panel of experts in diabetes met to review the role of PPG within the context of the overall metabolic syndrome, in the development of complications in Type 2 diabetes.Post-prandial hyperglycaemia is a risk indicator for micro- and macrovascular complications, not only in patients with Type 2 diabetes but also in those with impaired glucose tolerance. In addition, the metabolic syndrome confers an increased risk of CVD morbidity and mortality. The debate focused on the relative contributions of postprandial hyperglycaemia, the metabolic syndrome and, in particular, raised triglyceride levels in the postprandial state, to the development of cardiovascular complications of diabetes.The panel recommended that in the prevention and management of microvascular complications of Type 2 diabetes, targeting both chronic and acute glucose fluctuations is necessary. Lowering the macrovascular risk also requires control of (postprandial) triglyceride levels and other components of the metabolic syndrome.

Published
2004

34. Associations of metabolic variables with arterial stiffness in type 2 diabetes mellitus: focus on insulin sensitivity and postprandial triglyceridaemia

Author

van Dijk, RAJM, Bakker, SJL, Scheffer, PG, Heine, RJ, Stehouwer, CDA, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), and Groningen Kidney Center (GKC)

Subjects
BODY-COMPOSITION, type 2 diabetes mellitus, DISTENSIBILITY, LEFT-VENTRICULAR FAILURE, AORTIC STIFFNESS, BLOOD-PRESSURE, common carotid artery, CORONARY HEART-DISEASE, femoral artery, compliance, CARDIOVASCULAR-DISEASE, RISK-FACTORS, FOLLOW-UP, FEMORAL ARTERIES
Abstract

Background Type 2 diabetes mellitus is associated with an increased risk of atherothrombotic disease, which may in part be mediated through increased arterial stiffness. We investigated to what extent increased arterial stiffness is associated with cardiovascular risk factors that commonly cluster in type 2 diabetes. Design In this cross-sectional, observational study we assessed, in 81 subjects with type 2 diabetes, local distensibility and compliance of the common carotid and femoral arteries, and carotido-femoral transit time. We subsequently investigated whether these measures of arterial stiffness were determined by diabetes duration, blood pressure, lipid levels (including fasting and postprandial triglyceridaemia), hyperglycaemia, BMI, waist-to-hip ratio, insulin resistance (as measured by a euglycaemic, hyperinsulinaemic clamp), hyperinsulinaemia, cigarette smoking, or the use of alcohol. Results In multivariate analysis, insulin-mediated glucose uptake was positively [standardized beta, 0.21 (P = 0.05)] associated with the carotid artery compliance coefficient, and the use of alcohol was negatively associated with the femoral artery compliance coefficient [standardized beta, -0.25 (P = 0.03)]. Except for mean arterial pressure, which was negatively associated with all outcome variables, the other cardiovascular risk factors that we investigated were not significantly associated with the distensibility coefficients of both the carotid and femoral artery, or with the carotido-femoral transit time. Conclusions In subjects with type 2 diabetes mellitus, insulin resistance and the use of alcohol were associated with increased arterial stiffness, which supports the hypothesis that increased arterial stiffness can act as a mediating factor in the association between type 2 diabetes mellitus and increased risk of atherothrombotic disease. We found no evidence for an association between fasting or postprandial triglyceridaemia and arterial stiffness.

Published
2003

35. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects

Author

Bakker, SJL, ter Maaten, JC, Popp-Snijders, C, Slaets, JPJ, Heine, RJ, Gans, ROB, Health Psychology Research (HPR), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), and Groningen Kidney Center (GKC)

Subjects
endocrine system, endocrine system diseases, RECEPTOR, WOMEN, THYROID-HORMONE, CORONARY HEART-DISEASE, LDL, COENZYME-A REDUCTASE, SUBCLINICAL HYPOTHYROIDISM, RISK-FACTORS, SERUM-LIPIDS, lipids (amino acids, peptides, and proteins), hormones, hormone substitutes, and hormone antagonists, RESISTANCE
Abstract

High levels of TSH are associated with an increased cardiovascular risk. Many cardiovascular risk factors cluster within the insulin resistance syndrome. It is not known whether levels of TSH cluster as well. We conducted this research to test the hypothesis that TSH, insulin sensitivity, and levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are interdependent in euthyroid subjects. Levels of TSH, free thyroid hormone, and serum Lipids were measured in fasting serum samples taken before performance of a hyperinsulinemic euglycemic clamp to assess insulin sensitivity in 46 healthy euthyroid subjects with a mean TSH of 1.8 +- 0.7 mU/L. Significant age- and sex-adjusted partial correlations of TSH with LDL-C (r = 0.48; P

Published
2001

39. Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene

Author

't Hart, LM, Hansen, T, Rietveld, I, Dekker, JM, Nijpels, G, Janssen, GMC, Arp, Pascal, Uitterlinden, André, Jorgensen, T, Borch-Johnsen, K, Pols, Huib, Pedersen, O, Duijn, Cornelia, Heine, RJ, Maassen, JA, 't Hart, LM, Hansen, T, Rietveld, I, Dekker, JM, Nijpels, G, Janssen, GMC, Arp, Pascal, Uitterlinden, André, Jorgensen, T, Borch-Johnsen, K, Pols, Huib, Pedersen, O, Duijn, Cornelia, Heine, RJ, and Maassen, JA

Published
2005

40. Genetic factors and insulin secretion: gene variants in the IGF genes

Author

't Hart, LM, Fritsche, A, Rietveld, I, Dekker, JM, Nijpels, G, Machicao, F, Stumvoll, M, Duijn, Cornelia, Häring, HU, Heine, RJ, Maassen, JA, van Haeften, TW, 't Hart, LM, Fritsche, A, Rietveld, I, Dekker, JM, Nijpels, G, Machicao, F, Stumvoll, M, Duijn, Cornelia, Häring, HU, Heine, RJ, Maassen, JA, and van Haeften, TW

Published
2004

41. Verbesserung von Betazellfunktion und glykämischer Kontrolle nach einem Jahr Therapie mit Exenatide bei Metformin-behandelten Patienten mit Typ-2-Diabetes

Author

Bachmann, O, primary, Kazda, C, additional, Bunck, MC, additional, Diamant, M, additional, Cornér, A, additional, Eliasson, B, additional, Malloy, J, additional, Shaginian, RM, additional, Deng, W, additional, Kendall, DM, additional, Taskinen, MR, additional, Smith, U, additional, Yki-Jarvinen, H, additional, and Heine, RJ, additional

Published
2008
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44. Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes.

Author

Bunck MC, Cornér A, Eliasson B, Heine RJ, Shaginian RM, Taskinen MR, Smith U, Yki-Järvinen H, Diamant M, Bunck, Mathijs C, Cornér, Anja, Eliasson, Bjorn, Heine, Robert J, Shaginian, Rimma M, Taskinen, Marja-Riitta, Smith, Ulf, Yki-Järvinen, Hannele, and Diamant, Michaela

Abstract

Objective: We previously showed that exenatide (EXE) enhanced insulin secretion after 1 year of treatment, relative to insulin glargine (GLAR), with a similar glucose-lowering action. These effects were not sustained after a 4-week off-drug period. This article reports the results after additional 2 years of exposure.Research Design and Methods: Sixty-nine metformin-treated patients with type 2 diabetes were randomized to EXE or GLAR. Forty-six patients entered the 2-year extension study in which they continued their allocated therapy. Thirty-six completed (EXE: n = 16; GLAR: n = 20) the 3-year exposure period. Insulin sensitivity (M value) and β-cell function were measured by euglycemic hyperinsulinemic clamp followed by hyperglycemic clamp with arginine stimulation at pretreatment (week 52) and 4 weeks after discontinuation of study medication (week 56 and week 172). First-phase glucose stimulated C-peptide secretion was adjusted for M value and calculated as the disposition index (DI).Results: At 3 years, EXE and GLAR resulted in similar levels of glycemic control: 6.6 ± 0.2% and 6.9 ± 0.2%, respectively (P = 0.186). EXE compared with GLAR significantly reduced body weight (-7.9 ± 1.8 kg; P < 0.001). After the 4-week off-drug period, EXE increased the M value by 39% (P = 0.006) while GLAR had no effect (P = 0.647). Following the 4-week off-drug period, the DI, compared with pretreatment, increased with EXE, but decreased with GLAR (1.43 ± 0.78 and -0.99 ± 0.65, respectively; P = 0.028).Conclusions: EXE and GLAR sustained HbA(1c) over the 3-year treatment period, while EXE reduced body weight and GLAR increased body weight. Following the 3-year treatment with EXE, the DI was sustained after a 4-week off-drug period. These findings suggest a beneficial effect on β-cell health. [ABSTRACT FROM AUTHOR]

Published
2011
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45. Associations between features of glucose exposure and A1C: the A1C-Derived Average Glucose (ADAG) study.

Author

Borg R, Kuenen JC, Carstensen B, Zheng H, Nathan DM, Heine RJ, Nerup J, Borch-Johnsen K, Witte DR, ADAG Study Group, Borg, Rikke, Kuenen, Judith C, Carstensen, Bendix, Zheng, Hui, Nathan, David M, Heine, Robert J, Nerup, Jorn, Borch-Johnsen, Knut, and Witte, Daniel R

Abstract

Objective: Various methods are used to quantify postprandial glycemia or glucose variability, but few have been compared and none are standardized. Our objective was to examine the relationship among common indexes of postprandial glycemia, overall hyperglycemia, glucose variability, and A1C using detailed glucose measures obtained during everyday life and to study which blood glucose values of the day provide the strongest prediction of A1C.Research Design and Methods: In the A1C-Derived Average Glucose (ADAG) study, glucose levels were monitored in 507 participants (268 type 1 diabetic, 159 type 2 diabetic, and 80 nondiabetic subjects) with continuous glucose monitoring (CGM) and frequent self-monitoring of blood glucose (SMBG) during 16 weeks. We calculated several indexes of glycemia and analyzed their intercorrelations. The association between glucose measurements at different times of the day (pre- and postprandial) and A1C was examined using multiple linear regression.Results: Indexes of glucose variability showed strong intercorrelation. Among postprandial indexes, the area under the glucose curve calculated from CGM 2 h after a meal correlated well with the 90-min SMBG postprandial measurements. Fasting blood glucose (FBG) levels were only moderately correlated with indexes of hyperglycemia and average or postprandial glucose levels. Indexes derived with SMBG strongly correlated with those from CGM. Some SMBG time points had a stronger association with A1C than others. Overall, preprandial glucose values had a stronger association with A1C than postprandial values for both diabetes types, particularly for type 2 diabetes.Conclusions: Indexes of glucose variability and average and postprandial glycemia intercorrelate strongly within each category. Variability indexes are weakly correlated with the other categories, indicating that these measures convey different information. FBG is not a clear indicator of general glycemia. Preprandial glucose values have a larger impact on A1C levels than postprandial values. [ABSTRACT FROM AUTHOR]

Published
2010
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47. Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function.

Author

Simonis-Bik AM, Nijpels G, van Haeften TW, Houwing-Duistermaat JJ, Boomsma DI, Reiling E, van Hove EC, Diamant M, Kramer MH, Heine RJ, Maassen JA, Slagboom PE, Willemsen G, Dekker JM, Eekhoff EM, de Geus EJ, 't Hart LM, Simonis-Bik, Annemarie M, Nijpels, Giel, and van Haeften, Timon W

Abstract

Objective: Recently, results from a meta-analysis of genome-wide association studies have yielded a number of novel type 2 diabetes loci. However, conflicting results have been published regarding their effects on insulin secretion and insulin sensitivity. In this study we used hyperglycemic clamps with three different stimuli to test associations between these novel loci and various measures of beta-cell function.Research Design and Methods: For this study, 336 participants, 180 normal glucose tolerant and 156 impaired glucose tolerant, underwent a 2-h hyperglycemic clamp. In a subset we also assessed the response to glucagon-like peptide (GLP)-1 and arginine during an extended clamp (n = 123). All subjects were genotyped for gene variants in JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, THADA, ADAMTS9, NOTCH2/ADAMS30, DCD, VEGFA, BCL11A, HNF1B, WFS1, and MTNR1B.Results: Gene variants in CDC123/CAMK1D, ADAMTS9, BCL11A, and MTNR1B affected various aspects of the insulin response to glucose (all P < 6.9 x 10(-3)). The THADA gene variant was associated with lower beta-cell response to GLP-1 and arginine (both P < 1.6 x 10(-3)), suggesting lower beta-cell mass as a possible pathogenic mechanism. Remarkably, we also noted a trend toward an increased insulin response to GLP-1 in carriers of MTNR1B (P = 0.03), which may offer new therapeutic possibilities. The other seven loci were not detectably associated with beta-cell function.Conclusions: Diabetes risk alleles in CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B are associated with various specific aspects of beta-cell function. These findings point to a clear diversity in the impact that these various gene variants may have on (dys)function of pancreatic beta-cells. [ABSTRACT FROM AUTHOR]

Published
2010
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49. Microalbuminuria and cardiovascular autonomic dysfunction are independently associated with cardiovascular mortality: evidence for distinct pathways: the Hoorn Study.

Author

Beijers HJ, Ferreira I, Bravenboer B, Dekker JM, Nijpels G, Heine RJ, Stehouwer CD, Beijers, Hanneke J B H, Ferreira, Isabel, Bravenboer, Bert, Dekker, Jacqueline M, Nijpels, Giel, Heine, Robert J, and Stehouwer, Coen D A

Abstract

Objective: Microalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality.Research Design and Methods: We studied 490 individuals from a population-based cohort of individuals aged 50-75 years who were followed for a median period of 13.6 years. Microalbuminuria was defined as an albumin-to-creatinine ratio > or =2.0 mg/mmol in an early-morning spot-urine sample. Ten parameters reflecting different aspects of cardiovascular autonomic function were measured and compiled into a total score of C-AD (mean of separate z scores). The association between C-AD and microalbuminuria was estimated by multiple linear regression, and relative risks (RRs) for cardiovascular mortality were estimated by Cox proportional hazards analyses.Results: After adjustments for age, sex, glucose tolerance status, and other risk factors, C-AD was associated with microalbuminuria (beta = 0.16 [95% CI 0.01-0.33]), and both microalbuminuria (RR 2.09 [1.07-4.08]) and C-AD (1.74 [1.04-2.89]) were associated with cardiovascular mortality. These associations did not change after further mutual adjustment for C-AD (2.13 [1.09-4.17]) or microalbuminuria (1.76 [1.05-2.94]), respectively.Conclusions: Both microalbuminuria and C-AD are independently associated with cardiovascular mortality, and the excess mortality attributable to microalbuminuria cannot be explained by C-AD. [ABSTRACT FROM AUTHOR]

Published
2009
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