Tomasz Miazgowski

Duloxetine Versus Placebo in Patients With Chronic Low Back Pain: A 12-Week, Fixed-Dose, Randomized, Double-Blind Trial

UNLABELLED This randomized, double-blind, placebo-controlled study assessed efficacy and safety of duloxetine in patients with chronic low back pain (CLBP). Adults (n = 401) with a nonneuropathic CLBP and average pain intensity of ≥ 4 on an 11-point numerical scale (Brief Pain Inventory [BPI]) were treated with either duloxetine 60 mg once daily or placebo for 12 weeks. The primary measure was BPI average pain. Secondary endpoints included Patients Global Impressions of Improvement (PGI-I), Roland Morris Disability Questionnaire (RMDQ-24), BPI-Severity (BPI-S), BPI-Interference (BPI-I), and response rates (either ≥ 30% or ≥ 50% BPI average pain reduction at endpoint). Health outcomes included Short Form-36, European Quality of Life-5 Dimensions, and the Work Productivity and Activity Impairment questionnaire. Safety and tolerability were assessed. Compared with placebo-treated patients, duloxetine-treated patients reported a significantly greater reduction in BPI average pain (P ≤ .001). Similarly, duloxetine-treated patients reported significantly greater improvements in PGI-I, BPI-S, BPI-I, 50% response rates, and some health outcomes. The RMDQ and 30% response rate showed numerical improvements with duloxetine treatment. Significantly more patients in the duloxetine group (15.2%) than patients in the placebo group (5.4%) discontinued because of adverse events (P = .002). Nausea and dry mouth were the most common treatment-emergent adverse events with rates significantly higher in duloxetine-treated patients. PERSPECTIVE This study provides clinical evidence of the efficacy and safety of duloxetine at a fixed dose of 60 mg once daily in the treatment of chronic low back pain (CLBP). As of December 2009, duloxetine has not received regulatory approval for the treatment of CLBP.

The prevalence of 6 weeks postpartum abnormal glucose tolerance in Caucasian women with gestational diabetes.

AIMS To evaluate the incidence of impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes in 318 Caucasian women with gestational diabetes (GDM) at 6 weeks postpartum. METHODS All women had 75g OGTT and the following data were collected: age, height, weight, results of the challenge 50g and diagnostic 75g OGTT, and glycated hemoglobin (HbA1c). RESULTS 13.5% of women had abnormal glucose tolerance, including 1.3% of diabetes, 2.5% of IFG and 7.5% of IGT. None of the prepregnancy independent variables, such as age, body mass index, prior GDM, prior macrosomia, family history of type 2 diabetes and multiparity was a predictor for the abnormal OGTT. In contrast, pregnancy-related risk factors, like gestational week at GDM diagnosis (P=0.001), glucose values in the challenge (P=0.007) and diagnostic (P=0.02) OGTTs and HbA1c (P=0.01) were significantly associated with the persistence of glucose intolerance after delivery. CONCLUSION The incidence of postpartum abnormal glucose tolerance in Caucasian women with GDM was 13.5% and was associated with an early diagnosis of GDM, severity of hyperglycemia and requirement for insulin therapy. The diagnosis of GDM should initiate a lifelong monitoring of glucose tolerance to minimize the risk of developing overt diabetes.

Are short women at risk for gestational diabetes mellitus

OBJECTIVE The aim of the study was to assess the influence of height variations on the risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We analyzed the medical records of 1830 Caucasian women with GDM and 1011 healthy pregnant women. The following data were collected: age, prior macrosomia, prior GDM, parity, history of type 2 diabetes in first-degree relatives, weight before pregnancy, weight gain during pregnancy, glucose level at the first obstetric visit, results of the glucose challenge test and oral glucose tolerance test (OGTT), HbA1c, and method for treatment of GDM. RESULTS Women with GDM were significantly shorter than the healthy controls (165.7+/-5.6 vs 163.8+/-6.6 cm; P<0.001). The differences in height were not significant between GDM women who required insulin therapy and those treated with diet alone (P=0.12). All the studied variables, including height, were independently associated with GDM. Even after adjustment for confounding variables, height was still associated with GDM (odds ratio 0.958, 95% confidence interval: 0.94-0.97; P<0.00001). In women with GDM diagnosed by 75-g OGTT, we found a significant inverse association of height adjusted for age and pregravid weight with 2-h glucose level (beta=-0.12; P<0.0001). CONCLUSIONS Caucasian women with GDM are shorter than pregnant women without GDM regardless of the diagnostic criteria used or the severity of glucose intolerance. Although height is an independent predictor for GDM, its predictive value for identifying women at risk is relatively low and should not be considered in selective screening for this disease.

Factors influencing risk of macrosomia in women with gestational diabetes mellitus undergoing intensive diabetic care

AIMS The aim of study was to assess the impact of intensive diabetic care, defined as target values for fasting glucose of 60-90mg/dl and 1-h postprandial glucose of below 130mg/dl, on neonatal birth weight in relation to risk indicators for fetal macrosomia in women with gestational diabetes mellitus (GDM). METHODS In women with (N=543) and without GDM (N=1011) age, height, weight, previous GDM, history of macrosomia, family history of type 2 diabetes, parity and weight gain during pregnancy were recorded. RESULTS Neonatal birth weight and frequency distribution of macrosomia and infants with small for gestational age did not differ between women with and without GDM. Neonatal birth weight was strongly associated with traditional risk predictors for GDM, such like prior macrosomia (OR 5.03; 95%CI 3.36-7.53), prior GDM (OR 2.52; 95%CI 1.37-4.64) and prepregnancy body mass index (BMI)>23kg/m(2) (OR 1.82; 95%CI 1.27-2.63). CONCLUSIONS Neonatal birth weight and the incidence of macrosomia were similar in comparison of pregnancies with and without GDM. In the population of Caucasian women the strongest single predictors for macrosomia were prior macrosomia, BMI>23kg/m(2) and prior GDM.

Low predictive value of traditional risk factors in identifying women at risk for gestational diabetes

Background. There is no worldwide agreement on the best way to screen for gestational diabetes mellitus (GDM), and different diagnostic methods have been developed in order to identify women at risk. The aim of this study was to evaluate the prevalence and predictive value of the traditional risk indicators for GDM in a large group of Caucasian women. Methods. We evaluated the frequency distribution of age, body mass index (BMI), prior macrosomia, prior GDM, and family history of diabetes of 1,414 pregnant women with GDM and 1,011 healthy pregnant women. Results. The distribution of risk factors in both groups was different and significantly higher in GDM women. The cut‐off value for age was 28years, and 23kg/m2 for BMI. The accumulation of two or more risk factors was frequent in GDM, but not in healthy women. By multiple logistic regression, there were significant interactions between independent variables of interest and GDM (OR: 3.19; p<0.001; sensitivity: 57.9%, specificity: 69.8%). The strongest predictors were prior GDM (OR: 4.35; 95% CI: 2.42–7.82) and a family history of diabetes (OR: 3.03; 95% CI: 2.47–3.72); less predictive were age (OR: 1.69; 95% CI: 1.44–1.99), BMI (OR: 1.50; 95% CI: 1.28–1.77), and prior macrosomia (OR: 1.64; 95% CI: 1.19–2.26). Conclusions. Selective screening based on traditional risk factors for GDM had relatively low sensitivity, and identified <60% of Caucasian women at risk. The cut‐off value for BMI as a risk indicator (23kg/m2) was lower than that proposed by guidelines about screening for GDM.

Not insulin but insulin sensivity, leptin, and Cortisol are major factors regulating serum acylated ghrelin level in healthy women

It has been suggested that insulin and glucose are the most important factors for ghrelin secretion. Most of these studies were performed using total ghrelin assays, detecting two forms of ghrelin (acylated and desacyl), derived from the same peptide precursor but having different biological effects. This study was therefore designed to characterize associations between serum acylated ghrelin levels (Ghr), selected adipocytokines, hormones, and carbohydrate metabolism parameters in healthy women in stable energy metabolism. The study was performed on 32 healthy, normal-weight, non-pregnant women with normal [body mass index (BMI) 18.9–24.2 kg/m2] and stable (the difference between two measurements performed within 1 month being less than 0.5 kg) body weight, aged 22–47 yr. Leptin, Ghr, GH, IGF-I, cortisol, insulin, and glucose were measured in the early follicular phase of the menstruation cycle. Insulin sensivity was measured using quantitative insulin sensivity check index (QUICKI). Body composition was assessed by bioimpedance. We found a positive linear correlation between leptin and Ghr (r=0.375; p=0.034) and negative correlation between insulin and Ghr (r=−0.374; p=0.034). GH, IGF-I, adiponectin, and body composition parameters did not correlate with Ghr. In multiple regression analysis only QUICKI, leptin, glucose, and cortisol (positively) and age (negatively) accounted for 50% variation of Ghr. Insulin and BMI did not contribute significantly to the model. Our results suggest that in healthy women basal Ghr level is regulated by multiple factors, mainly by insulin sensivity, leptin, and adrenal glands activity. However, further studies are needed to elucidate the physiological mechanisms involved in acylated Ghr secretion.

Birth weight predicts the risk of gestational diabetes mellitus and pregravid obesity

OBJECTIVES It has been suggested that birth weight may determine metabolic abnormalities later in life. The aim of the current study was to assess the association between birth weight and future risk of gestational diabetes mellitus (GDM) and pregravid obesity in a homogenous sample of Caucasian Polish women. METHODS In this retrospective study, we collected the medical reports of 787 women with GDM and 801 healthy pregnant women. We analyzed the following data: birth weight, age, pregravid weight, prior GDM, prior macrosomia, parity, and family history of diabetes. RESULTS Birth weight was inversely associated with the risk of GDM; for each decrease in birth weight of 500 g, the risk increased by 11% (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.02-1.21). Birth weight was a strong predictor of GDM independent of other risk factors (OR, 1.19; 95% CI, 1.09-1.31), and it was positively correlated with pregravid weight (R = 0.21; P < 0.00001). An increase in birth weight of 500 g substantially increased the risk of overweight and obesity (OR, 1.17; 95% CI, 1.01-1.34 and OR, 1.35; 95% CI 1.11-1.64, respectively). Each of the traditional risk factors for GDM were also strong predictors of pregravid obesity: age (P < 0.0001), prior GDM (P < 0.01), prior macrosomia (P < 0.0001), multiparity (P < 0.0001), and maternal (but not paternal) history of diabetes (P < 0.0001). CONCLUSIONS Among Caucasian Polish women, the risk of GDM is associated with low birth weight, and pregravid obesity is associated with high birth weight. Traditional risk factors for GDM, including maternal (but not paternal) history of diabetes, are also risk factors for pregravid obesity.

The associations between G972R polymorphism of the IRS-1 gene, insulin resistance, salt sensitivity and non-dipper hypertension

The aim of this study was to assess the association between G972R polymorphism of the insulin receptor substrate-1 (IRS-1) gene and the circadian variation in blood pressure, insulin sensitivity and salt sensitivity in subjects with uncomplicated, never-treated essential hypertension receiving low-, normal- and high-salt diets. The study was performed on 115 subjects aged 27.48±5.1 years with never-treated, uncomplicated hypertension. In the 7-day consecutive period of time, subjects received a normal-, low- and high-salt diet. At the end of each dietary regimen, the following parameters were recorded: 24-h blood pressure monitoring, lipid profile, insulin level, glucose level, aldosterone level and plasma renin activity. Insulin resistance was evaluated by the homeostasis model assessment (HOMA). In comparison with Gly/Gly carriers, subjects with the G972R polymorphism had higher concentrations of total and LDL cholesterol and triglycerides and HOMA but lower HDL cholesterol. On a high-salt diet, patients with the G972R polymorphism had an increased risk for insulin resistance (odds ratio (OR)=11.42, 95% confidence interval (CI) 7.68–28.44), salt sensitivity (OR=5.38, 95% CI 1.14–25.34) and non-dipper hypertension (OR=3.6, 95% CI 1.07–12.09). Regardless of the dietary salt intake, blood pressure values were similar between G972R and Gly/Gly carriers. In conclusion, the results of our study suggest that the G972R polymorphism of the IRS-1 gene is associated with insulin resistance, salt sensitivity and non-dipper hypertension.

Adiponectin, visfatin and regional fat depots in normal weight obese premenopausal women

Normal weight obesity (NWO) is defined as percentage body fat (%BF) above 30% or %BF in the upper tertile in normal weight subjects. Using these criteria, we assessed lipid profiles, glucose metabolism parameters, blood pressure and regional fat in 91 premenopausal women with NWO and 54 age‐matched healthy controls.

Changes in adiponectin level and fat distribution in patients with type 2 diabetes

The aim of this study was to assess the impact of standard hypoglycaemic treatment strategies on adiponectin levels and fat distribution in patients with newly diagnosed type 2 diabetes mellitus (T2DM).