Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance

The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3'-untranslated region (3'UTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3'UTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p = 0.747). However, the insertion allele was associated with a significant reduction in weight (p = 0.016), BMI (p = 0.009), and waist circumference (p = 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p = 0.036), whereas men lost more weight and had a greater decrease in BMI. The pentanucleotide insertion/deletion polymorphism in the 3'UTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.     

Antiretroviral therapy and declining AIDS mortality in New York City

OBJECTIVE: This study estimates the impact of Highly Active Antiretroviral Therapy (HAART) and other antiretroviral therapy combinations on reducing mortality risk for a cohort of HIV-infected persons living in New York City. MATERIALS AND METHODS: Data for this study come from the CHAIN project, an ongoing multiwave longitudinal study of HIV-infected persons is living in New York City (n = 700) initiated in 1994. The study sample is drawn from the clients of 43 medical and social service agencies and is broadly representative of New York City residents, who were aware of their positive serostatus at time of enrollment. Occurrences of deaths were obtained through routine field tracking and searches of death certificates and an online death registry. Information on other study variables was obtained through in-person interviews. A Cox proportional hazard model was applied to estimate the effects of medication on mortality risk. RESULTS: Mortality rates for the CHAIN cohort dropped steadily from a high of 131 deaths per 1000 persons/year in 1995 to 31 deaths per 1000 persons/year in 1999, with the historically low mortality rates continuing through 2000. Current use of HAART was associated with a 50% reduction in mortality risk (hazard ratio = 0.51, P <0.01). CONCLUSIONS: These results demonstrate that in the case of HAART, the therapeutic benefits of an innovative but costly medical treatment are reaching populations that traditionally have poor access to quality health care.     

Effects of estradiol,phytoestrogens, and Ginkgo biloba extracts against 1-methyl-4-phenyl-pyridine-induced oxidative stress

Oxidative stress has been recently considered as a mediator of nerve cell death in several neurodegenerative diseases. We studied the effect of the parkinsonism-inducing toxine 1-methyl-4-phenyl-pyridine (MPP+) on several parameters of cell distress using native and neuronal PC12 cells. Then, since estrogens have been reported to prevent neuronal degeneration caused by oxidative damage, we investigated the ability of 17beta- estradiol (E2); two Ginkgo biloba extracts, EGb 761 and Cp 202; as well as two flavonoids, quercetin and kaempferol, to rescue PC12 cells submitted to MPP+- induced oxidative stress. Our results consistently show that both Ginkgo biloba extracts could prevent cell death in native and neuronal PC12 cells, while in neuronal PC12 cells also quercetin and E2 could reverse MPP+ neurotoxic effet. Western blot analysis demonstrated that MPP+ injuries might modulate dopamine transporter (DAT) protein expression but not estrogen receptor beta (ERbeta) protein expression. EGb 761 and Cp 202 also modulate DAT and ERbeta protein expression in neuronal cells. From these studies, we outline the importance of testing estrogen-like plant-derived molecules as potent antioxidants and examine their effect on protein expression.     

Why do WIC participants fail to pick up their checks? An urban study in the wake of welfare reform

OBJECTIVES: This study explored whether work or immigration concerns affect women's participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: The sample included women who had withdrawn from the WIC program and current WIC clients from 1 center in New York City. Logistic regression analyses were used to predict noncollection of checks; demographic characteristics, program participation, and problems with the WIC program were independent variables. RESULTS: Strong predictors of noncollection of checks were job conflicts, transportation or illness problems, and WIC receipt by the woman herself (rather than by her children). CONCLUSIONS: Employment conflicts were related to failure to pick up WIC checks; immigration concerns were not. As a means of enhancing WIC participation, flexibility is recommended in terms of center hours, locations, and staffing and program check distribution policies.     

The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes

OBJECTIVE--To investigate the efficacy and safety of miglitol in combination with metformin in improving glycemic control in outpatients in whom type 2 diabetes is insufficiently controlled by diet alone. RESEARCH DESIGN AND METHODS--In this multicenter, double-blind, placebo-controlled study, 324 patients with type 2 diabetes were randomized, after an 8-week placebo run-in period, to treatment with either placebo, miglitol alone, metformin alone, or miglitol plus metformin for 36 weeks. The miglitol was titrated to 100 mg three times a day and metformin was administered at 500 mg three times a day. The primary efficacy criterion was change in HbA(1c) from baseline to the end of treatment. Secondary parameters included changes in fasting and postprandial plasma glucose and insulin levels, serum triglyceride levels, and responder rate. RESULTS--A total of 318 patients were valid for intent-to-treat analysis. A reduction in mean placebo-subtracted HbA(1c) of -1.78% was observed with miglitol plus metformin combination therapy, which was significantly different from treatment with metformin alone (-1.25; P = 0.002). Miglitol plus metformin also resulted in better metabolic control than metformin alone for fasting plasma glucose (-44.8 vs. -20.4 mg/dl; P = 0.0025), 2-h postprandial glucose area under the curve (-59.0 vs. -18.0 mg/dl; P = 0.0001), and responder rate (70.6 vs. 45.52%; P = 0.0014). All therapies were well tolerated. CONCLUSIONS--In type 2 diabetic patients, miglitol in combination with metformin gives greater glycemic improvement than metformin monotherapy.     

Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial

Context  The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns. Objective  To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an -glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT). Design, Setting, and Participants  International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years. Intervention  Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714). Main Outcome Measures  The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (=" BORDER="0">140/90 mm Hg). Results  Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P = .03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P = .02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P = .006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P = .02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P = .004) associated with acarbose treatment was still statistically significant. Conclusion  This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.      

The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial

Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and antiatherogenic properties. Therefore, the adiponectin gene is a promising candidate gene for type 2 diabetes. We investigated the single nucleotide polymorphisms (SNPs) +45T/G and +276G/T of the adiponectin gene as predictors for the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial, which aimed to investigate the effect of acarbose compared with placebo on the prevention of type 2 diabetes. Compared with the TT genotype, the G-allele of SNP +45 was associated with a 1.8-fold risk for type 2 diabetes (95% CI 1.12-3.00, P = 0.015) in the placebo group. Subjects treated with placebo and simultaneously having the G-allele of SNP +45 and the T-allele of SNP +276 (the risk genotype combination) had a 4.5-fold (1.78-11.3, P = 0.001) higher risk of developing type 2 diabetes compared with subjects carrying neither of these alleles. Women carrying the risk genotype combination had an especially high risk of conversion to diabetes (odds ratio 22.2, 95% CI 2.7-183.3, P = 0.004). In conclusion, the G-allele of SNP +45 is a predictor for the conversion to type 2 diabetes. Furthermore, the combined effect of SNP +45 and SNP +276 on the development of type 2 diabetes was stronger than that of each SNP alone.     

Sexual behaviors and sexual risk in a prospective cohort of HIV-positive men and women in New York City, 1994-2002: implications for prevention.

As an ever-increasing number of people infected with HIV are living longer, healthier lives, concerns about continued transmission are growing along with an awareness of the need to develop "prevention for positives." This study of HIV-positive adults in New York City is the first examination of patterns of sexual behavior in a large, representative cohort of HIV-infected individuals followed over an extended time period. A total of 968 HIV-positive adults were interviewed every 6-12 months between 1994 and 2002 and reported considerable variability in sexual behaviors over time. Many persons were not sexually active at all for months at a time; some continued to have multiple partners. Over one third of the cohort had one or more periods when they had engaged in unprotected sex with a partner who was HIV-negative or status unknown (unsafe sex) and one in five reported exchanging sex. Periods of unsafe sex alternated with periods of safer sex. Predictors of sexual risk varied by gender, and among men who had sex with men, and men sexually active with women only. Contextual factors such as partner relations, housing status, and receipt of HIV services were as important as individual attributes as predictors of unsafe sex and sex exchange. The variability observed in sexual risk behavior reported over time provides new insight into the importance of engaging persons living with HIV in ongoing prevention programs.