Associations between decreases in adiposity and reductions in HbA1c and insulin use in the Look AHEAD cohort

Objective: The objective of this study was to elucidate associations between adiposity reduction and changes in HbA1c and insulin use among adults with type 2 diabetes and overweight or obesity. Methods: Changes in BMI, waist circumference, and total percent fat mass were obtained over 8 years among 1316 individuals (aged 45–76 years) enrolled in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss. Generalized linear models were used to assess relationships between 5% decreases in adiposity measures with glycated hemoglobin (HbA1c) and insulin use over time. Results: A 5% reduction in total percent fat was associated with 0.15% (95% CI: 0.12%–0.18%) lower mean HbA1c. Similarly, 5% reductions in waist circumference and BMI were also associated with slightly lower mean HbA1c: 0.16% (95% CI: 0.13%–0.19%) and 0.13% (95% CI: 0.11%–0.16%), respectively. These reductions were associated with lower odds of insulin use over time, ranging from 21% lower odds for a 5% reduction in percent body fat to 32% lower odds for 5% reductions in waist circumference and BMI. Associations were evident across subgroups defined by sex, diabetes duration, obesity status, and intervention assignment. Conclusions: Reductions in adiposity are associated with stabilized and slightly lower HbA1c and a marked reduction in the need for insulin therapy. These benefits generalize across clinical subgroups.