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Cited by 369Gestational Diabetes Research and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsPancreatic function and diabetes

The DOI matches its Crossref record.

Insulin Action During Pregnancy: Studies with the Euglycemic Clamp Technique

Ryan, Edmond A, O'Sullivan, Mary Jo, Skyler, Jay S·1985·Diabetes
DOI 10.2337/diab.34.4.380
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Abstract

To assess the mechanisms responsible for the insulin resistance associated with both normal human pregnancy and gestational-onset diabetes, we have measured exogenous glucose disposal using sequential insulin infusions with the euglycemic glucose clamp technique and erythrocyte insulin binding. Three groups of women were studied: nonpregnant women with normal glucose tolerance (N = 7, mean age 32.9 ± 2.1 yr), pregnant women with normal glucose tolerance (N = 5, mean age 24.8 ± 3.5 yr), and pregnant women with gestational-onset diabetes (N = 5, mean age 34.6 ± 2.6 yr). Despite normal plasma glucose levels obtained during a 100-g oral glucose tolerance test, plasma insulin levels were significantly elevated in the pregnant women compared with the nonpregnant control subjects, suggesting a state of insulin resistance. Insulin binding to erythrocytes was similar in all three groups (maximum specific binding being 5.0 ± 0.6%, 5.5 ± 1.1%, and 6.0 ± 0.7% in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively). In vivo peripheral insulin action was measured using the euglycemic glucose clamp technique during an insulin infusion of 40 mil/ m2 · min, with blood glucose clamped at a concentration of 75 mg/dl using a variable glucose infusion. Glucose infusion rates were 213 ± 11 mg/m2 min, 143 ± 23 mg/m2 · min, and 57 ± 18 mg/m2 · min in nonpregnant, nondiabetic pregnant, and gestationalonset diabetic women, respectively. This demonstrates that pregnant subjects display a state of insulin resistance, and that this appears to be more marked in gestational-onset diabetic subjects. To further define the possible mechanism of insulin resistance during pregnancy, the insulin infusion rate was increased to 240 mU/m2 · min and further euglycemic clamp measurements performed. Glucose infusion rates were 372 ± 11 mg/m2 · min, 270 ± 31 mg/m2 · min, and 157 ± 26 mg/m2 · min, in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively. This demonstrates a shift to the right of the dose-response curve of insulin action and suggests that the insulin resistance of pregnancy may include a decrease in presumed “maximum” insulin responsivity. In four subjects, studies were repeated in the postpartum period, and these demonstrated that the insulin resistance of pregnancy is ameliorated shortly after delivery. These studies suggest that the insulin resistance of pregnancy results from a target cell defect in insulin action beyond the initial step of insulin binding to cellular receptors, a postreceptor (or postbinding) defect in insulin action.

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Metadata

Authors
Ryan, E. A., O'Sullivan, M. J., & Skyler, J. S.
Affiliations
  • University of Miami (US)
  • Departments of Medicine, Pediatrics, and of Obstetrics and Gynecology, University of Miami, School of Medicine Miami, Florida
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1985-04-01
Volume
34
Issue
4
Pages
380-389
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.34.4.380
OpenAlex
W2169708340
Cited by
369
References
0
Citations by year
2026: 5 · 2025: 10 · 2024: 4 · 2023: 15 · 2022: 9 · 2021: 16 · 2020: 15 · 2019: 12 · 2018: 12 · 2017: 7 · 2016: 13 · 2015: 14 · 2014: 8 · 2013: 9 · 2012: 10
FWCI
6.83
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Center for Research Resources (RRO 7022-14)
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 › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Keywords
insulin resistance, pregnancy, gestational diabetes mellitus, glucose disposal, insulin action, hyperinsulinemic-euglycemic clamp, hyperinsulinemia, glucose tolerance, insulin infusion rate, peripheral glucose uptake, insulin receptor substrate 2, IRS-1, insulin receptor tyrosine kinase
MeSH terms
Adult, Blood Glucose, Erythrocytes, Estradiol, Female, Food, Glucose Tolerance Test, Humans, Infusions, Parenteral, Insulin, Insulin Resistance, Placental Lactogen, Pregnancy, Pregnancy in Diabetics, Progesterone, Receptor, Insulin

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