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Mechanisms of the Age-Associated Deterioration in Glucose Tolerance
Open accessAbstract
Glucose tolerance decreases with age. For determining the cause of this decrease, 67 elderly and 21 young (70.1 ± 0.7 vs. 23.7 ± 0.8 years) participants ingested a mixed meal and received an intravenous injection of glucose. Fasting glucose and the glycemic response above basal were higher in the elderly than in the young participants after either meal ingestion (P < 0.001) or glucose injection (P < 0.01). Insulin action (Si), measured with the meal and intravenous glucose tolerance test models, was highly correlated (r = 0.72; P < 0.001) and lower (P ≤ 0.002) in the elderly than in the young participants. However, when adjusted for differences in percentage body fat and visceral fat, Si no longer differed between groups. When considered in light of the degree of insulin resistance, all indexes of insulin secretion were lower (P < 0.01) in the elderly participants, indicating impaired β-cell function. Hepatic insulin clearance was increased (P < 0.002), whereas total insulin clearance was decreased (P < 0.002) in the elderly subjects. Multivariate analysis (r = 0.70; P < 0.001) indicated that indexes of insulin action (Si) and secretion (Phitotal) but not age, peak oxygen uptake, fasting glucose, degree of fatness, or hepatic insulin clearance predicted the postprandial glycemic response. We conclude that the deterioration in glucose tolerance that occurs in healthy elderly subjects is due to a decrease in both insulin secretion and action with the severity of the defect in insulin action being explained by the degree of fatness rather than age per se.
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“Furthermore, use of the meal minimal model in conjunction with the triple tracer method permits robust model assessments of indices of insulin action on the periphery (SI) and on the liver (SIL), glucose effectiveness (SG), insulin secretion, and β-cell function (disposition index).[49][50][51][52][53][54][55][56][57][58][59][60][61]”
From Developing the UVA/Padova Type 1 Diabetes Simulator: Modeling, Validation, Refinements, and Utility (2023) · cites this paper as [49]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“These sophisticated models became possible because of unique phenotypic data of carbohydrate metabolism obtained from studies conducted in >200 adults and children applying the triple tracer technique to derive key metabolic indices and parameters.[48][49][50][51][52][53][54]”
From Developing the UVA/Padova Type 1 Diabetes Simulator: Modeling, Validation, Refinements, and Utility (2023) · cites this paper as [49]
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“our results are consistent with a growing body of evidence that indicates that age-related changes in adiposity and physical inactivity are the primary determinants of the age-related declines in insulin sensitivity rather than chronological age (6,7,31–33).”
From Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function (2010) · cites this paper as [7]
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“Lower fasting glucose levels and greater postprandial glucose disappearance rates in elderly women than in men were also observed in another study (7).”
From Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function (2010) · cites this paper as [7]
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“which is consistent with a recent report in a large number of people (7) that demonstrated that after adjusting for body composition and cardiorespiratory fitness, the age-related differences in insulin action were eliminated.”
From Age, Obesity, and Sex Effects on Insulin Sensitivity and Skeletal Muscle Mitochondrial Function (2010) · cites this paper as [7]
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“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 [23]
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Metadata
- Authors
- Basu, R., Breda, E., Oberg, A. L., Powell, C. C., Dalla Man, C., Basu, A., Vittone, J. L., Klee, G. G., Arora, P., Jensen, M. D., Toffolo, G., Cobelli, C., & Rizza, R. A.
- Affiliations
- Mayo Clinic (US)
- University of Padua (IT)
- Department of Information Engineering, University of Padua, Padua, Italy
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-07-01
- Volume
- 52
- Issue
- 7
- Pages
- 1738-1748
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2139834641
- Semantic Scholar
- d8e228956833647e46e0380931e47b93ca54183f
- Cited by
- 440
- References
- 58
- Citations by year
- 2026: 8 · 2025: 23 · 2024: 22 · 2023: 17 · 2022: 23 · 2021: 27 · 2020: 19 · 2019: 22 · 2018: 17 · 2017: 14 · 2016: 24 · 2015: 18 · 2014: 16 · 2013: 26 · 2012: 22
- FWCI
- 15.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- American Diabetes Association
- Mayo Foundation for Medical Education and Research
- Novo Nordisk
- U.S. Public Health Service (RR-00585)
- National Institute on Aging (AG14383, P01AG014383)
- National Institute of Biomedical Imaging and Bioengineering (P41EB001975)
- National Center for Research Resources (RR-00585, M01RR000585)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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, insulin secretion, beta-cell function, postprandial glycemic response, hepatic insulin clearance, fat mass, visceral fat, older adults, glucose tolerance test
- MeSH terms
- Insulin Secretion, Adult, Aged, Aging, Blood Glucose, C-Peptide, Eating, Fatty Acids, Nonesterified, Glucagon, Glucose, Glucose Tolerance Test, Humans, Hydrocortisone, Insulin, Body Mass Index, Palmitic Acid, Dehydroepiandrosterone Sulfate, Human Growth Hormone
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