title: Age-related reduction in glucose elimination is accompanied by reduced glucose effectiveness and increased hepatic insulin extraction in man.
abstract: This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness (SG), and hepatic extraction (HE) of insulin are altered by age when glucose tolerance is normal. A frequently sampled i.v. glucose tolerance test was performed in 20 elderly (E, 10/10 male/female, all 63 yr old) and in 20 young subjects (Y, 10/10 male/female, all 27 yr old), who were similar in body mass index and 2-h blood glucose during oral glucose tolerance test. E exhibited impaired glucose elimination (i.v. tolerance index, 1.31 +/- 0.10 vs. 1.70 +/- 0.12% min-1; P = 0.019). First-phase insulin secretion and SI did not differ between the groups, whereas E had lower glucose sensitivity of second-phase insulin secretion (0.40 +/- 0.07 vs. 0.70 +/- 0.08 (pmol/L)min-2/(mmol/L), P = 0.026), lower SG, 0.017 +/- 0.002 vs. 0.025 +/- 0.002 min-1, P = 0.004), and higher HE (81.3 +/- 2.4 vs. 73.2 +/- 2.1%, P = 0.013). Across both groups, SG correlated positively with glucose tolerance index (r = 0.58, P < 0.001) and negatively with HE (r = -0.54, P < 0.001). Plasma leptin and glucagon did not change by age, whereas plasma pancreatic polypeptide (PP) was higher in E (122 +/- 18 vs. 66 +/- 6 pg/mL, P = 0.004). PP did not, however, correlate to any other parameter. We conclude that E subjects with normal oral glucose tolerance have reduced SG, impaired second-phase insulin secretion, and increased HE, whereas SI and first-phase insulin secretion seem normal. SG seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute.
authors.affiliation: Department of Medicine, Lund University, Malmö, Sweden. bo.ahren@medforsk.mas.lu.se
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: G
authors.initials: G
authors.lastname: Pacini
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007700:Kinetics; D020738:Leptin; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010191:Pancreatic Polypeptide / Q000097:blood; D011506:Proteins / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D020738:Leptin; D011506:Proteins; D010191:Pancreatic Polypeptide; D005934:Glucagon