Insulin Resistance · 14 cited studies
Research on Insulin Resistance
Insulin resistance is the central node of metabolic syndrome — the upstream lesion behind prediabetes, type-2 diabetes, fatty liver, PCOS, and a major component of cardiovascular risk. Petersen & Shulman's mechanism reviews (Physiological Reviews 2018, JCI 2016) trace it to ectopic lipid accumulation in liver and skeletal muscle disrupting insulin-receptor signalling via diacylglycerol-PKCε. The Newcastle/DiRECT trial line of work (Taylor, Lim, Lean) demonstrates the lesion is reversible: an 8-week very-low-calorie diet normalised fasting glucose and beta-cell function, and the 5-year DiRECT extension showed durable T2D remission when weight loss is maintained. Tools like HOMA-IR (Wallace 2004) provide screening; CGM data (Hall 2018) shows that even 'normoglycemic' adults frequently spike post-meal. Below: the mechanism and reversal literature.
- Strong evidence2018
Mechanisms of Insulin Action and Insulin Resistance
Petersen MC, Shulman GI · Physiological Reviews
Comprehensive review of intramyocellular and hepatic lipid as primary drivers of insulin resistance.
Insulin ResistanceSource ↗ - Strong evidence2011
Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol
Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R · Diabetologia
Newcastle study: very-low-calorie diet normalised fasting glucose and beta-cell function within 8 weeks.
Insulin ResistanceSource ↗ - Strong evidence2018
Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial
Lean MEJ et al. · The Lancet
DiRECT trial: 46% achieved T2D remission at 12 months via structured low-calorie weight-loss program.
Insulin ResistanceSource ↗ - Strong evidence2021
Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2)
Davies M et al. · The Lancet
STEP 2: 9.6% body-weight reduction with semaglutide 2.4 mg in T2D over 68 weeks vs 3.4% placebo.
- Strong evidence2016
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux
Samuel VT, Shulman GI · Journal of Clinical Investigation
Comprehensive mechanism review: ectopic lipid in liver and muscle drives insulin resistance via DAG-PKCε.
Insulin ResistanceSource ↗ - Strong evidence2004
Use and abuse of HOMA modeling
Wallace TM, Levy JC, Matthews DR · Diabetes Care
Practical guide to HOMA-IR/HOMA-β interpretation — the calculator screening foundation.
Insulin ResistanceSource ↗ - Moderate evidence2016
Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome
Lustig RH et al. · Obesity
Isocaloric fructose restriction in obese children improved fasting glucose, lipid panel, and DNL within 9 days.
Insulin ResistanceSource ↗ - Strong evidence2024
Beta-cell function and remission of type 2 diabetes (5-year DiRECT extension)
Taylor R et al. · The Lancet Diabetes & Endocrinology
5-year DiRECT extension: T2D remission durable when weight loss maintained; relapse predicts beta-cell decline.
Insulin ResistanceSource ↗ - Moderate evidence2018
Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss
Sutton EF et al. · Cell Metabolism
Early 6h eating window improved insulin sensitivity, BP, and oxidative stress in prediabetic men with no weight change.
- Strong evidence2012
Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption
Buxton OM et al. · Science Translational Medicine
3 weeks of sleep restriction + circadian disruption produced prediabetic-grade insulin resistance and lower metabolic rate.
- Moderate evidence2013
Resistance training for diabetes prevention and therapy: experimental findings and molecular mechanisms
Strasser B, Pesta D · BioMed Research International
Resistance training improves insulin sensitivity ~30% via increased muscle mass and GLUT4 translocation.
- Strong evidence2018
Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome
Teede HJ et al. · Human Reproduction
International evidence-based PCOS guideline: lifestyle (diet + exercise) is first-line; metformin and inositol have additional benefit.
- Moderate evidence2007
Metabolic endotoxemia initiates obesity and insulin resistance
Cani PD et al. · Diabetes
High-fat diet raised circulating LPS (endotoxemia), which drove insulin resistance and inflammation in mice.
- Moderate evidence2005
Role of stress in the pathogenesis of the metabolic syndrome
Rosmond R · Psychoneuroendocrinology
Reviews HPA-axis dysregulation as a unifying driver of insulin resistance, visceral adiposity, dyslipidaemia.
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