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Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of pima indians
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BACKGROUND: The relative roles of obesity, insulin resistance, insulin secretory dysfunction, and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus (NIDDM) are controversial. We conducted a prospective study to determine which of these factors predicted the development of the disease in a group of Pima Indians. METHODS: A body-composition assessment, oral and intravenous glucose-tolerance tests, and a hyperinsulinemic--euglycemic clamp study were performed in 200 non-diabetic Pima Indians (87 women and 113 men; mean [+/- SD] age, 26 +/- 6 years). The subjects were followed yearly thereafter for an average of 5.3 years. RESULTS: Diabetes developed in 38 subjects during follow-up. Obesity, insulin resistance (independent of obesity), and low acute plasma insulin response to intravenous glucose (with the degree of obesity and insulin resistance taken into account) were predictors of NIDDM: The six-year cumulative incidence of NIDDM was 39 percent in persons with values below the median for both insulin action and acute insulin response, 27 percent in those with values below the median for insulin action but above that for acute insulin response, 13 percent in those with values above the median for insulin action and below that for acute insulin response, and 0 in those with values originally above the median for both characteristics. CONCLUSIONS: Insulin resistance is a major risk factor for the development of NIDDM: A low acute insulin response to glucose is an additional but weaker risk factor.
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“Insulin resistance and concurrent relative insulin deficiency and glucagon dysregulation underlie T2D pathophysiology.33–35”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [35]
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“However, progressive β-cell failure is required and ultimately responsible for type 2 diabetes to become fully manifest ( 1 , 34 , 35 , 37 , 38 ).”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [35]
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“Thus, re-examination of data from some other studies of high risk subjects with NGT would suggest that the conclusions in those papers disputing the presence of beta-cell dysfunction are erroneous because no difference in the insulin responses existed between groups despite the presence of insulin resistance, indicating impaired beta-cell adaptation [108, 109, 110, 111, 112, 113, 114].”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [113]
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Metadata
- Authors
- Lillioja, S., Mott, D. M., Spraul, M., Ferraro, R., Foley, J. E., Ravussin, E., Knowler, W. C., Bennett, P. H., & Bogardus, C.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1993-12-30
- Volume
- 329
- Issue
- 27
- Pages
- 1988-1992
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2334309509
- Cited by
- 1,508
- References
- 27
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 30 · 2023: 22 · 2022: 34 · 2021: 38 · 2020: 39 · 2019: 37 · 2018: 40 · 2017: 30 · 2016: 40 · 2015: 52 · 2014: 44 · 2013: 45 · 2012: 44
- FWCI
- 30.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin resistance, type 2 diabetes, Pima Indians, obesity, acute insulin response, hepatic glucose production, insulin action, diabetes risk factors, hyperinsulinemic-euglycemic clamp, glucose tolerance
- MeSH terms
- Insulin Secretion, Adult, Arizona, Body Composition, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Glucose, Glucose Tolerance Test, Humans, Indians, North American, Insulin, Insulin Resistance, Liver, Male, Obesity, Prospective Studies, Risk Factors, Proportional Hazards Models
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