Effect of chronic treatment with lacidipine or lisinopril on intracellular partitioning of glucose metabolism in type 2 diabetes mellitus.

Antihypertensive treatment is frequently needed in type 2 diabetes. In this study we measured the rates of total, oxidative, and nonoxidative glucose disposal, glycogen synthesis, glycolysis, endogenous glucose production, and lipid oxidation using a 4-h euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 300 pmol/L) clamp in combination with a dual glucose tracer infusion ([3-(3)H]- and [U-14C] D-glucose) and indirect calorimetry in 40 nonobese subjects with type 2 diabetes. Subjects were studied twice: after a 4-week run-in period and after a 16-week period of double blind, randomized treatment with 4-6 mg/day lacidipine, a calcium channel blocker (n = 19), or 10-20 mg/day lisinopril, an angiotensin-converting enzyme inhibitor (n = 21). Antihypertensive treatment resulted in a significant increase in total glucose disposal during insulin clamp as well as in basal and insulin-stimulated nonoxidative glucose disposal rates. On the contrary, oxidative glucose disposal was significantly decreased by antihypertensive treatment, mainly in the basal state. The changes in glucose disposal rates were not significantly different in subjects treated with lacidipine and in those treated with lisinopril. The suppression of endogenous glucose production during insulin clamp was significantly greater after lacidipine than after lisinopril. These results suggest that treatment of subjects with type 2 diabetes with either lacidipine or lisinopril has no adverse effect on glucose metabolism. Conversely, both drugs seem to improve insulin sensitivity.

Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients.

Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to test whether antihypertensive treatment with the calcium antagonist lacidipine can improve endothelium-dependent vasodilation in essential hypertensive patients. In 12 normotensive subjects (mean age, 47.8+/-8.6 years; blood pressure, 118.6+/-4.2/76.7+/-3.9 mm Hg) and 19 hypertensive patients (mean age, 49.4+/-10.2 years; blood pressure; 153.5+/-13.3/101.3+/-6.4 mm Hg), we studied forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute) and bradykinin (5, 15, and 50 ng/100 mL per minute), two endothelium-dependent vasodilators that act through different receptors and signal transduction pathways, and sodium nitroprusside (1, 2, and 4 microg/100 mL per minute), an endothelium-independent vasodilator. In essential hypertensive patients, vascular reactivity was repeated during prolonged (8 weeks of oral treatment at 6 mg/d) lacidipine administration and 2 weeks after withdrawal of chronic (32-week) treatment. Hypertensive patients showed significantly (P<.01) blunted vasodilation in response to acetylcholine (vascular resistance, 31.5+/-4.9 to 7.6+/-2.4 SU) and bradykinin (vascular resistance, 32.3+/-5.8 to 8.5+/-3.0 SU) compared with control subjects (vascular resistance: acetylcholine, 24.3+/-3.9 to 3.7+/-1.2 SU; bradykinin, 24.7+/-0.4 to 4.1+/-1.3 SU), whereas the response to sodium nitroprusside was similar. After either 8 or 32 weeks of lacidipine treatment, the vasodilation in response to acetylcholine (30.6+/-7.7 to 5.7+/-1.5 and 34.3+/-6.6 to 5.9+/-1.9 SU, respectively) and bradykinin (31.3+/-7.2 to 6.4+/-1.6 and 33.7+/-5.4 to 6.1+/-1.5 SU, respectively), but not to sodium nitroprusside, proved to be significantly (P<.05) increased compared with baseline. In essential hypertensive patients, oral treatment with lacidipine increased forearm vasodilation in response to acetylcholine and bradykinin, suggesting that this drug can improve endothelial function in patients with essential hypertension.

Ranitidine multicenter study on slow-response duodenal ulcer patients.

Twenty-six Italian Centers participated in the present study, the aim of which was to compare, in a double blind manner, the effectiveness of ranitidine 150 mg b.i.d. and ranitidine 300 mg b.i.d. in duodenal ulcer patients, who were considered likely to be slow-responders on the basis of clinical and anamnestic criteria. The results of this study show no statistically significant differences in healing rates between the two groups of patients treated with the different doses of ranitidine. After 4 weeks of treatment, healing rates were 73.3% for ranitidine 150 mg b.i.d. (131 patients) and 76.1% for ranitidine 300 mg b.i.d. (134) patients). After 8 weeks of treatment, cumulative healing rates were 91.5% and 93.9%, respectively. There were no differences in the relief of symptoms. The percentage of ulcers healed after four weeks of treatment with ranitidine 150 mg b.i.d. was lower than generally reported (1, 2), probably reflecting the strict selection criteria. However, at least in this population, the higher dose, with its increased inhibition of gastric acid secretion, failed to offer any significant advantage. Other factors, not dealt with in this study, might help identify the slow-responder and the non-responder, as also those who would benefit from an increased dose.

Different dosage regimens of ranitidine in the short-term therapy of duodenal ulcer: a multicentre trial.

A multicentre clinical trial was conducted in 114 Italian endoscopy centres in order to evaluate the comparative efficacy of four different ranitidine dosage regimens in the short-term treatment of active duodenal ulcer. Results were analysed in a total of 1745 patients randomly allocated to treatment with ranitidine 150 mg twice daily - morning and 19h30 (440 patients), ranitidine 150 mg twice daily - morning and 22h30 (438 patients), ranitidine 300 mg once daily at 19h30 (434 patients) or ranitidine 300 mg once daily at 22h30 (433 patients). The four groups were well matched for patient characteristics at entry. Initial treatment was for three weeks, with continuation to six weeks in cases with endoscopically unhealed ulcers at three weeks. Efficacy was evaluated in terms of endoscopic ulcer healing and control of pain symptoms in 24 h (daytime, nocturnal, daytime plus nocturnal). No statistically significant differences were found between any of the groups either as regards control of pain symptoms or ulcer healing rates (mean healing rates at three and six weeks were 77% and 98%, respectively). The results in this very large patient sample confirm equivalent efficacy of twice daily and single bedtime dose regimens and provide no evidence for superior efficacy of early evening compared with bedtime administration. In the population as a whole, concomitance of the three main risk factors (more than 20 cigarettes/day, ulcer size greater than 1 cm, deformation of the duodenal cap) was associated with a distinctly lower three-week healing rate (40.9% versus 87.4% in patients presenting none of these factors), though this difference tended to disappear at six weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma cortisol concentration following breakfasts of different composition in healthy subjects.

We measured plasma cortisol concentrations following breakfasts of different fat:carbohydrate ratio in 23 healthy subjects. A meal-related peak of plasma cortisol concentration was not found, as well as any difference in plasma cortisol levels following the two meals. Since the two meals elicited plasma glucose and plasma insulin levels which were significantly different, it is suggested that plasma cortisol is not acutely affected by ambient glucose and insulin concentrations. The same results were found when the study group was subdivided in nonobese (n = 13) and obese (Body Mass Index greater than n = 10), thus confirming the previous statement in the presence of different body weights.