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Background/objectives: Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. Methods: We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. Results: The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (−1.5 mmol/l mean PPG [95% CI −1.9, −1.1] by acarbose, and −1.6 [−1.9, −1.4] by miglitol) as compared to individuals without diabetes (−0.4 [95% CI −0.5, −0.3] by acarbose, and −0.6 [−0.8, −0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43−54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. Conclusions: The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors. Methods: Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection, age, BMI, waist circumference, use of anti-hypertensive medication, current smoking and parental history of diabetes remained in sex-specific linear regression models. To minimize overfitting of coefficients, we performed internal validation using bootstrapping techniques. Explained variance, discrimination and calibration were assessed using R2, classification tables (comparing highest/lowest 50% HbA1c levels) and calibration graphs. The model was externally validated in 2,765 non-diabetic subjects of the population-based cohort METSIM. Results: At baseline, mean HbA1c level was 5.6% (38 mmol/mol). After a mean follow-up of six years, mean HbA1c level was 5.7% (39 mmol/mol). Calibration graphs showed that predicted HbA1c levels were somewhat underestimated in the Inter99 cohort and overestimated in the Hoorn and KORA cohorts, indicating that the model’s intercept should be adjusted for each cohort to improve predictions. Sensitivity and specificity (95% CI) were 55.7% (53.9, 57.5) and 56.9% (55.1, 58.7) respectively, for women, and 54.6% (52.7, 56.5) and 54.3% (52.4, 56.2) for men. External validation showed similar performance in the METSIM cohort. Conclusions/interpretation: In the non-diabetic population, our DIRECT-DETECT prediction model, including readily available predictors, has a relatively low explained variance and moderate discriminative performance, but can help to distinguish between future highest and lowest HbA1c levels. Absolute HbA1c values are cohort-dependent. [ABSTRACT FROM AUTHOR]

Objective: To determine the level of diabetes-related symptom distress and its association with negative mood in subjects participating in a targeted population-screening program, comparing those identified as having type 2 diabetes vs. those who did not.Research Design and Methods: This study was conducted within the framework of a targeted screening project for type 2 diabetes in a general Dutch population (age 50-75 years). The study sample consisted of 246 subjects, pre-selected on the basis of a high-risk profile; 116 of whom were subsequently identified as having type 2 diabetes, and 130 who were non-diabetic subjects. Diabetes-related symptom distress and negative mood was assessed approximately 2 weeks, 6 months, and 12 months after the diagnosis of type 2 diabetes, with the Type 2 Diabetes Symptom Checklist and the Negative well-being sub scale of the Well-being Questionnaire (W-BQ12), respectively.Results: Screening-detected diabetic patients reported significantly greater burden of hyperglycemic (F = 6.0, df = 1, p = 0.015) and of fatigue (F = 5.3, df = 1, p = 0.023) symptoms in the first year following diagnosis type 2 diabetes compared to non-diabetic subjects. These outcomes did not change over time. The total symptom distress (range 0-4) was relatively low for both screening-detected diabetic patients (median at approximately 2 weeks, 6 months, and 12 months; 0.24, 0.24, 0.29) and non-diabetic subjects (0.15, 0.15, 0.18), and not significantly different. No average difference and change over time in negative well-being was found between screening-detected diabetic patients and non-diabetic subjects. Negative well-being was significantly positive related with the total symptom distress score (regression coefficient beta = 2.86, 95% CI 2.15-3.58).Conclusions: The screening-detected diabetic patients were bothered more by symptoms of hyperglycemia and fatigue in the first year following diagnosis type 2 diabetes than non-diabetic subjects. More symptom distress is associated with increased negative mood in both screening-detected diabetic patients and non-diabetic subjects. [ABSTRACT FROM AUTHOR]

Background: Ethnic minority populations in Western societies suffer from a disproportionate burden of type 2 diabetes (T2D). Insight into the role of dietary patterns in T2D may assist public health nutrition efforts in addressing these health disparities. Objective: We explored the association between dietary patterns and biomarkers of T2D in 5 ethnic groups living in Amsterdam, Netherlands. Methods: A total of 3776 men and women aged 18-70 y of Dutch, South Asian Surinamese, African-Surinamese, Turkish, and Moroccan origin from the HELIUS (HEalthy LIfe in an Urban Setting) study were included. Diet was assessed by using a food-frequency questionnaire, and dietary patterns were derived separately per ethnic group. First, food group-based dietary patterns were derived by using principal components analysis and the association with glycated hemoglobin (HbA1c) and plasma fasting glucose was assessed by using multivariable linear regression. Second, biomarker-driven dietary patterns based on HbA1c and fasting glucose concentrations were derived by applying reduced rank regression. Results: Two comparable food group-based dietary patterns were identified in each ethnic group: a ''meat and snack'' pattern and a "vegetable" pattern. The meat-and-snack pattern derived within the Dutch origin population was significantly associated with HbA1c (β = 0.09; 95% CI: 0.00, 0.19) and fasting glucose (β = 0.18; 95% CI: 0.09, 0.26) concentrations. A biomarker-derived pattern characterized by red and processed meat was observed among Dutch-origin participants; however, among ethnic minority groups, this pattern was characterized by other foods including ethnicity-specific foods (e.g., roti, couscous). Conclusions: Although similar food group dietary patterns were derived within 5 ethnic groups, the association of the meat-and-snack pattern with fasting glucose concentrations differed by ethnicity. Taken together with the finding of ethnic differences in biomarker-driven dietary patterns, our results imply that addressing T2D risk in multiethnic populations requires ethnicity-specific approaches. [ABSTRACT FROM AUTHOR]

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity--related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites--glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)--and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits. [ABSTRACT FROM AUTHOR]

OBJECTIVE--In the general population, a low ankle-brachial index (ABI) (<0.9) is strongly associated with (cardiovascular) mortality. However, the association between the ABI and mortality may be weaker in individuals with diabetes, as ankle pressures may be elevated by medial arterial calcification and arterial stiffening, which occur more frequently in diabetes. Therefore, the aim of this study was to compare the association between ABI and mortality in individuals without and with diabetes. RESEARCH DESIGN AND METHODS--We studied the associations between ABI and cardiovascular and all-cause mortality in 624 individuals from the Hoorn study, a population-based cohort of 50- to 75-year-old individuals (155 with diabetes and 469 without) followed for a median period of 17.2 years. Data were analyzed using Cox proportional hazards models. RESULTS--During the follow-up period, 289 of 624 (46.3%) participants died (97 of 155 with and 192 of 469 without diabetes and 52 of 65 with and 237 of 559 without ABI <0.9): 85 (29.4%) of CVD (30 of 155 with and 55 of 469 without diabetes and 20 of 65 with and 65 of 559 without ABI <0.9). A low ABI was strongly associated with cardiovascular mortality (relative risk 2.57 [95% CI 1.50-4.40]) and all-cause mortality (2.02 [1.47-2.76]), after adjustment for Framingham risk factors. The associations of the ABI with mortality did not differ between individuals without and with diabetes for cardiovascular (Pinteraction = 0.45) or all-cause (Pinteraction = 0.63) mortality. CONCLUSIONS--In the Hoorn Study, associations between ABI and cardiovascular and all-cause mortality were similar in individuals without and with diabetes. Future studies should investigate, in both individuals without and with diabetes, whether measurement of ABI can be used to guide treatment decisions. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS--A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20-79 years. RESULTS--A total of 35 studies (1980-2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5-34.8) for any DR, 6.96% (6.87-7.04) for proliferative DR, 6.81% (6.74-6.89) for diabetic macular edema, and 10.2% (10.1-10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS--There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabeticmacular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics. [ABSTRACT FROM AUTHOR]

Aims Higher plasma B-type natriuretic peptide (BNP) in a non-heart failure (HF) range predicts HF and cardiovascular disease (CVD) mortality in the general population. Heart failure is highly prevalent in type 2 diabetes mellitus (T2DM), but associations of BNP to left ventricular (LV) mass and function in individuals with a different glucose status have not been compared. We therefore aimed to explore (i) the association of BNP levels in a non-HF range with structural and functional markers of LV function, and (ii) possible effect modification by glucose tolerance categories. Methods and results Linear regression analyses were performed to investigate associations of BNP with 2D echocardiographic measures of LV mass index, LV systolic function, and markers of LV diastolic function in a population-based study of men and women with normal glucose metabolism (NGM, n = 197), impaired glucose metabolism (IGM, n = 128), or T2DM (n = 204). Patients were aged between 50 and 87 years, had BNP levels below 50 pmol/L, and no LV wall motion abnormalities. B-type natriuretic peptide levels ranged from 0.4 to 46.1 pmol/L, the median was 4.2 pmol/L. Higher BNP was significantly associated with increased LV mass and deteriorated LV diastolic function, but not with LV systolic function. B-type natriuretic peptide was more strongly associated with LV diastolic function in T2DM compared with NGM and IGM. Conclusion B-type natriuretic peptide was associated with LV mass and markers of LV diastolic function, and the association of BNP with the latter appeared to be particularly strong in individuals with T2DM. This implies that the presence or absence of T2DM should be taken into account if BNP levels are used to assess CVD risk. [ABSTRACT FROM AUTHOR]

Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure. We investigated this relationship and its modification by hyperglycemia and oxidative stress in a population-based cohort of elderly subjects with normal glucose metabolism (n=267), impaired glucose metabolism (n=189), and type 2 diabetes (n=290). In an age- and sex-adjusted linear regression model, plasma myeloperoxidase was positively associated with systolic blood pressure (2.10 mm Hg per 1 SD increment of myeloperoxidase [95% CI: 0.66 to 3.54]), and this association was stronger at higher levels of fasting glucose (0.61 [-1.70 to 2.93], 1.33 [-1.43 to 4.10], and 3.42 [1.01 to 5.82] for increasing tertiles of glucose) and higher plasma levels of oxidized low-density lipoprotein (0.92 [-1.31 to 3.14], 2.00 [-0.71 to 4.70], and 3.58 [0.98 to 6.19] for increasing tertiles of oxidized low-density lipoprotein). Likewise, the relationship between myeloperoxidase and blood pressure was strongest under conditions associated with oxidative stress, like obesity, low high-density lipoprotein cholesterol, metabolic syndrome, and type 2 diabetes. The strength of these associations was only marginally attenuated by adjustment for other cardiovascular risk factors. Our data demonstrate that myeloperoxidase is positively and independently associated with blood pressure, and this association is strongest in subjects with (hyperglycemia-induced) oxidative stress. These observations, together with emerging evidence that myeloperoxidase-derived oxidants contribute to the initiation and propagation of cardiovascular disease, identify myeloperoxidase as a promising target for drug development. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To evaluate to what extent the association between family history of diabetes and risk of type 2 diabetes can be explained by excess adiposity and lifestyle risk factors. RESEARCH DESIGN AND METHODS -- We analyzed data from 73,227 women who participated in the Nurses' Health Study cohort. A family history of diabetes was defined as having at least one first-degree family member with diabetes. Lifestyle factors, weight, and height were assessed by using validated questionnaires, and BMI was calculated. The relative risk of type 2 diabetes was estimated using Cox proportional hazards analysis. RESULTS -- We documented 5,101 cases of type 2 diabetes during 20 years of follow-up. The age-adjusted relative risk of type 2 diabetes in participants with a family history was 2.27 (95% CI 2.14-2.40) compared with the risk in those without a family history of diabetes. Participants with a family history of diabetes had a higher BMI and were more likely to have a parental history of obesity. BMI explained 21.1% (19.4-22.9) of the association between family history of diabetes and risk of type 2 diabetes. Intakes of red meat, alcohol, and sugar-sweetened beverages explained 1.1% (0.8-1.3), 4.8% (4.3-5.3), and 2.8% (2.4-3.2) of this association, respectively. CONCLUSIONS -- These results suggest that excess adiposity and, to a lesser extent, specific dietary habits can explain a substantial part of the association between having a family history of diabetes and risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

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 β-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 β-cell response to GLP-1 and arginine (both P < 1.6 x 10-3), suggesting lower β-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 β-cell function. CONCLUSIONS--Diabetes risk alleles in CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B are associated with various specific aspects of β-cell function. These findings point to a clear diversity in the impact that these various gene variants may have on (dys)function of pancreatic β-cells. Diabetes 59: 293-301, 2010 [ABSTRACT FROM AUTHOR]

The objective of this investigation was to determine the relation between baseline glucose, insulin, adiponectin, and leptin levels and subsequent 6-year weight and waist change in older men and women without diabetes in a prospective cohort study. Participants were 1,198 Dutch men and women without diabetes who were aged 50–77 years when baseline metabolic and anthropometric measurements were evaluated (1989–1991). Approximately 6 years later, body weight and waist circumference were re-measured at a follow-up examination (1996–1998). Metabolic variables (fasting plasma glucose, 2-h postchallenge plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and leptin) were evaluated as predictors of changes in weight and waist circumference. Postchallenge plasma glucose (mmol/l) significantly predicted less gain in both weight and waist circumference (β = −0.28 kg, s.e. = 0.11; β = −0.31 cm, s.e. = 0.14, respectively) during follow-up. Leptin (µg/l) significantly predicted greater increases in weight (β = 0.29 kg, s.e. = 0.07) and waist (β = 0.16 cm, s.e. = 0.08) among men and in waist among women (β = 0.06 cm, s.e. = 0.02). Fasting plasma glucose (mmol/l) predicted an increase in waist among women (β = 1.59 cm, s.e. = 0.63), but not in men (β = −0.74 cm, s.e. = 0.55). Adiponectin and insulin did not predict weight or waist change. The authors conclude that lower postchallenge plasma glucose and higher fasting leptin levels significantly predicted long-term increases in weight and waist circumference. In contrast, measures of insulin resistance and adiponectin were not associated with weight change in this cohort of older persons without diabetes.Obesity (2009) 17 8, 1609–1614. doi:10.1038/oby.2008.666 [ABSTRACT FROM AUTHOR]

Mitochondria play an important role in many processes, like glucose metabolism, fatty acid oxidation and ATP synthesis. In this study, we aimed to identify association of common polymorphisms in nuclear-encoded genes involved in mitochondrial protein synthesis and biogenesis with type II diabetes mellitus (T2DM) using a two-stage design. In the first stage, we analyzed 62 tagging single nucleotide polymorphisms (SNPs) in the Hoorn study (n=999 participants) covering all common variation in 13 biological candidate genes. These 13 candidate genes were selected from four clusters regarded essential for correct mitochondrial protein synthesis and biogenesis: aminoacyl tRNA synthetases, translation initiation factors, tRNA modifying enzymes and mitochondrial DNA transcription and replication. SNPs showing evidence for association with T2DM were measured in second stage genotyping (n=10164 participants). After a meta-analysis, only one SNP in SIRT4 (rs2522138) remained significant (P=0.01). Extending the second stage with samples from the Danish Steno Study (n=1220 participants) resulted in a common odds ratio (OR) of 0.92 (0.85–1.00), P=0.06. Moreover, in a large meta-analysis of three genome-wide association studies, this SNP was also not associated with T2DM (P=0.72). In conclusion, we did not find evidence for association of common variants in 13 nuclear-encoded mitochondrial proteins with T2DM.European Journal of Human Genetics (2009) 17, 1056–1062; doi:10.1038/ejhg.2009.4; published online 11 February 2009 [ABSTRACT FROM AUTHOR]

Abstract: Patients with type 2 diabetes mellitus (DM2) have an increased risk of cardiovascular disease (CVD). Myeloperoxidase (MPO), expressed in leukocytes and released upon activation, is associated with CVD and endothelial dysfunction. Postprandial leukocyte recruitment and activation with subsequent MPO release may contribute to atherosclerosis and CVD. We hypothesized that MPO may increase in the postprandial state because of postprandial leukocyte recruitment and/or activation, especially in subjects with DM2. One hundred postmenopausal women, aged 50 to 65 years (66 with normal glucose metabolism [NGM] and 34 with DM2), received 2 consecutive fat-rich meals and 2 consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before (t = 0) and at 2, 4, and 8 hours after breakfast; lunch was given at t = 4. Plasma MPO concentration was measured by sandwich enzyme-linked immunosorbent assay. The number of leukocytes in fasting blood samples was higher in DM2 compared with NGM (6.1 ± 1.4 and 5.4 ± 1.2 × 109/L, respectively; P < .05). Baseline MPO concentration did not significantly differ between NGM and DM2 (51.4 ± 12.9 and 54.5 ± 18.4 μg/L, respectively; P = .39). Baseline MPO was positively associated with leukocytes (r = 0.20, P < .05) and inversely associated with high-density lipoprotein cholesterol (r = −0.22, P < .05). Leukocytes increased from 5.0 ± 1.5 to 6.1 ± 1.5 × 109/L and from 5.8 ± 1.4 to 6.6 ± 1.4 × 109/L in NGM and DM2, respectively (both P < .01), after the fat-rich meals. In contrast to our hypothesized increase in MPO, we found a significant decrease in MPO in NGM (both meal types) and DM2 (fat-rich meals only). Our findings provide no support to our initial hypothesis that meal-induced release of MPO might be a mechanism that contributes to CVD risk. [Copyright &y& Elsevier]

OBJECTIVE -- To optimize identification of future diabetic patients, the American Diabetes Association (ADA) introduced criteria for impaired fasting glucose (IFG) in 1997 (IFG 6.1 mmol/l [IFG6.1]) and lowered the threshold from 6.1 to 5.6 mmol/l (IFG5.6) in 2003. Our aim was to assess the consequences of lowering the IFG cutoff on the risk of cardiovascular disease (CVD) mortality and to evaluate whether this risk is explained by a conversion to type 2 diabetes within 6.4 years. RESEARCH DESIGN AND METHODS -- In a population-based cohort, the Hoorn Study, plasma glucose was determined in 1989 and 1996 (n = 1,428). Subjects were classified in 1.989 according to 1997 and 2003 ADA criteria. Subjects with IFG in 1989 were further classified according to diabetes status in 1996. Hazard ratios for CVD mortality (n = 81) in the period 1996-2005 were adjusted for age and sex. RESULTS -- Subjects with IFG6.1, but not IFG5.6, had a significantly higher CVD mortality risk than normal fasting glucose (NFG) subjects. Subjects who converted from IFG to diabetes (IFG6.1: 42%; IFG5.6: 21%) had a more than twofold risk of CVD mortality (IFG6.1: 2.47 [1.17-5.19]; IFGS.6: 2.14 [1.12-4.10]) than subjects with NFG. IFG subjects who did not develop diabetes did not have significantly higher CVD mortality risks (IFG6.1: 1.50 [0.72-3.151; IFGS.6: 1.15 [0.69-1.93]). CONCLUSIONS -- The lower cutoff for IFG (ADA 2003 criteria) results in a category of IFG that no longer represents a high-risk state of CVD. Furthermore, only subjects who convert from IFG to diabetes have a high risk of CVD mortality. [ABSTRACT FROM AUTHOR]

Background: In patients with type 2 diabetes, the risk for cardiovascular disease is substantial. To achieve a more favourable risk profile, lifestyle changes on diet, physical activity and smoking status are needed. This will involve changes in behaviour, which is difficult to achieve. Cognitive behavioural therapies focussing on self-management have been shown to be effective. We have developed an intervention combining techniques of Motivational Interviewing (MI) and Problem Solving Treatment (PST). The aim of our study is to investigate if adding a combined behavioural intervention to managed care, is effective in achieving changes in lifestyle and cardiovascular risk profile. Methods: Patients with type 2 diabetes will be selected from general practices (n = 13), who are participating in a managed diabetes care system. Patients will be randomised into an intervention group receiving cognitive behaviour therapy (CBT) in addition to managed care, and a control group that will receive managed care only. The CBT consists of three to six individual sessions of 30 minutes to increase the patient's motivation, by using principles of MI, and ability to change their lifestyle, by using PST. The first session will start with a risk assessment of diabetes complications that will be used to focus the intervention. The primary outcome measure is the difference between intervention and control group in change in cardiovascular risk score. For this purpose blood pressure, HbA1c, total and HDL-cholesterol and smoking status will be assessed. Secondary outcome measures are quality of life, patient satisfaction, physical activity, eating behaviour, smoking status, depression and determinants of behaviour change. Differences between changes in the two groups will be analysed according to the intention-to-treat principle, with 95% confidence intervals. The power calculation is based on the risk for cardiovascular disease and we calculated that 97 patients should be included in every group. Discussion: Cognitive behavioural therapy may improve self-management and thus strengthen managed diabetes care. This should result in changes in lifestyle and cardiovascular risk profile. In addition, we also expect an improvement of quality of life and patient satisfaction. Trial registration: Current Controlled Trials ISRCTN12666286. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS -- The Hoorn Study is a cohort study among Caucasians, aged 50-75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS -- Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23-1.18) in men and 0.15 (0.06-0.39) in women for type 2 diabetes and 0.90 (0.51-1.61) and 0.28 (0.16-0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32-1.91] and 0.62 [0.21-1.81]) and with IGM (1.20 [0.61-2.35] and 0.48 [0.26-0.90]), respectively. CONCLUSIONS -- A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes. [ABSTRACT FROM AUTHOR]

The short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) protein is involved in the penultimate step of mitochondrial fatty acid oxidation. Previously, it has been shown that mutations in the corresponding gene (HADHSC) are associated with hyperinsulinism in infancy. The presumed function of the SCHAD enzyme in glucose-stimulated insulin secretion led us to the hypothesis that common variants in HADHSC on chromosome 4q22-26 might be associated with development of type 2 diabetes. In this study, we have performed a large-scale association study in four different cohorts from the Netherlands and Denmark (n = 7,365). Direct sequencing of HADHSC cDNA and databank analysis identified four tagging single nucleotide polymorphisms (SNPs) including one missense variant (P86L). Neither the SNPs nor haplotypes investigated were associated with the disease, enzyme function, or any relevant quantitative measure (all P > 0.1). The present study provides no evidence that the specific HADHSC variants or haplotypes examined do influence susceptibility to develop type 2 diabetes. We conclude that it is unlikely that variation in HADHSC plays a major role in the pathogenesis of type 2 diabetes in the examined cohorts. Diabetes 55:3193-3196, 2006 [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To study the relationship of nonproliferative and proliferative retinopathy with all-cause mortality and cardiovascular disease (CVD) incidence in type 1 diabetic patients and, additionally, the role of cardiovascular risk factors in these associations. RESEARCH DESIGN AND METHODS -- This prospective study included 2,237 type 1 diabetic patients from 31 centers in 16 European countries at baseline, aged 15-60 years, who were examined for retinopathy by taking two-field 45° fundus photographs, which were centrally graded. Mortality and cardiovascular morbidity follow-up was assessed 6-8 years after baseline examination according to a standardized protocol. RESULTS -- After 7.9 years of follow-up, 64 patients had died and 128 patients had incident CVD. The age- and sex-adjusted hazard ratios (HIEs) of all-cause mortality were 1.45 (95% CI 0.71-2.96) and 4.16 (1.96- 8.84) in patients with nonproliferative and proliferative retinopathy at baseline, respectively. Adjustments for cardiovascular risk factors completely obliterated the association with nonproliferative retinopathy, whereas the association with proliferative retinopathy remained twofold increased, although nonsignificant. The age- and sex-adjusted HRs of incident CVD were 1.73 (1.15-2.60) and 2.05 (1.22-3.45) in patients with nonproliferative and proliferative retinopathy, respectively. After adjustments for cardiovascular risk factors, both associations were attenuated and lost statistical significance. CONCLUSIONS -- This study shows that type 1 diabetic patients with nonproliferative or proliferative retinopathy have an increased risk for all-cause mortality and incident CVD. The presence of cardiovascular risk factors explained the associations to a large extent, except for the associations with proliferative retinopathy, which suggests that other shared mechanisms may be involved. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- This meta-analysis was undertaken to obtain insight regarding the shape and strength of the relationship between alcohol consumption and the risk of type 2 diabetes, the effects of adjustment for confounders, and the effect of modification by type 2 diabetes definition, sex, and BMI. RESEARCH DESIGN AND METHODS -- The 15 original prospective cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average, were followed for 12 years. RESULTS -- After pooling the data, a U-shaped relationship was found. Compared with nonconsumers, the relative risk (RR) for type 2 diabetes in those who consumed ≤6 g/day alcohol was 0.87 (95% CI 0.79-0.95). For the moderate consumption ranges of 6-12, 12-24, and 24-48 g/day, RRs of 0.70 (0.61-0.79), 0.69 (0.58-0.81), and 0.72 (0.62-0.84) were found, respectively. The risk of type 2 diabetes in heavy drinkers (≥48 g/day) was equal to that in nonconsumers (1.04 [0.84-1.29]). In general, nonsignificant trends for larger RR reduction associated with moderate alcohol consumption were observed for women compared with men, for crude compared with multivariate-adjusted analyses, and for studies that used self-reports instead of testing for type 2 diabetes definition. No differences in RR reductions were found between individuals with low or high BMI. CONCLUSIONS -- The present evidence from observational studies suggests an ∼30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction is observed in consumers of ≥48 g/day. [ABSTRACT FROM AUTHOR]

Objective: Waist and hip circumferences have been shown to have independent and opposite associations with glucose levels. Waist circumference is positively associated with glucose levels, whereas hip circumference is negatively associated. It is unclear which tissues are involved in the pathophysiological mechanism causing these associations. The main goal was to determine which tissue in the trunk and legs, fat or lean tissue, is associated with measures of glucose metabolism.Research Design and Methods: In 623 participants of the third examination of the Hoorn Study, whole-body dual-energy X-ray absorptiometry was performed to determine fat and lean soft-tissue mass in the trunk and legs. Fasting and 2-h postload glucose levels after 75-g oral glucose tolerance test (OGTT) were determined. After exclusion of known diabetic patients, cross-sectional analyses were performed in 275 men aged 60-87 years (140 with normal glucose metabolism, 92 with impaired glucose metabolism; and 43 with diabetes) and in 281 women (148 with normal glucose metabolism, 90 with impaired glucose metabolism, and 43 with diabetes).Results: Greater trunk fat mass was associated with higher glucose levels after adjustment for age, trunk lean mass, leg lean mass, and leg fat mass. Standardized beta (95% CI) in men were 0.44 (0.25-0.64) for fasting and 0.41 (0.22-0.60) for postload glucose. For women, these values were 0.49 (0.35-0.63) and 0.47 (0.33-0.61), respectively. In contrast, in the same regression models, a larger leg fat mass was associated with lower glucose levels. Standardized beta in men were -0.24 (-0.43 to -0.05) and -0.12 (-0.31 to 0.07) and in women -0.24 (-0.37 to -0.10) and -0.27 (-0.40 to -0.13) for fasting and postload glucose, respectively. In these models, larger leg lean mass was also associated with lower glucose levels but was only statistically significant in men.Conclusions: If trunk fat is taken into account, accumulation of fat in the legs seems to be protective against a disturbed glucose metabolism, particularly in women. Further research is needed to unravel underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To compare steroids and their associations in men with type 1 diabetes and healthy control subjects.Research Design and Methods: We studied 52 adult men with type 1 diabetes without microvascular complications, compared with 53 control subjects matched for age and BMI. Steroids and their binding globulins were assessed in a single venous blood sample and a 24-h urine sample.Results: In adult men with type 1 diabetes, total testosterone did not differ from healthy control subjects, but sex hormone-binding globulin (SHBG) (42 [14-83] vs. 26 [9-117] nmol/l, P < 0.001), cortisol-binding globulin (CBG; 0.87 +/- 0.17 vs. 0.73 +/- 0.10 nmol/l, P < 0.001), and cortisol levels (0.46 +/- 0.16 vs. 0.39 +/- 0.14 nmol/l, P < 0.01) were higher. The free testosterone index was lower (60 [17-139] vs. 82 [24-200], P < 0.001), and the calculated free testosterone was slightly lower (497 [115] vs. 542 [130], P < 0.064), but the pituitary-gonadal axis was not obviously affected in type 1 diabetes. The calculated free serum cortisol was not different, and 24-h urinary free cortisol excretion was lower in type 1 diabetes (121 [42-365] vs. 161 [55-284] nmol/24 h, P < 0.009). Testosterone was mainly associated with SHBG. Estimated portal insulin was a contributor to SHBG in control subjects but not in type 1 diabetes. Cortisol was associated with CBG. HbA(1c) contributed to CBG in men with diabetes but not in control subjects, whereas estimated portal insulin did not contribute.Conclusions: Adult men with fairly controlled type 1 diabetes without complications who are treated with subcutaneous insulin have a tendency to hypogonadism, as reflected by lower free testosterone levels in the presence of similar total testosterone levels and higher SHBG levels. [ABSTRACT FROM AUTHOR]

In the present study we examined the association between baseline alcohol consumption and 10-year mortality in subjects with normal and abnormal glucose levels (diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)). Furthermore, we assessed the 6-year cumulative incidence of diabetes in categories of alcohol consumption. In the Hoorn Study, which started in 1989, alcohol intake was assessed by questionnaire in 2393 subjects who were subsequently categorised into four groups of alcohol consumption (non-drinkers, up to 10 g per day, 10–30 and ≥30 g per day). Glucose tolerance status by oral glucose tolerance test was classified according to the WHO-1999 diagnostic criteria. Subjects who drank up to 10 g per day of alcohol had the lowest mortality risk. The age- and sex-adjusted mortality risks for non-drinkers were 1.55 (1.04–2.32) for subjects with normal glucose levels and 1.72 (1.05–2.82) for subjects with abnormal glucose levels. The risk of diabetes was also lowest for subjects who consumed up to 10 g per day: 8.0 versus 12.9% for non-drinkers (P<0.05). Higher alcohol intakes were associated with increasing risks for mortality and diabetes. Adjustment for classical cardiovascular risk factors and other lifestyle variables did not materially affect the estimates. In conclusion, moderate alcohol consumption was associated with a lower risk for mortality and diabetes. [Copyright &y& Elsevier]

Reports on a study done on the relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population. Relation of baseline fasting and postload glucose levels and other risk factors to the incidence of diabetes; Demographic information; Results; Conclusions.

The article compares' risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association and the United Nations World Health Organization glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects. Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.

OBJECTIVE -- The purpose of this study was to determine the associations between diabetes-related symptom distress, glucose metabolism status, and comorbidities of type 2 diabetes. RESEARCH DESIGN AND METHODS-- This was a cross-sectional sample of 281 individuals with normal glucose metabolism (NGM), 181 individuals with impaired glucose metabolism (IGM), and 107 subjects with type 2 diabetes. We used the revised type 2 Diabetes Symptom Checklist (DSC-R) to assess diabetes-related symptom distress. RESULTS-- The total symptom distress score (range 0-100) was relatively low for diabetic subjects (mean ± SD 8.4 ± 9.4), although it was significantly different from that for subjects with IGM (6.5 ± 7.1) and NGM (6.1 ± 7.9) (F = 3.1, 2 d.f., P = 0.046). Ischemic heart disease was associated with elevated DSC-R scores on three subscales, whereas depression showed higher symptom distress levels across all DSC-R domains. CONCLUSIONS -- Worsening glucose metabolism is associated with increasing diabetes-related symptom distress. This relationship is attenuated by ischemic heart disease and particularly by depression. [ABSTRACT FROM AUTHOR]

Presents the definitions of diabetes and impaired fasting glucose. Clinical symptoms of type 2 diabetes; Details of oral glucose tolerance test and impaired glucose tolerance; Definition of diabetes introduced by the American Diabetes Association in 1997; Association of postload glucose on the risk of cardiovascular disease.

The article presents a response to the comment made by Bastard and Fellahi on the authors' study on the association between reduced insulin sensitivity and higher risk of increasing albuminuria, which includes the concern raised over the relationship between albuminuria and other surrogates of insulin sensitivity like triglycerides and glucose index.

A response from the author of the article "Associations Between the Ankle-Brachial Index and Cardiovascular and All-Cause Mortality Are Similar in Individuals Without and With Type 2 Diabetes: Nineteen-Year Follow-Up of a Population-Based Cohort Study" in a 2013 issue is presented.

Studies the association between diabetic retinopathy and cardiovascular and all-cause mortality risks in diabetic and nondiabetic individuals. Contribution of cardiovascular risk factors and risk factors of retinopathy; Analysis of cox proportional hazards.

Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: Further evidence for a link between microalbuminuria and endothelial dysfunction—The Hoorn Study. Background Extensive endothelial dysfunction (i.e., affecting many aspects of endothelial function) has been hypothesized to explain why microalbuminuria (MA) is associated with cardiovascular disease risk. However, it is not clear whether MA is specifically associated with impaired endothelial nitric oxide (NO) synthesis in individuals without and with type 2 diabetes. Methods We did a population-based study in 645 individuals (mean age 68 years; 248 with normal glucose metabolism, 137 with impaired glucose metabolism, and 260 with type 2 diabetes) and investigated associations of MA [present (urinary albumin-creatinine ratio ≥2 mg/mmol) versus absent, and in four categories (<2, ≥2 to 5, ≥5 to 10, ≥10 mg/mmol)] with ultrasonically measured brachial artery endothelium-dependent, flow-mediated (FMD; an estimate of endothelial NO synthesis) and endothelium-independent, nitroglycerin-induced vasodilation (NID). Results FMD was 0.12 mm in the presence of MA ( N =93; 49 with diabetes), and 0.18 in its absence ( P =0.002). After adjustment for age, sex, baseline arterial diameter, and other potential confounders, FMD was 0.038 mm (95% CI, 0.001 to 0.075) lower in the presence of MA ( P =0.04), and decreased linearly across MA categories [by 0.027 mm (0.007 to 0.046) per category increase of MA; P =0.007]. NID was similar in individuals with and without MA. Results were similar in individuals without and with diabetes. Conclusion Microalbuminuria is linearly associated with impaired endothelium-dependent, flow-mediated vasodilation in elderly individuals without and with diabetes. These findings support the concept that impaired endothelial nitric oxide synthesis plays a role in the association of microalbuminuria with cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (DM2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. Impaired endothelial synthesis of nitric oxide (NO) is an important feature of atherothrombosis and can be estimated from endothelium-dependent flow-mediated dilation (FMD). It is controversial whether or not FMD is impaired in DM2 and IGM. We investigated this issue in a population-based setting. Methods and results: In the study population (n=650; 246 with normal glucose metabolism (NGM), 135 with IGM and 269 with DM2; mean age: 67.6 years), FMD and endothelium-independent nitroglycerine-mediated dilation (NMD) were ultrasonically estimated from the brachial artery and expressed as the absolute change in diameter in mm. The increase in diameter (mean ± standard deviation) in NGM, IGM and DM2 was 0.19±0.15, 0.19±0.18 and 0.13±0.17 for FMD and 0.45±0.21, 0.43±0.24 and 0.45±0.25 for NMD. After adjustment for age, sex, baseline diameter and percentage increase in peak systolic velocity, DM2, as compared to NGM, remained associated with impaired FMD (regression coefficient β (95%CI)) as compared to NGM, -0.06 mm (-0.09 to -0.03). IGM was not associated with impaired FMD (β, 0.01 mm (-0.02 to 0.04)). Additional adjustment for conventional cardiovascular risk factors did not alter these associations. Hyperglycemia or hyperinsulinemia explained 2% of the association between DM2 and FMD. NMD was not associated with glucose tolerance. Conclusions: This study shows that DM2 is independently associated with impaired FMD. Hyperglycemia and hyperinsulinemia contribute minimally to this association. Impaired FMD may therefore, in part, explain the increased cardiovascular disease risk in DM2, whereas the normal FMD in IGM suggests that other forms of endothelial dysfunction are important in explaining the increased cardiovascular disease risk in IGM. [Copyright &y& Elsevier]