Multi-year reproducibility of hyperinsulinemic euglycemic clamp-derived insulin sensitivity in free-living adults: association with incident prediabetes in the pop-abc study
Open accessAbstract
Objective The hyperinsulinemic euglycemic clamp (HEC) is the "gold standard" for measuring insulin sensitivity (Si-clamp). Here, we determined the reproducibility of serial HEC data in healthy subjects.Research design and methods The Pathobiology of Prediabetes in A Biracial Cohort study assessed incident prediabetes in healthy African Americans (AA) and European Americans (EA) with parental type 2 diabetes mellitus during 5.5 years of follow-up. Assessments included anthropometry, OGTT, and HEC. Ninety subjects (44 AA, 46 EA) who underwent Year-1HEC consented to Year-3 HEC. We calculated coefficients of variation (CVs), 95% limits of agreement, and repeatability coefficients for Year-1 and Year-3 data, and assessed the association of change in Si-clamp with incident prediabetes.Results The mean (SD) baseline age was 47.5 ± 8.13y, body mass index was 30.4 ± 9.16 kg/m 2, fasting plasma glucose was 93.7 ± 7.82 mg/dL and 2-hrPG was 126 ± 26.8 mg/dL. Si-clamp (umol/kg/min·pmol/L-1) was 0.071 ± 0.04 in Year 1 and 0.067 ± 0.04 in Year 3 (P = 0.22). Year 1 and Year 3 values were strongly correlated (r = 0.81, P < 0.0001); the CV was 13.6% and repeatability coefficient was ±0.025. Intrasubject differences in serial Si-clamp were less than the repeatability coefficients and within the 95% limits of agreement. After 5.5 years of follow-up, 40 subjects progressed to prediabetes and 50 were nonprogressors. The change in Si-clamp was greater in progressors than nonprogressors (-10% vs. -2.5%, P = 0.02).Conclusions The HEC is reproducible over ~2 years in free-living individuals, with a temporal decline in Si-clamp that predicts prediabetes risk.
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Type 2 diabetes often remains undiagnosed for years because it is frequently asymptomatic.
“T2D remains undiagnosed for years in many affected persons because they are frequently asymptomatic; therefore, screening individuals with multiple risk factors is needed to reduce the risk of long-term complications.38,39”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [38]
The Introduction and Results address insulin sensitivity and progression to prediabetes, not how long type 2 diabetes remains undiagnosed. Searches for asymptomatic or undiagnosed diabetes found no passage explaining a years-long diagnostic delay (section labels available; page numbers not provided). (LLM, conf=0.76)
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- Authors
- James, D., Umekwe, N., Edeoga, C., Nyenwe, E., & Dagogo-Jack, S.
- Affiliations
- University of Tennessee Health Science Center (US)
- ORCID
- Nyenwe, Ebenezer
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 109
- Pages
- 154263
- ISSN
- 0026-0495 (ISSN-L)
- PMC
- PMC7387175
- OpenAlex
- W3028231374
- Cited by
- 23
- References
- 28
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 DK067269-04s1)
- American Diabetes Association (7-07-MN-13)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- hyperinsulinemic-euglycemic clamp, insulin sensitivity, reproducibility, prediabetes, type 2 diabetes risk, African Americans, European Americans, prediabetes progression
- MeSH terms
- Adult, Anthropometry, Black or African American, Diabetes Mellitus, Type 2, Follow-Up Studies, Glucose Tolerance Test, Humans, Hyperinsulinism, Insulin Resistance, Male, Middle Aged, Prediabetic State, Predictive Value of Tests, Time Factors, Reproducibility of Results, Glucose Clamp Technique, White People, Healthy Volunteers
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