Obesity and Metabolic Syndrome Predict Polyneuropathy Over 5 Years in Recent‐Onset Type 2 Diabetes and Normal Glucose Tolerance

AIMS: To evaluate the impact of obesity and metabolic syndrome (MetS) on distal sensorimotor polyneuropathy (DSPN) over 5 years of recent-onset type 2 diabetes and normal glucose tolerance (NGT). MATERIALS AND METHODS: Individuals with recent-onset type 2 diabetes and NGT (n = 355/181) matched for age and sex underwent reference tests of DSPN. Intraepidermal nerve fibre density (IENFD) was assessed in a subset (n = 100/117). Subgroups (n = 198/64) were reevaluated 5 years later. MetS was defined by International Diabetes Federation criteria and DSPN by the Toronto consensus criteria. RESULTS: After adjustment for age, sex, height, smoking history, and HbA1c, IENFD was inversely associated with weight and the number of MetS components in NGT, but not in type 2 diabetes. Lower sural sensory nerve action potential was associated with higher weight in both groups. Higher baseline weight was associated with incident DSPN in NGT. Obesity and MetS at baseline were associated with higher odds of neuropathic deficits at follow-up in type 2 diabetes (OR [95% CI] for obesity 3.00 [1.06-8.51] and MetS 8.25 [1.02-66.91]). CONCLUSIONS: Higher weight is independently associated with early nerve fibre loss and dysfunction, regardless of hyperglycaemia. In recent-onset type 2 diabetes, obesity and MetS predict neuropathic deficits 5 years later, suggesting that timely weight management may be critical to prevent DSPN.