A preliminary multicentre study of the treatment of recently diagnosed type 1 diabetes by combination nicotinamide-cyclosporin therapy.

The aim of the present study, a pilot trial, was to find out if nicotinamide (50 mg kg-1 day-1) in combination with cyclosporin A favours remission in recently diagnosed Type 1 diabetic patients, and if it postpones relapse even when cyclosporin A is administered in decreasing doses (trough blood level 300-500 micrograms l-1 until month 4, and 100-300 micrograms l-1 until month 9) and then discontinued. The criteria for inclusion in the study and the follow-up protocol were the same as those used in the Cyclosporin Diabetes France (CDF) programme in which all five of the centres involved in this study participated. The data of the present preliminary open study were therefore compared retrospectively with those of the placebo (CDF-placebo) and cyclosporin (CDF-active) group of the CDF programme. Clinical remission (fasting plasma glucose less than 7.8 mmol l-1, postprandial plasma glucose less than 11.1 mmol l-1, HbA1c less than 7.5% with neither insulin nor oral hypoglycaemic agents) was achieved within 6 months in 12 out of 35 patients (34%) vs 16 out of 63 (25%) in CDF-active and 11 out of 59 (19%) in CDF-placebo. Remission was achieved by month 9 in 6 out of 35 patients (17%) vs 13 out of 54 (24%) in CDF-active and 3 out of 52 (6%) in CDF-placebo. By 12 months remission persisted in 3 out of 35 patients (9%) vs 11 out of 63 (17%) in CDF-active and 0 out of 52 (0%) in CDF-placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nicotinamide treatment on the residual insulin secretion in type 1 (insulin-dependent) diabetic patients.

In vivo and in vitro experiments have shown that nicotinamide enhances the regeneration of rat B cells. Nicotinamide has been administered to human subjects at a dose of 3 g/day for more than one year without any serious side effects. A trial was conducted to study if nicotinamide could protect B cells in Type I (insulin-dependent) diabetic patients with established diabetes, but still with residual insulin secretion, the latter being evaluated throughout the study period. A randomized double-blind study was carried out on 26 Type I diabetic patients aged 15 to 40 years who had been treated with insulin for 1 to 5 years but who had a residual insulin secretion characterized by a glucagon stimulated C-peptide level higher than 0.1 nmol/l. They were given either 3 g/day of nicotinamide or a placebo for nine months. At baseline the treated and control groups did not differ according to age, diabetes duration, insulin dose, HbA1c or C-peptide levels. Three patients dropped out of the study. At 9 months there were no significant changes in the insulin doses required. However, HbA1c rose in the control group (8.1 +/- 0.4 vs 9.8 +/- 0.5%, p less than 0.05) but not in the nicotinamide treated group (7.5 +/- 0.5 vs 6.9 +/- 0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effect of glyburide on insulin sensitivity in type I diabetic patients.

Possible extrapancreatic effects of glyburide on insulin action were studied in six patients with insulin-dependent diabetes mellitus. Each patient was studied on two separate occasions with continuous iv infusions of either glyburide (0.3 mg/h after a 1-mg iv bolus dose) or NaCl. During the studies blood glucose concentrations were controlled by a glucose-controlled infusion system (Biostator). The study included the 12-h period after the evening meal, followed by a 4-h period during which euglycemic hyperinsulinemic clamp studies were performed at two rates of insulin infusion: 1 and 10 mU/kg.min. During the glyburide infusion, the Biostator-determined insulin delivery rate was similar to that during the NaCl infusion for the first 6 h after the meal, but it decreased by 32% between the 6th and 12th hours after the meal. During the hyperinsulinemic clamp studies, glucose was delivered at a significantly higher rate when glyburide was infused; this was true for both rates of insulin infusion [5.6 +/- 1.9 (+/- SD) vs. 3.6 +/- 1.4 mg/kg.min and 12.1 +/- 2.4 vs. 9.1 +/- 2.1 mg/kg.min; P less than 0.05, glyburide vs. NaCl, respectively]. Plasma C-peptide was undetectable in all patients during both studies. These results indicate that 1) glyburide has an acute effect on insulin action in insulin-dependent diabetic patients; and 2) this effect occurs at physiological as well as pharmacological insulin concentrations.