Practice Update: DIABETES

MICROVASCULAR COMPLICATIONS 15

scores were 1.9 ± 0.04 and 1.8 ± 0.04 in the ILI and DSE groups, respectively (difference not statistically significant). After 1 year, when weight loss was maximal in the ILI group (8.6 ± 6.9%) compared with DSE (0.7 ± 4.8%), the respec- tive MNSI scores were 1.7 ± 0.04 and 2.0 ± 0.04 (p ≤ 0.001). Subsequently, the scores increased gradually in both groups, but remained signifi- cantly lower in the ILI group for the first 3 years and at the end of follow-up. In both groups,

there was a significant association between changes in the MNSI scores and changes in body weight, HbA1c and serum lipids. There were no significant between-group differences in the proportions of participants with MNSI physical examination scores ≥2.5, considered to be indicative of diabetic neuropathy. The light touch sensation measured separately in either the right or left big toes (halluces) did not differ between ILI and DSE, but when the data were combined for both toes, light touch was better preserved in the ILI group. CONCLUSIONS/INTERPRETATION ILI resulted in a significant decrease in questionnaire-based DPN, which was associated with the magnitude of weight loss. In both the ILI and DSE groups, changes in the MNSI score were also related to changes in HbA1c and lipids. There were no significant effects of ILI on physical examination measures of DPN conducted 1–2.3 years after termination of the active intervention, except for light touch sensation, which was significantly better in the ILI group when measurements were combined for both toes. However, a potential limiting factor to the interpretation of the physi- cal examination data is that no baseline studies are available for comparison. Effects of a long-term lifestyle modification programme on peripheral neuropathy in over- weight or obese adults with type 2 diabetes: the Look AHEAD Study. Diabetologia 2017 Mar 27;[EPub Ahead of Print], The Look AHEAD Research Group. naltrexone-bupropion, and liraglutide. Mean weight loss varies from 4% to 9%, with phen- termine-TPM generally associated with the highest loss (8.6–9.3%), with 70% of patients experiencing >10% weight loss. It has been shown to improve symptoms using the Nor- folk QOL-DN (quality of life) tool, improve physical measures of neuropathy, and induce regeneration of IENF. It is now being examined in the US in a multicenter study and no doubt will surely be a wonderful antidote to our intrinsically slothful popula- tion! The Holy Grail for neuropathy, which is the major contributor to foot ulcers and amputations, is an agent that addresses the underlying biology of the disease, and there are many in the wings including gene therapy. In 1982, an editorial in The Lancet said, “All we can do for neuropathy is make the diagnosis and commiserate with the patient.” Now there is a whole lot more!

outcomes. Neuropathy evaluations included the Michigan Neuropathy Screening Instrument (MNSI) questionnaire completed at baseline in 5145 participants (ILI n = 2570, DSE n = 2575) and repeated annually thereafter and the MNSI phys- ical examination and light touch sensation testing conducted in 3775 participants (ILI n = 1905, DSE n = 1870) 1–2.3 years after discontinuation of the intervention. RESULTS At baseline, the MNSI questionnaire

are considered compatible with neuropa- thy and scores above 4 are abnormal. At baseline, the MNSI questionnaire scores were 1.9 ± 0.04 and 1.8 ± 0.04 in the ILI and DSE groups, respectively (P = NS). After 1 year, weight loss was maximal in the ILI group (8.6% ± 6.9%) compared with DSE (0.7% ± 4.8%); the respective MNSI scores were 1.7 ± 0.04 and 2.0 ± 0.04 (P ≤ 0.001), indicating progression in the DSE group. Subsequently, the scores increased gradually in both groups, but remained sig- nificantly lower in the ILI group for the first 3 years and at the end of follow-up. In both groups, there was a significant associa- tion between changes in the MNSI scores and changes in body weight, HbA1c, and serum lipids. There were no significant between-group differences in the propor- tions of participants with MNSI physical examination scores ≥2.5, considered to be indicative of diabetic neuropathy. The light touch sensation measured separately in either the right or left big toes (halluces) did not differ between ILI and DSE, but when the data were combined for both toes, light touch was better preserved in the ILI group. The authors conclude that lifestyle changes

are associatedwith loss of weight, which low- ers the risk for questionnairebut not objective neuropathy. The pattern of response to the intervention is very much akin to that seen in the Diabetes Control and Complications Trial (DCCT) and in the DPP trial wherein there is an initial response in the active group and this is slowly reversed, albeit at a slower rate, than in the conventionally treated group. This is the Nike curve of diabetes management. It argues for a window of opportunity when aggressive treatment will have a maximal effect, which wanes. However, lifestyle inter- ventions are very difficult to sustain and may paradoxically encourage increased caloric intake and sedentary behavior. Patients fre- quently adapt by reducing activity levels when not exercising and increasing caloric intake following exercise bouts. Thus, while this literature supports the premise that CSPN and DPN associ- ated with metabolic syndrome may be amenable to therapy, development of a well-tolerated, sustainable, pharmacologic approach is needed. There are five drugs available in the United States for long-term weight loss: orlistat, lorcaserin, phentermine-topiramate (TPM),

Dr Vinik is Professor of Medicine/Pathology/ Neurobiology, and Director of Research and Neuroendocrine Unit at Eastern Virginia Medical School, Strelitz Diabetes Center, Virginia.

VOL. 1 • NO. 1 • 2017