Biomedical subjects

Naveed Sattar

Publications and source records attributed to Naveed Sattar.

95 records · Page 6Linked to original sources

PubMed2002

Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial.

Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A number of reports show that the biguanide metformin improves ovarian function. However, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 94 patients randomized, 2 withdrew before treatment commenced, 47 received placebo, and 45 received metformin (850 mg, twice a day). The numbers discontinuing the study prematurely were higher in the treatment group (n = 15) than the placebo group (n = 5; P < 0.05). The ovulation frequency assessed by the ratio of luteal phase weeks to observation weeks was significantly (P < 0.01) higher in the treated group (23%) compared with the placebo (13%), and the time to first ovulation was significantly (P < 0.05) shorter [23.6 d; 95% confidence interval (CI), 17, 30; compared with 41.8 d; 95% CI, 28, 56]. The proportion of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of metformin on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the metformin group. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the metformin group, whereas the placebo group actually increased weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the metformin-treated group. Metabolic risk factor benefits of metformin treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy. There was an inverse relationship between body mass and treatment efficacy. We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries.

Adult↗

PubMed2002

A specific elevation in tissue plasminogen activator antigen in women with polycystic ovarian syndrome.

There is increasing evidence that elevated plasma levels of hemostatic factors [fibrinogen, factor VII, von Willebrand factor, fibrin D-dimer, and tissue plasminogen activator (t-PA) antigen] are independently linked to risk for coronary heart disease (CHD). Women with polycystic ovary syndrome (PCOS) are insulin-resistant and have increased risk for CHD and type 2 diabetes, but there are few data on hemostatic markers in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index (BMI) were recruited. Insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique. Factor VIIc was determined by a clotting assay; fibrinogen was determined by nephelometry; and t-PA, D-dimer, and von Willebrand factor antigens were measured by ELISA techniques. Of these hemostatic markers, only t-PA concentration was significantly (P = 0.013) elevated in women with PCOS relative to controls. t-PA correlated with BMI in both PCOS and controls (r = 0.428, P < 0.1; and r = 0.686, P < 0.01) and inversely with the insulin sensitivity index (r = -0.590, P < 0.05; and r = -0.620, P < 0.05, respectively). After further adjustment for BMI and insulin sensitivity, there remained a significant difference in t-PA between cases and controls (P = 0.017). Together, age and insulin sensitivity explained 39% of the variance in t-PA in women with PCOS (P < 0.05). Total testosterone did not correlate significantly with t-PA in either group. We conclude that women with PCOS have significantly increased t-PA concentrations relative to women with normal menstrual rhythm and normal androgens. We suggest that elevated t-PA and dysfibrinolysis may be a factor in the increased cardiovascular morbidity seen in PCOS.

Adult↗

PubMed2002

C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study.

Accumulating evidence implicates inflammation as a potential pathway in the pathogenesis of type 2 diabetes. The objective of the present study was to assess the ability of C-reactive protein (CRP) to predict the development of diabetes in middle-aged men in the West of Scotland Coronary Prevention Study. Baseline plasma samples for CRP measurement were available for 5,245 men of whom 127 were classified as having a transition from normal glucose control to overt diabetes during the study, based on American Diabetes Association criteria. Baseline CRP was an important predictor of the development of diabetes in univariate analysis (hazard ratio [HR] for an increase of 1 SD = 1.55; 95% CI 1.32-1.82; P < 0.0001). In multivariate analysis, CRP remained a predictor of diabetes development (HR 1.30; 95% CI 1.07-1.58; P = 0.0075) independent of other clinically employed predictors, including baseline BMI and fasting triglyceride and glucose concentrations. Moreover, there was a graded increase in risk across CRP quintiles throughout the study, evident at even 1 year of follow-up. The highest quintile (CRP >4.18 mg/l) was associated with a greater than threefold risk of developing diabetes (HR 3.07; 95% CI 1.33-7.10) in a multivariate analysis at 5 years. Thus, CRP predicts the development of type 2 diabetes in middle-aged men independently of established risk factors. Because CRP, the most commonly used acute-phase protein in clinical practice, is very stable in serum, our observations have clinical potential in helping to better predict individuals destined to develop type 2 diabetes. They also add to the notion that low-grade inflammation is important in the pathogenesis of type 2 diabetes.

Acute-Phase Reaction↗

PubMed2002

Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study.

OBJECTIVE: Recent evidence suggests that C-reactive protein (CRP) may predict development of diabetes in Caucasian populations. We evaluated CRP as a possible risk factor of the development of diabetes and metabolic syndrome in a 6-year study of 515 men and 729 women from the Mexico City Diabetes Study. RESEARCH DESIGN AND METHODS: Baseline CRP, indexes of adiposity, and insulin resistance (homeostasis model assessment [HOMA-IR]) were used to predict development of the metabolic syndrome, defined as including two or more of the following: 1) dyslipidemia (triglyceride >/=2.26 mmol/l or HDL cholesterol </=0.91 mmol/l in men and </=1.17 mmol/l in women; <35 and 40 mg/dl for men and women); 2) hypertension (blood pressure >140/90 mmHg or on hypertensive medication); or 3) diabetes (1999 World Health Organization criteria). RESULTS: At baseline, CRP correlated significantly (P < 0.001) with all metabolic indexes in women, but less so in men. After 6 years, 14.2% of men and 16.0% of women developed the metabolic syndrome. Compared with tertile 1, women with CRP in the highest tertile had an increased relative risk of developing the metabolic syndrome by 4.0 (95% CI 2.0-7.9) and diabetes by 5.5 (2.2-13.5); these risks changed minimally after adjusting for BMI or HOMA-IR. The area under receiver-operating characteristic (ROC) curve for the prediction of the development of the syndrome was 0.684 for CRP, increasing to 0.706 when combined with BMI and to 0.710 for a complex model of CRP, BMI, and HOMA-IR. CONCLUSIONS: CRP was not a significant predictor of the development of the metabolic syndrome in men. Our data strongly support the notion that inflammation is important in the pathogenesis of diabetes and metabolic disorders in women.

Area Under Curve↗

PubMedDate not supplied

Elimination of electrically induced iontophoretic artefacts: implications for non-invasive assessment of peripheral microvascular function.

Iontophoretic assessment of skin microvascular function is complicated by the occurrence of electrically induced hyperaemia, especially at the cathode. Studies were performed to identify means of reducing such effects. Skin vasodilator responses were measured using a laser Doppler imager that controlled iontophoretic current delivery. A novel feature involved monitoring voltage across the iontophoresis chambers. Comparison between responses to vehicle (distilled H(2)O), acetylcholine (ACh) and sodium nitroprusside (SNP) showed electrically induced hyperaemia at the cathode associated with the vehicle, whose time course overlapped with that of the SNP response. Voltage across the chambers containing drugs dissolved in H(2)O was significantly (p = 0.018, n = 7) lower than the voltage profile of H(2)O alone. H(2)O iontophoresis was associated with cathodal hyperaemic responses in most subjects, whereas a 0.5% NaCl vehicle produced lower voltages and eliminated this artefact. Voltage.time integral rather than charge was the prime determinant of electrically induced hyperaemic responses. No significant correlation was found between skin fold thickness and either calculated skin resistance (r(2) = 0.0002) or vascular response to ACh (r(2) = 0.13). Smaller chamber size led to higher voltages and greater electrically induced hyperaemic responses. These appear to be prostaglandin dependent as they were ablated by cyclooxygenase inhibition. Use of a low-resistance vehicle combined with larger chamber sizes and lower currents can prevent such artefacts, thereby increasing the robustness of this methodology for clinical assessment of endothelial function.

Acetylcholine↗