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Insulin Resistance

Pharmacology · NLM MeSH · updated 2026-10-29 · version 1

Citations verified against PubMedNot yet clinician-reviewed9 referencesApproximately 4 min read

Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis.

Table of Contents

1. Definition2. Research landscape3. Reading the evidence4. Open-access studies5. Key reviews6. References7. About this article

Definition and research guide

This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.

Content available: 3 complete abstracts (749 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.

Definition

Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis.

Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.

Also known as: Resistance, Insulin; Insulin Sensitivity; Sensitivity, Insulin.

Where it fits in the MeSH classification

Broader topics
Hyperinsulinism; Drug Resistance
Narrower topics
Metabolic Syndrome

Related concepts

  • Insulin
  • Hyperglycemia
  • Ketosis

Research landscape

PubMed indexes 114,071 records tagged with the MeSH heading “Insulin Resistance” (counts retrieved 2026-10-29). 30,971 of them (27.2%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 49,520 records.

Reviews account for 23,247 records (20.4%) and meta-analyses for 1,816. Randomized controlled trials number 6,235 (5.5%) as a share of all records on the topic.

PubMed records by publication periodthrough 1999: 6,739 records; 2000-2009: 26,841 records; 2010-2019: 49,520 records; 2020 onward: 30,971 records6,739through 199926,8412000-200949,5202010-201930,9712020 onward
Records in PubMed indexed with this heading, by publication period. Real counts from NCBI E-utilities; the final period covers only part of the current year. Volume reflects how much has been published, not how strong the evidence is.
Show the data
PeriodRecords
through 19996,739
2000-200926,841
2010-201949,520
2020 onward30,971
Share of records by publication typeReviews: 20.4 percent; Meta-analyses: 1.6 percent; Randomized controlled trials: 5.5 percentReviews20.4% (23,247)Meta-analyses1.6% (1,816)Randomized controlled trials5.5% (6,235)
Share of all PubMed records on this heading that carry each publication type. Types overlap with other records, so the shares do not sum to 100%.
Publication-type chart data
Publication types among 114,071 PubMed records
TypeRecordsShare
Reviews23,24720.4%
Meta-analyses1,8161.6%
Randomized controlled trials6,2355.5%

Method: PubMed query "Insulin Resistance"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.

Reading the evidence in pharmacology

Drug evidence builds in layers: laboratory pharmacology describes how a compound acts, pharmacokinetic studies describe how the body handles it, and randomized trials test whether it helps and what harms it causes. Post-marketing surveillance and observational studies reveal rarer adverse effects but cannot prove causation. This page is educational and is not a recommendation to start, stop or change any medicine; decisions about treatment belong with a qualified clinician.

Evidence from open-access studies

These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.

Study comparison — selected abstracts, not a systematic review
Study / authorsYearSource label / designEurope PMC citationsLicence / source
From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS
Khatun M, Lundin K, Tuuri T, Piltonen T, Tapanainen JS, Salumets A
2026Review article
Design not recorded in structured metadata
2cc by
PMID 42412303 · DOI · PMC13550076
Serum Copper-to-Zinc Ratio and Oxidative Stress Are Associated with Anemia in Older Adults with Cardiovascular-Kidney-Metabolic Syndrome
Bruschetta G, Gembillo G, Lo Cicero L, D'Ascola A, Bruno F, Corsonello A, et al.
2026Research article
Design not recorded in structured metadata
2cc by
PMID 42450113 · DOI · PMC13361404
Beyond MVPA minutes: physical activity phenotypes are associated with metabolic profiles in children with obesity
Gatti A, Vandoni M, Cavallo C, Carnevale Pellino Carnevale Pellino V, Rossi V, Odone A, et al.
2026Research article
Design not recorded in structured metadata
1cc by
PMID 42560380 · DOI · PMC13447327

From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS [1]

Review article Khatun M, Lundin K, Tuuri T, Piltonen T, Tapanainen JS, Salumets A · · 2026 · cited 2 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine-metabolic disorder affecting up to 18% of women worldwide and remains the leading cause of anovulatory infertility.
Closing excerpt
Integrating CRISPR‑based functional genomics with stem cell research may shift PMOS management from symptom‑focused care to targeted, mechanism‑driven interventions that could modify the course of PMOS (Graphical Abstract).
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (191 words)

Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine-metabolic disorder affecting up to 18% of women worldwide and remains the leading cause of anovulatory infertility. Despite extensive research, current treatments primarily target symptoms, including menstrual irregularities, hyperandrogenism, and metabolic dysfunction, without addressing the underlying molecular and tissue-level disturbances. Advances in multi‑omic profiling have identified disruptions across neuroendocrine, metabolic, inflammatory, and extracellular matrix pathways, alongside genetic susceptibility at loci such as DENND1A, CYP17A1, LHCGR, FSHR, IRS1, and PPARG. However, the functional roles of many variants remain unresolved. CRISPR/Cas9 gene editing enables precise interrogation of these pathways, while stem cell-based platforms, including mesenchymal stem cells (MSCs), exosomes, and gene-edited induced pluripotent stem cells (iPSCs), may serve as complementary platforms for regeneration and disease modeling. Preclinical studies demonstrate that MSCs and their derivatives modulate inflammation, restore ovarian structure, and improve metabolic parameters, while iPSC-based models enable patient-specific investigation of steroidogenic and metabolic abnormalities. Translational challenges remain, including targeted delivery, off-target effects, phenotypic heterogeneity, and regulatory considerations. Integrating CRISPR‑based functional genomics with stem cell research may shift PMOS management from symptom‑focused care to targeted, mechanism‑driven interventions that could modify the course of PMOS (Graphical Abstract).

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42412303 · DOI · PMC13550076

Serum Copper-to-Zinc Ratio and Oxidative Stress Are Associated with Anemia in Older Adults with Cardiovascular-Kidney-Metabolic Syndrome [2]

Research article Bruschetta G, Gembillo G, Lo Cicero L, D'Ascola A, Bruno F, Corsonello A, et al. · · 2026 · cited 2 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Chronic oxidative stress is a molecular hallmark of cardiovascular-kidney-metabolic (CKM) syndrome, yet its contribution to CKM-associated anemia beyond erythropoietin deficiency and iron restriction is poorly characterized.
Closing excerpt
Together with selenium, cadmium, RDW, and uric acid, it defines an oxidative stress-driven hematological pathway that may contribute to the development and progression of anemia in patients with CKM syndrome.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (343 words)

Chronic oxidative stress is a molecular hallmark of cardiovascular-kidney-metabolic (CKM) syndrome, yet its contribution to CKM-associated anemia beyond erythropoietin deficiency and iron restriction is poorly characterized. The serum copper-to-zinc (Cu/Zn) ratio reflects impaired Cu/Zn-SOD1 antioxidant capacity and inflammatory trace-element imbalance, but its relationships with circulating redox biomarkers and its hematological relevance in CKM syndrome has never been explored in a community-dwelling cohort of older adults. We analyzed 2391 NHANES 2011-2016 participants ≥ 50 years of age with CKM stage I-IV. To explore whether the serum Cu/Zn ratio was associated with oxidative stress and immunomodulatory biomarkers as well as with the odds of anemia, we used survey-weighted Spearman correlations, linear regression (outcome: hemoglobin), and logistic regression (outcome: anemia); multivariate models were adjusted for a panel of antioxidant or immunomodulatory biomarkers (selenium, vitamin D), pro-oxidant biomarkers (lead, cadmium, cotinine, uric acid), red cell distribution width (RDW) as a composite biomarker of erythrocyte stress, neutrophil-to-lymphocyte ratio (NLR), CKM stage, and comorbidities. The molecular targets of the nine biomarkers were mapped onto a protein-protein interaction network using the STRING database v12.0 to contextualize regression findings within a systems biology framework. Anemia was present in 205 participants (8.6%). The Cu/Zn ratio was inversely correlated with the antioxidant marker selenium (r = -0.19; p p p < 0.001), consistent with its role as a hub within the CKM redox network. In fully adjusted models, a higher Cu/Zn ratio was independently associated with prevalent anemia (OR = 2.94; 95% CI: 1.61-5.37) and lower hemoglobin (β = -0.55 g/dL); among included biomarkers, selenium and cadmium were independently protective (OR = 0.76 per 10 µg/L and 0.23 per µg/dL, respectively), and RDW and uric acid were independently harmful (OR = 2.20 per 1% and 1.33 per mg/dL, respectively). The Cu/Zn ratio correlated with both antioxidant depletion and pro-oxidant accumulation in CKM syndrome and was independently associated with anemia within this oxidative network. Together with selenium, cadmium, RDW, and uric acid, it defines an oxidative stress-driven hematological pathway that may contribute to the development and progression of anemia in patients with CKM syndrome.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42450113 · DOI · PMC13361404

Beyond MVPA minutes: physical activity phenotypes are associated with metabolic profiles in children with obesity [3]

Research article Gatti A, Vandoni M, Cavallo C, Carnevale Pellino Carnevale Pellino V, Rossi V, Odone A, et al. · · 2026 · cited 1 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Pediatric obesity is associated with early cardiometabolic risk, yet MVPA alone may not capture meaningful variation in movement behavior.
Closing excerpt
Conclusion: Multidimensional PA phenotypes derived from accelerometry identify clinically meaningful differences in body composition and metabolic risk beyond MVPA duration, supporting phenotype-based approaches for pediatric obesity risk stratification and intervention design.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (215 words)

Pediatric obesity is associated with early cardiometabolic risk, yet MVPA alone may not capture meaningful variation in movement behavior. We applied DDRTree to accelerometry data to identify multidimensional physical activity phenotypes in children and adolescents with obesity and assessed their associations with body composition and cardiometabolic. This cross-sectional study included 91 children and adolescents with obesity (43% girls), aged 6-17 years, who wore a thigh-mounted accelerometer for 7 days. Multidimensional accelerometry features were extracted and PA phenotypes identified using DDRTree, an unsupervised reversed graph-embedding method that maps high-dimensional data onto a low-dimensional branching manifold. DDRTree identified 3-PA phenotypes. Anthropometry, metabolic outcomes, and a continuous metabolic syndrome risk score were compared across phenotypes using ANCOVA adjusted for age and sex. DDRTree identified three PA phenotypes: Sedentary (24%), Light Activity (55%), and Higher Activity (21%); only three participants met MVPA recommendations. Compared with the Sedentary Pattern, the Higher Activity Pattern accumulated 122 min/day less sedentary time and 16.5 min/day more MVPA (p < 0.001) and showed lower fat mass percentage, higher fat-free mass percentage, higher insulin sensitivity (SPISE), and a lower metabolic risk score (p ≤ 0.05).Conclusion: Multidimensional PA phenotypes derived from accelerometry identify clinically meaningful differences in body composition and metabolic risk beyond MVPA duration, supporting phenotype-based approaches for pediatric obesity risk stratification and intervention design.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42560380 · DOI · PMC13447327

Key reviews and meta-analyses

The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.

  • Research article Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis [4]
    En Li Cho E, Ang CZ, Quek J, Fu CE, Lim LKE, Heng ZEQ, et al. · Gut · 2023 · cited 258 times (Europe PMC)
  • Research article Triglyceride-glucose index and heart failure: a systematic review and meta-analysis [5]
    Khalaji A, Behnoush AH, Khanmohammadi S, Ghanbari Mardasi K, Sharifkashani S, Sahebkar A, et al. · Cardiovasc Diabetol · 2023 · cited 147 times (Europe PMC)
  • Research article Systematic Review and Meta-Analysis of the Impact of Bariatric Surgery on Future Cancer Risk [6]
    Wilson RB, Lathigara D, Kaushal D · Int J Mol Sci · 2023 · cited 107 times (Europe PMC)
  • Research article Short-chain fatty acids and insulin sensitivity: a systematic review and meta-analysis [7]
    Pham NHT, Joglekar MV, Wong WKM, Nassif NT, Simpson AM, Hardikar AA · Nutr Rev · 2024 · cited 97 times (Europe PMC)
  • Research article Association between triglyceride glucose index and risk of cerebrovascular disease: systematic review and meta-analysis [8]
    Yan F, Yan S, Wang J, Cui Y, Chen F, Fang F, et al. · Cardiovasc Diabetol · 2022 · cited 87 times (Europe PMC)
  • Research article Association of Insulin Resistance With Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: Systematic Review and Meta-analysis [9]
    Sun R, Wang J, Li M, Li J, Pan Y, Liu B, et al. · Diabetes Care · 2024 · cited 74 times (Europe PMC)

References

  1. Khatun M, Lundin K, Tuuri T, Piltonen T, Tapanainen JS, Salumets A. From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS. . 2026. PMID 42412303 · DOI · PMC13550076
  2. Bruschetta G, Gembillo G, Lo Cicero L, D'Ascola A, Bruno F, Corsonello A, et al.. Serum Copper-to-Zinc Ratio and Oxidative Stress Are Associated with Anemia in Older Adults with Cardiovascular-Kidney-Metabolic Syndrome. . 2026. PMID 42450113 · DOI · PMC13361404
  3. Gatti A, Vandoni M, Cavallo C, Carnevale Pellino Carnevale Pellino V, Rossi V, Odone A, et al.. Beyond MVPA minutes: physical activity phenotypes are associated with metabolic profiles in children with obesity. . 2026. PMID 42560380 · DOI · PMC13447327
  4. En Li Cho E, Ang CZ, Quek J, Fu CE, Lim LKE, Heng ZEQ, et al.. Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis. Gut. 2023. PMID 37491159 · DOI
  5. Khalaji A, Behnoush AH, Khanmohammadi S, Ghanbari Mardasi K, Sharifkashani S, Sahebkar A, et al.. Triglyceride-glucose index and heart failure: a systematic review and meta-analysis. Cardiovasc Diabetol. 2023. PMID 37679763 · DOI · PMC10486123
  6. Wilson RB, Lathigara D, Kaushal D. Systematic Review and Meta-Analysis of the Impact of Bariatric Surgery on Future Cancer Risk. Int J Mol Sci. 2023. PMID 37047163 · DOI · PMC10094585
  7. Pham NHT, Joglekar MV, Wong WKM, Nassif NT, Simpson AM, Hardikar AA. Short-chain fatty acids and insulin sensitivity: a systematic review and meta-analysis. Nutr Rev. 2024. PMID 37290429 · DOI · PMC10777678
  8. Yan F, Yan S, Wang J, Cui Y, Chen F, Fang F, et al.. Association between triglyceride glucose index and risk of cerebrovascular disease: systematic review and meta-analysis. Cardiovasc Diabetol. 2022. PMID 36324146 · DOI · PMC9632026
  9. Sun R, Wang J, Li M, Li J, Pan Y, Liu B, et al.. Association of Insulin Resistance With Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: Systematic Review and Meta-analysis. Diabetes Care. 2024. PMID 39018337 · DOI

About this article

Sources
NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
Verification
Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
Review state
automated source verified; no human expert review has been recorded yet.
Version
1, last updated 2026-10-29.

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Related research topics

  • Drug ResistancePharmacology
  • Drug TolerancePharmacology
  • Type 1 Diabetes MellitusImmunology
  • Down-RegulationPharmacology
  • Drug InteractionsPharmacology
  • HormesisPharmacology

All 99 articles in Pharmacology →

At a glance

114,071
PubMed records on this heading
27%
published since 2020
23,247
review articles
6,235
randomized trials
9
verified references below

Counts come from PubMed on 2026-10-29; they show how much has been written, not how strong the evidence is.

Related topics See all →

  • Drug ResistancePharmacology
  • Drug TolerancePharmacology
  • Type 1 Diabetes MellitusImmunology
  • Down-RegulationPharmacology
  • Drug InteractionsPharmacology

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