Cited by 98Gestational Diabetes Research and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

Increased Skeletal Muscle Tumor Necrosis Factor-α and Impaired Insulin Signaling Persist in Obese Women With Gestational Diabetes Mellitus 1 Year Postpartum

Open access
Friedman, Jacob E., Kirwan, John P., Jing, Ming, Presley, Larraine, Catalano, Patrick M.·2008·Diabetes

Abstract

OBJECTIVE: Women with gestational diabetes mellitus (GDM) demonstrate chronic and progressive insulin resistance and a markedly increased risk of converting to type 2 diabetes after pregnancy. However, the cellular mechanisms underlying this insulin resistance are unknown. RESEARCH DESIGN AND METHODS: We investigated the progression of insulin resistance in nine obese women with GDM during late pregnancy (30-36 weeks) and 1 year postpartum. Skeletal muscle biopsies were obtained at each visit, and insulin resistance was determined by the hyperinsulinemic-euglycemic clamp technique. RESULTS: Insulin resistance was not significantly improved in GDM women (4.1 +/- 0.4 vs. 5.8 +/- 1.1 10(-2) mg x kg FFM x min(-1)/microU x ml(-1)). Subjects did not experience significant weight loss postpartum. Body weight, fat mass, fasting glucose, and plasma tumor necrosis factor (TNF)-alpha remained higher 1 year postpartum than seen in previously studied normal glucose-tolerant women. Skeletal muscle TNF-alpha mRNA was elevated five- to sixfold in GDM women and remained higher 1 year postpartum. While levels of insulin receptor (IR), IR substrate (IRS)-1, and p85 alpha improved postpartum, insulin-stimulated IR tyrosine phosphorylation and receptor tyrosine kinase activity did not significantly improve postpartum in GDM. The levels of (312)Ser-IRS-1 also did not improve postpartum and correlated with TNF-alpha mRNA (r(2) = 0.19, P < 0.03), consistent with a state of subclinical inflammation and chronic skeletal muscle insulin resistance. CONCLUSIONS: These results suggest the mechanisms underlying chronic insulin resistance in GDM women may be driven by increased inflammation that impinges on the IR and IRS-1 signaling cascade in skeletal muscle. These findings have important implications for the health of GDM women during subsequent pregnancies and their risk for progression to type 2 diabetes.

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Registry

Crossref · 10.2337/db07-1356

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68 of 68 references verified0 citation errors · 0 not checkable

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  • Many molecular changes in insulin signaling in GDM persist beyond pregnancy.

    “Many of these molecular changes persist beyond pregnancy [86].”

    From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [86]

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Authors
Friedman, J. E., Kirwan, J. P., Jing, M., Presley, L., & Catalano, P. M.
Affiliations
  • University of Colorado Denver (US)
  • Cleveland Clinic (US)
  • Case Western Reserve University (US)
  • MetroHealth Medical Center (US)
Venue
Diabetes
Published
2008-03-01
Volume
57
Issue
3
Pages
606-613
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2103887497
Cited by
98
References
68
Citations by year
2026: 6 · 2025: 6 · 2024: 1 · 2023: 8 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 9
FWCI
5.48
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (KL2TR000440)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK048520, DK-62115)
  • National Center for Research Resources (M01RR000080, RR 00080)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD11089, R01HD022965)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
gestational diabetes mellitus, insulin resistance, TNF-α, skeletal muscle, postpartum period, obesity, type 2 diabetes risk, insulin receptor tyrosine phosphorylation, IRS-1 serine phosphorylation, insulin receptor substrate, subclinical inflammation, hyperinsulinemic-euglycemic clamp
MeSH terms
Adult, Female, Humans, Inflammation, Insulin, Insulin Resistance, Obesity, Pregnancy, Risk Factors, Time Factors, Tumor Necrosis Factor-alpha, Signal Transduction, Diabetes, Gestational, Muscle, Skeletal, Postpartum Period

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