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Aims: To present the longer‐term impact of multifactorial treatment of type 2 diabetes on self‐reported health status, diabetes‐specific quality of life, and diabetes treatment satisfaction at 10‐year follow up of the ADDITION‐Europe trial. Methods: The ADDITION‐Europe trial enrolled 3057 individuals with screen‐detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care. The trial ended in 2009 and a 10‐year follow‐up was performed at the end of 2014. We measured self‐reported health status (36‐item Short‐Form Health Survey and EQ‐5D), diabetes‐specific quality of life (Audit of Diabetes‐Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed‐effects model was applied to estimate the effect of intensive treatment (intention‐to‐treat analyses) on patient‐reported outcome measures for each centre. Centre‐specific estimates were pooled using a fixed effects meta‐analysis. Results: There was no difference in patient‐reported outcome measures between the routine care and intensive treatment arms in this 10‐year follow‐up study [EQ‐5D: –0.01 (95% CI –0.03, 0.01); Physical Composite Score (36‐item Short‐Form Health Survey): –0.27 (95% CI –1.11, 0.57), Audit of Diabetes‐Dependent Quality of Life questionnaire: –0.01 (95% CI –0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: –0.20 (95% CI –0.70, 0.29)]. Conclusions: Intensive, multifactorial treatment of individuals with screen‐detected type 2 diabetes did not affect self‐reported health status, diabetes‐specific quality of life, or diabetes treatment satisfaction at 10‐year follow‐up compared to routine care. What's new?: The burden of diabetes and its treatment may cause psychosocial stress.Good metabolic control improves psychosocial well‐being.Identifying people early in the disease course through screening and introducing long‐term intensive treatment does not cause psychosocial harm.Clinicians and public health systems implementing early detection and intensive treatment protocols for type 2 diabetes do not need to worry that these may have a long‐term adverse impact on peoples' psychosocial well‐being. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years). Methods The patients were well controlled with regard to HbA1c, lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold ( n = 319), 10 g monofilament ( n = 543) and the Michigan Neuropathy Screening Instrument questionnaire ( n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form ( n = 882). Results No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing. Conclusion Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes. [ABSTRACT FROM AUTHOR]

Aims Modulation of dopamine receptor D2 ( DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Methods Four potentially functional variants in the coding region of the DRD2/ ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. Results rs1800497 at the DRD2/ ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10−4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women ( P = 5.5*10−4) but again not in men ( P = 0.34). Conclusion The present data identify DRD2/ ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene. [ABSTRACT FROM AUTHOR]

CONTEXT:Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in β-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus.OBJECTIVE:To determine the influence of a functional UCP2 promoter polymorphism (−866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes.DESIGN:We genotyped UCP2 rs659366 in a total of 17 636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations.RESULTS:We found no consistent associations between the UCP2 −866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12 984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15 107 individuals showed no association. The −866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05).CONCLUSIONS:The UCP2 −866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis. [ABSTRACT FROM AUTHOR]

ims/hypothesis: A genome-wide association study in the Japanese population reported two genome-wide significant loci associated with type 2 diabetes of which the VPS13C/ C2CD4A/ C2CD4B locus was replicated in Europeans. We looked for potential associations between the diabetogenic VPS13C/ C2CD4A/ C2CD4B rs7172432 variant and diabetes-related intermediary traits. Methods: We genotyped the rs7172432 variant in the population-based Inter99 cohort ( n = 6,784) and analysed quantitative diabetes-related traits in 5,722 non-diabetic participants who all were examined by an OGTT. Results: The diabetes-associated A allele was associated with 0.60 cm higher waist circumference ( p = 0.004), 0.037 mmol/l higher fasting plasma glucose ( p = 4 × 10) and 0.11 mmol/l higher plasma glucose at 30 min during an OGTT ( p = 4 × 10). In analyses adjusted for concomitant insulin sensitivity levels the diabetogenic allele was associated with a lower acute glucose-stimulated insulin response (GSIR) as estimated by 30 min serum insulin ( β = −0.039, p = 2 × 10), insulinogenic index ( β = −0.057, p = 1 × 10) and BIGTT-acute insulin release ( β = −0.041, p = 9 × 10). As rs7172432 is situated in a region previously associated with glycaemic traits, we tested linkage disequilibrium (LD) with the reported regional lead single-nucleotide polymorphisms for fasting (rs11071657) and 2 h plasma glucose (rs17271305), and performed conditional analyses of rs7172432. Rs7172432 showed moderate LD with rs11071657 and rs17271305 ( R < 0.34) and we found strong association by almost unchanged effect sizes of rs7172432 with plasma glucose and estimates of GSIR in analyses conditional on rs11071657 and rs17271305. Conclusions/interpretation: The diabetogenic VPS13C/ C2CD4A/ C2CD4B rs7172432 A allele associates with GSIR in non-diabetic individuals from the general population, suggesting an impaired beta cell function as an intermediary diabetes-related trait. [ABSTRACT FROM AUTHOR]