Deterioration of insulin sensitivity and glucose effectiveness with age and hypertension.

BACKGROUND: This study examined the relative role of age and hypertension in deterioration of insulin-dependent (insulin sensitivity, S(I)) and insulin-independent (glucose effectiveness, S(G)) actions on glucose tolerance. METHODS: We applied the minimal model of glucose kinetics to estimate S(I) and S(G) indexes from insulinemia and glycemia data detected during a frequently sampled intravenous glucose tolerance test performed in 21 normoglycemic subjects who were not affected by the metabolic syndrome (MS): seven young normotensive subjects (YN; mean age 29.3 +/- 1.5 years), six elderly normotensive subjects (EN; mean age 57.0 +/- 3.4 years) and eight elderly hypertensive patients (EH; mean age 62.1 +/- 2.1 years). RESULTS: Both normotensive subject groups (YN and EN) showed no significant difference in S(I) estimates despite significantly different age, whereas a significant reduction was evident in the EH patients compared with these groups. Mean estimates of S(G) showed no significant difference in elderly subject groups (EN and EH), irrespective of hypertension, whereas a significant increase was evident in the YN (analysis of variance followed by Scheffé test, P < .05). CONCLUSIONS: Our study demonstrates that, in the absence of MS: 1) insulin sensitivity in normotensive subjects is independent of age; b) hypertension is associated with insulin resistance in elderly subjects; and c) age is a primary predictor of deterioration in glucose effectiveness, independent of hypertension.

Insulin resistance in hypertension quantified by oral glucose tolerance test: comparison of methods.

Four methods reported in the literature for evaluation of insulin sensitivity indexes from oral glucose tolerance tests (OGTTs) were analyzed and compared in order to test their ability to discriminate the insulin-resistant state in hypertension. To this aim, 15 normoglycemic subjects, not affected by metabolic syndrome, underwent a 22-sample, 300-minute OGTT. Eight subjects were normotensive (mean age, 47.0 +/- 4.2 years) and 7 were hypertensive (mean age, 53.6 +/- 1.6 years). The following insulin sensitivity indexes were computed and compared: (a) 2 indexes, ISIE22/300 and ISIE8/180, provided by an integral equation (IE) method applied to the full OGTT and to a reduced 8-sample, 180-minute data subset, respectively; (b) 2 indexes, ISOGIS180 and ISOGIS120, computed by the oral glucose, insulin sensitivity (OGIS) method, which only requires 3 blood samples taken within 180 and 120 minutes, respectively; (c) an index, ISISI, which considers fasting and mean insulinemia and glycemia measured during a 5-sample, 120-minute OGTT; and (d) an index, ISMCR, which considers body mass index and requires 2 blood samples taken within 120 minutes. Except the ISOGIS180, all other indexes were able to detect a significant reduction (unpaired Student t test, P < .05) of insulin sensitivity in our hypertensive group compared with the normotensive group. Failure of ISOGIS180 was explained by the fact that this index did not capture the information portrayed by the peak of insulinemia in hypertensive patients, which occurred around the 90th minute. Intraclass correlation coefficients higher than 0.89 demonstrated a substantial agreement between ISIE22/300 and ISIE8/180 indexes. These are the only indexes characterized by units of measure consistent with the definition of insulin sensitivity as the ability of insulin to enhance glucose effectiveness.

Interaction between glucose metabolism and endogenous insulin release in hypertension.

The minimal model approach was applied to examine the dynamic interaction between glucose metabolism and endogenous insulin release during an intravenous glucose tolerance test (IVGTT) in a group of hypertensive patients (H group) compared with a group of normotensive subjects (N group). A modified version of the classical minimal model of C-peptide kinetics and secretion was used to evaluate the total amount of insulin secretion per unit of distribution volume (TIS) together with 3 indexes of beta-cell function (the basal, Phi(b), first, Phi1, and second phase, Phi2, beta-cell sensitivity to glucose). These indexes were associated with estimates of glucose effectiveness (S(G)) and insulin sensitivity (S(I)) provided by the classical minimal model of glucose kinetics. No significant differences were found in Phi(b), Phi1, and Phi2 estimates between the H group and the N group. In the H group, the average TIS was 54% higher (P <.05) than in the N group, while S(G) and S(I) estimates showed a 44% decrease (P <.05) and a 51% decrease (P <.05), respectively. These results suggest that hyperglycemia observed in our H group during IVGTT is a compensatory response to insulin resistance (low S(I)) and to the reduced ability of glucose to promote its own metabolism (low S(G)). This hyperglycemic state causes a larger than normal stimulation of beta cell, which explains insulin hypersecretion (higher TIS) even in the presence of normal beta-cell sensitivity values of Phi(b), Phi1, and Phi2.