c-peptide and benfluorex

To determine the effect of benfluorex on glycaemic control in obese insulin-requiring Type 2 diabetes, 76 patients (aged 53.8 +/- 12.8 years) receiving insulin (> or = 0.5 IU/kg) and an appropriate low-calorie diet were evaluated after a 1-month run-in followed by a 3-month double-blind treatment period (3 tablets daily) with benfluorex (B; n = 37) vs placebo (P; n = 39). At inclusion, the B and P groups respectively did not differ in body weight (80.9 +/- 10.3 vs 77.2 +/- 9.1 kg), body mass index (BMI) (30.1 +/- 4.6 vs 29.0 +/- 2.3 kg/m2) or fasting blood glucose (11.22 +/- 4.33 vs 10.35 +/- 4.42 mmol/l). However, daily insulin dose and HbA1c levels were higher in the B group (59.9 +/- 18.6 vs 50.4 +/- 12.8 IU, p = 0.012; and 7.72 +/- 1.60 vs 6.96 +/- 1.27%, p = 0.025, respectively). After 3 months of treatment, the decrease in daily insulin dose was greater in the B group (8.7 +/- 10.1 vs 2.7 +/- 8.1 IU; p = 0.032), with a decrease in HbA1c (-0.73 +/- 1.74%, p = 0.026), vs no change in the P group (+0.01 +/- 1.65%, NS) and a tendency towards a greater decrease in fasting blood glucose (-1.43 +/- 5.41 vs +0.42 +/- 3.78 mmol/l respectively). Body weight and BMI were also lower in the B group (1.77 ñ 2.27 vs 0.21 ñ 2.68 kg, p = 0.013; and 0.64 +/- 0.84 vs 0.07 +/- 1.07 kg/m2, p = 0.019, respectively) in parallel with the decrease in insulin dose. Triglycerides decreased in the B group vs an increase in the P group (-0.54 +/- 2.04 vs +0.21 +/- 0.70 mmol/l p = 0.06). Total cholesterol decreased within the B group (-0.47 +/- 1.01 mmol/l; p = 0.013) and vs the P group (intergroup p = 0.006). Adverse events were reported in 11 patients in the B group vs 5 in the P group (NS), causing dropout in only one case (intercurrent illness, P group). Addition of benfluorex in obese insulin-requiring Type 2 diabetes thus enhances glycaemic control and lowers both daily insulin requirement and body weight. Benfluorex + insulin is a valid alternative for obese patients who remain poorly controlled despite insulin or who require high doses of insulin.

Topics: Adolescent; Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Fenfluramine; Humans; Hypolipidemic Agents; Insulin; Insulin Resistance; Male; Middle Aged; Monitoring, Physiologic; Obesity; Postprandial Period

Most obese patients with noninsulin-dependent diabetes mellitus (NIDDM) are initially treated with diet, then with oral hypoglycemic agents, eventually with insulin. However several reports indicate that in these patients insulin therapy has little chance to control glucose metabolism, promotes weight gain and arterial hypertension, and is likely to aggravate insulin resistance. In this randomized, double-blind trial vs. placebo (P) we evaluated in 29 obese NIDDM patients poorly controlled by insulin (daily insulin doses 48.7 +/- 4.0 U/day, HbA1c 10 +/- 0.27%, mean daily blood glucose levels 12.3 +/- 0.3 mmol/L, fasting C-peptide 1.8 +/- 0.2, C-peptide after 1 mg iv glucagon 3.2 +/- 0.3 ng/mL, means +/- SE), the clinical and metabolic effects of benfluorex (B), a lipid-lowering drug able to improve insulin sensitivity. After a 2-3 week run-in period (1 tablet P at dinner and diet 800 cal/day to lose 5% of the initial body weight (BWi), patients received a 1000 kcal/day diet and were randomized to B, 150 mg/ tablet, or P (3 tablets/day); the time limit was set at a 10% decrease of BWi or at 90 days. At the end of run-in there was a significant reduction of BWi (P < 0.001), fasting (P = 0.002) and mean daily blood glucose levels (P < 0.001), triglycerides (P = 0.02), cholesterol (P < 0.001) and daily insulin doses (P < 0.001). At the end of the double-blind trial, weight-loss was greater (P < 0.05), faster (P = 0.018), and more frequent (P < 0.05) with B than with P, and systolic blood pressure (P < 0.05) decreased only with B. Considering only patients with a 10% decrease of BWi (B = 15, P = 10), HbA1c (P < 0.001) decreased only with B, while fasting insulin levels decreased with both B (P < 0.01) and with P (P < 0.05). Insulin sensitivity was evaluated by means of a double infusion test (LDIGIT, insulin 25 mU/Kg/h plus glucose 4 mg/kg/min, lasting 150 min) at the end of run-in and at the end of the double-blind trial; at the end of the double-blind trial steady state blood glucose (SSBG, P < 0.05), free fatty acids (FFA, P < 0.05) and blood beta-hydroxybutyrate (P < 0.05) decreased only with B, while blood glycerol decreased both with both P (P < 0.05) and B (P < 0.06). At the end of the double-blind trial, C-peptide release was unchanged with either P or B. In conclusion, benfluorex potentiates the effects of hypocaloric diet on weight loss and on glycemic control in obese NIDDM patients treated with insulin, and this effect seems to be the result of an

Topics: 3-Hydroxybutyric Acid; Appetite Depressants; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Fenfluramine; Glucose; Glycerol; Humans; Hydroxybutyrates; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; Obesity; Placebos

Benfluorex hydrochloride has known lipid- and glucose-lowering effects. We evaluated the change in lipids, fasting glucose, and insulin sensitivity in ten obese type 2 diabetic patients after treatment with benfluorex or a placebo for 2 weeks using a double-blind, cross-over design. Insulin sensitivity was measured using the euglycaemic-hyperinsulinaemic glucose clamp technique at two insulin infusion rates for 2 h each: 0.05 U/kg per h (clamp 1) and 0.10 U/kg per h (clamp 2). Mean fasting glucose decreased from 13.1 +/- 1.1 to 10.2 +/- 0.9 mmol/l after benfluorex (p < 0.001) and rose from 11.9 +/- 0.9 to 13.3 +/- 1.0 mmol/l after the placebo (p = 0.028). Insulin did not change significantly. Glucose uptake (GU) as a parameter for insulin sensitivity was compared for treatment with benfluorex versus the placebo. Total GU during clamp 1 was 643.4 +/- 323.8 mmol after benfluorex and 250.1 +/- 193.3 mmol after the placebo (p = 0.035), and during clamp 2, 2490.7 +/- 490.5 mmol after benfluorex and 1544.3 +/- 693.9 mmol after the placebo (p = 0.018). The dynamic analysis on the last 30 min of clamp 2 showed a significant difference in glucose infusion rate (GIR) profile, with mean levels yielding 5.36 mmol/kg per min after benfluorex and 3.87 mmol/kg per min after the placebo (p = 0.018); there were no differences in plasma insulin concentrations or plasma glucose levels. It is concluded that in this short-term study benfluorex increases insulin sensitivity in obese type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Blind Method; Fenfluramine; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Middle Aged; Obesity

To evaluate the change in lipids and insulin sensitivity in 10 obese type II diabetic patients after treatment with benfluorex or placebo for 2 wk.. The study had a double-blind, cross-over design. Insulin sensitivity was measured with the euglycemic hyperinsulinemic glucose clamp technique at two different insulin infusion rates: 0.05 (clamp 1) and 0.10 U.kg-1.h-1 (clamp 2).. Subanalysis of the glucose infusion rate under steady-state conditions in the last 30 min of clamp 2 yielded a glucose infusion rate of 5.36 and 3.87 mmol.kg-1.min-1 after benfluorex and placebo, respectively (P = 0.018).. Benfluorex increases insulin sensitivity in obese type II diabetic patients.

Topics: Apolipoprotein A-I; Apolipoproteins B; Appetite Depressants; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fenfluramine; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Middle Aged; Multivariate Analysis; Obesity; Placebos; Triglycerides

Benfluorex is a hypolipidemic agent with biguanide-like properties. Its action on glucose metabolism was evaluated in 6 NIDDM patients previously treated with diet alone. Before and after 1 month of benfluorex therapy (450 mg/day p.o.), an euglycemic (100 mg/dl) insulin (40 mU/m2/min) clamp was performed along with 3-3H-glucose infusion and indirect calorimetry. Benfluorex did not affect body weight, while it reduced fasting plasma glucose (144 +/- 16 vs 119 +/- 8 mg/dl; P < 0.05), glycosylated hemoglobin (6.8 +/- 0.8 vs 6.4 +/- 0.4 percent) and fructosamine (2.9 +/- 0.6 vs 2.4 +/- 0.2 mmol/l; P < 0.05). Both triglycerides (2.3 +/- 0.6 vs 1.9 +/- 0.5 mmol/l) and total cholesterol (5.7 +/- 0.7 vs 5.2 +/- 0.6 mmol/l) declined. No changes occurred in plasma fatty acid, insulin, and C-peptide. Basal hepatic glucose production did not change and it was completely suppressed during the clamp studies both before and after benfluorex. Basal oxidation rates of carbohydrates and lipids did not change significantly. During the insulin clamp study, insulin-mediated glucose disposal increased after benfluorex (5.7 +/- 0.3 vs 4.8 +/- 0.2 mg/kg/min; P < 0.01). Lipid oxidation was equally suppressed before and after therapy with benfluorex. Glucose oxidation was not enhanced after benfluorex while non-oxidative glucose metabolism was significantly improved (2.2 +/- 0.7 vs 3.4 +/- 0.4 mg/kg/min; P < 0.05).. short-term benfluorex administration a) improves glucose and lipid control, b) improves insulin action by enhancing non-oxidative glucose metabolism, c) does not affect basal insulin secretion. The long-term effect of benfluorex treatment remains to be evaluated.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Fenfluramine; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Hypolipidemic Agents; Insulin; Liver; Male; Middle Aged