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Cytochrome P450 2E1 (CYP2E1) is a phase I detoxification enzyme, which is induced by chronic alcohol consumption. It is involved in the activation of numerous carcinogens and in the production of free radicals. As it has previously been shown to be induced in diabetic and obese rats, the aim of this study was to investigate its induction level in poorly-controlled diabetics and in obese patients (Body Mass Index > 30 kg/m2). CYP2E1 activity was determined in 35 diabetic and 17 obese patients by using the in vivo chlorzoxazone hydroxylation test. Even though the glucidic parameters were highly disturbed (mean fasting glycemia > 7.9 mmol/L, post prandial glycemia > 12.2 mmol/L and fructosamine > 326 mumol/L), CYP2E1 activity was not enhanced either in insulin-dependent diabetics (IDDs, n = 7) nor in non-obese non-insulin-dependent diabetics (NIDDs, n = 15) when compared to controls (n = 42) (0.21 +/- 0.03, 0.33 +/- 0.03 and 0.30 +/- 0.02, respectively, mean +/- SEM). However, this activity was lower in IDDs when compared to NIDDs (P < 0.05). In obese patients, with (n = 13) or without (n = 17) NIDD mellitus, CYP2E1 activity was increased by a mean of 40% when compared to controls. In addition, positive correlations were found in all subjects (controls or patients, n = 74) between CYP2E1 activity and serum cholesterol (r = 0.42, P < 0.0001), triglycerides (r = 0.44, P < 0.0001) and BMI (r = 0.36, P < 0.001). Accordingly, subjects with cholesterol and/or triglyceride serum levels above 6.4 and 1.8 mmol/L, respectively, displayed a mean increase of 40% of their CYP2E1 activity vs subjects within the above values. It is believed that individuals with increased CYP2E1 activity are more susceptible to the adverse effects of CYP2E1-mediated activation of toxins and carcinogens.

OBJECTIVE:To determine the effect of orlistat on weight reduction and the long-term maintenance of this weight loss when associated with a continuous mildly reduced energy diet. DESIGN: A multicenter, 18-month, double-blind study conducted in 81 hospital centers. Patients were randomized to orlistat 120 mg or placebo three times daily in conjunction with a mildly reduced-energy diet maintained throughout the study. SUBJECTS: In total, 696 otherwise healthy, overweight patients aged 18-65 y (BMI Z28 kg/m 2 ) were randomized to treatment with orlistat (n ¼ 346) or placebo (n ¼ 350). MEASUREMENTS: Body weight, anthropometry, lipid and glycemic control parameters and blood pressure. RESULTS: After 18 months, patients treated with orlistat lost significantly more body weight compared with placebo (À6.570.8 vs À3.070.8%; P ¼ 0.0005). After 12 months, 32.9% of orlistat vs 24.5% of placebo patients lost Z10% of their initial weight (P ¼ 0.04). A significantly greater number of patients receiving orlistat treatment maintained this Z10% weight loss compared to those receiving placebo (28.1 vs 13.8%; Po0.0001). Compared with placebo, orlistat was associated with a greater decrease in fasting blood glucose (À0.8670.12 vs À0.2970.18 mmol/l; Po0.05) and LDL-cholesterol (À13.071.3 vs À7.071.3%; Po0.001). CONCLUSION: A clinically meaningful reduction in body weight and the maintenance of this weight loss is achievable with orlistat treatment and dietary restriction over a period of 18 months. This weight loss resulted in an improvement in risk factors for coronary heart disease.

Educating GPs in the French adaptation of the SDM programme improves glycaemic control in a primary care setting, without significantly increasing healthcare costs.

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