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Cited by 1,967Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsPancreatic function and diabetes

Profound Peripheral Insulin Resistance, Independent of Obesity, in Polycystic Ovary Syndrome

Dunaif, Andrea, Segal, Karen R, Futterweit, Walter, Dobrjansky, Areta·1989·Diabetes
DOI 10.2337/diab.38.9.1165
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Abstract

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of the polycystic ovary syndrome (PCO). However, controversy exists as to whether insulin resistance results from PCO or the obesity that is frequently associated with it. Thus, we determined in vivo insulin action on peripheral glucose utilization (M) and hepatic glucose production (HGP) with the euglycemic glucose-clamp technique in obese (n = 19) and nonobese (n = 10) PCO women and age- and body-composition-matched normal ovulatory women (n = 11 obese and n = 8 nonobese women). None had fasting hyperglycemia. Two obese PCO women had diabetes mellitus, established with an oral glucose tolerance test; no other women had impairment of glucose tolerance. However, the obese PCO women had significantly increased fasting and 2-h glucose levels after an oral glucose load and increased basal HGP compared with their body-composition-matched control group. There were statistically significant interactions between obesity and PCO in fasting glucose levels and basal HGP (P < .05). Steady-state insulin levels of ∼100 μU/ml were achieved during the clamp. Insulin-stimulated glucose utilization was significantly decreased in both PCO groups whether expressed per kilogram total weight (P < .001) or per kilogram fat free mass (P < .001) or when divided by the steady-state plasma insulin (I) level (M/I, P < .001). There was residual HGP in 4 of 15 obese PCO, 0 of 11 obese normal, 2 of 10 nonobese PCO, and 0 of 8 nonobese normal women. The metabolic clearance rate of insulin did not differ in the four groups. We conclude that 1) PCO women have significant insulin resistance that is independent of obesity, changes in body composition, and impairment of glucose tolerance, 2) PCO and obesity have a synergistic deleterious effect on glucose tolerance, 3) hyperinsulinemia in PCO is not the result of decreased insulin clearance, and 4) PCO is associated with a unique disorder of insulin action.

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Authors
Dunaif, A., Segal, K. R., Futterweit, W., & Dobrjansky, A.
Affiliations
City University of New York (US)
ORCID
Dunaif, Andrea
Venue
Diabetes
Publisher
American Diabetes Association
Published
1989-09-01
Volume
38
Issue
9
Pages
1165-1174
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.38.9.1165
OpenAlex
W2106378688
Cited by
1,967
References
0
Citations by year
2026: 14 · 2025: 29 · 2024: 31 · 2023: 45 · 2022: 73 · 2021: 54 · 2020: 55 · 2019: 48 · 2018: 52 · 2017: 68 · 2016: 74 · 2015: 81 · 2014: 82 · 2013: 75 · 2012: 77
FWCI
11.98
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Center for Research Resources (RR‑00071)
  • NIH Clinical Center
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-00608)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
polycystic ovary syndrome, insulin resistance, hyperinsulinemia, obesity, hepatic glucose production, peripheral glucose utilization, glucose tolerance, insulin clearance, insulin action, fat-free mass
MeSH terms
Adolescent, Adult, Blood Glucose, Fasting, Female, Glucose Tolerance Test, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Obesity, Polycystic Ovary Syndrome, Gonadal Steroid Hormones, Glucose Clamp Technique

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