Pathogenesis of Age-Related Glucose Intolerance in Man: Insulin Resistance and Decreased β-Cell Function*
Abstract
To identify the pathogenic factors responsible for glucose intolerance of aging, we measured a variety of metabolic parameters, including insulin sensitivity and islet cell function, in 10 young (18-36 yr old) and 10 older (57-82 yr old) men of normal body weight. Subject groups had equivalent fasting plasma glucose and fat cell size values. Frequently sampled iv glucose tolerance tests were performed, and the data were analyzed by computer using the minimal model approach. This technique yields the following measures: SI, the insulin sensitivity index; phi 1 and phi 2, indices of first and second phase beta-cell responsiveness to glucose; n, fractional insulin clearance, and SG, a measure of dynamic glucose disappearance dependent on glucose per se. We also evaluated beta-cell responsiveness independently by measuring the plasma insulin response to arginine injections at three levels of glycemia and calculated potentiation slope from the relationship between the acute insulin response to arginine and the prestimulus glucose level. The older men were glucose intolerant (glucose disappearance rate, 1.32% min-1) compared to the younger men (glucose disappearance rate, 2.21% min-1; P less than 0.01). This intolerance was the result of both a beta-cell defect and insulin resistance. The potentiation slope (r = -0.67; P less than 0.02) and phi 2 (r = -0.47; P less than 0.05) both decreased with age. In addition, SI in the older group was diminished 63% (2.4 vs. 6.5; 10(-4) min-1/microU/ml; P less than 0.001) and was unrelated to differences in body fat. No differences were found in either n or SG. These studies suggest that the diminished glucose tolerance of aging in normal weight men has multifactorial causality. Both beta-cell dysfunction and insulin resistance are important. In contrast, we found little evidence for changes in insulin clearance or insulin-independent glucose disappearance contributing to age-related glucose intolerance.
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Insulin sensitivity is influenced by genetics, age, acute exercise, physical fitness, dietary nutrients, medications, obesity and body fat distribution.
“insulin sensitivity is influenced by a number of different factors such as genetics [20], age [21, 22], acute exercise [23], physical fitness [24], dietary nutrients [25], medications [26, 27, 28], obesity [9, 10, 29, 30, 31, 32] and body fat distribution [31, 33, 34, 35, 36, 37, 38].”
From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [22]
Other studies have demonstrated that diabetes can be prevented or delayed by lifestyle change and medication.
“Other studies have also demonstrated that diabetes can be prevented (or delayed) by lifestyle change (23,24) and medication (25,26), but the DPP provides unique information about prevention in older adults.”
From ]. The Influence of Age on the Effects of Lifestyle Modification and Metformin in Prevention of Diabetes (2006) · cites this paper as [24]
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- Authors
- CHEN, M., BERGMAN, R. N., PACINI, G., & PORTE, D.
- Affiliations
- University of Southern California (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1985-01
- Volume
- 60
- Issue
- 1
- Pages
- 13-20
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2037808521
- Cited by
- 353
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 9 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 6 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 11 · 2012: 12
- FWCI
- 16.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01am029867-04, 5r01am012829-17)
- National Center for Research Resources (RR 37)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- insulin resistance, beta-cell dysfunction, aging, insulin sensitivity index, glucose tolerance, insulin clearance, glucose disappearance, minimal model analysis, islet function
- MeSH terms
- Adipose Tissue, Adolescent, Adult, Aged, Aging, Arginine, Blood Glucose, Glucose Tolerance Test, Humans, Injections, Intravenous, Insulin, Insulin Resistance, Islets of Langerhans, Kinetics, Male, Middle Aged
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