Body mass index and peripheral neuropathy across the glucose tolerance spectrum in Japanese adults

To examine the association between obesity, defined using population-specific body mass index (BMI) thresholds, and peripheral neuropathy across the glucose tolerance spectrum in Japanese adults.

This cross-sectional study included 353 Japanese adults: 90 with normal glucose tolerance (NGT), 55 with impaired glucose tolerance (IGT), and 208 with type 2 diabetes mellitus. Participants were stratified by BMI (<25 vs ≥25 kg/m²) according to Japan Society for the Study of Obesity criteria. Peripheral neuropathy was assessed using the Neuropathy Disability Score, nerve conduction studies, quantitative sensory testing, and corneal confocal microscopy (CCM). Associations between BMI and neuropathy measures were examined using regression models adjusted for age and sex.

BMI-related differences in neuropathy measures were predominantly confined to participants with type 2 diabetes mellitus. Within this group, higher BMI was associated with greater neuropathy severity (adjusted P = 0.01) and a higher prevalence of Toronto-defined neuropathy (adjusted odds ratio 3.3, 95% CI 1.4-7.7; P = 0.01). In contrast, obesity was not independently associated with neuropathy measures in NGT or IGT participants. Corneal nerve fiber length was significantly reduced in IGT compared with NGT (P < 0.001), indicating early small-fiber involvement related to glycemic status rather than adiposity.

In Japanese adults, obesity at population-specific BMI thresholds exacerbates peripheral neuropathy primarily in established type 2 diabetes mellitus. Early small-fiber abnormalities are detectable in IGT and appear driven by glucose dysregulation rather than obesity alone. These findings highlight population-specific patterns of neuropathy risk and support early identification of nerve involvement across the glucose tolerance spectrum in East Asian populations.