Investigators conducted a post hoc exploratory analysis of 2,891 participants from the Look AHEAD (Action for Health in Diabetes) randomized trial to examine whether type 2 diabetes (T2D) subgroups were associated with incident peripheral neuropathy (PN) and whether intensive lifestyle intervention (ILI) modified PN risk compared with diabetes support and education (DSE). The results of the analysis were published in the Diabetes, Obesity, and Metabolic CARE. Participants had T2D and overweight or obesity and were originally randomized to ILI or DSE.

Using k-means clustering based on BMI, waist circumference, age at diabetes diagnosis, and glycated hemoglobin (HbA1c), four distinct T2D subgroups were identified: high HbA1c, obesity, older onset, and younger onset. PN was assessed using the Michigan Neuropathy Screening Instrument questionnaire and physical examination. Incidence of PN differed significantly by subgroup (P=0.001), with the younger onset subgroup demonstrating the lowest PN risk.
The association of ILI with PN risk was null and did not differ across T2D subgroups (interaction P=0.20).

Limitations include single-time-point PN assessment approximately a decade after baseline, inability to assess time-to-event, potential variability in PN ascertainment sensitivity, selection bias as the analytic sample represented 56% of the original cohort, post hoc data-driven subgroup classification, and lack of adjustment for longitudinal changes in glycaemia, weight, or medication use.

In this exploratory analysis, PN probability varied across data-derived T2D subgroups. Intensive lifestyle intervention did not appear to modify subgroup-specific PN risk.