Increased Left Ventricular Torsion in Uncomplicated Type 1 Diabetic Patients: The role of coronary microvascular function

We used speckle tracking echocardiography to study the early changes in left ventricular (LV) torsion in young patients with uncomplicated type 1 diabetes and stress magnetic resonance imaging (MRI) to assess its interrelationships with coronary microangiopathy

Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes: Secondary Analysis (DEVOTE 11)

Introduction: The associations of chronic kidney disease (CKD) severity, cardiovascular disease (CVD), and insulin with the risks of major adverse cardiovascular events (MACE), mortality, and severe hypoglycemia in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk are not known. This secondary, pooled analysis of data from the DEVOTE trial examined whether baseline glomerular filtration rate (GFR) categories were associated with a higher risk of these outcomes. Methods: DEVOTE was a treat-to-target, double-blind trial involving 7637 patients with T2D at high CV risk who were randomized to once-daily treatment with either insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). Patients with estimated GFR data at baseline (n = 7522) were analyzed following stratification into four GFR categories. Results: The risks of MACE, CV death, and all-cause mortality increased with worsening baseline GFR category (P < 0.05), with a trend towards higher rates of severe hypoglycemia. Patients with prior CVD, CKD (estimated GFR < 60 mL/min/m2), or both were at higher risk of MACE, CV death, and all-cause mortality. Only CKD was associated with a higher rate of severe hypoglycemia, and the risk of MACE was higher in patients with CVD than in those with CKD (P = 0.0003). There were no significant interactions between randomized treatment and GFR category. Conclusion: The risks of MACE, CV death, and all-cause mortality were higher with lower baseline GFR and with prior CVD, CKD, or both. The relative effects of degludec versus glargine U100 on outcomes were consistent across baseline GFR categories, suggesting that the lower rate of severe hypoglycemia associated with degludec use versus glargine U100 use was independent of baseline GFR category. Funding: Novo Nordisk

A genetic locus on chromosome 2q24 predicting peripheral neuropathy risk in type 2 diabetes: Results from the ACCORD and BARI 2D studies

Genetic factors have been postulated to be involved in the etiology of diabetic peripheral neuropathy (DPN), but their identity remains mostly unknown. The aim of this study was to conduct a systematic search for genetic variants influencing DPN risk using two wellcharacterized cohorts. A genome-wide association study (GWAS) testing 6.8 million single nucleotide polymorphisms was conducted among participants of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial. Included were 4,384 white case patients with type 2 diabetes (T2D) and prevalent or incident DPN (defined as a Michigan Neuropathy Screening Instrument clinical examination score &gt;2.0) and 784 white control subjects with T2D and no evidence of DPN at baseline or during follow-up. Replication of significant loci was sought among white subjects with T2D (791 DPN-positive case subjects and 158 DPNnegative control subjects) from the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) trial. Association between significant variants and gene expression in peripheral nerves was evaluated in the Genotype-Tissue Expression (GTEx) database. A cluster of 28 SNPs on chromosome 2q24 reached GWAS significance (P &lt; 5×10-8) in ACCORD. The minor allele of the lead SNP (rs13417783,minor allele frequency = 0.14) decreased DPN odds by 36%(odds ratio [OR] 0.64, 95% CI 0.55-0.74, P = 1.9×10-9). This effect was not influenced by ACCORD treatment assignments (P for interaction = 0.6) or mediated by an association with known DPN risk factors. This locus was successfully validated in BARI 2D (OR 0.57, 95%CI 0.42-0.80,P=9×10-4; summary P=7.9×10-12). In GTEx, the minor, protective allele at this locus was associated with higher tibial nerve expression of an adjacent gene (SCN2A) coding for human voltage-gated sodium channel NaV1.2 (P = 9×10-4). To conclude, we have identified and successfully validated a previously unknown locus with a powerful protective effect on the development of DPN in T2D. These results may provide novel insights into DPN pathogenesis and point to a potential target for novel interventions

Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K.

OBJECTIVE - To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy. RESEARCH DESIGN AND METHODS - Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (NSS) and neuropathy disability score (NDS). RESULTS - Prevalence of painful symptoms (NSS ≥5) and PDN (NSS ≥5 and NDS ≥3) was 34 and 21%, respectively. Painful symptoms occurred in 26% of patients without neuropathy (NDS ≤2) and 60% of patients with severe neuropathy (NDS >8). Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7-2.4], P < 0.001) and not affected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol. Women had 50% increased adjusted risk of painful symptoms compared with men (OR = 1.5 [1.4-1.6], P < 0.0001). Despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001). South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms compared with other ethnic groups (P < 0.0001). CONCLUSIONS - One-third of all community-based diabetic patients have painful neuropathy symptoms, regardless of their neuropathic deficit. PDN was more prevalent in patients with type 2 diabetes, women, and people of South Asian origin. This highlights a significant morbidity due to painful neuropathy and identifies key groups who warrant screening for PDN. © 2011 by the American Diabetes Association

Prevalence of Microvascular and Macrovascular Disease in the Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) Study Cohort

Aims: The Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) trial is a randomized clinical trial comparing glycemic effects of four diabetes medications added to metformin in type 2 diabetes (T2D). Microvascular and macrovascular diseases are secondary outcomes. We evaluated the prevalence and risk factor relationships for microvascular and macrovascular complications in the GRADE cohort at study entry. Methods: Complication prevalence and risk factors were analyzed based on data from screening in all consenting participants meeting GRADE eligibility. Logistic regression and Z-statistics were used to assess risk factor relationships with complications. Results: We enrolled 5047 T2D participants [mean age 57 years; 36% female; mean known T2D duration 4 years (all < 10 years); mean HbA1c 8.0% (∼64 mmol/mol) at screening]. Urinary albumin/creatinine ratio (ACR) ≥ 30 mg/gram was present in 15.9% participants; peripheral neuropathy (by Michigan Neuropathy Screening Instrument) in 21.5%; cardiovascular autonomic neuropathy by electrocardiography-derived indices in 9.7%; self-reported retinopathy in 1.0%. Myocardial infarction ascertained by self-report or electrocardiogram was present in 7.3%, and self-reported history of stroke in 2.0%. Conclusions: In the GRADE cohort with < 10 years of T2D and a mean HbA1c of 8.0%, diabetes complications were present in a substantial fraction of participants, more so than might otherwise have been expected