Association of Type 2 Diabetes Subgroups With Incident Peripheral Neuropathy

Peripheral neuropathy (PN) is a complication of type 2 diabetes (T2D). Whether T2D subgroups differ in PN risk and modify the effect of intensive lifestyle intervention (ILI) on PN prevention remains unknown. We assessed 1) whether T2D subgroups were associated with the incidence of PN and 2) whether the impact of ILI compared with control on risk for PN differed by T2D subgroups.

We included 2,891 Look AHEAD (Action for Health in Diabetes) participants with T2D and overweight or obesity randomly assigned to ILI or diabetes support and education (DSE). We used k-means clustering techniques with data on BMI, waist circumference, age of diabetes diagnosis, and glycated hemoglobin (HbA_1c) to characterize T2D subgroups at randomization. PN was ascertained using the Michigan Neuropathy Screening Instrument questionnaire and physical examination. We estimated marginal probabilities for PN according to T2D subgroup with adjustment for potential confounders and attrition and examined whether ILI modified any associations.

Four distinct T2D subgroups were identified and characterized by high HbA_1c, obesity, older onset, and younger onset. Incidence of PN differed by T2D subgroup (P = 0.001), and individuals in the younger onset T2D subgroup had the lowest risk for PN. The association of ILI with PN risk was null and did not differ by T2D subgroups (interaction P = 0.20).

Among individuals with T2D and overweight or obesity, the probability of developing PN differs by disease subgroups, and subgroup-specific risk does not appear to be ameliorated by lifestyle intervention.