Insulin sensitivity and secretion in healthy elderly human subjects with ‘abnormal’ glucose tolerance

Abstract

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 [6(14)C] 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 mumol kg-1 min-1). Glucose turnover was similar in both groups at step 1 (EAGT 13.2 +/- 0.8, YAGT 13.4 +/- 0.8 mumol kg-1 min-1) and step 2 (EAGT 25.1 +/- 3.1, YAGT 27.2 +/- 2.7 mumol kg-1 min-1). HGO was lower in the EAGT subjects at step 1 (2.3 +/- 0.4 vs. 4.3 +/- 0.6 mumol 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).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of endogenous glucose production after a mixed meal in type 2 diabetes

“…It is unlikely that this had a major impact on initial rates of EGP suppression. Age per se is unlikely to be responsible, as neither peripheral nor hepatic insulin sensitivity changes with age, provided physical activity and obesity are matched (11). The considerable difference in body mass index (BMI; 30 vs. 21 kg/m 2 ) between the previously studied subjects and the control subjects in the present study may explain the observations.…”

Beta cell function declines with age in glucose tolerant Caucasians

“…Apart from a few exceptions ( DeFronzo, 1979; Bourey et al ., 1993 ), there is substantial evidence supporting the age‐associated decline of beta cell function ( Gumbiner et al ., 1989 ; Chen et al ., 19 85; Pacini et al ., 1990 ; Broughton et al ., 1991 ; Broughton et al ., 1992 ; Coon et al ., 1992 ; Ahraen & Pacini, 1998; Iozzo et al ., 1999 ). However, all studies but one ( Iozzo et al ., 1999 ) were based on the case‐control observations from a relatively small sample size.…”

“…The purpose of this study was to investigate the effect of age on insulin sensitivity and beta cell function. Since inconsistent results have been reported in the past ( Chen et al ., 1985 ; Pacini et al ., 1990 ; Broughton et al ., 1991 ; Broughton et al ., 1992 ; Coon et al ., 1992 ; O'Shaughnessy et al ., 1992 ; Elahi et al ., 1993 ; Ferrannini et al ., 1996 ; Iozzo et al ., 1999 ), every effort has been made to minimize the impact of confounding factors and to enhance the chance of detecting a true difference. In the present study, we eliminated two key confounding factors, hypertension and abnormal glucose tolerance, that contribute independently to either insulin resistance or beta cell dysfunction.…”