Peripheral and Autonomic Neuropathy in South Asians and White Caucasians with Type 2 Diabetes Mellitus: Possible Explanations for Epidemiological Differences.

Objectives. To compare the prevalence of diabetic peripheral neuropathy (DPN) and that of cardiac autonomic neuropathy (CAN) between South Asians and White Caucasians with type 2 diabetes and to explore reasons for observed differences. Methods. A cross-sectional study of casually selected South Asian and White Caucasian adults attending a hospital-based diabetes clinic in the UK. DPN and CAN were assessed using the Michigan Neuropathy Screening Instrument (MNSI) and heart rate variability testing, respectively. Results. Patients (n = 266) were recruited (47.4% South Asians). DPN was more common in White Caucasians compared to South Asians (54.3% versus 38.1%, p = 0.008). Foot insensitivity as assessed by 10 g monofilament perception was more common in White Caucasians (43.9% versus 23.8%, p = 0.001). After adjustment for confounders, White Caucasians remained twice as likely to have DPN as South Asians, but the impact of ethnicity became nonsignificant after adjusting for adiposity measures or height. No difference in prevalence of standardized CAN test abnormalities was detected between ethnicities. Skin microvascular assessment demonstrated that South Asians had reduced heating flux but preserved acetylcholine response. Conclusions. South Asians with type 2 diabetes have fewer clinical signs of DPN compared to White Caucasians. Differences in adiposity (and its distribution) and height appear to explain these differences.

Novel therapeutics for type 2 diabetes: insulin resistance.

Insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes (T2D) and cardiovascular disease. Hence improving IR is a major target of treatment in patients with T2D. Obesity and lack of exercise are major causes of IR. However, recent evidence implicates sleep disorders and disorders of the circadian rhythm in the pathogenesis of IR. Weight loss and lifestyle changes are the cornerstone and most effective treatments of IR, but adherence and patient's acceptability are poor. Bariatric surgery results in significant and sustainable long-term weight loss associated with beneficial impact on IR and glucose metabolism, making this an attractive treatment option for patients with T2D. Currently available pharmacological options targeting IR (such as metformin and thiazolidinediones) do not maintain glycaemic measures within targets long term and can be associated with significant side effects. Over the last two decades, many pharmacological agents targeting different aspects of the insulin signalling pathway were developed to improve IR, but only a minority reached clinical trials. Such treatments need to be specific and reversible as many of the components of the insulin signalling pathway are involved in other cellular functions such as apoptosis. Recent evidence highlighted the role of circadian rhythm and sleep-related disorders in the pathogenesis of IR. In this article, we review the latest developments in the pharmacological and non-pharmacological interventions targeting IR including bariatric surgery. We will also review the role of circadian rhythm and sleep-related disorders in the development and treatment of IR.