Targeting Insulin Resistance Through Nutrition: Pathophysiological Insights and Dietary Interventions

Background: Insulin resistance (IR) is a hallmark of metabolic disorders including type 2 diabetes mellitus (T2DM), metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, polycystic ovary syndrome (PCOS), and cardiovascular diseases. It arises from impaired insulin signaling in muscle, liver, and adipose tissue, driven by ectopic lipid accumulation, chronic inflammation, oxidative stress, and gut microbiota dysbiosis. Methods: This narrative review synthesizes IR mechanisms and the evidence on specific dietary patterns. A structured search of PubMed/MEDLINE and Embase (up to January 2026) prioritized RCTs, systematic reviews, meta-analyses, and clinical guidelines. Results: IR assessment relies on the hyperinsulinemic–euglycemic clamp as gold standard, with HOMA-IR and QUICKI as validated clinical surrogates. The Mediterranean diet is the most evidence-supported strategy, with consistent HOMA-IR reductions, a 31% decrease in T2DM incidence (PREDIMED-Plus), and demonstrated efficacy across T2DM, MASLD, and PCOS. Low-GI and DASH diets improve postprandial insulin dynamics and are particularly effective in PCOS. Low-carbohydrate and ketogenic diets produce the largest short-term reductions in fasting glucose and insulin secretion, though long-term sustainability requires further study. Plant-based diets and intermittent fasting improve IR primarily via weight loss and gut microbiota modulation. Most studies rely on surrogate IR indices and are short-term (≤26 weeks). Conclusions: Dietary pattern selection should be individualized according to metabolic phenotype, comorbidities, and adherence potential. Larger, longer, head-to-head trials measuring hard clinical outcomes are needed.