Biomedical subjects

D A Garcia-Estevez

Publications and source records attributed to D A Garcia-Estevez.

3 recordsLinked to original sources

PubMed1998

Minimal model of glucose metabolism: modified equations and its application in the study of insulin sensitivity in obese subjects.

As implemented in their program MINMOD, some of the parameters and variables of the equations representing Bergman and coworkers' minimal model of glucose metabolism have no simple rational relationship with the kinetic constants and constants of proportionality of the minimal model as such. In this work we implemented the original version of the minimal model, which does not suffer from this problem, and used it to investigate the source of insulin resistance among obese but otherwise healthy subjects. A fasting sampled intravenous glucose tolerance (FSIGT) test was performed in 38 healthy subjects of varying degrees of obesity (standard FSIGT test in 21 and tolbutamide FSIGT test in 17 subjects) in order to compare MINMOD and 'modified' equations (MI). Insulin sensitivity index (SI) in obese subjects was significantly lower than in lean subjects (4.58 +/- 3.5 vs. 11.7 +/- 4.3. 10(-5) min-1 (pmol.l-1)-1, P < 0.0001). The lower SI in obese subjects was a consequence P3 parameter (0.178 +/- 0.08 vs. 0.440 +/- 0.26.10(-5) min-2 (pmol.l-1)-1, P < 0.01), being p2 similar between obese and lean subjects (0.389 +/- 0.19 vs. 0.376 +/- 0.19.10(-1) min-1, NS). SI index correlated with p3 (r = 0.73, P < 0.0001), but not with p2 (r = 0.01, NS). Using these results and assuming that interstitial insulin is higher in obese subjects than in lean subjects, we have demonstrated that the proportionality constants of the model (k4 and k6) were lower in obese subjects than in lean subjects, but not the rate constant for insulin transfer across capillaries, k2. Our results suggest that the modified equations are a better theoretical approach to the minimal model method; and that low insulin sensitivity in obese subjects is due to receptor and/or post-receptor events rather than to slow transfer of insulin across capillary endothelium into the interstitial space.

Adult↗

PubMed1997

Insulin sensitivity, glucose effectiveness, and beta-cell function in obese males with essential hypertension: investigation of the effects of treatment with a calcium channel blocker (diltiazem) or an angiotensin-converting enzyme inhibitor (quinapril).

It has been suggested that hyperinsulinemia secondary to insulin resistance may be a pathogenetic factor common to obesity, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. Furthermore, beta-blockers and thiazide diuretics have been shown to be capable of increasing insulin resistance and thus of inducing NIDDM in predisposed individuals. We used the minimal model approach (MMA) to glucose metabolism and insulin kinetics to compare peripheral insulin sensitivity and beta-cell function in hypertensive and normotensive obese men. The hypertensive group consisted of 37 obese men with mild to moderate hypertension; following a drug-free period of 4 weeks, 20 of these subjects received diltiazem and 17 quinapril over the 12-week study period. The normotensive (control) group contained 17 obese men without microalbuminuria, dyslipidemia, or a family history of essential hypertension or NIDDM. Before and at the end of the 12-week study period, subjects underwent frequently sampled intravenous glucose tolerance (FSIGT) tests. The results were used to estimate an insulin sensitivity index (S(I)), a glucose effectiveness index (S(G)), and beta-cell sensitivity to glucose indices during first- and second-phase insulin secretion (phi1 and phi2) using the minimal models of glucose metabolism and insulin kinetics. No significant differences in S(I) or S(G) were detected between the hypertensive and control groups. Twelve weeks' treatment with diltiazem led to a slight but significant increase in phi1; however, neither diltiazem nor quinapril had significant effects on S(I) or S(G). We conclude that men with obesity and hypertension have no greater insulin resistance than those with obesity alone, suggesting that hypertension is not generally associated with any significant increase in insulin resistance. Treatment with diltiazem or quinapril does not have undesirable effects on glucose metabolism. However, treatment with diltiazem led to a significant increase in beta-cell sensitivity to glucose; this is of particular interest, given the importance of phi1 for peripheral glucose uptake.

Adolescent↗

PubMed1997

Insulin sensitivity and beta-cell function in essential hypertension and normotensive first-degree relatives of hypertensive subjects.

We investigated glucose metabolism and beta-cell function in normotensive subjects with one essential-hypertensive parent and in subjects with mild/moderate essential hypertension (eHT) before and after 12-week treatment with nitrendipine. The hypertensive-parent group comprised 12 normotensive subjects, and the hypertensive group 15 subjects with mild/moderate eHT. A corresponding control group composed of 20 normotensive subjects was also investigated. All subjects underwent a frequently sampled intravenous glucose tolerance test (FSIGT). Hypertensive subjects underwent FSIGT testing before and after 12 weeks of treatment with nitrendipine (20 mg per day). Insulin sensitivity, glucose effectiveness and beta-cell function were investigated using the minimal model technique on the basis of FSIGT test data. No significant differences were detected in any of the minimal-model parameters either between the hypertensive-parent group and the control, or between the hypertensive group (before nitrendipine treatment) and the control. Twelve weeks of anti-hypertensive treatment with nitrendipine led to an increase in glucose effectiveness and a non-significant increase in glucose tolerance, but had no significant effects on other minimal-model parameters or on the serum lipid profile. Our results suggest that eHT cannot be considered consistently associated with insulin resistance. Nitrendipine treatment appears to have no undesirable effects on peripheral sensitivity to insulin or on beta-cell function. However, the 12-week course led to a 72% increase in glucose effectiveness.

Adult↗