Divergent complication patterns of type 2 diabetes in African individuals who are lean versus overweight or obese: a multi-cohort analysis

Abstract

Nearly 40% of African adults with type 2 diabetes are lean (BMI <25 kg/m2). Emerging evidence suggests that type 2 diabetes in African individuals who are lean may represent a distinct phenotype driven by impaired insulin secretion rather than insulin resistance, raising concerns about treatment mismatch and divergent disease outcomes. We examined complication profiles in Africans with type 2 diabetes who are lean vs overweight/obese. We analysed harmonised, individual-level cross-sectional data from two large, well-characterised African cohorts (Africa America Diabetes Mellitus study, n=2790; Research on Obesity and Diabetes among African Migrants study, n=541; total n=3331) of adults with type 2 diabetes from Ghana, Nigeria and Kenya. Participants were classified as lean (BMI <25 kg/m2) or overweight/obese (BMI ≥25 kg/m2). Robust Poisson regression, adjusted for age, sex, education and treatment, assessed associations with retinopathy, chronic kidney disease, stroke, hypertension and 10-year cardiovascular disease risk. Cohort-specific estimates were pooled using random effects, followed by mediation analysis examining contributions of lifestyle and metabolic markers to observed differences. Type 2 diabetes in Africans who are lean was characterised by lower beta cell function and low insulin levels. Compared with individuals who are overweight/obese, adults who are lean showed a higher prevalence of retinopathy (pooled prevalence ratio [pPR] 1.36 [95% CI 1.13, 1.63]) and stroke (pPR 1.41 [95% CI 1.01, 1.99]), but lower hypertension (pPR 0.77 [95% CI 0.71, 0.85]) and 10-year cardiovascular disease risk (pPR 0.85 [95% CI 0.74, 0.97]). Chronic kidney disease prevalence did not differ between groups. Body fat percentage accounted for most differences (up to 92%). Complication patterns in Africans with type 2 diabetes who are lean vs overweight/obese follow divergent paths. In Africa, where nearly 24 million people have type 2 diabetes, two-fifths of whom are lean, our findings add to growing evidence that lean type 2 diabetes may be a distinct phenotype, underscoring the urgent need for investigation into better-targeted management for this large, potentially mistreated, population.