Does the Carbohydrate-Insulin Model Explain Obesity? Evidence from Mechanistic and Clinical Studies: A Critical...

The Carbohydrate-Insulin Model (CIM) of obesity proposes that dietary carbohydrates particularly high-glycemic carbohydrates, drive weight gain by stimulating insulin secretion, thereby promoting fat storage, increasing hunger, and reducing energy expenditure (EE). According to this framework, hyperinsulinemia is viewed as the primary causal factor in obesity, with positive energy balance emerging as a downstream consequence of altered fuel partitioning. In contrast, the Energy Balance Model (EBM) conceptualizes obesity as the result of sustained excess energy intake (EI) relative to expenditure, with insulin dysregulation arising secondary to increased adiposity.

This review critically evaluates the CIM across eleven complementary lines of evidence, including isocaloric and ad libitum dietary interventions, EE studies, population-level dietary trends, glycemic index (GI) manipulations, Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies, overfeeding experiments, the insulinotropic effects of protein, central effects of insulin on appetite, insulin spikes and 24-hour fat balance, temporal relationships between hyperinsulinemia and obesity, and de novo lipogenesis (DNL). Although some findings remain compatible with contemporary formulations of the CIM, several lines of evidence are difficult to reconcile with some of its central predictions (i.e. the insulinotropic yet anti-obesogenic effects of dietary protein, the central anorexigenic role of insulin). However, many studies aimed at directly testing its predictions are limited in their ability to definitively distinguish between competing models owing to design constraints, intervention-related confounding, or limitations in the available data. Any single line of evidence reviewed in this article may be insufficient, in isolation, to draw definitive conclusions regarding the validity of the CIM. However, when considered collectively, the available mechanistic, clinical, and epidemiological evidence suggests that the CIM may not provide a fully comprehensive explanation for the etiology of common obesity. While insulin dynamics and carbohydrate quality are undoubtedly relevant to metabolic health and body-weight regulation, the available evidence does not consistently support their role as the primary drivers of obesity proposed by contemporary formulations of the CIM.