Why does type 2 diabetes mellitus impair weight reduction in patients with obesity? A review

BACKGROUND: A common adiposopathic complication of obesity is type 2 diabetes mellitus. Healthful weight reduction in patients with obesity can improve glucose metabolism and potentially promote remission of type 2 diabetes mellitus. However, weight-reduction in patients with increased adiposity is impaired among patients with type 2 diabetes mellitus compared to patients without diabetes mellitus. METHODS: Data for this review were derived from PubMed and applicable websites. RESULTS: Among patients with increased body fat, the mechanisms underlying impaired weight reduction for those with type 2 diabetes mellitus are multifactorial, and include energy conservation (i.e., improved glucose control and reduced glucosuria), hyperinsulinemia (commonly found in many patients with type 2 diabetes mellitus), potential use of obesogenic anti-diabetes medications, and contributions from multiple body systems. Other factors include increased age, sex, genetic/epigenetic predisposition, and obesogenic environments. CONCLUSIONS: Even though type 2 diabetes mellitus impairs weight reduction among patients with increased adiposity, clinically meaningful weight reduction improves glucose metabolism and can sometimes promote diabetes remission. An illustrative approach to mitigate impaired weight reduction due to type 2 diabetes mellitus is choosing anti-diabetes medications that increase insulin sensitivity and promote weight loss and deprioritize use of anti-diabetes medications that increase insulin exposure and promote weight gain.