ArticleClinical science (London, England : 1979)2023
Aetiology of Type 2 diabetes in people with a 'normal' body mass index: testing the personal fat threshold hypothesis.
Article in Clinical science (London, England : 1979), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Cardiorenal Mortality and Safety Outcomes of GLP-1 Receptor Agonists in Type 2 Diabetes With BMI Below 27 kg/mDiabetes, obesity & metabolism · 2026Article
- Adipose Tissue Expandability as a Link Between Nutrition and Obesity-Related Metabolic Risk: Insights from Bariatric Surgery.Nutrients · 2026Review
- Defining Healthy Weight Loss and Target Weight in the Era of Highly Effective Treatment of Patients With Obesity.Journal of cachexia, sarcopenia and muscle · 2026Review
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- Impact of overweight and obesity on fasting insulin secretion in men and women without diabetes: effect sizes and mechanisms.Diabetologia · 2026Article
- Fuel toxicity-associated spectrum (FTAS): a unifying nomenclature for metabolic disorders.Cardiovascular diabetology. Endocrinology reports · 2026Review
- Undiagnosed Diabetes in Metabolically Unhealthy Normal Weight Adults: A Cross-Sectional Analysis of National Health and Nutrition Examination Survey Cycle 2017-2020 in the United States.Journal of clinical medicine · 2026Article
- The Global Obesity Epidemic: Epidemiology, Health Burden and Policy Priorities.European cardiology · 2026Review
- Deviation From Genetically Predicted BMI and All-Cause Mortality: A Cohort Study in the UK Biobank.Obesity (Silver Spring, Md.) · 2026Article
- Chestnut-derived ellagitannins (FT50) protect against western diet-induced metabolic dysfunction and preserve beta cell function in mice.Frontiers in endocrinology · 2026Article
- Mildly elevated liver lipid content is characterised by reduced insulin sensitivity.JHEP reports : innovation in hepatology · 2025Article
- The Pivotal Role of the Western Diet, Hyperinsulinemia, Ectopic Fat, and Diacylglycerol-Mediated Insulin Resistance in Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Type 2 diabetes mellitus: Isn't it time to update the terminology?World journal of diabetes · 2025Review
- The Twin Cycle Hypothesis of type 2 diabetes aetiology: From concept to national NHS programme.Experimental physiology · 2025Review
- Aetiology of type 2 diabetes: an experimental medicine odyssey.Diabetologia · 2025Review
- Glycaemic and Weight Control in People Aged 65 or Younger Newly Diagnosed with Type 2 Diabetes in Spain: Insights from the PRIORITY-T2D Study.Advances in therapy · 2025Observational
- Ultra-Processed Foods and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): What Is the Evidence So Far?Nutrients · 2025Review
- Review
- Exploring Therapeutic Targets for Preventing Cardiac Arrest by Modulating Dyslipidemia and 25-Hydroxyvitamin D Metabolism: A Mendelian Randomization Study.Human mutation · 2025Article
- Nutrition Interventions for Remission of Type 2 Diabetes: Potential Role for Diabetes-Specific Nutrition Formulas.Clinical diabetes : a publication of the American Diabetes Association · 2025Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
Abstract
Weight loss in overweight or obese individuals with Type 2 diabetes (T2D) can normalize hepatic fat metabolism, decrease fatty acid oversupply to β cells and restore normoglycaemia. One in six people has BMI <27 kg/m2 at diagnosis, and their T2D is assumed to have different aetiology. The Personal Fat Threshold hypothesis postulated differing individual thresholds for lipid overspill and adverse effects on β-cell function. To test this hypothesis, people with Type 2 diabetes and body mass index <27kg/m2 (n = 20) underwent repeated 5% weight loss cycles. Metabolic assessments were carried out at stable weight after each cycle and after 12 months. To determine how closely metabolic features returned to normal, 20 matched normoglycemic controls were studied once. Between baseline and 12 months: BMI fell (mean ± SD), 24.8 ± 0.4 to 22.5 ± 0.4 kg/m2 (P<0.0001) (controls: 21.5 ± 0.5); total body fat, 32.1 ± 1.5 to 27.6 ± 1.8% (P<0.0001) (24.6 ± 1.5). Liver fat content and fat export fell to normal as did fasting plasma insulin. Post-meal insulin secretion increased but remained subnormal. Sustained diabetes remission (HbA1c < 48 mmol/mol off all glucose-lowering agents) was achieved by 70% (14/20) by initial weight loss of 6.5 (5.5-10.2)%. Correction of concealed excess intra-hepatic fat reduced hepatic fat export, with recovery of β-cell function, glycaemic improvement in all and return to a non-diabetic metabolic state in the majority of this group with BMI <27 kg/m2 as previously demonstrated for overweight or obese groups. The data confirm the Personal Fat Threshold hypothesis: aetiology of Type 2 diabetes does not depend on BMI. This pathophysiological insight has major implications for management.
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Registered trials
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