Practice Update: DIABETES

MICROVASCULAR COMPLICATIONS 14

Effects of a long-term lifestyle modification program on peripheral neuropathy in obese adults with type 2 diabetes Diabetologia Take-home message • The authors of this randomized study investigated the effect of a long-term, inten- sive lifestyle intervention (ILI) on diabetic peripheral neuropathy in overweight and obese individuals with type 2 diabetes. A total of 2570 patients were assigned to ILI, and 2575 were assigned to a control group who received diabetes support and education. Interventions continued for 9 to 11 years after randomization. The ILI group experienced more weight loss and achieved better scores on a neuropathy screening tool than the control group 1 year after the interventions began. After the interventions were terminated, there was no difference between the groups in physical exam measures for peripheral neuropathy except for better light touch sensation in the ILI group. Changes in neuropathy screening tool score were strongly correlated with changes in HbA1c, lipid profiles, and body weight in both treatment groups. • Intensive lifestyle intervention resulted in significant weight loss and some modest improvements in measures of peripheral neuropathy in overweight and obese individuals with type 2 diabetes.

fiber density (IENFD) and neuropathic pain. Similarly, in a 4-year randomized trial, type 2 diabetic participants without baseline DPN assigned to 4 hours of observed treadmill walkingweekly improved vibration detection and NCS, and were significantly less likely to develop neuropathy symptoms than controls. The Look AHEAD study began in 2001 with 5145 overweight or obese people with type 2 diabetes aged 45 to 76 years old randomized to intensive life style interven- tion (ILI; n= 2570) or a diabetes support and education group (DSE; n= 2575), and the interventions were terminated in Septem- ber 2012, 9 to 11 years after randomization. Patients completed annually the Michigan Neuropathy Screening Instrument (MNSI), a compendium of 15 questions related to symptoms of neuropathy, and an examina- tion and measurement of touch perception with a 10-g monofilament. The MNSI has 15 questions, 13 of which are positive and 2 are negative, with a maximal total score of 15. The NMSI physical exam scores 1 point for each of deformities, dryness and cracking of skin, loss of sensory percep- tion, absence of ankle reflexes, and loss of vibration perception. Scores above 2.5 METHODS Beginning in 2001, a total of 5145 over- weight or obese people with type 2 diabetes, aged 45-76 years, participating in the multicentre Look AHEAD (Action for Health in Diabetes) study were randomised to ILI (n = 2570) or to a diabe- tes support and education (DSE) control group (n = 2575) using a web-based management system at the study coordinating centre at Wake Forest School of Medicine (Winston-Salem, NC, USA). Randomisationwas stratified by clinical centre and was not revealed to the clinical staff responsible for obtaining data on study outcomes. Because of the nature of the study, patients and the local cen- tre interventionists were not blinded to the study group assignments. In addition, the coordinating centre staff members responsible for data man- agement and statistical analyses were not blinded to the study group assignments. The interventions were terminated in September 2012, 9–11 years after randomisation, but both groups continued to be followed for both primary and secondary The Holy Grail for neuropathy is an agent that addresses the underlying biology of the disease, and there are many in the wings including gene therapy. Abstract AIMS/HYPOTHESIS The aim of this study was to evaluate the effects on diabetic peripheral neuropathy (DPN) of a long-term intensive life- style intervention (ILI) programme designed to achieve and maintain weight loss.

COMMENT By Aaron I. Vinik MD, PhD, FCP, MACP, FACE T he explosion in the epidemic of obesity in the US and globally is closely being followed by an epidemic in diabetes. Somewhat disconcerting is the 44% increase in type 2 diabetes in children, many of whom will not live beyond 30 years of age because of the early development of diabetes and its complications, including neuropathy. There is also a growing consensus that obesity and dyslipidemia are critical contributors to neuropathy in diabetes. Among a cohort of 217 patients participating in the Utah Dia- betic Neuropathy Study without neuropathy symptoms, or with symptoms for fewer than 5 years, obesity andmetabolic syndromewere potent neuropathy risk factors. The relative risk of diabetic peripheral neuropathy (DPN) was 4.0 (95% CI, 1.1–14.4) for those with met- abolic syndrome and 4.1 (95% CI, 1.1–15.0) for obese participants (P < 0.02). Metabolic syndrome is associated with neuropathy risk in human disease and ani- mal models. The type of neuropathy is frequently a sen- sory/motor neuropathy as occurs in DPN. More frequently, cryptogenic sensory

polyneuropathy (CSPN) is found to co-segre- gatewithmetabolic syndromeor prediabetes in up to 70%of cases. Multiple animal models of diet-induced obesity demonstrate neurop- athy with loss of intraepidermal nerve fibers (IENF), which is reversible with a program of exercise and nutritional restriction. Exer- cise-based lifestyle interventions improve metabolism and result in nerve regeneration in prediabetic and diabetic neuropathy. Exer- cise increases insulin production, reverses or prevents diabetes, and reduces neuropathic pain, inflammatory cytokine production, and nerve conduction study (NCS) features of neuropathy in animal models. Studies, including the Diabetes Preven- tion Program (DPP), demonstrate that exercise and diet counseling may normal- ize metabolic syndrome features (obesity, hypertriglyceridemia) and reduce diabetes risk. The Impaired Glucose Tolerance Neu- ropathy trial, led by the University of Utah, provided a DPP-based intervention to 32 impaired glucose tolerance (IGT) patients with neuropathy. After 1 year, there was sig- nificant improvement in weight, glucose tolerance, and lipid parameters, and signif- icant improvement in intraepidermal nerve

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