ReviewDiabetes2015
Insulin resistance as a physiological defense against metabolic stress: implications for the management of subsets of type 2 diabetes.
Review in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 219 citations in OpenAlex.
- Trial
- Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes: a randomised cross-over trial.Cardiovascular diabetology · 2016Trial
- Epicatechin and High-Molecular Weight Fraction Do Not Recapitulate the Antiobesity and Antidiabetes Activities of Whole Cocoa Extract.Journal of agricultural and food chemistry · 2026Article
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Lipid droplet-associated proteins: Roles in cardiovascular diseases.Journal of lipid research · 2026Review
- Why hyperinsulinemia is detrimental to weight loss: insights from type 1 diabetes.BMC medicine · 2026Review
- Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood-brain barrier responses to an inflammatory stimulus.Brain, behavior, and immunity · 2026Article
- Hypothesis: Nutrient Off-Loading and Ectopic Fat Reduction Reverse Insulin Resistance and Improve Cardiovascular Outcomes in Type 2 Diabetes-A Narrative Review.International journal of molecular sciences · 2026Review
- Observational studies on the association of outpatient antidiabetic medication use and COVID-19 outcomes: are the findings more relevant to diabetes management than to COVID-19 pathology? A mini-review.Frontiers in clinical diabetes and healthcare · 2026Review
- Close multilevel links between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus.Metabolism open · 2025Review
- 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
- Trends in Hyperinsulinemia and Insulin Resistance Among Nondiabetic US Adults, NHANES, 1999-2018.Journal of clinical medicine · 2025Article
- Associations of the triglyceride-glucose index and triglyceride-glucose/body mass index with all-cause mortality in Chinese centenarians.BMC geriatrics · 2025Article
- Impact of TCF7L2 rs7903146 on clinical presentation and risk of complications in patients with type 2 diabetes.Diabetes, obesity & metabolism · 2025Article
- Exploring the TyG Index and the Homeostasis Model Assessment of Insulin Resistance as Insulin Resistance Markers: Implications for Fibromyalgia Management and Understanding-A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Unraveling the RKIP-YY1 axis: immune crosstalk in the pathogenesis of metabolic disorders.Frontiers in immunology · 2025Review
- Recent advances ofFrontiers in pharmacology · 2025Review
- Comprehensive treatment of diabetic endothelial dysfunction based on pathophysiological mechanism.Frontiers in medicine · 2025Review
- Article
- The Causal Role of Ectopic Fat Deposition in the Pathogenesis of Metabolic Syndrome.International journal of molecular sciences · 2024Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 4 countries.
Funding
Abstract
Stratifying the management of type 2 diabetes (T2D) has to take into account marked variability in patient phenotype due to heterogeneity in its pathophysiology, different stages of the disease process, and multiple other patient factors including comorbidities. The focus here is on the very challenging subgroup of patients with T2D who are overweight or obese with insulin resistance (IR) and the most refractory hyperglycemia due to an inability to change lifestyle to reverse positive energy balance. For this subgroup of patients with T2D, we question the dogma that IR is primarily harmful to the body and should be counteracted at any cost. Instead we propose that IR, particularly in this high-risk subgroup, is a defense mechanism that protects critical tissues of the cardiovascular system from nutrient-induced injury. Overriding IR in an effort to lower plasma glucose levels, particularly with intensive insulin therapy, could therefore be harmful. Treatments that nutrient off-load to lower glucose are more likely to be beneficial. The concepts of "IR as an adaptive defense mechanism" and "insulin-induced metabolic stress" may provide explanation for some of the unexpected outcomes of recent major clinical trials in T2D. Potential molecular mechanisms underlying these concepts; their clinical implications for stratification of T2D management, particularly in overweight and obese patients with difficult glycemic control; and future research requirements are discussed.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.