Insulin Resistance, Hyperinsulinemia, and Mitochondria Dysfunction in Nonobese Girls With Polycystic Ovarian Syndrome
Open accessAbstract
Obese girls with polycystic ovarian syndrome (PCOS) have decreased insulin sensitivity (IS), muscle mitochondrial dysfunction and increased liver fat, which may contribute to their increased risk for type 2 diabetes. Less is known regarding normal-weight girls with PCOS. Normal-weight girls with PCOS [n =18, age 15.9 ± 1.8 years, body mass index (BMI) percentile 68 ± 18] and normal-weight controls (NWC; n = 20; age 15.0 ± 2.1 years, BMI percentile 60 ± 21) were studied. Tissue-specific IS was assessed with a four-phase hyperinsulinemic-euglycemic clamp with isotope tracers and a 2-hour oral glucose tolerance test (OGTT). Hepatic fat was determined using magnetic resonance imaging. Postexercise muscle mitochondrial function was assessed with 31P MR spectroscopy. Both groups had similar demographics, anthropomorphics, physical attributes, habitual physical activity levels and fasting laboratory values, except for increased total testosterone and DHEAS in PCOS. Clamp-assessed peripheral IS was lower in PCOS (10.4 ± 2.4 mg/kg/min vs 12.7 ± 2.1; P = 0.024). The 120-minute OGTT insulin and glucose concentrations were higher in PCOS (114 IU/mL ± 26 vs 41 ± 25, P = <0.001 and 119 ± 22 mg/dL vs 85 ± 23, P = 0.01, respectively). Muscle mitochondrial ADP and phosphocreatine time constants were slower in PCOS. Despite a higher percentage liver fat in PCOS, hepatic IS was similar between groups, as was adipose IS. Normal-weight girls with PCOS have decreased peripheral IS and muscle mitochondrial dysfunction, abnormal glucose disposal, relative postprandial hyperinsulinemia, and increased hepatic fat compared to NWC. Despite a normal BMI, multiple aspects of metabolism appear altered in normal-weight girls with PCOS.
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Alternative mechanisms of the pathogenesis of prediabetes and T2D in subjects with PCOS are muscle mitochondrial dysfunction and the gut microbiome.
“Alternative mechanisms of the pathogenesis of prediabetes and T2D in subjects with PCOS are muscle mitochondrial dysfunction [28] and the gut microbiome [29].”
From From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management (2020) · cites this paper as [28]
Normal-weight adolescent girls with PCOS have peripheral insulin resistance, increased liver fat, and muscle mitochondrial dysfunction compared with normal-weight girls.
“Normal-weight adolescent girls with PCOS have peripheral IR, increased liver fat, and muscle mitochondrial dysfunction compared with normal-weight girls [70].”
From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [70]
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- Authors
- Cree-Green, M., Rahat, H., Newcomer, B. R., Bergman, B. C., Brown, M. S., Coe, G. V., Newnes, L., Garcia-Reyes, Y., Bacon, S., Thurston, J. E., Pyle, L., Scherzinger, A., & Nadeau, K. J.
- Affiliations
- University of Colorado Anschutz (US)
- James Madison University (US)
- Colorado School of Public Health (US)
- ORCID
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2017-06-01
- Volume
- 1
- Issue
- 7
- Pages
- 931-944
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC5686696
- OpenAlex
- W2621206961
- Cited by
- 82
- References
- 50
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 6 · 2022: 10 · 2021: 13 · 2020: 14 · 2019: 16 · 2018: 4 · 2017: 1
- FWCI
- 11.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Children's Hospital Colorado
- National Institutes of Health (UL1TR001082)
- Anschutz Medical Campus, University of Colorado
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK088971, K23DK107871, T32DK063687, P30DK048520)
- National Center for Research Resources (TL1RR025778, K23RR020038)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD057022)
- Colorado Clinical and Translational Sciences Institute
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- polycystic ovary syndrome, insulin resistance, hyperinsulinemia, mitochondrial dysfunction, muscle mitochondria, liver fat, hepatic insulin sensitivity, peripheral insulin sensitivity, type 2 diabetes risk, testosterone, dehydroepiandrosterone sulfate
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