The Insulin Change, Not the Insulin Level: A Mass-Balance Resolution to the High-Carb vs. Keto Debate

The high-carbohydrate versus ketogenic diet debate has been conducted largely in terms of baseline insulin levels. Proponents of insulin-centric explanations argue that high baseline insulin predicts fat accumulation. Sceptics argue that baseline insulin does not predict fat loss once energy balance is controlled. Both positions have obscured the mechanistically relevant variable. The mass-balance analysis of visceral adipose tissue (VAT) clearance establishes that the effect of insulin on VAT lipolysis is proportional to the change in insulin concentration, not to its baseline level. Visceral adipocytes exhibit reduced insulin receptor autophosphorylation and impaired IRS-1-associated PI 3-kinase signalling, resulting in a blunted antilipolytic response to insulin compared with subcutaneous adipocytes. The antilipolytic effect is non-linear (more precisely, sigmoidal): the dose-response curve is shifted to the right in large, insulin-resistant adipocytes, meaning that a moderate reduction in insulin may produce little additional lipolysis, while a large reduction crosses the threshold and releases the brake substantially. This explains why a moderate carbohydrate restriction may not produce the VAT reduction seen with ketogenic or fasting interventions. Sex differences further modulate the response: men have more VAT and are more insulin resistant at a given BMI, while women have more subcutaneous fat but VAT is more strongly associated with insulin resistance when present. The debate should be reframed: the question is not whether insulin matters, but how much insulin needs to fall. The evidence says it does, and the relationship is non-linear. The threshold is individual-specific and depends on adipocyte size, insulin sensitivity, and body composition.