Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes

Aims/hypothesis: An abnormal urinary albumin excretion rate (AER) is often the first clinically detectable manifestation of diabetic nephropathy. Our aim was to estimate the heritability and to detect genetic variation associated with elevated AER in patients with type 1 diabetes. 
 Methods: The discovery phase genome-wide association study (GWAS) included 1,925 patients with type 1 diabetes and with data on 24 h AER. AER was analysed as a continuous trait and the analysis was stratified by the use of antihypertensive medication. Signals with a p value <10^{−4 were followed up in 3,750 additional patients with type 1 diabetes from seven studies.} 
 Results: The narrow-sense heritability, captured with our genotyping platform, was estimated to explain 27.3% of the total AER variability, and 37.6% after adjustment for covariates. In the discovery stage, five single nucleotide polymorphisms in the GLRA3 gene were strongly associated with albuminuria (p < 5 × 10^{−8). In the replication group, a nominally significant association (p = 0.035) was observed between albuminuria and rs1564939 in GLRA3, but this was in the opposite direction. Sequencing of the surrounding genetic region in 48 Finnish and 48 UK individuals supported the possibility that population-specific rare variants contribute to the synthetic association observed at the common variants in GLRA3. The strongest replication (p = 0.026) was obtained for rs2410601 between the PSD3 and SH2D4A genes. Pathway analysis highlighted natural killer cell mediated immunity processes.} 
 Conclusions/interpretation: This study suggests novel pathways and molecular mechanisms for the pathogenesis of albuminuria in type 1 diabetes.

Chronic kidney disease and diabetes in the National Health Service:a cross-sectional survey of the UK National Diabetes Audit

We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large UK-based diabetes population.

Obesity and kidney disease in type 1 and 2 diabetes: an analysis of the National Diabetes Audit

Background: Obesity is increasingly prevalent in many countries. Obesity is a major risk factor for the development of type 2 diabetes but its relationship with diabetic kidney disease (DKD) remains unclear. Some studies have suggested that the metabolic syndrome (including obesity) may be associated with DKD in type 1 diabetes. Aim: To investigate the association between obesity and DKD. Design: Retrospective cross-sectional study. Methods: National Diabetes Audit data were available for the 2007–08 cycle. Type 1 and 2 diabetes patients with both a valid serum creatinine and urinary albumin:creatinine ratio were included. DKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, albuminuria or both. Logistic regression was used to analyse associations of obesity (body mass index ≥30 kg/m2) and other variables including year of birth, year of diagnosis, ethnicity and stage of kidney disease. Results: A total of 58 791 type 1 and 733 769 type 2 diabetes patients were included in the analysis. After adjustment, when compared with type 1 diabetes patients with normal renal function those with DKD were up to twice as likely to be obese. Type 2 DKD patients were also more likely to be obese. For example, type 2 diabetes patients with an eGFR <15 ml/min/1.73 m2 and normoalbuminuria, microalbuminuria or macroalbuminuria were all more likely to be obese; odds ratios (95% CI) 1.65 (1.3–2.1), 1.56 (1.28–1.92) and 1.27 (1.05–1.54), respectively. Conclusions: This study has highlighted a strong association between obesity and kidney disease in type 1 diabetes and confirmed their association in type 2 diabetes.

Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes

Hyperglycemia plays a pivotal role in the development and progression of vascular complications, which are the major sources of morbidity and mortality in diabetes. Furthermore, these vascular complications often persist and progress despite improved glucose control, possibly as a result of prior episodes of hyperglycemia. Epigenetic modifications mediated by histone methyltransferases are associated with gene-activating events that promote enhanced expression of key proinflammatory molecules implicated in vascular injury. In this study, we investigated genetic polymorphisms of the SETD7, SUV39H1, and SUV39H2 methyltransferases as predictors of risk for micro- and macrovascular complications in type 1 diabetes.

A Posteriori Dietary Patterns Are Related to Risk of Type 2 Diabetes: Findings from a Systematic Review and Meta-Analysis

Our review and meta-analysis examined the association between a posteriori–derived dietary patterns (DPs) and risk of type 2 diabetes mellitus. MEDLINE and EMBASE were searched for articles published up to July 2012 and data were extracted by two independent reviewers. Overall, 19 cross-sectional, 12 prospective cohort, and two nested case-control studies were eligible for inclusion. Results from cross-sectional studies reported an inconsistent association between DPs and measures of insulin resistance and/or glucose abnormalities, or prevalence of type 2 diabetes. A meta-analysis was carried out on nine prospective cohort studies that had examined DPs derived by principle component/factor analysis and incidence of type 2 diabetes risk (totaling 309,430 participants and 16,644 incident cases). Multivariate-adjusted odds ratios were combined using a random-effects meta-analysis. Two broad DPs (Healthy/Prudent and Unhealthy/Western) were identified based on food factor loadings published in original studies. Pooled results indicated a 15% lower type 2 diabetes risk for those in the highest category of Healthy/Prudent pattern compared with those in the lowest category (95% CI 0.80 to 0.91; P<0.0001). Compared with the lowest category of Unhealthy/Western DP, those in the highest category had a 41% increased risk of type 2 diabetes (95% CI 1.32 to 1.52; P<0.0001). These results provide evidence that DPs are consistently associated with risk of type 2 diabetes even when other lifestyle factors are controlled for. Thus, greater adherence to a DP characterized by high intakes of fruit, vegetables, and complex carbohydrate and low intakes of refined carbohydrate, processed meat, and fried food may be one strategy that could have a positive influence on the global public health burden of type 2 diabetes.

Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: A prospective study

Objective: Plasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes. Research design and methods: tHcy levels were measured once, in plasma obtained in 1997–1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC “Year 6” (1998–2000) and “Year 12” (2004–2006), using B-mode ultra-sonography. Results: After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p < 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors. Conclusions: In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997–1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.

Preconception counselling for women with diabetes: An online resource

Pre-pregnancy care impacts positively on pregnancy outcome, yet the majority of women continue to receive suboptimal support in this area owing to a lack of awareness about the importance of pregnancy planning. An innovative preconception counselling resource has been developed in Northern Ireland (originally as a DVD and later in an online format), in collaboration with end users to raise awareness of planning for pregnancy. This educational resource is now embedded in routine care in the region as a preconception counselling tool, being adopted by all diabetes care teams and many GP practices. It also recently received national recognition, winning the “Best improvement programme for pregnancy and maternity” category at the 2013 Quality in Care Diabetes awards. This article presents the background to the resource’s development, as well as experiences from its production and roll-out.