Cited by 738Gestational Diabetes Research and ManagementPregnancy and preeclampsia studiesAdipokines, Inflammation, and Metabolic Diseases

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TNF-α Is a Predictor of Insulin Resistance in Human Pregnancy

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Kirwan, John P., Hauguel-De Mouzon, Sylvie, Lepercq, Jacques, Challier, Jean-Claude, Huston-Presley, Larraine, Friedman, Jacob E., Kalhan, Satish C., Catalano, Patrick M.·2002·Diabetes

DOI 10.2337/diabetes.51.7.2207

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Abstract

Historically, insulin resistance during pregnancy has been ascribed to increased production of placental hormones and cortisol. The purpose of this study was to test this hypothesis by correlating the longitudinal changes in insulin sensitivity during pregnancy with changes in placental hormones, cortisol, leptin, and tumor necrosis factor (TNF)-α. Insulin resistance was assessed in 15 women (5 with gestational diabetes mellitus [GDM] and 10 with normal glucose tolerance) using the euglycemic-hyperinsulinemic clamp procedure, before pregnancy (pregravid) and during early (12–14 weeks) and late (34–36 weeks) gestation. Body composition, plasma TNF-α, leptin, cortisol, and reproductive hormones (human chorionic gonadotropin, estradiol, progesterone, human placental lactogen, and prolactin) were measured in conjunction with the clamps. Placental TNF-α was measured in vitro using dually perfused human placental cotyledon from five additional subjects. Compared with pregravid, insulin resistance was evident during late pregnancy in all women (12.4 ± 1.2 vs. 8.1 ± 0.8 10−2 mg · kg−1 fat-free mass · min−1 · μU−1 · ml−1). TNF-α, leptin, cortisol, all reproductive hormones, and fat mass were increased in late pregnancy (P < 0.001). In vitro, most of the placental TNF-α (94%) was released into the maternal circulation; 6% was released to the fetal side. During late pregnancy, TNF-α was inversely correlated with insulin sensitivity (r = −0.69, P < 0.006). Furthermore, among all of the hormonal changes measured in this study, the change in TNF-α from pregravid to late pregnancy was the only significant predictor of the change in insulin sensitivity (r = −0.60, P < 0.02). The placental reproductive hormones and cortisol did not correlate with insulin sensitivity in late pregnancy. Multivariate stepwise regression analysis revealed that TNF-α was the most significant independent predictor of insulin sensitivity (r = −0.67, P < 0.0001), even after adjustment for fat mass by covariance (r = 0.46, P < 0.01). These observations challenge the view that the classical reproductive hormones are the primary mediators of change in insulin sensitivity during gestation and provide the basis for including TNF-α in a new paradigm to explain insulin resistance in pregnancy.

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Authors: Kirwan, J. P., Hauguel-De Mouzon, S., Lepercq, J., Challier, J.-C., Huston-Presley, L., Friedman, J. E., Kalhan, S. C., & Catalano, P. M.
Affiliations: MetroHealth (US)
Département d’Endocrinologie, Institut Cochin de Génétique Moléculaire, Paris, France
Institut Cochin (FR)
Hôpital Cochin (FR)
University of Colorado Health (US)
ORCID: Kirwan, John P.
Lepercq, Jacques
Friedman, Jacob E.
Kalhan, Satish C.
Catalano, Patrick M.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2002-07-01
Volume: 51
Issue: 7
Pages: 2207-2213
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.51.7.2207
OpenAlex: W2130148279
Cited by: 738
References: 46
Citations by year: 2026: 22 · 2025: 26 · 2024: 24 · 2023: 33 · 2022: 36 · 2021: 34 · 2020: 36 · 2019: 47 · 2018: 37 · 2017: 34 · 2016: 38 · 2015: 37 · 2014: 40 · 2013: 38 · 2012: 33
FWCI: 19.22
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (11089, HD-22965, HD-11089)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD11089, HD-22965)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: insulin resistance, pregnancy, TNF-α, gestational diabetes mellitus, insulin sensitivity, placental hormones, cortisol, leptin, human placental lactogen, human chorionic gonadotropin, hyperinsulinemic-euglycemic clamp, fat mass, reproductive hormones, body composition, estradiol
MeSH terms: Adult, Blood Glucose, Body Composition, Female, Gestational Age, Chorionic Gonadotropin, Humans, Hydrocortisone, Infusions, Intravenous, Insulin, Insulin Resistance, Placenta, Placental Lactogen, Predictive Value of Tests, Pregnancy, Prolactin, Reference Values, Regression Analysis, Tumor Necrosis Factor-alpha, Glucose Clamp Technique, Diabetes, Gestational, Glucose Intolerance, Leptin

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TNF-α Is a Predictor of Insulin Resistance in Human Pregnancy

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