INSULIN SENSITIVITY AND SECRETION IN HEALTHY ELDERLY HUMAN-SUBJECTS WITH ABNORMAL GLUCOSE-TOLERANCE

Glucose tolerance deteriorates dramatically with advancing age. It is not known whether the underlying pathophysiology is different in older subjects. We employed a two step hyperinsulinaemic euglycaemic glucose clamp with [6C-14] glucose infusion to compare peripheral and hepatic insulin sensitivity in eight elderly (EAGT) with eight young (YAGT) subjects with abnormal (matched) glucose tolerance and nine elderly subjects with normal glucose tolerance (ENGT). There was no difference in basal HGO (EAGT 14.5 +/- 0.9, YAGT 15.3 +/- 1.1-mu-mol kg-1 min-1). Glucose turnover was similar in both groups at step 1 (EAGT 13.2 +/- 0.8, YAGT 13.4 +/- 0.8-mu-mol kg-1 min-1) and step 2 (EAGT 25.1 +/- 3.1 YAGT 27.2 +/- 2.7 mu-mol kg-1 min-1). HGO was lower in the EAGT subjects at step 1 (2.3 +/- 0.4 vs. 4.3 +/- 0.6-mu-mol kg-1 min-1 P = 0.01). Incremental serum insulin response to oral glucose was comparable (EAGT 66.8 +/- 11.6 YAGT 57.8 +/- 12.2 mU l-1.h). Compared to the ENGT group the EAGT group was insulin resistant with a lower MCR of glucose at step 1 (2.03 +/- 0.28 vs. 3.23 +/- 0.44 ml kg-1 min-1 P=0.04) and at step 2 (6.18 +/- 0.83 vs. 9.64 +/- 0.38 ml kg-1 min-1 P=0.004) and had a lower early insulin response (AUC 0-30 min 5.9 +/- 1.1 vs. 9.8 +/- 1.4 mU l-1.h P = 0.04). We conclude that elderly and young subjects with abnormal glucose tolerance have similar pathophysiology but in such older subjects insulin suppression of HGO is similar to that seen in normal older subjects. Compared to normal elderly subjects the EAGT subjects are insulin resistant and have reduced early insulin secretion and both of these factors are importnat determinants of the glycaemic change.