Chronic Use of Sweeteners and Insulin Resistance

The aim of this paper is to critically analyze the available data on the chronic use of low-calorie sweeteners (LCS) and their potential impact on the development of insulin resistance (IR). Insulin resistance, a key element of metabolic syndrome and a risk factor for type 2 diabetes, is increasing in parallel with the rising consumption of sweeteners used as sugar substitutes. The review covers the classification of LCS (synthetic, natural, sugar alcohols), their metabolism, and biological mechanisms that may modulate carbohydrate metabolism. Potential pathways of action include activation of sweet taste receptors T1R2/T1R3 in the intestine and pancreas, effects on incretin secretion, modulation of gut microbiota, regulation of appetite in the central nervous system, and interactions with insulin signaling pathways in peripheral tissues. Clinical studies indicate that short-term LCS intake usually does not affect glycemia and insulinemia in healthy individuals. However, in people with obesity or without prior exposure, an increased glycemic and insulin response has been observed, particularly after sucralose. Stevia has shown hypoglycemic benefits in some studies, while aspartame remains largely neutral. Data on saccharin and microbiota suggest possible individual sensitivity. Observational studies associate chronic LCS intake with a higher risk of type 2 diabetes, although this may result from reverse causality. The conclusions emphasize that LCS may support sugar and body weight reduction when used as part of a healthy lifestyle. However, they do not provide universal protection against IR, and their effects depend on the type of sweetener, metabolic status, and gut microbiota. Long-term randomized studies including diverse populations are required.