Why hyperinsulinemia is detrimental to weight loss: insights from type 1 diabetes

The global rise in obesity prevalence poses a major health challenge due to its links to hypertension, stroke, type 2 diabetes, cardiovascular disease, depression, and cancer. Effective non-pharmacological strategies are essential to curb this epidemic. Insulin is a major regulator of body weight. It not only mediates glucose uptake but also inhibits hepatic glucose production, lipolysis, and enhances lipogenesis.

Type 1 diabetes provides insights on insulin's role in weight regulation. Prior to diagnosis, insulin deficiency commonly produces unintentional weight loss, whereas initiation of exogenous insulin therapy typically restores body mass. Scientific research in non-diabetic populations, including Mendelian randomization studies, has identified elevated insulin secretion as a key contributor to weight gain. Conversely, reductions in insulin secretion have been shown to facilitate weight loss, even in the absence of caloric restriction. One strategy to keep circulating insulin concentrations low is the application of carbohydrate unit tables to estimate expected postprandial glucose excursions in insulin-deficient patients and anticipated insulin responses in non-diabetic individuals. This approach facilitates avoidance of foods that provoke large insulin responses. A complementary approach is postprandial self-monitoring of blood glucose (SMBG). In non-diabetic individuals, this allows for personalized assessment of glycemic and insulin responses to meals. The effectiveness of this approach in promoting weight reduction has been demonstrated across multiple studies. During fasting or adherence to low-carbohydrate diets, circulating insulin concentrations remain low, permitting unrestrained adipose tissue lipolysis and promoting fatty acid oxidation for energy production. Self-monitoring of breath acetone (SMBA) provides a simple, non-invasive biomarker of this metabolic state. Recent findings indicate that a single carbohydrate-rich meal during a ketogenic state suppresses fat mobilization for several days-a phenomenon suggestive of a "memory effect" of insulin on lipolysis inhibition. Although underlying mechanisms remain to be elucidated, awareness of this effect may improve dietary regimens.

Insights from type 1 diabetes offer advice for managing weight development by minimizing episodes of hyperinsulinemia. Effective non-pharmacological measures include the use of carbohydrate unit tables combined with SMBG for avoiding post-meal hyperglycemia and hyperinsulinemia. Additionally, SMBA provides a non-invasive marker of sustained fat mobilization and can help identify and prevent periods of insulin-induced fat accumulation.