High-glycemic dietary patterns, hyperinsulinemia and insulin resistance in cancer risk: Causal appraisal using Bradford hill criteria: A Review

High-glycemic index (GI) and glycemic load (GL) dietary patterns are characterized by rapid glucose absorption and pronounced postprandial insulin excursions. Repeated exposure to such metabolic surges may induce chronic compensatory hyperinsulinemia and, over time, contribute to the development of insulin resistance distinct but biologically interconnected states implicated in carcinogenesis through activation of insulin/IGF-1 signaling, hormonal modulation, inflammation, and altered cellular metabolism. Although epidemiological studies have reported associations between high-GI/GL diets and several cancers, the extent to which dysregulation of insulin pathways mediates these relationships remains uncertain. This structured narrative review synthesized evidence from prospective cohort studies, case-control studies, randomized controlled feeding trials, and biomarker-based investigations published between 2000 and 2025. Eligible studies examined associations between GI/GL and cancer outcomes; GI/GL and insulin-related biomarkers (fasting insulin, C-peptide, HOMA-IR); and hyperinsulinemia or insulin resistance in relation to cancer incidence or prognosis. Evidence was evaluated along the hypothesized pathway from high-GI/GL exposure to hyperinsulinemia, progression to insulin resistance, and subsequent cancer development, with attention to temporality, dose-response relationships, attenuation analyses, and biological plausibility. High-GI/GL diets demonstrate modest positive associations with breast, colorectal, endometrial, ovarian, and liver cancers, particularly among individuals with obesity or metabolic dysfunction, whereas findings for pancreatic, prostate, and lung cancers are inconsistent or null. Controlled feeding trials consistently show that high-GI diets increase postprandial insulin responses and may impair insulin sensitivity over time. Prospective biomarker studies generally report stronger associations between chronic hyperinsulinemia or elevated HOMA-IR and cancer risk than those observed for GI/GL alone. In several cohorts, adjustment for insulin-related biomarkers attenuated diet-cancer associations by approximately 20-40%, supporting partial but incomplete mediation. Overall, the converging epidemiological, experimental, and mechanistic evidence is consistent with a partially mediated pathway linking high-glycemic diets to selected cancers through insulin pathway dysregulation; however, effect sizes are modest, formal longitudinal mediation analyses remain limited, and residual confounding cannot be excluded. Further studies incorporating repeated metabolic assessments and modern causal mediation approaches are needed to clarify the proportion of diet-related cancer risk attributable specifically to hyperinsulinemia and insulin resistance.