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The metabolic and cardiovascular effects of nitrendipine and cilazapril in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM) were compared. After at least 6 weeks of a washout period, 20 NIDDM patients who had diastolic blood pressure in the range of 90-105 mm Hg received a single-blind placebo for 4 weeks and then were randomized to receive 20 mg nitrendipine once daily and 5 mg cilazapril once daily each for 12 weeks according to a crossover, double-blind procedure. Nitrendipine and cilazapril reduced diastolic blood pressure levels 12% and 13%, left ventricular mass index (LVMI) levels 13% and 12%, and raised whole glucose disposal levels 18% and 19.5%, respectively. Only nitrendipine reduced glucose-stimulated insulin levels. Nitrendipine is as effective as cilazapril in lowering diastolic blood pressure and LVMI levels and in increasing glucose disposal levels in these patients.

OBJECTIVE To investigate the effect of iloprost infusion on insulin action. RESEARCH DESIGN AND METHODS Thirteen healthy subjects and 13 non-insulin-dependent diabetes mellitus (NIDDM) patients matched for age (68.2 ± 0.5 vs. 67.9 ± 0.5 years, NS), gender ratio (7 men:6 women vs. 6 men:7 women), body weight, body fat distribution, arterial blood pressure, and plasma triglycéride levels (1.89 ± 0.09 vs. 1.87 ± 0.08 mmol/l, NS) were studied. In eight healthy subjects and eight NIDDM patients, we studied insulin action by euglycemic glucose clamp (insulin infusion rate 2 mU · kg−1 · min−1) along with saline and iloprost delivery (0.7 ng · kg−1 · min−1). In the other five subjects of each group, forearm blood flow and insulin-mediated glucose uptake during saline and iloprost infusion (0.7 ng · kg−1 · min1) were investigated. RESULTS Iloprost infusion improved insulin-stimulated whole-body glucose uptake and oxidative and nonoxidative glucose metabolism in both study groups. Forearm blood flow under basal conditions and with insulin infusion (2 mU · kg−1 · min−1) did not show any significant difference from that during saline and iloprost infusion (0.7 ng · kg−1 · min−1) in healthy subjects and diabetic patients. CONCLUSIONS Iloprost infusion improves insulin action in healthy subjects and NIDDM patients.

OBJECTIVE To compare the effects of tolrestat and placebo in patients with subclinical diabetic neuropathy. RESEARCH DESIGN AND METHODS Non-insulin-dependent diabetes mellitus (NIDDM) patients with early involvement of the autonomic nervous system were identified by only one pathological (outside the 99% confidence interval of the normal population) squatting test (vagal or sympathetic). Fifty-seven patients entered a randomized, placebo-controlled, double-blind, parallel 52-week study of tolrestat at a dose of 200 mg/day. Cardiovascular reflex tests (squatting vagal and sympathetic tests, pressure gain, deep breathing, lying-to-standing, Valsalva maneuver, and orthostatic hypertension), vibration thresholds, tendon reflexes, and muscle strength were assessed throughout the study. RESULTS At 12 months, nerve function significantly improved in patients receiving tolrestat and deteriorated in patients taking placebo. At baseline, the squatting vagal test was normal in 16 patients in the tolrestat group and in 15 patients in the placebo group. At 12 months, 25 patients taking tolrestat had a normalized squatting test, but only 6 patients taking placebo did (P = 0.02). Vibration perception threshold improved by a value of 6 ± 3 V in the tolrestat group (P < 0.001) and deteriorated by a value of 3 ± 1.8 V (P < 0.001) in the placebo group. CONCLUSIONS Tolrestat may be useful in the primary prevention of diabetic neuropathy.

Twenty elderly (77 +/- 0.4 y), nonobese [body mass index (in kg/m2) 26.4 +/- 0.5] subjects with normal glucose tolerance were submitted to a euglycemic hyperinsulinemic (3.5 pmol.min/kg) glucose clamp in a double-blind, crossover, randomized procedure after 4 mo treatment with either vitamin E (900 mg d-alpha-tocopherol/d, Ephynal; Roche, Milan, Italy) or placebo. Body mass index was practically unchanged throughout the study. After the glucose clamp, insulin-mediated stimulation 2 of whole-body glucose disposal (18.4 +/- 0.5 vs 26.1 +/- 0.6 mumol.min/kg lean body mass P < 0.02) was significantly potentiated by vitamin E rather than placebo administration. Furthermore, net changes in plasma vitamin E concentrations correlated with net changes in insulin-stimulated whole-body glucose disposal (r = 0.60 P < 0.003). Plasma vitamin E concentrations seem to play an important role in the modulation of insulin action in elderly people.

OBJECTIVE To determine the effects of metformin on blood pressure, left ventricular mass, and some metabolic and endocrine parameters in nondiabetic, obese, hypertensive women. RESEARCH DESIGN AND METHODS Twelve obese, nondiabetic, hypertensive women received 850 mg metformin 2 times/day for 12 wk and placebo for another 12 wk, according to a double-blind, cross-over, randomized design. All patients were hospitalized 4 times, i.e., before randomization and after each treatment (metformin or placebo), to conduct metabolic and cardiovascular investigations (oral glucose tolerance test, euglycemic clamp associated with indirect calorimetry, and echocardiography). RESULTS Fasting glucose, HbA1c, fasting and glucose-stimulated insulin, blood pressure and left ventricular mass, cholesterol, triglycerides, and fibrinogen decreased significantly after metformin treatment, whereas high-density lipoprotein cholesterol increased. The improvement in glucose metabolism resulted from increased sensitivity to insulin. CONCLUSIONS These findings suggest that metformin treatment in obese, nondiabetic, hypertensive women produces a more favorable cardiovascular risk profile.

The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent (type II) diabetic patients. Nine elderly non-obese noninsulin-dependent (type II) diabetic patients, treated by diet only, participated in the study, which was designed as randomized, double blind, and cross-over. Each patient was followed up for a prestudy period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation (15.8 mmol/day) for 4 weeks. At the end of each treatment period, a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3-3H]glucose infusion and indirect calorimetry was performed. Magnesium supplementation resulted in significantly increased plasma and erythrocyte magnesium levels, whereas body weight and fasting plasma glucose did not change. In the last 60 min of the glucose clamp, insulin-mediated glucose disappearance, total body glucose disposal (24.5 +/- 0.4 vs. 28.2 +/- 0.7 mumol/kg.min; P0.005), and glucose oxidation (13.0 +/- 0.4 vs. 16.3 +/- 0.8 mumol/kg.min; P0.01) were increased after chronic magnesium supplementation. Endogenous glucose production, nonoxidative glucose disposal, lipid and protein oxidation, and insulin MCR were not affected. In conclusion, a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients. Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes.

In forty healthy subjects with normal glucose tolerance divided by age into four groups (group A, subjects with mean age25 years [n = 10]; group B, subjects with mean age40 years [n = 9]; group C, subjects with mean age60 years [n = 11]; group D, subjects with mean age75 years [n = 10]) and were matched for body mass index (BMI), lean body mass (LBM), mean arterial blood pressure, and sedentary life style, we determined the plasma O2- production, reduced to oxidized glutathione level ratio (GSH/GSSG), and plasma membrane microviscosity. Euglycemic hyperinsulinemic (1 mU/kg.min-1 for 120 minutes) glucose clamp with simultaneous D-3-H glucose infusion and indirect calorimetry allowed determination of glucose turnover parameters and substrate oxidation. In the oldest group of subjects, a significant increase in plasma O2-production and membrane microviscosity associated with a significative reduction in glucose disappearance rate (Rd), total body glucose disposal (TBGD), and nonoxidative glucose metabolism was found. In group D subjects (n = 10), all of these changes were correlated with one another. In a multiple regression analysis of the pooled data from all study subjects (n = 40), only plasma O2- production levels displayed a statistically significant relation with TBGD and nonoxidative glucose metabolism. In conclusion, in aged patients a significant relationship between free radical production and insulin action seems to exist.

In newly-diagnosed untreated (n = 24) and thiazide treated (n = 18) hypertensive patients erythrocyte ion content and plasma ion and metabolite levels were determined. Thiazide treated patients had lower arterial blood pressure, plasma ion levels, erythrocyte magnesium and potassium content but higher fasting plasma insulin (66 +/- 7 v 87 +/- 8 pmol/L P < .02), triglycerides (1.88 +/- 0.24 v 2.34 +/- 0.44 mmol/L P < .05), free fatty acids (0.68 +/- 0.11 v 0.81 +/- 0.18 mmol/L P < .05). Subsequently, in a double-blind fashion and in random order thiazide diuretic treated patients were assigned to two groups: the first (n = 9) taking magnesium (15.8 mmol/day) and the other (n = 9) a placebo. Each treatment period lasted 8 weeks. At the end of each treatment period, each patient underwent blood sampling for determination of erythrocyte ion content and plasma ion and metabolite levels and was submitted to an euglycemic hyperinsulinemic (1 mU/kg/min for 120 min) glucose clamp. In this latter test D-3-H glucose infusion and indirect calorimetry allowed determination of glucose turnover parameters and substrate oxidation respectively. Chronic magnesium administration (CMA) raised fasting plasma (0.79 +/- 0.03 v 0.83 +/- 0.02 mmol/L, P < .05) and erythrocyte (1.98 +/- 0.08 v 2.35 +/- 0.03 mmol/L, P < .01) magnesium content. Along with insulin infusion, CMA improved glucose uptake, glucose metabolic clearance rate, and oxidative glucose metabolism. In the multiple linear regression analysis of the pooled basal data (n = 42), erythrocyte magnesium content displayed an independent correlation with basal plasma insulin levels (t = -2.08, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

In healthy subjects (n = 10) and non-insulin-dependent (type II) diabetics (n = 10) matched for age [43.1 +/- 2.2 vs. 41 +/- 4.4 yr, P = not significant (NS)], body mass index (25.1 +/- 1.1 vs. 26 +/- 0.8 kg/m2, P = NS), gender ratio [5 males (M)/5 females (F) vs. 5M/5F], and mean arterial blood pressure (105 +/- 7 vs. 106 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after glutathione infusion (15 mg/min) and the relative increase in the plasma reduced (GSH)/oxidized (GSSG) glutathione ratio. The rise in the plasma GSH/GSSG ratio significantly improved total body glucose disposal in healthy subjects and in diabetic patients. In this latter group, GSH infusion potentiated the beta-cell response to glucose slightly. In controls and diabetics, insulin infusion with a simultaneous increase in the plasma GSH/GSSG ratio significantly enhanced nonoxidative glucose disposal without affecting oxidative glucose metabolism. After glutathione infusion, all metabolic and hormonal changes correlated with a significant decline in plasma membrane microviscosity. In conclusion, the plasma GSH/GSSG ratio seems to play a major role in the modulation of glucose homeostasis mainly in diabetics.