Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease.
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In normoglycemic offspring of two type 2 diabetic parents, low insulin sensitivity (S(I)) and low insulin-independent glucose effectiveness (S(G)) predict the development of diabetes one to two decades later. To determine whether low S(I), low S(G,) or low acute insulin response to glucose are predictive of diabetes in a population at low genetic risk for disease, 181 normoglycemic individuals with no family history of diabetes (FH-) and 150 normoglycemic offspring of two type 2 diabetic parents (FH+) underwent i.v. glucose tolerance testing (IVGTT) between the years 1964-82. During 25 +/- 6 years follow-up, comprising 2,758 person years, the FH- cohort (54 +/- 9 years) had an age-adjusted incidence rate of type 2 diabetes of 1.8 per 1,000 person years, similar to that in other population-based studies, but significantly lower than 16.7 for the FH+ cohort. Even when the two study populations were subdivided by initial values of S(I) and S(G) derived from IVGTT's performed at study entry, there was a 10- to 20-fold difference in age-adjusted incidence rates for diabetes in the FH- vs. FH+ individuals with low S(I) and low S(G). The acute insulin response to glucose was not predictive of the development of diabetes when considered independently or when assessed as a function of S(I), i.e., the glucose disposition index. These data demonstrate that low glucose disposal rates are robustly associated with the development of diabetes in the FH+ individuals, but insulin resistance per se is not sufficient for the development of diabetes in individuals without family history of disease and strongly suggest a familial factor, not detectable in our current measures of the dynamic responses of glucose or insulin to an IVGTT is an important risk factor for type 2 diabetes. Low S(I) and low S(G), both measures of glucose disposal, interact with this putative familial factor to result in a high risk of type 2 diabetes in the FH+ individuals, but not in the FH- individuals.
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Insulin resistance is not predictive of diabetes in individuals without a family history of diabetes, indicating that additional unidentified factors are necessary for disease progression.
“However, insulin resistance is not predictive of diabetes in individuals without a family history of diabetes, indicating that additional unidentified factors are necessary for disease progression (30).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [30]
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- Authors
- Goldfine, A. B., Bouche, C., Parker, R. A., Kim, C., Kerivan, A., Soeldner, J. S., Martin, B. C., Warram, J. H., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Joslin Diabetes Center, One Joslin Place, Boston, MA 02215; Harvard Medical School, 25 Shattuck Street, Boston, MA 02215; and Beth Israel Medical Center, Biometrics Center/E-GZ814, 330 Brookline Avenue, Boston, MA 02215
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-02-18
- Volume
- 100
- Issue
- 5
- Pages
- 2724-2729
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC151408
- OpenAlex
- W2142797092
- Cited by
- 99
- References
- 30
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2019: 1 · 2018: 1 · 2017: 6 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 9 · 2012: 7
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (P30 DK36836, RR 01032, DK 36836)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK 02795, K23DK002795, P30-DK36836, R01-DK-45935, R01 DK-33201, R01DK045935, R01DK033201, P30DK036836)
- National Center for Research Resources (M01-RR-01032, M01RR001032)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 2 diabetes, insulin resistance, insulin sensitivity, acute insulin response to glucose, family history of diabetes, diabetes risk prediction, glucose disposal, normoglycemic adults
- MeSH terms
- Adult, Age Factors, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Family Health, Female, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Regression Analysis, Risk Factors, Time Factors, Cohort Studies
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