title: Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance.
abstract: 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 <or= 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 beta-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 (Phi(total)) 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.
authors.affiliation: Endocrine Research Unit, Mayo Medical School, Rochester, Minnesota, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
authors.forename: Elena
authors.initials: E
authors.lastname: Breda
authors.forename: Ann L
authors.initials: AL
authors.lastname: Oberg
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Powell
authors.forename: Chiara
authors.initials: C
authors.lastname: Dalla Man
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.forename: Janet L
authors.initials: JL
authors.lastname: Vittone
authors.forename: George G
authors.initials: GG
authors.lastname: Klee
authors.forename: Puneet
authors.initials: P
authors.lastname: Arora
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jensen
authors.forename: Gianna
authors.initials: G
authors.lastname: Toffolo
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004435:Eating / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood* / Q000378:metabolism*; D000078790:Insulin Secretion; D019308:Palmitic Acid / Q000097:blood
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019382:Human Growth Hormone; D019308:Palmitic Acid; D019314:Dehydroepiandrosterone Sulfate; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone