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Background Most clinicians acknowledge that type 2 diabetes is multifactorial and has heterogeneous characteristics, but neither prevention nor treatment is systematically stratified. To address the heterogeneity of the disease, we examined whether patients diagnosed on the basis of fasting glucose concentrations, those diagnosed on the basis of 2 h concentrations, and those diagnosed on the basis of both criteria differed in terms of pathogenesis or cardiovascular risks. Methods Retrospectively, we analysed trajectories of cardiometabolic risk factors and 10 year cardiovascular risks in the prospective Whitehall II study cohort by use of multilevel longitudinal modelling. Participants were diagnosed by 75 g oral glucose-tolerance tests. We classified those diagnosed with type 2 diabetes into three subgroups: diagnosed on the basis of fasting glucose concentrations, diagnosed on the basis of 2 h glucose concentrations, and diagnosed on the basis of both concentrations. We also developed a classification tree for identification of individuals who are likely to have high fasting and 2 h glucose concentrations, but for whom only fasting concentrations are available. Results Median follow-up was 14•2 years with 15 826 person-examinations (1991–2009). Of 10 308 individuals, 6843 were included and 6569 remained diabetes free. 274 cases of type 2 diabetes were identified: 55 had high fasting glucose concentrations only, 148 had high 2 h concentrations only, and 71 had high fasting and 2 h concentrations. At diagnosis, participants with high fasting and 2 h glucose concentrations had higher mean body-mass indices (30•9 kg/m² [SD 5•7]) than did those with high fasting concentrations (28•4 kg/m² [4•4]; p=0•0009) or 2 h concentrations (27•9 kg/m² [4•9]; <0•0001). Mean glycated haemoglobin A1c concentrations were also higher in the fasting and 2 h subgroup (7•4% [1•6]) than in the fasting (5•9% [0•5]; <0•0001) or 2 h (5•9% [0•6]; <0•0001) sugroups. Additionally, the fasting and 2 h subgroup had a higher proportion of individuals with moderate or high risk of cardiovascular disease than did the fasting subgroup (p=0•02). A classic pattern of β-cell decompensation before diagnosis was noted only in the fasting and 2 h subgroup. Additionally, glucose concentrations and insulin resistance accelerated more substantially before diagnosis in the fasting and 2 h subgroup than in the fasting subgroup or the 2 h subgroup. Interpretation Patients with type 2 diabetes diagnosed on the basis of increased fasting glucose concentrations or 2 h glucose concentrations, or both, have distinct cardiometabolic risk development before diagnosis. Funding UK Medical Research Council, UK Economic and Social Research Council, British Heart Foundation, UK Health and Safety Executive, UK Department of Health, US National Heart Lung and Blood Institute, US National Institute on Aging, US Agency for Health Care Policy Research, and John D and Catherine T MacArthur Foundation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intake of carbohydrates which elicit a large glycemic response is hypothesized to increase the risk of diabetes. However, studies assessing the relationship between glycemic index (GI) and glycemic load (GL) and diabetes are inconsistent. Only few studies have studied the relationship between GI and GL and markers of glucose metabolism, mostly in western populations. Objective: To determine the relationship between GI and GL and indices of glucose metabolism and prevalence of diabetes in Greenland''s Inuit population. Design: The Inuit Health in Transition Study is a geographically representative cross-sectional study among aged ≥18years. Diet was assessed using a 67-item food frequency questionnaire. Logistic and linear regression was used to assess the association between GI and GL and diabetes, impaired fasting glucose, impaired glucose tolerance, HbA1c, fasting plasma glucose, 2h plasma glucose, HOMA2-IR and HOMA2-%β. Results: No association was found between GI and GL and diabetes. GL was significantly inversely associated with IFG (OR: 0.91 (0.84–0.98)). While GI was positively associated with FPG, GL was positively associated with both HOMA2-IR and HOMA2-%β and inversely associated with IFG. Conclusion: These findings do not support a link between dietary GI or GL and risk of type 2 diabetes among Greenland''s Inuit population. [Copyright &y& Elsevier]

Background: Few studies have examined the long-term effect of habitual diet on risks of incident diabetes, coronary heart disease, and mortality. Objective: We analyzed the prospective relation of dietary patterns with incident chronic disease and mortality during 15 y of follow-up in the Whitehall II study. Design:Weconducted a prospective analysis (106 633 person-years at risk) among men and women (n = 7731) with a mean age of 50 y at the time of dietary assessment (127-item food-frequency questionnaire). Coronary death or nonfatal myocardial infarction and incident diabetes were verified by record tracing and oral-glucosetolerance tests. Results: Cluster analysis identified 4 dietary patterns at baseline. The patterns were termed unhealthy (white bread, processed meat, fries, and full-cream milk; n = 2665), sweet (white bread, biscuits, cakes, processed meat, and high-fat dairy products; n = 1042), Mediterranean-like (fruit, vegetables, rice, pasta, and wine; n = 1361), and healthy (fruit, vegetables, whole-meal bread, low-fat dairy, and little alcohol; n = 2663). Compared with the unhealthy pattern, the healthy pattern reduced the risk of coronary death or nonfatal myocardial infarction and diabetes; hazard ratios (95% CI) were 0.71 (0.51, 0.98) and 0.74 (0.58, 0.94), respectively, after adjustment for age, sex, ethnicity, dietary energy misreporting, social position, smoking status, and leisure-time physical activity. Dietary pattern was not associated with all-cause mortality. Residual confounding by socioeconomic factors was unlikely to account for the observed dietary effects. Conclusions: The healthy eating pattern reduced risks of diabetes and major coronary events. Such dietary patterns offer considerable health benefits to individuals and contribute to public health. [ABSTRACT FROM AUTHOR]

Abstract: Objectives:: To assess whether the validity of endothelial function measurement by flow-mediated dilatation (FMD) is affected by local brachial artery stiffness (distensibility coefficient; DC) and arterial wall thickness (intima-media thickness, IMT). Background:: FMD measurement relies on assessment of arterial diameter change. Increased IMT and decreased DC might physically limit dilatation of the brachial artery in spite of healthy endothelium. Methods:: DC, IMT and FMD of the brachial artery were simultaneously measured in 349 patients with advanced atherosclerosis or cardiovascular risk factors. The relations between FMD and age, and FMD and current smoking were regarded as a proxy for the relation between FMD and true endothelial function. Results:: The relations between FMD and age, and FMD and smoking, were significantly modified by brachial artery DC. No modification was found for IMT. The interaction terms were statistically significant (p =0.03 and 0.04, respectively). The relation between FMD and age, and FMD and smoking was progressively more pronounced in patients with more elastic arteries. Conclusion:: The results of our study indicate that increased arterial stiffness may interfere with valid measurement of FMD and that patients with stiff arteries may be considered for exclusion from analyses involving FMD to ensure its validity. [Copyright &y& Elsevier]

Objectives: The aim of this research was to study whether the relation between endothelial function measured by flow-mediated dilation (FMD) of the brachial artery and cardiovascular risk factors is affected by the baseline cardiovascular risk. Background: Flow-mediated dilation of the brachial artery is widely used as a measure of endothelial function. Relations between FMD and most cardiovascular risk factors have been described. Methods: We performed a meta-regression analysis of 211 selected articles (399 populations) reporting on FMD and cardiovascular risk factors. Mean values of FMD; age; proportion of men; proportion of smokers; blood pressure; lipids; glucose; and the presence of diabetes mellitus, of hyperlipidemia, and of hypertension were retrieved from the articles. The 10-year risk of coronary heart disease (CHD) for each population was estimated based on the Framingham risk score. The relation between FMD and cardiovascular risk factors was assessed within each risk category by linear regression analysis, adjusting for age and gender, and weighted for the study size. Results: A relation between FMD and cardiovascular risk factors was most clear in the category with lowest baseline risk (below 2.8% per decade). In populations with low baseline risk, for each % increase in Framingham risk, FMD decreased by 1.42% (95% confidence interval: 0.65 to 2.19). In medium- and high-risk populations, FMD was not related to risk (−0.02% [−0.27 to 0.22] and 0.06% [−0.02 to 0.13], respectively). These findings were independent of differences in brachial lumen diameter and technical aspects of the FMD measurement. Conclusions: Only in populations at low risk, endothelial function measured by FMD is related to the principal cardiovascular risk factors, and to the estimated 10-year risk of CHD. [Copyright &y& Elsevier]

Purpose Classical regression models might give an incomplete picture of the associations between predictors and outcomes. We investigated associations between gestational weight gain (GWG) and birth weight along the entire birth weight distribution with quantile regression and estimated effects of hypothetical prevention strategies. Methods The GWG–birth weight association was analyzed using quantile and classical regression models on data from a population-based gestational diabetes screening ( n = 4760) at the Szent Imre Teaching Hospital in Budapest, Hungary (2002–2005). Birth weight distributions were modeled based on hypothetical GWG changes. Results At a body mass index of 20 kg/m 2 , a 1-kg difference in GWG was associated with a 14.2 g (95% confidence interval, 10.0–20.9) higher birth weight at the fifth percentile of the birth weight distribution and a 29.0 g (21.3–35.6) higher birth weight at the 95th percentile. The coefficient from linear regression was 20.7 (17.5–24.0). Estimates differed modestly between the two regressions at a body mass index of 30 kg/m 2 . A population-wide 2-kg decrease in GWG would rather affect the risk of macrosomia (−1.8%) than that of low birth weight (+0.4%). In contrast, a 3-kg decrease in GWG among overweight and obese women would lower macrosomia more modestly (−0.8%). Conclusions A population-wide lowering of GWG would lead to greater improvements in the right tail of the birth weight distribution. [ABSTRACT FROM AUTHOR]

Aims: We examined whether social relations are associated with the risk of developing type 2 diabetes mellitus (T2DM) and furthermore, whether social relations modify the association between depressive symptoms and incident T2DM. We hypothesized that the risk of developing T2DM would be lower for individuals with stronger social relations compared to those with weaker social relations, and that the association between depressive symptoms and incident T2DM would be attenuated for those with stronger social relations.Methods: Non-diabetic participants (n=7662) of the "English Longitudinal Study of Ageing" (3398 men) aged 50-91years were followed until 2012/2013, after baseline assessment of depressive symptoms, social support, relational strain, and network size. Hazard ratios (HR) for incident diabetes were calculated using Cox proportional hazard models, adjusting for relevant confounders.Results: Age and sex adjusted HRs showed that social relations were associated with incident diabetes (Support: HR 0.98 95% CI 0.97; 0.99, Strain: HR 1.02 95% CI 1.01; 1.04, Networklimited: HR 1.19 95% CI 0.98; 1.44), however, when adjusted for age, sex, ethnicity, marital status, household wealth, health behaviour, and body mass index the associations were attenuated and were no longer statistically significant. Depressive symptoms were associated with higher diabetes risk. This effect was not modified by any of the social variables.Conclusions: People with stronger social relations are at lower risk of developing T2DM; however, this effect is largely explained by known diabetes risk factors. No evidence was found that stronger social relations reduce the association between depressive symptoms and incident T2DM. [ABSTRACT FROM AUTHOR]

Aims: To examine the prevalence of micro- and macrovascular complications and their associated clinical characteristics at time of type 2 diabetes (T2D) diagnosis.Methods: We examined the prevalence of complications and associated clinical characteristics among 6958 newly diagnosed T2D patients enrolled in the prospective Danish Center for Strategic Research in T2D cohort during 2010-2016. We calculated age- and gender-adjusted prevalence ratios (aPRs) of complications using log-binomial and Poisson regression.Results: In total, 35% (n=2456) T2D patients had diabetic complications around diagnosis; 12% (n=828) had microvascular complications, 17% (n=1186) macrovascular complications, and 6% (n=442) had both. HbA1c levels of ≥7% were associated with microvascular complications [HbA1c 7%-8%; aPR: 1.35, 95% confidence interval (CI): 1.12-1.62] but not macrovascular complications [aPR: 0.91, 95% CI: 0.76-1.08]. High C-peptide≥800pmol/L was associated with macrovascular [aPR 1.34, 95% CI: 1.00-1.80] but not microvascular [aPR 0.97, 95% CI: 0.71-1.33] complications. Macrovascular complications were associated with male sex, age>50years, obesity, hypertriglyceridemia, low HDL cholesterol, smoking, elevated CRP levels, and anti-hypertensive therapy. Microvascular complications were associated with high blood pressure, hypertriglyceridemia, and absence of lipid-lowering therapy.Conclusions: One-third of patients with T2D had diabetes complications around time of diagnosis. Our findings suggest different pathophysiological mechanisms behind micro- and macrovascular complications. [ABSTRACT FROM AUTHOR]

Aims: Traditionally, fasting and 2-hour post challenge plasma glucose have been used to diagnose diabetes. However, evidence indicates that clinically relevant pathophysiological information can be obtained by adding intermediate time-points to a standard oral glucose tolerance test (OGTT).Methods: We studied a population-based sample of 3666 Asian Indians without diabetes from the CARRS-Chennai Study, India. Participants underwent a three-point (fasting, 30-min, and 2-h) OGTT at baseline. Patterns of glycemic response during OGTT were identified using latent class mixed-effects models. After a median follow-up of two years, participants had a second OGTT. Logistic regression adjusted for diabetes risk factors was used to compare risk of incident diabetes among participants in different latent classes.Results: We identified four latent classes with different glucose patterns (Classes 1-4). Glucose values for Classes 1, 2, and 4 ranked consistently at all three time-points, but at gradually higher levels. However, Class 3 represented a distinct pattern, characterized by high 30-min (30minPG), normal fasting (FPG) and 2-h (2hPG) plasma glucose, moderately high insulin sensitivity, and low acute insulin response. Approximately 22% of participants were categorized as Class 3, and had a 10-fold risk of diabetes compared to the group with the most favorable glucose response, despite 92.5% of Class 3 participants having normal glucose tolerance (NGT) at baseline.Conclusions: Elevated 30minPG is associated with high risk of incident diabetes, even in individuals classified as NGT by a traditional OGTT. Assessing 30minPG may identify a subgroup of high-risk individuals who remained unidentified by traditional measures. [ABSTRACT FROM AUTHOR]

Background Sedentary behavior is regarded as a distinct risk factor for cardiometabolic morbidity and mortality, but knowledge of the efficacy of interventions targeting reductions in sedentary behavior is limited. Purpose To investigate the effect of an individualized face-to-face motivational counseling intervention aimed at reducing sitting time. Design A randomized, controlled, observer-blinded, community-based trial with two parallel groups using open-end randomization with 1:1 allocation. Setting/participants A total of 166 sedentary adults were consecutively recruited from the population-based Health2010 Study. Intervention Participants were randomized to a control (usual lifestyle) or intervention group with four individual theory-based counseling sessions. Main outcome measures Objectively measured overall sitting time (ActivPAL 3TM, 7 days); secondary measures were breaks in sitting time, anthropometric measures, and cardiometabolic biomarkers, assessed at baseline and after 6 months. Data were collected in 2010–2012 and analyzed in 2013–2014 using repeated measures multiple regression analyses. Results Ninety-three participants were randomized to the intervention group and 73 to the control group, and 149 completed the study. The intervention group had a mean sitting time decrease of –0.27 hours/day, corresponding to 2.9% of baseline sitting time (hours/day); the control group increased mean sitting time by 0.06 hours/day. The between-group difference in change, –0.32 hours/day (95% CI=–0.87, 0.24, p =0.26), was not statistically significant. Significant differences in change in fasting serum insulin of –5.9 pmol/L (95% CI=–11.4, –0.5, p =0.03); homeostasis model assessment–estimated insulin resistance of –0.28 (95% CI=–0.53, –0.03, p =0.03); and waist circumference of –1.42 cm (95% CI=–2.54, –0.29, p =0.01) were observed in favor of the intervention group. Conclusions Although the observed decrease in sitting time was not significant, a community-based, individually tailored, theory-based intervention program aimed at reducing sitting time may be effective for increasing standing and improving cardiometabolic health in sedentary adults. Trial registration This study is registered at Clinicaltrials.gov (NCT00289237). [ABSTRACT FROM AUTHOR]

Background: Previous research suggests a link between antidepressant use and diabetes, but it is unclear whether the association is causal or attributable to detection/ascertainment bias. To examine this, we assessed the associations of antidepressant use with change in glucose levels and incidence of undiagnosed and diagnosed diabetes. Methods: During an 18-year period, we monitored antidepressant use, glucose levels, and diabetes status in 5978 civil servants (70.9% male, age range 39–64 years) free of diabetes at baseline (the Whitehall II study). Use of medication and plasma glucose were assessed at four study screenings: 1991/1993, 1997/1999, 2003/2004, and 2008/2009. Incident diabetes cases were classified as either diagnosed (n = 294) if detected using self-report of physician diagnosis and/or the use of diabetes medication or undiagnosed (n = 346) if detected based on fasting and/or 2-hour postload glucose levels using an oral glucose tolerance test at the study screenings. Results: Incidence of diagnosed diabetes was higher among antidepressant users than nonusers (odds ratio 3.10, 95% confidence interval: 1.66–5.78). However, antidepressant use was not associated with undiagnosed diabetes at any follow-up examination nor with higher fasting or 2-hour postload plasma glucose levels or increasing glucose levels over time. Odds ratio for undiagnosed diabetes for antidepressant users versus nonusers was .88 (95% confidence interval: .45–1.72, p = .70). The mean difference in glucose changes between participants reporting antidepressant use at three screenings compared with those not on antidepressant treatment was .0 mmol/L. Conclusions: The link between antidepressant use and diabetes risk may not be causal in nature. [Copyright &y& Elsevier]