Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.     

Post-thaw sperm motility, cAMP concentration and membrane lipid peroxidation after stimulation with pentoxifylline and platelet-activating factor

Earlier studies have demonstrated that pentoxifylline (PTX) and platelet-activating factor (PAF) can significantly improve the motion parameters of post-thaw human spermatozoa. This study has investigated the effects of PAF, PTX and their combination on cyclic adenosine monophosphate (cAMP) concentrations and membrane lipid peroxidation (LPO) in post-thaw human spermatozoa. Washed spermatozoa from normal volunteers (n = 10) were cryopreserved in Test-yolk buffer using a standard protocol. After 2 weeks the sperm samples were thawed, washed and incubated with either 1 microM PAF, 3 mM PTX or 0.5 microM PAF plus 1.5 mM PTX. Video sequences were recorded at 0, 30, 60, and 120 min for analysis of sperm motion parameters using the Cell Track Sperm Analysis System. Concentrations of cAMP were assessed by radioimmunoassay, and LPO levels were measured by malondialdehyde-thiobarbituric acid reactivity. Our studies indicate a time-course stimulatory effect with overall maximal stimulation observed in samples treated with the combination of PAF and PTX. The maximal stimulation of percentage motility compared to control was observed at 60 min in samples treated with PAF, PTX, or PAF plus PTX. PAF plus PTX stimulated straight-line velocity (VSL), curvilinear velocity (VCL) and lateral head displacement (ALH) after 30 min incubation. The primary effect of PAF was observed on VSL, while the main effect of PTX was on VCL. cAMP concentrations were 3-fold higher than controls in samples treated with PTX or PAF plus PTX. cAMP concentrations in PAF-treated samples did not differ significantly from controls. No significant differences were observed between any groups for LPO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria

A total of 10 restriction site polymorphisms have been identified at the human phenylalanine hydroxylase locus using a full-length human phenylalanine hydroxylase cDNA clone as a hybridization probe to analyze human genomic DNA. These polymorphic patterns segregate in a Mendelian fashion and concordantly with the disease state in various PKU kindreds. The frequencies of the restriction site polymorphisms at the human phenylalanine hydroxylase locus among Caucasians are such that the observed heterozygosity in the population is 87.5%. Thus, most families with a history of classical phenylketonuria can take advantage of the genetic analysis for prenatal diagnosis and carrier detection of the hereditary disorder.     

Effect of dietary selenium on tumor induction by an oncogenic virus

Streptokinase-streptodornase (SK-SD) induced immediate and delayed skin test reactions in a high proportion of patients with disorders in which beta-streptococcal infection may be involved. The P-K test and absorption experiments with antigen or anti-IgE suggested that the immediate reaction was mediated by specific IgE antibody against SK-SD. Furthermore, the ratio of specific IgE antibody against SK-SD to total IgE was roughly calculated to be 20 percent. Finally, the RAST technique was applied to detect specific IgE antibody against SK-SD which showed high radiocounts bound to SK-SD-coupled particles in the sera of nephrotic patients who had a strong immediate reaction against SK-SD and a severe disease state.     

Initial experience of clinical pharmacology and clinical pharmacy interactions in a clinical pharmacokinetics consultation service

International statistics indicate that there is a close correlation between the consumption of saturated fats (dairy fats and meat fats) and the mortality from coronary heart disease (CHD), and this conception has been confirmed by many epidemiological studies. Such studies alone, however, cannot prove the existence of a cause-and-effect relationship between these two variables; dietary intervention trials are needed. The Finnish Mental Hospital Study was such a trial, conducted in two hospitals near Helsinki in 1959--1971. Practically total replacement of dairy fats by vegetable oils in the diets of these hospitals was followed by a substantial reduction in the mortality of men from CHD. Total mortality also appeared to be reduced. As to the causes of death other than CHD, none was significantly influenced by dietary change. This was also true for malignant neoplasms. To alleviate the burden of CHD on public health, many investigators have recommended important changes in the quantity and quality of dietary fats.     

The quantity and distribution of radiolabeled dexamethasone delivered to tissue by iontophoresis

A pilot study was conducted in the first of two monkeys using either radiolabeled Dm-Na-P or radiolabeled hydrocortisone sodium succinate, together with lidocaine HCl. This study indicated an approximately tenfold increase in the quantity of Dm-Na-P delivered to the test electrodes (4 mA; 20 minutes) whereas the quantity of hydrocortisone delivered from the test electrodes was only marginally (approximately 10%) increased as compared with that from the controls. In terms of an anti-inflammatory activity, the effective dose of Dm-Na-P in all tissue layers underlying the test electrodes was at least tenfold that of the hydrocortisone. Therefore, further trials with hydrocortisone were abandoned. In the second animal, positive test electrodes (5 mA; 20 minutes, were sited over five joints on the right side of the body and matching control electrodes (0 mA; 20 minutes) were placed over corresponding joints on the left side of the body. The control and test electrodes each contained 1.0 ml tritium-labeled Dm-Na-P (approximately 4.0 mg) and 2.0 ml 4% lidocaine HCl (80 mg). Local tissue concentrations of Dm-Na-P were higher than those that would be obtained by systematic therapy and lower than would be obtained by local injection.     

Satiety elicited by the C-terminal octapeptide of cholecystokinin-pancreozymin in normal and VMH-lesioned rats

The frequency and severity of CNSLD was studied in workers of an Hungarian firm (Ganz-Mavag) by means of questionnaire. Symptoms of CNSLD can be found more frequently in workers with air pollution than in those without. The symptoms of CNSLD show an age-dependence with regard to frequency and grade of severity, the single symptoms of CNSLD not occurring simultaneously and changing in their proportional frequency.