TY - JOUR
T1 - Mechanisms of the age-associated deterioration in glucose tolerance
T2 - Contribution of alterations in insulin secretion, action, and clearance
AU - Basu, Rita
AU - Breda, Elena
AU - Oberg, Ann L.
AU - Powell, Claudia C.
AU - Man, Chiara Dalla
AU - Basu, Ananda
AU - Vittone, Janet L.
AU - Klee, George G.
AU - Arora, Puneet
AU - Jensen, Michael D.
AU - Toffolo, Gianna
AU - Cobelli, Claudio
AU - Rizza, Robert A.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - 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.
AB - 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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U2 - 10.2337/diabetes.52.7.1738
DO - 10.2337/diabetes.52.7.1738
M3 - Article
C2 - 12829641
AN - SCOPUS:0038353641
SN - 0012-1797
VL - 52
SP - 1738
EP - 1748
JO - Diabetes
JF - Diabetes
IS - 7
ER -