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Age-Related Reduction in Glucose Elimination Is Accompanied by Reduced Glucose Effectiveness and Increased Hepatic Insulin Extraction in Man¹

Department of Medicine (B.A.), Lund University, S-205 02 Malmö, Sweden; and Institute of Systems Science and Biomedical Engineering (G.P.) (LADSEB-CNR), I-35127 Padua, Italy

Address all correspondence and requests for reprints to: Dr. Bo Ahrén, Department of Medicine, Malmö University Hospital, S-205 02 Malmö, Sweden. E-mail: bo.ahren{at}medforsk.mas.lu.se

This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness (S_G), and hepatic extraction (HE) of insulin are altered by age when glucose tolerance is normal. A frequently sampled iv 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 (iv tolerance index, 1.31 ± 0.10 vs. 1.70 ± 0.12% min^-1; P = 0.019). First-phase insulin secretion and S_I 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 S_G, 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, S_G 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 S_G, impaired second-phase insulin secretion, and increased HE, whereas S_I and first-phase insulin secretion seem normal. S_G seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute.

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