Sitagliptin vs. pioglitazone as add-on treatments in patients with uncontrolled type 2 diabetes on the maximal dose of metformin plus sulfonylurea.

AIMS: To compare the efficacy of sitagliptin versus pioglitazone as add-on drugs in patients with poorly controlled diabetes with metformin and sulfonylureas. METHODS: This is a randomized, open-label, parallel assignment clinical trial. Patients who had inadequate glycemic control [7% (53 mmol/mol) ≤ A1C < 11% (97 mmol/mol)] despite a minimum 6-month period of active treatment with metformin 2000 mg/day plus gliclazide 240 mg/day were enrolled in the study. HbA1C, fasting blood glucose (FBG), fasting plasma lipid parameters [total cholesterol (TC0, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)], systolic and diastolic blood pressure (SBP, DBP), weight, waist circumference, and body mass index were measured at baseline and after 17, 34, and 52 weeks of treatment. Generalized estimating equation analysis was done to compare treatment groups for continuous efficacy parameters. RESULTS: No significant difference in HbA1C reduction was observed between the treatment groups during the study course. (P = 0.149, adjusted P = 0.434; coefficient - 0.11 ± 0.08). The FBG (P = 0.032; coefficient 7.44 ± 3.48), HDL-C (P = 0.001; coefficient - 2.69 ± 0.83), TG (P = 0.027; coefficient 12.63 ± 5.71) and SBP (P < 0.001; coefficient 5.43 ± 1.26) changes from baseline, and weight gain were greater in the pioglitazone group. The mean changes in LDL-C and TC from baseline to week 52 were greater in the sitagliptin group (P = 0.034; coefficient - 7.40 ± 3.50, P = 0.013; coefficient - 7.16 ± 2.88, respectively). CONCLUSION: Sitagliptin and pioglitazone were equally effective in improvement of HbA1C. There were some differences in terms of lipid indices, weight gain, and SBP. The current study confirmed that both sitagliptin and pioglitazone are effective treatment options and the decision should be made for each individual based on the baseline characteristics.

Retinal nerve fibre layer thickness is reduced in metabolic syndrome.

AIMS: To investigate retinal nerve fibre layer (RNFL) thickness in people with metabolic syndrome (MetS) and healthy controls. METHODS: A cross-sectional study was performed from March 2014 to January 2016. All participants underwent anthropometric and serological biochemical measurements, ophthalmological examination, and spectral-domain optical coherence tomography (SD-OCT). Individuals with elevated intraocular pressure, glaucoma, diabetic retinopathy and other ocular disorders were excluded. T-test, Chi square and general linear models were used to analyse the data. RESULTS: In total, 278 eyes from 139 participants were investigated [median (interquartile range) age: 37 (32-43) years]. RNFL thickness was lower in the nasal superior (107.8 ± 19.5µm) and temporal superior (135.7 ± 18.9µm) sectors in MetS group compared with the control group (114.6 ± 22.4 µm, P = 0.013 and 140.7 ± 18.2 µm, P = 0.027, respectively). After multiple adjustments for age, gender and the side of the examined [right (OD)/left (OS)] eye, MetS was independently associated with a lower RFNL thickness in the nasal superior (ß = 0.20, P = 0.009) and temporal superior (ß = 0.14, P = 0.048) sectors. RNFL thickness was significantly reduced in participants with higher numbers of metabolic abnormalities, independent of age, gender and the side of the examined eye (P = 0.043). CONCLUSION: Our findings demonstrate that MetS is independently associated with reduced RNFL thickness, suggesting that neurodegeneration is implicated in pathogenesis of MetS.

Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical Trial.

Introduction: Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. Methods: 66 patients with major depressive disorder accompanied by anxious distress were randomly assigned to receive either saffron (30 mg/day) or citalopram (40 mg/day) for 6 weeks. Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) were used to assess treatment effect during the trial. Results: 60 participants finished the study. Patients who received either saffron or citalopram showed significant improvement in scores of the Hamilton Rating Scale for Depression (P-value<0.001 in both groups) and Hamilton Rating Scale for Anxiety (P-value<0.001 in both groups). Comparison of score changes between the 2 trial arms showed no significant difference (P-value=0.984). Frequency of side effects was not significantly different between the 2 groups. Discussion: The present study indicates saffron as a potential efficacious and tolerable treatment for major depressive disorder with anxious distress.

Primary Antibody Deficiency in a Tertiary Referral Hospital: A 30-Year Experiment.

BACKGROUND: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders (PID), with a broad spectrum of clinical features ranging from severe and recurrent infections to asymptomatic disease. OBJECTIVES: The current study was performed to evaluate and compare demographic and clinical data in the most common types of PAD. MATERIALS AND METHODS: We performed a retrospective review of the medical records of all PAD patients with a confirmed diagnosis of common variable immunodeficiency (CVID), hyper IgM syndrome (HIgM), selective IgA deficiency (SIgAD), and X-linked agammaglobulinemia (XLA) who were diagnosed during the last 30 years at the Children's Medical Center, Tehran, Iran. RESULTS: A total number of 280 cases of PAD (125 CVID, 32 HIgM, 63 SIgAD, and 60 XLA) were enrolled in the study. The median (range) age at the onset of disease in CVID, HIgM, SIgAD, and XLA was 2 (0-46), 0.91 (0-9), 1 (0-26), and 1 (0-10) years, respectively. Gastrointestinal infections were more prevalent in CVID patients, as were central nervous system infections in XLA patients. Autoimmune complications were more prevalent in HIgM patients, malignancies in CVID patients, and allergies in SIgAD patients. The mortality rate for CVID, HIgM, and XLA was 27.2%, 28.1%, and 25%, respectively. No deaths were reported in SIgAD patients. CONCLUSIONS: SIgAD patients had the best prognosis. While all PAD patients should be monitored for infectious complications, special attention should be paid to the finding of malignancy and autoimmune disorders in CVID and HIgM patients, respectively.

Circulating levels of fibroblast growth factor 21 in early-stage diabetic kidney disease.

AIMS/PURPOSE: Fibroblast growth factor 21 (FGF21), a hepatoadipokine with pleiotropic metabolic regulatory actions, is emerging as a novel biomarker of progressive nephropathy. We sought to evaluate circulating FGF21 and its association with clinical and biochemical characteristics as well as the urinary albumin excretion (UAE) rates in a population of patients with type 2 diabetes (T2D) with or without microalbuminuria and their matched healthy controls. METHODS: Cross-sectionally, 130 consecutive individuals comprising patients with T2D with (n = 44) or without (n = 44) microalbuminuria and their healthy controls (n = 42) were recruited for analysis. Various demographic, clinical and biochemical parameters were assessed. RESULTS: Serum FGF21 levels were significantly elevated in patients with microalbuminuria [median (interquartile range, IQR): 269.50 (188.50) pg/mL] compared to their normoalbuminuric peers with T2D [median (IQR): 103.50 (75.75) pg/mL] and nondiabetic people [median (IQR): 99.00 (126.75) pg/mL]. While serum FGF21, diastolic blood pressure and duration of diabetes mellitus (DDM) were independently associated with microalbuminuria in the baseline logistic regression model, FGF21 and DDM emerged as significant correlates in the multivariate adjusted model (OR for FGF21 = 1.060, 95% CI = 1.011-1.110, P < .016). CONCLUSIONS: Serum FGF21 level is strongly associated with early-stage diabetic kidney disease in the high-risk population of patients with T2D (particularly with circulating FGF21 values rising above 181 pg/mL). The association of serum FGF21 with subclinical stages of diabetic nephropathy may unearth perspectives on early detection and prevention of the advanced stages of chronic diabetes microvascular complications through effective FGF21-targeted therapy.

The comparative effect of pioglitazone and metformin on serum osteoprotegerin, adiponectin and intercellular adhesion molecule concentrations in patients with newly diagnosed type 2 diabetes: a randomized clinical trial.

AIM: The etiologic role of inflammatory pathways in the development of diabetic complications, especially cardiovascular events, has been established. The anti-inflammatory role of metformin and pioglitazone has been described; however, no study to date has compared the efficacy of these common oral agents in this regard. In this study, the authors aimed to compare the anti-inflammatory properties of pioglitazone and metformin, with respect to their effect on serum concentrations of highly sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), intercellular adhesion molecule-1 (ICAM-1) and adiponectin. METHODS: In an open-label randomized clinical trial, 117 patients with newly diagnosed type 2 diabetes mellitus were visited; 84 fulfilled the inclusion criteria, and were randomly allocated to 2 arms receiving either 1,000 mg/d metformin or 30 mg/d pioglitazone, respectively. Biochemical assessments were made at baseline and the end of the 3 months trial. RESULTS: Significant reduction in FPG, insulin and HbA1c in women and men of both arms were observed. Log-hsCRP values significantly decreased in both arms. A decreasing, but non-significant trend in log-OPG levels was observed in women of the metformin arm (p=0.063). A greater reduction in log-ICAM levels was identifiable in men receiving pioglitazone compared to the other arm (p=0.008); in addition, the same trend was observed in log-OPG values (p=0.029). Nonetheless, reduction in log-ICAM and log-OPG levels was comparable between the 2 arms. A significant increase in adiponectin was observed in both men and women in the pioglitazone arm (p<0.001), whereas changes were non-significant in the metformin arm. CONCLUSION: Remarkably, patients receiving pioglitazone revealed more significant reduction in inflammatory markers.