Research in brief

Abstract

Initiating type 2 diabetes glucose-lowering treatment with medications other than metformin could lead to an increased risk of treatment intensification, suggest the authors of a cohort study. With use of information from a US national health insurance database, researchers reviewed data for 15 516 individuals who received prescriptions for oral anti-hyperglycaemic drugs. 8964 (58%) of 15 516 individuals initiated glucose-lowering therapy with metformin. Sulfonylureas were the second most common drug class with which to initiate treatment, despite being associated with an increased risk of hypoglycaemia (hazard ratio 2·71, 95% CI 1·58–4·66) and congestive cardiac failure (1·19, 1·10–1·28). Compared with metformin, starting type 2 diabetes treatment with a sulfonylurea, thiazolidinedione, or DPP-4 inhibitor was more likely to lead to the addition of further medication (p<0·001). Whether the effect of lowering blood pressure on cardiovascular risk varies according to drug class in obese individuals is the topic of a recent meta-analysis. Individual patient data for 135 715 people included in 22 trials were analysed by researchers. The composite primary outcome of total major cardiovascular events (n=14 353) did not differ according to drug class between the normal weight, overweight, or obese groups. Using BMI as a continuous variable, angiotensin-converting enzyme inhibitors were associated with a lower risk of major cardiovascular events than diuretics (hazard ratio 0·93, 95% CI 0·89–0·98) or calcium channel antagonists (0·93, 95% CI 0·89–0·98) per 5 kg/m2 higher BMI. However, the authors note that “the data do not provide a strong case for a change in clinical practice, such that particular drug classes are directed specifically towards obese patients”. New research provides insight into the response of white adipose tissue in humans to seasonality and cold stimulus. With the use of subcutaneous adipose tissue samples from the thigh or abdomen of 71 generally healthy participants, gene expression was assessed by researchers. Compared with abdominal adipose tissue samples obtained in summer, samples obtained in winter had higher levels of UCP1 and PGC1 A mRNAs, and increased expression of other genes implicated in lipolysis and energy utilisation (p<0·05). The effect of seasonality on UCP1 mRNA was diminished in obese individuals. Subcutaneous adipose tissue samples obtained from the thighs of seven participants after acute exposure to cold stimulus in summer had 2·7-times higher levels of PGC1α mRNA compared with unexposed samples (p=0·015). The InterAct Consortium underlines the importance of smoking cessation for prevention of type 2 diabetes in their latest publication. With the use of data from the multicentre EPIC-InterAct study, the risk of diabetes attributed to smoking was calculated. 10 327 individuals with incident type 2 diabetes and 13 863 subcohort individuals (676 cases of incident diabetes) were included in the calculations. In analyses adjusted for age, education, and lifestyle, the risk of developing diabetes in men was higher in former (hazard ratio 1·40, 95% CI 1·26–1·55) and current smokers (1·43, 1.27–1·61) compared with non-smokers. Smoking imparted risks for diabetes in women as well, albeit at a lower level. Ornstrup and colleagues have investigated the effect of resveratrol on bone in a small placebo-controlled trial. In the 16-week single-centre study, 74 obese men with metabolic syndrome were randomly assigned to receive oral placebo, resveratrol 1 g daily, or resveratrol 150 mg daily. At week 16, the group receiving 1 g resveratrol daily had a higher percentage change in bone alkaline phosphatase from baseline compared with placebo (difference 15·2%, SD 3·7%, p<0·001). The effect of resveratrol on bone alkaline phosphatase was dose-dependent. Lumbar spine trabecular volumetric bone mineral density increased in the high dose resveratrol group compared with placebo (p=0·043). The authors propose that additional studies in people at risk of osteoporosis should be done. In a 24-week double-blind trial, Rosenstock and colleagues investigated a triple therapy strategy for treatment intensification in individuals with type 2 diabetes who had poor glycaemic control with metformin alone. Patients were randomly assigned to add-on therapy with saxagliptin (n=176), dapagliflozin (n=179), or both (n=179). The change in HbA1c from baseline in the triple therapy group was −1·5%, compared with −1·2% in the dapagliflozin group (treatment difference −0·27%, 95% CI −0·48% to −0·05%, p=0·0166) and −0·9% in the saxagliptin group (treatment difference −0·59%, −0·81% to −0·37%, p<0·0001). Longer-term studies are needed to adequately assess the sustainability of glycaemic control and safety of triple therapy.