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We estimated proportions of different types of diabetes, comorbidities, treatment (the use of oral glucose-lowering agents and insulin), control (hyperglycemia, dyslipidemia and hypertension) and chronic microvascular and macrovascular complications among people with diabetes presenting to the tertiary-care academic diabetes outpatient clinics in Iran. This study is the prospective analysis of data (n = 30,202) from the registry of university-affiliated adult outpatient diabetes clinics in the country during 2015–2016. The proportions of type 1 diabetes, types 2 diabetes, and other types of diabetes were 11.4%, 85.5%, and 1.3%, respectively. The frequencies of drug-naivety, use of oral agents, insulin monotherapy and insulin combination therapy were 2.9%, 60.5%, 11.5%, and 25.1%, respectively. Around 13.2%, 11.9% and 43.3% of patients with diabetes had controlled hyperglycemia, hyperlipidemia and hypertension, respectively. The proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot, and ischemic heart disease were 21.9%, 17.6%, 28.0%, 6.2%, and 23.9%, respectively. Despite the wide availability of medications and insulin coverage in Iran, the estimated national control of hyperglycemia, hyperlipidemia and hypertension (especially for young men and old women) remains subpar. The present study further suggests that the frequencies of chronic vascular complications among patients with diabetes are relatively high in Iran.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since samedi 17 septembre 2016

AIMS: To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus, and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months. METHODS: This study was designed as a randomized, open-label, clinical trial. Before allocation, sixty medication-naïve, newly-diagnosed, type 2 diabetes patients underwent a 75 g oral glucose tolerance test (OGTT). Afterwards, using a randomized trial design (IRCT201102275917N1) patients were allocated to either the metformin (1000 mg daily) or pioglitazone (30 mg daily) arm, and were reexamined after three months. Serum insulin, plasma glucose, and orexin concentrations were measured at baseline, during OGTT, and after three months. RESULTS: Orexin concentrations significantly decreased after OGTT (0 vs. 120 min: 0.63 ± 0.07 vs. 0.31 ± 0.03 ng/ml, p < 0.001). Insulin resistance determined by homeostasis model assessment of insulin resistance (HOMA-IR) was significantly and negatively correlated with orexin (r = -0.301, p = 0.024). Furthermore, orexin concentrations were significantly and positively correlated with the insulin sensitivity index derived from OGTT (r = 0.326, p = 0.014). Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26% (p = 0.025) and 14% (p = 0.076), respectively. Between-group analysis showed that changes in orexin concentrations with metformin and pioglitazone were not significantly different (p = 0.742). CONCLUSIONS: There was a negative association between peripheral orexin concentrations and insulin resistance in type 2 diabetes patients. Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control.

Aims/purpose Fibroblast growth factor 21 (FGF21) is a major metabolic regulator in the body that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome. However, little is known regarding the circulating levels of FGF21 in type 2 diabetic retinopathy (T2DR) and its association with the severity of the condition. Methods In a cross-sectional setting, 142 individuals, consisting of (1) T2DM patients without T2DR, (2) T2DM patients with T2DR, and (3) healthy control subjects were recruited for this study. Various clinical and biochemical parameters were assessed and entered for analysis. Results Serum FGF21 levels were significantly elevated in T2DM subjects without retinopathy (103.50 [75.75] pg/mL) compared with healthy controls (99.00 [126.75] pg/mL). Circulating FGF21 levels were comparable across different stages of T2DR (233.00 [109.00] for nonproliferative type 2 diabetic retinopathy [NPT2DR] vs. 215.00 [122.00] for proliferative type 2 diabetic retinopathy [PT2DR] groups, P = 361). FGF21, triglycerides, and duration of diabetes mellitus were significantly associated with T2DM in baseline models. However, after adjustment for potential confounders, in the final multivariate model, FGF21 emerged as the only significant factor associated with T2DM (OR = 13.772, 95% CI = 3.062–61.948, P = 001). Conclusions Serum FGF21 concentrations are markedly elevated in patients with T2RN. The association between FGF21 and T2DR appears to be independent of the effects of potential confounding variables. These findings may suggest FGF21 as a novel surrogate diagnostic biomarker in initial stages of T2DR (particularly with FGF21 values above 135.5 pg/mL).

Background The aim of the present study was to determine the prevalence of metabolic syndrome and its individual components among the Iranian adult population in 2011 and to investigate changes between 2007 and 2011. Methods Data from two rounds of the Surveillance of Risk Factors of Non-communicable Diseases national surveys conducted in 2007 and 2011 were pooled. Metabolic syndrome was defined according to International Diabetes Federation criteria. Results In 2007, the prevalence of metabolic syndrome among adults aged 25–64 years was 35.95 (95% confidence interval [CI] 34.27–37.63), which decreased to 32.96 (95% CI 30.73–35.18) in 2011 (P = 0.0108). Despite this overall decline, the prevalence of central obesity (P = 0.1383), raised triglycerides (P = 0.3058), and reduced high-density lipoprotein cholesterol (HDL-C; P = 0.5595) remained constant. There was a trend towards a decline in the proportion of individuals with increased blood pressure (P = 0.0978), and the proportion of adults with increased fasting plasma glucose (FPG) increased (P < 0.0001). In 2011, the prevalence of central obesity, raised triglycerides, reduced HDL-C, increased blood pressure and increased FPG was 51.88 (95% CI 48.97–54.79), 36.99 (95% CI 34.52–39.45), 54.72 (95% CI 50.87–58.57), 38.92 (95% CI 36.19–41.64), and 24.97 (95% CI 22.02–27.93) respectively. Conclusions Over the period 2007–11, the prevalence of metabolic syndrome has decreased slightly in Iran, although prevalence of increased FPG has increased significantly. One-third of the Iranian adult population is diagnosed with metabolic syndrome.

Background: The prevalence of diabetes has steadily increased in Iran from the time of the first published nationally representative survey in 1999 and despite efforts and strategies to reduce disease burden. Objectives: The aim of the present review was to describe the current status of diabetes care in Iran. Methods: A selective review of the relevant literature, focusing on properly conducted studies, describing past and present diabetes care strategies, policies, and outcomes in Iran was performed. Findings: The quality of diabetes care has gradually improved as suggested by a reduction in the proportion of undiagnosed patients and an increase in affordability of diabetes medications. The National Program for Prevention and Control of Diabetes has proven successful at identifying high-risk individuals, particularly in rural and remote-access areas. Unfortunately, the rising tide of diabetes is outpacing these efforts by a considerable margin. Conclusions: Substantial opportunities and challenges in the areas of prevention, diagnosis, and management of diabetes exist in Iran that need to be addressed to further improve the quality of care and clinical outcomes.

Objective: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel Na V 1.8 encoding gene ( SCN10A ) in vivo in patients with multiple sclerosis (MS). Methods: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate differences in cerebellar functional connectivity. All participants were genotyped for 4 potentially functional SCN10A polymorphisms. Results: Two SCN10A polymorphisms in high linkage disequilibrium ( r 2 = 0.95) showed significant association with MSFC performance in patients with MS (rs6795970: p = 6.2 × 10 −4 ; rs6801957: p = 0.0025). Patients with MS with rs6795970 AA genotype performed significantly worse than rs6795970 G carriers in MSFC ( p = 1.8 × 10 −4 ) and all of its subscores. This association was independent of EDSS and cerebellar atrophy. Although the genotype groups showed no difference in regional brain volumes, rs6795970 AA carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant SCN10A –genotype effect was observed on MSFC performance in healthy participants. Conclusions: Our data suggest that SCN10A variation substantially influences functional status, including prominent effects on motor coordination in patients with MS. These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that sodium channel Na V 1.8 could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS.

Aims Fetuin-A is a circulating glycoprotein capable of inhibiting insulin signaling both in vivo and in vitro and is positively associated with insulin resistance. Osteoprotegerin (OPG) acts as a regulatory molecule with increased levels in the early stages of diabetes and atherosclerosis, and is also associated with insulin resistance. We investigated the effects of pioglitazone and metformin as representative insulin-sensitizing therapies on fetuin-A and OPG levels. Materials and methods In a randomized clinical trial setting ( NCT02027103 ), 88 patients with newly diagnosed type 2 diabetes were randomly assigned to pioglitazone (30 mg/day, n = 46) or metformin (1000 mg/day, n = 42) for 12 weeks. Various anthropometric and metabolic parameters, fetuin-A, OPG, highly sensitive C-reactive protein (hsCRP), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured at baseline and after three months. Results The reduction in fasting plasma glucose and haemoglobin A1c levels was comparable in the two arms. Pioglitazone resulted in a significant reduction in both fetuin-A and OPG in men, but only fetuin-A in women. Metformin was only effective in lowering OPG levels in women. When compared, both medications were equally effective with regard to fetuin-A and OPG reduction in women ( p = 0.413 and 0.359, respectively). In men, pioglitazone more effectively decreased fetuin-A levels in both uni- ( p = 0.011) and multivariate models ( p = 0.015) and OPG levels in only uni- ( p = 0.023) but not the multivariate model ( p = 0.547). Conclusions Metformin and pioglitazone differentially affect fetuin-A and osteoprotegrin levels in diabetic women and men. The level of change may not necessarily be associated with the amelioration of insulin resistance.

Background Osteoprotegerin plays a critical role in the pathogenesis of atherosclerosis. Elevated osteoprotegerin concentrations have been reported in microvascular complications of diabetes. Patients with diabetes are at increased risk of macrovascular complications, particularly peripheral artery disease (PAD). Aim To investigate the association between osteoprotegerin concentration and PAD in diabetes. Methods In a cross-sectional setting, patients with type 2 diabetes for > 5 years and no apparent diabetic foot ulcer were recruited. Patients underwent colour Doppler ultrasonography of lower limbs and were designated PAD+ if arterial narrowing was detected. Ankle-brachial index (ABI) was measured. Serum osteoprotegerin concentrations were determined. Results Ninety-eight patients (47 PAD+, 51 PAD–) were recruited. Osteoprotegerin concentrations (median [interquartile range]) were significantly higher in PAD+ versus PAD– patients (0.80 [0.50–1.95] ng/mL vs 0.30 [0.25–0.40] ng/mL; P

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are dysregulated in metabolic syndrome (MetS) and associated with atherosclerosis and cardiovascular disease (CVD). Previous studies on the association between MMPs/TIMPs and MetS are controversial. We aimed to evaluate circulating MMP-8, MMP-9 and TIMP-1 in a group of MetS individuals and healthy controls to find the potential marker associated with MetS and its components.243 MetS individuals participated in a nested case-control design, of whom 63 were excluded (study subjects for analysis n=180; 87 MetS cases, 93 controls). We employed the International Diabetes Federation criteria using national waist circumference cutoffs for case definition. Anthropometric and biochemical measurements were done using standard methods.Plasma MMP-8, TIMP-1, tumor necrosis factor-alpha (TNF-α), highly sensitive C-reactive protein (hs-CRP) and MMP-8/TIMP-1 ratio were significantly higher in MetS cases (P for all0.05). Each component of MetS except raised fasting plasma glucose positively correlated with MMP-8 and numbers of MetS components increased with higher MMP-8. In all regression models, MMP-8 was a significant predictor of MetS and in the final model the relationship persisted even after adjusting for pro-inflammatory cytokines hs-CRP and TNF-α (odds ratio=6.008, 95% confidence interval: 1.612-22.389, P=0.008).Strong associations of MMP-8 with components of MetS in univariate, bivariate and multivariate models suggest plasma MMP-8 as a potential cardiometabolic risk marker for MetS. Higher MMP-8 in MetS is possibly mediated through mechanisms both dependent and independent of chronic low grade inflammation.

HSCT has substantially improved pediatric acquired SAA patients' outcomes. Retrospectively, we attempted to assess the outcome of MRD HSCT in 65 pediatric patients referred to a single center from 1992 to 2012. We were particularly interested to find out whether source of SC (PB, n = 40 and BM, n = 25) significantly impacts EFS and GVHD incidence. With a median follow-up of 45 months, total EFS was 87.7%; EFS for PB and BM groups was 87.5% and 88%, respectively. Acute GVHD (grades 3-4) occurred in 13 patients (PB, n = 10 [25%] and BM, n = 3 [12%]), acute GVHD (grades 2-4) occurred in 24 (PB, n = 16 [40%] and BM, n = 8 [32%]). Extensive chronic GVHD occurred in five patients (PB, n = 3 [7.5%] and BM, n = 2 [8%]). Cox regression revealed that elapsed time of

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.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.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 (p0.001), whereas changes were non-significant in the metformin arm.Remarkably, patients receiving pioglitazone revealed more significant reduction in inflammatory markers.

Background Nephropathy is a major complication of type 2 diabetes mellitus (T2DM) and is heralded by the insidious development of microalbuminuria (MA). It is suggested that the serum levels of Intercellular Adhesion Molecule-1 (ICAM-1) is correlated with diabetic nephropathy. In this cross-sectional study, we evaluated serum ICAM-1 level in diabetic patients with and without MA. Methods A total of 187 participants were enrolled and were classified into three groups including 40 healthy controls and 2 diabetic groups with (n = 59) or without MA (n = 88). Serum levels of ICAM-1, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and C-reactive protein (CRP) were measured in all three groups. Statistical analyses were performed using the SPSS software. A P-value less than 0.05 was considered statistically significant. Results Serum levels of ICAM-1 were significantly higher in diabetic patients irrespective of MA. Moreover, ICAM-1 levels in patients with MA were significantly higher than patients without MA. Patients with MA had significantly higher age and blood pressure compared to those without MA (P = 0.001). Serum levels of ICAM-1 were significantly correlated with age and HbA1c. Conclusions Overall, serum ICAM-1 levels were significantly higher in T2DM patients with MA and it may be associated with the severity of diabetic kidney disease.

Background: Coronary heart disease (CHD) is one of the most common causes of mortality worldwide. The national prevalence remains unclear in most of the developing countries. Objective: This study sought to estimate national prevalence of self-reported CHD and chronic stable angina pectoris in the general adult population of Iran using data from the fourth round of the Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2011) survey. Methods: The analysis comprised data of 11,867 civilian, nonhospitalized and noninstitutionalized residents ages 6 to 70 years of age. The calculated prevalence of self-reported CHD and chronic stable angina pectoris were extrapolated to the Iranian adult population who were >20 years old using the complex sample analysis. The factor analysis was performed for clustering of the associated cardiometabolic risk factors among people ages >40 years of age. Results: The estimated national prevalence of self-reported CHD and chronic stable angina pectoris were 5.3% (95% confidence interval: 4.6 to 5.9) and 7.7% (95% confidence interval: 4.6 to 8.7), respectively. Higher prevalence of these conditions were observed among the older people, urban residents, and women. Factor analysis generated 4 distinct factors that were mainly indicators of dyslipidemia, hypertension, central obesity, hyperglycemia, and tobacco smoking. The factor incorporating hypertension was a significant correlate of selfreported CHD. Conclusions: We report concerning prevalence of self-reported CHD and chronic stable angina pectoris in the adult population of Iran. The constellation of raised systolic and diastolic blood pressures was significantly predictive of the presence of self-reported CHD. Highlights The prevalence of self-reported CHD and chronic stable angina pectoris was determined in the adult population of Iran in 2011. The estimated national prevalence of self-reported CHD was calculated at 5.3% (95% CI: 4.6 to 5.9). The estimated national prevalence of chronic stable angina pectoris was calculated at 7.7% (95% CI: 4.6 to 8.7). Hypertension was an independent correlate of self-reported CHD and chronic angina pectoris among Iranian adult population. Monitoring people with raised SBP and DBP should be the focus of future nationwide CHD prevention programs.

This study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy.In an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400mg plus daily dose of losartan 50mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50mg (losartan arm) during a 12-week follow-up period.Serum NT-proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT-proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively).Circulating NT-proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm.

Metformin and pioglitazone are believed to exert their long-term benefits by means of amelioration of chronic low-grade inflammation, a key event in development of diabetes and its long-term complications. The present trial was designed to investigate the comparative efficacy of the two anti-diabetes medications on serum concentrations of YKL-40, a novel marker of inflammation. In a parallel-group, open-label, randomized trial setting (ClinicalTrials.gov Identifier No. NCT01521624), 84 newly diagnosed, medication-naive type 2 diabetes patients were assigned to metformin 1,000 mg daily (n = 42) or pioglitazone 30 mg daily (n = 42). Serum concentrations of YKL-40, along with highly sensitive C-reactive protein, indices of glycemic control and lipid profile were measured at baseline and after 3 months. In the analyzed sample (metformin = 40, pioglitazone = 42), both medications were equally effective with regard to control of hyperglycemia, and hsCRP reduction (p > 0.05). However, metformin caused a significant decline in weight (p = 0.005), BMI (p = 0.004), and total cholesterol levels (p = 0.028) of the patients. Metformin also significantly reduced YKL-40 concentrations after 3 months (1.90 ± 17 vs. 1.66 ± 0.15 µg/L, p = 0.019). The amount of change in the pioglitazone arm did not reach statistical significance (2.18 ± 0.14 vs. 2.25 ± 0.16 µg/L, p = 0.687). When compared, metformin was significantly more effective than pioglitazone with respect to YKL-40 reduction in both univariate (p = 0.020, effect size = 6.7 %) and multivariate models (p = 0.047, effect size = 5.7 %). Metformin is more effective in reduction of YKL-40 concentration in short term and the effect seems to be independent of degree of glycemic control, or hsCRP reduction.

Background: Previous studies evaluating the relationship between serum vaspin concentrations and metabolic syndrome (MetS) have yielded contrasting results. Additionally, contribution of general and abdominal obesity, chronic inflammation, and insulin resistance to this relationship remains unknown. Methods: In a cross-sectional setting, we investigated the association between vaspin and MetS in 145 subjects ranging from normoglycemia to type 2 diabetes. Vaspin concentrations were measured using enzyme-linked immunosorbent assay. Results: Women had 29% higher vaspin concentrations compared with men. Subjects with MetS (51% of all participants) had higher vaspin concentrations (P=0.019 in women and P

To estimate the prevalence and trends of diabetes mellitus (DM) and impaired fasting glucose (IFG), 2005-2011, and to determine the contribution of obesity to DM prevalence.Data from Surveillance of Risk Factors of Non-communicable Diseases (SuRFNCD) conducted in 2005, 2007, and 2011 were gathered. DM was defined as presence of self-reported previous diagnosis or a fasting plasma glucose (FPG)≥7 mmol/L. IFG was diagnosed with FPG levels between 5.6 and 6.9 mmol/L. Prevalence rates for 2011 and trends for 2005-2011 were determined by extrapolating survey results to Iran's adult population. Population attributable fraction (PAF) of obesity was also calculated.In 2011, IFG and total DM prevalence rates were 14.60% (95%CI: 12.41-16.78) and 11.37% (95%CI: 9.86-12.89) among 25-70 years, respectively. DM was more common in older age (p0.0001), in women (p = 0.0216), and in urban-dwellers (p = 0.0001). In 2005-2011, trend analysis revealed a 35.1% increase in DM prevalence (OR: 1.04, 95%CI: 1.01-1.07, p = 0.011); albeit, IFG prevalence remained relatively unchanged (OR: 0.98, 95%CI: 0.95-1.00, p = 0.167). In this period, DM awareness improved; undiagnosed DM prevalence decreased from 45.7% to 24.7% (p0.001). PAF analysis demonstrated that 33.78%, 10.25%, and 30.56% of the prevalent DM can be attributed to overweight (BMI≥25kg/m(2)), general obesity (BMI≥30 kg/m(2)), and central obesity (waist circumference≥90 cm), respectively. Additionally, the DM increase rate in 2005-2011, was 20 times higher in morbidly obese compared with lean individuals.More than four million Iranian adults have DM which has increased by 35% over the past seven years, owing in large part, to expanding obesity epidemic.

Recent studies have suggested that pioglitazone exerts anti-oxidant properties which may countervail oxidative stress (OS). We aimed to elucidate the effects of pioglitazone on OS modulation and to compare its effects with metformin.Data from the randomized clinical trial (registration no.NCT01521624) were used. Newly diagnosed type 2 diabetes patients were assigned to pioglitazone 30mg daily (n=30), metformin 1000mg daily (n=50), or no medication (n=49). Recommendations for exercise and dietary modifications were provided for three groups. Serum concentrations of advanced oxidation protein products(AOPP), advanced glycation end products(AGE), ferritin reducing ability of plasma(FRAP), and enzymatic activities of paraoxonase(PON), lecithin-cholesterol asyltransferase(LCAT), and lipoprotein lipase(LPL) were measured at baseline and after three months.In comparison with no medication, pioglitazone proved to be superior in OS amelioration (p0.05 in all analyses). Compared with metformin, both medications were equally effective in decrement of AOPP and AGE, along with increment of PON (p=0.688, 0.140, and 0.273, respectively). FRAP concentrations increased significantly with metformin (p=0.012). On the other hand, pioglitazone yielded better efficacy in restoration of LCAT and LPL enzymatic activities (p=0.037, and0.001, respectively).Similar to metformin, three months treatment with Pioglitazone is beneficial in terms of OS alleviation and anti-oxidant capacity restoration.

Mousavi jazi M, Solgi G, Asl roosta H, Noshad S, Moslemi N, Sadrimanesh R,Moradi B, Amirzargar A. HLA-DRB and HLA-DQA/HLA-DQB allele andhaplotype frequencies in Iranian patients with aggressive periodontitis. J PeriodontRes 2013; doi: 10.1111/jre.12043. © 2013 John Wiley & Sons A/SBackground and Objective: Genetic backgrounds play a key role in susceptibilityto and protection against a spectrum of periodontal diseases. Like other infec-tious diseases, the human leukocyte antigen (HLA) have been found to beassociated with periodontitis. This study aimed to investigate differences in alleleand haplotype frequencies of HLA class II antigens in a sample of Iranianpatients with aggressive periodontitis compared with a healthy control group.Material and Methods: Fifty unrelated patients with aggressive periodontitis and130 healthy volunteers were enrolled in this study. HLA genotyping for HLA-DRB, HLA-DQA1 and HLA-DQB1 was performed using the PCR withsequence-specific primers. Allele and haplotype frequencies were comparedacross groups.Results: The frequencies of HLA-DQA1*03:01, HLA-DQB1*03:02 and HLA-DQB1*03:05 alleles, as well as that of the HLA-DRB1*04:01 allele, were signifi-cantly higher in patients with aggressive periodontitis compared with controlsubjects (p = 0.01, p = 0.04, p = 0.05 and p = 0.04, respectively). In contrast, thefrequency of the HLA-DQB1*0603 allele was significantly lower in patients withaggressive periodontitis compared with control subjects (p = 0.006; odds ratio =0.20). With regard to haplotype association, a significantly higher frequency oftwo haplotypes – HLA-DRB1*04:01/HLA-DQA1*03:01/HLA-DQB1*03:02 andHLA-DRB1*16:01/HLA-DQA1*01:03/HLA-DQB1*05:01 – was observed inpatients with aggressive periodontitis compared with healthy controls (p = 0.01,odds ratio = 2.56 and p = 0.05, odds ratio = 5.38, respectively).Conclusion: These results provide additional evidence that class II HLA poly-morphisms, particularly in the DQ locus, are associated with protection againstand susceptibility to aggressive periodontitis.M. Mousavi jazi

Background The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). Methods It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2–0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2–0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed. Results HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P

Studies have emerged to demonstrate bidirectional changes in circulating cytokines of inflammation in active diabetic foot ulcers (DFU). To further expand the understanding of inflammatory status present in chronic active DFU, we comparatively assessed the associations of selected pro-inflammatory cytokines and 25-hydroxyvitamin D (25(OH)D) with the presence of DFU. In a cross-sectional setting, thirty patients with type 2 diabetes and active DFU matched with thirty control non-ulcerative patients with type 2 diabetes and twenty-eight healthy subjects underwent anthropometric and biochemical assessment of study parameters. Recruited patients with DFU were selected from the grade II active chronic DFU at the time of hospitalisation according to the University of Texas wound classification system. Patients with DFU and controls had comparable age, sexual distribution, diastolic blood pressure and TAG, LDL-cholesterol and glycated Hb. The trend changes from healthy controls towards DFU showed a significant increase for serum monocyte chemoattractant protein-1, IL-6, 25(OH)D and highly sensitive C-reactive protein and a decrease for IL-8. In the multivariate adjusted logistic regression model, 25(OH)D emerged as the only independent correlate of DFU (OR 2·194; 95 % CI 1·003, 4·415). Unprecedented increase of serum 25(OH)D in chronic active DFU is possibly related to a selective alteration in the inflammatory status. In particular, 25(OH)D and IL-8 seem to share a common pathway in the pathogenesis of diabetic foot.

Vascular endothelial growth factor (VEGF) has long been recognized as a hypotensive mediator. Little is known regarding the contribution of polymorphisms in VEGF gene to essential hypertension (EH), however. We aimed to investigate the association between +405 VEGF C/G single nucleotide polymorphism (SNP) and occurrence of EH in a sample of patients with diabetes. A study population of 474 subjects with diabetes of which 45.6% (216) had EH was enrolled in this study. Interviews and physical examinations were performed in a clinical setting. Subjects were matched in baseline anthropometric and biochemical characteristics except for total cholesterol. Genotyping of +405 VEGF C/G (rs2010963) SNP was carried out using polymerase chain reaction-restriction fragment length polymorphism. The allelic distribution of the sample did not violate Hardy-Weinberg equilibrium. Subjects with EH had a higher frequency of G allele (P = 0.005). Additionally, those with EH had a significantly higher frequency of GG genotype (P = 0.015). In multivariate logistic regression models controlling for possible confounders, having GG against CC genotype was associated with an odds ratio of 2.51 (95% CI: 1.44-4.38; P = 0.001). Moreover, presence of each G allele was linked to a 1.58-fold increase in risk of having EH (95% CI: 1.200-2.086; P = 0.001). In conclusion, +405 VEGF C/G SNP is associated with EH in patients with diabetes, suggesting presence of G allele and GG or CG genotype confer susceptibility towards EH.

Graves’ disease (GD) is the most common cause of thyrotoxicosis and often involves the orbits. Graves’ ophthalmopathy (GO), also known as Thyroid Eye Disease (TED), can be clinically significant and advance to sight-threatening stages. Our knowledge of the immunogenetic pathophysiology of GO is rapidly expanding. The present review is an attempt to summarize the current state of knowledge on the immunogenetics of GO. First we briefly review the epidemiology and clinical importance of GO, and then we describe in detail the macromolecular pathogenesis and finally immunogenetics of GO. Discrepancies between the results from various reports and the limitations of the available data are discussed. In particular, there is a scarcity of data from non-Asian populations. While several studies have demonstrated significant associations between polymorphisms in certain genes (especially CTLA-4, HLA-DRB-1, and TNF-α), there is a need for studies that investigate the relationship between polymorphisms and both serum and local concentrations of the resulting proteins. A complete understanding of GO susceptibility and pathogenesis has not been yet possible due to a number of important knowledge gaps that need to be filled by future research.

It has been shown that elevated levels of alanine and aspartate aminotransferases (ALT and AST) are associated with insulin resistance and type 2 diabetes mellitus; however, the pattern of this association in diabetic patients with negative or mild steatosis is not well understood. The aim of this study was to assess the association between elevated liver enzymes and insulin resistance in diabetic subjects without ultrasound signs of nonalcoholic fatty liver disease (NAFLD) (i.e., with less than 30% steatosis).In a cross-sectional study, a total of 670 diabetic subjects without established causes of liver injury were included. Patients with evidence of NAFLD in ultrasonography were not included. Fasting blood samples were obtained and plasma glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profile were measured. Three indices of insulin sensitivity/insensitivity: Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and McAuley were also calculated.Elevated ALT was significantly (p 0.001) correlated with fasting insulin, C-peptide, HOMA-IR, QUICKI, McAuley, and waist circumference. The same correlations were also observed for AST, which in all cases were weaker than ALT. Multivariate regression analysis showed that, among the above-mentioned variables, only HOMA-IR and fasting insulin were independently correlated with both ALT and AST. This correlation was independent of body mass index (BMI) or waist circumference.In type 2 diabetes, in the absence of a detectable steatosis by ultrasonography, ALT and AST are associated with hyperinsulinemia and insulin resistance, independent of obesity. This finding possibly indicates that in diabetes a mild stage of steatosis is sufficient to mediate the association between insulin resistance and aminotransferases.

Little evidence exists regarding the association of leptin with metabolic syndrome (MetS) as defined by conventional criteria. Moreover, the contribution of obesity to this relationship is not well understood. This study aimed to evaluate the association between leptin concentrations with MetS in obese and nonobese subjects.Data from the Third National Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD) in Iran was used. In a cross-sectional study of 3045 adults (48.2% men) aged 25-64 years, anthropometric indices, blood pressure, fasting plasma glucose, fasting insulin, lipid profile [triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides], and fasting leptin were measured. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also calculated.Leptin concentrations were 2.6 fold higher in women compared with men. Subjects with MetS had significantly higher leptin concentrations. Leptin concentrations increased steadily with an increment in the number of MetS components (p0.001). Leptin was significantly associated with MetS after adjustment for age, cigarette smoking, medication use, physical activity, HOMA-IR, and LDL-C. The significant association between leptin and MetS persisted after adjustment for body mass index (OR: 1.31, 95% CI: 1.09-1.58 in males and 1.17, 95% CI: 1.01-1.38 in females) and waist circumference (OR: 1.24 95% CI: 1.01-1.51 in men and 1.22, 95% CI: 1.04-1.43 in women). After dividing subjects into obese and nonobese, leptin concentrations were again significantly higher in subjects with MetS in both groups.We demonstrated that leptin concentrations are significantly associated with International Diabetes Federation (IDF)-defined MetS, independent of overall and central obesity. Our findings point to an independent role for leptin in development of MetS.

The metabolic syndrome (MetS), a constellation of cardiovascular risk factors, is a growing health challenge worldwide. Most studies on MetS epidemiology are from developed countries. The Middle East is lagging behind in understanding the epidemiology of MetS and its risk factors in the region. This is partly owing to a scarcity of high-quality, nationally representative studies. In a series of recent national surveys, we have studied the epidemiology of MetS and its risk factors in Iran. We review the current situation in the region and highlight current gaps of knowledge and epidemiological concepts that need to be taken into account when doing population-level health programming. We explore the results of our national surveys as successful examples along this path.

Heart failure's (HF) incidence rate is higher in African-Americans compared with Caucasians, possibly due to the higher prevalence of atherosclerosis risk factors. Despite the higher incidence, previous studies have reported a modest survival advantage for African-Americans with hospitalized HF. We

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. 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. 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

The constellation of metabolic abnormalities seen in metabolic syndrome (MetS) has been linked to atherosclerosis and adverse cardiovascular outcomes due to heightened inflammation. Accumulating evidence suggests that peripheral 5-hydroxyindole-3-acetic acid (5-HIAA), the derivative end-product of serotonin (5-HT), might be involved in the pathogenesis of obesity, and abnormal lipid and glucose metabolism. We examined the association between serum 5-HIAA concentrations and MetS and also highly sensitive C-reactive protein (hsCRP).We assessed 180 healthy adults (110 males and 70 females) in a cross-sectional setting. Anthropometric indices and blood pressure were measured, as were laboratory parameters including fasting 5-HIAA concentrations. The associations between 5-HIAA and individual components of MetS, as well as MetS as a single entity, were investigated with bivariate correlation and logistic regression analyses.Eighty-nine individuals (49.4%) were diagnosed with MetS. Significant correlations were found between 5-HIAA concentrations and age (r = 0.184), waist circumference (r = 0.415), high-density lipoprotein (HDL) cholesterol (r = -0.148), systolic blood pressure (r = 0.374), diastolic blood pressure (r = 0.355), homeostasis model assessment of insulin resistance (r = 0.201), and hsCRP (r = 0.453) were found (P.05 in all tests). In logistic regression, 5-HIAA was significantly associated with 4 MetS components including central obesity, raised triglycerides, raised blood pressure, and raised fasting plasma glucose (FPG) (P.05). Moreover, 5-HIAA was a predictor of MetS as a single entity, and the relationship persisted after adjusting for hsCRP (odds ratio [OR] = 4.41, 95% confidence interval [CI]: 2.58-7.67, P.001).Elevated concentrations of 5-HIAA are seen in individuals with MetS. Increased 5-HIAA is also associated with hsCRP, a marker of chronic low-grade inflammation underlying MetS.

Small dense low-density lipoprotein (sd-LDL) has been demonstrated to be associated with cardiovascular diseases (CVD). The proposed atherogenic properties of hypoadiponectinemia might be mediated through increased sd-LDL. In this study, the associations of sd-LDL with cardiovascular and other complications of diabetes, and also with plasma levels of adiponectin, were investigated in diabetic patients.173 patients, with documented type 2 diabetes mellitus, were enrolled in this cross-sectional study. Laboratory, anthropometric, and clinical characteristics were all determined. The presence of CVD, hypertention, and microalbuminuria were also evaluated. Homeostasis model assessment of insulin resistance was calculated.Sd-LDL concentrations were significantly lower in patients with CVD than those without CVD (p = 0.020); and also lower in hypertensive patients relative to non-hypertensive ones (p = 0.008). Serum levels of adiponectin were significantly lower in patients with CVD (p0.001), and hypertension (p = 0.002), compared with those without each of these complications. Sd-LDL and adiponectin concentrations were positively correlated (r = 0.36, p0.001). Sd-LDL was also significantly associated with HbA1c (r = 0.24, p = 0.002).Our data suggest that decreased levels of adiponectin might be associated with developing complications of diabetes. This study did not provide any supportive results for the association of increased sd-LDL concentrations with CVD; neither for its association with other complications of diabetes.

Background Addition of spironolactone (SPR) to angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) might provide antiproteinuric effects beyond what is gained by either medication alone. This study was designed to assess the long-term efficacy of SPR/ARB combination in comparison with the standard ACE/ARB regimen in diabetic nephropathy. Methods In an open-label, parallel-group, single-center, randomized clinical trial (NCT01667614), 136 patients with diabetes and proteinuria, already treated with enalapril and losartan, were included. In 74 patients, ACE inhibitors were discontinued. After a wash-out period of 2 weeks, 25 mg SPR daily was initiated. The remainder of the patients (n = 62) received ACE inhibitors and ARBs as before. Patients were followed every 3 months for 18 months. During each visit, systolic and diastolic blood pressure (BP), urinary albumin excretion (UAE), serum creatinine, estimated glomerular filtration rate (eGFR) and serum potassium concentrations were determined. Results After 18 months, three patients in the SPR/ARB group developed asymptomatic hyperkalemia. SPR/ARB significantly reduced both systolic and diastolic BP (P < 0.001 and 0.001, respectively). SPR/ARB decreased UAE by 46, 72 and 59% after 3, 12 and 18 months, respectively. Compared with the continuation regimen, SPR/ARB was superior in UAE reduction (P = 0.017 after 18 months), independent of BP change. In both groups, eGFR declined significantly over the trial course and the decline rate did not differ significantly between the two groups. Conclusions Addition of SPR to ARB provides added benefits with respect to BP control and proteinuria diminution. These antiproteinuric effects are not accompanied by prevention of eGFR loss compared with conventional therapy with ACE/ARB.

Background: The aim of the current study was to evaluate the association of osteoprotegerin and vascular endothelial growth factor (VEGF) with glycemic indices and diabetes status. Methods: A total of 44 normoalbuminuric Type 1 diabetic patients and 44 healthy control subjects, matched for age, body mass index, sex ratio, and lipid measures were enrolled. Univariate and multivariate logistic regression analyses were used to determine the association of osteoprotegerin and VEGF with diabetes status. Further, linear regression analysis was performed to investigate the roles of osteoprotegerin and VEGF as determinants of glycated hemoglobin (HbA1c). Results: Osteoprotegerin and VEGF were significantly elevated in diabetic subjects (2.76±0.85 vs 2.26±0.75 pmol/l and 187.1±92.7 vs 125.9±52.3 pg/ml, respectively, p

Aims/Introduction Chemerin, a novel member of the family of adipocytokines, has been shown to be associated with insulin resistance, as well as micro- and macrovascular complications of diabetes. We investigated the effects of pioglitazone and metformin, two commonly prescribed antidiabetic agents, on the reduction of serum chemerin concentrations. Materials and Methods In an open-labeled randomized clinical trial, 81 patients with newly diagnosed type 2 diabetes who were not taking antidiabetic medications were recruited. Patients were randomly assigned to either pioglitazone 30 mg daily or metformin 1,000 mg daily. Serum chemerin concentrations, indices of glycemic control, serum lipids concentrations, and anthropometric parameters were measured at baseline and after 3 months. Results Pioglitazone and metformin did not alter waist circumference, weight or body mass index after 3 months. In contrast, all indices of glycemia and insulin resistance improved substantially after 3 months’ treatment with both medications (P

Purpose.We sought to investigate the utility of classification and regression trees (CART) classifier to differentiate benign from malignant nodules in patients referred for thyroid surgery.Methods.Clinical and demographic data of 271 patients referred to the Sadoughi Hospital during 2006–2011 were collected. In a two-step approach, a CART classifier was employed to differentiate patients with a high versus low risk of thyroid malignancy. The first step served as the screening procedure and was tailored to produce as few false negatives as possible. The second step identified those with the lowest risk of malignancy, chosen from a high risk population. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the optimal tree were calculated.Results.In the first step, age, sex, and nodule size contributed to the optimal tree. Ultrasonographic features were employed in the second step with hypoechogenicity and/or microcalcifications yielding the highest discriminatory ability. The combined tree produced a sensitivity and specificity of 80.0% (95% CI: 29.9–98.9) and 94.1% (95% CI: 78.9–99.0), respectively. NPV and PPV were 66.7% (41.1–85.6) and 97.0% (82.5–99.8), respectively.Conclusion.CART classifier reliably identifies patients with a low risk of malignancy who can avoid unnecessary surgery.

We read with great interest the article by Fischer et al. (1) that was recently published in Diabetes Care . Although we congratulate the authors for their encouraging findings on the impressive role of text messaging support for weight loss management in prediabetes, their results raise several important concerns. It is very surprising that weight loss was observed only among Spanish speakers but not in the English-speaking group (1). Do the authors feel confident about the internal validity of their findings (i.e., non–quasi-experiment design), considering the potential diversities in educational status, income, type of cell phones (touch tone, large-screen displays), socioeconomic background, and type of personality (motivation, incorporation of family and friends into …

We read with great interest the study by Sharif et al. (1) of 1,829 patients with type 2 diabetes (T2D) from the Second Manifestations of ARTerial disease (SMART) cohort. Here, we would like to suggest a different interpretation of their findings in light of the results from our ongoing cohort of Iranian patients with T2D (2). We believe that the chameleon behavior of HDL cholesterol (HDL-c) might be ascribed to the chronic systematic inflammatory status. Hence, we investigated the association of serum C-reactive protein (CRP), a marker of chronic low-grade inflammation, with HDL-c, LDL cholesterol (LDL-c), and cardiovascular events. In our cohort of 2,607 patients with T2D who were followed for an …

The aim of the study was to assess the effects of metformin on serum concentrations of vaspin and adiponectin in diabetes. Randomized clinical trial of 99 newly diagnosed, medication-naive, type 2 diabetes patients (NCT01521624) was carried out. Patients were randomly assigned to either metformin 1 000 mg daily plus advice for exercise and lifestyle modification (n=50) or modification alone (n=49). A third group of 50 normoglycemic subjects were also enrolled to compare adipokine concentrations between healthy and diabetes subjects. Serum concentrations of adipokines were measured at baseline and after 12 weeks using ELISA method. Healthy subjects had significantly higher adiponectin levels, but lower concentrations of serum vaspin (p

To determine the appropriate threshold of body mass index (BMI) associated with increased risk of cardiovascular diseases in a large representative sample of an Iranian population.Data of third national surveillance of risk factors of non-communicable diseases (SuRFNCD-2007) were used in this study. Sensitivity, specificity, and shortest distance on the receiver-operating characteristic (ROC) curves were used to determine gender-specific optimal cut-offs of BMI for cardiometabolic risk factors including elevated blood pressure, low high-density lipoprotein cholesterol, high triglycerides, high fasting plasma glucose and for ≥ 2 of the aforementioned risk factors.There was a continuous increase in the prevalence of cardiometabolic risk factors with increasing BMI (p0.001). At the BMI of 25-29 kg/m(2) men were at higher risk of cardiovascular diseases compared to women (p0.001). The appropriate BMI cut-offs ranged from 24.6-26.1 kg/m(2) for men and from 26.9-28.8 kg/m(2) for women. The optimal BMI cut-offs for identifying any two or more of those risk factors were 25.2 and 27.3 kg/m(2) in men and women, respectively.In men the appropriate BMI cut-offs are ~25 kg/m(2), while in women higher BMI values are associated with risk of cardiovascular diseases.

Aims To assess the effects of two commonly used oral hypoglycemic medications metformin and pioglitazone on serum concentrations of omentin and leptin in patients with newly diagnosed type 2 diabetes. Methods In a clinical trial setting (NCT01593371), patients were randomly allocated to either metformin 1000 mg daily (n = 41), or pioglitazone 30 mg daily (n = 50). Serum concentrations of omentin and leptin were measured at baseline and after 12 weeks. Patients' weight, waist circumference, blood pressure, fasting plasma glucose, fasting insulin, HbA1c, highly sensitive C-reactive protein, and serum lipids were also measured at the two visits. Results Baseline concentrations of omentin and leptin were not different between the two arms of the trial. After three months, metformin decreased both omentin and leptin concentrations in women, and leptin concentrations only in men. On the other hand, pioglitazone reduced both adipokines only in women, but not men. Univariate and multivariate ANCOVA models revealed that both interventions are equally effective in reducing omentin concentration (p = 0.497 for women and 0.344 for men in multivariate models controlling for the effects of confounding variables). Similarly, neither medication was more effective in reducing leptin concentrations after three months (p = 0.822 for women and 0.441 for men in multivariate models). Conclusions Metformin and pioglitazone at pharmacologic doses are equally effective in alteration of serum omentin and leptin concentrations in patients with diabetes, albeit sex differences in response to medications exist. Implication of these findings on long term management and complication prevention of diabetes needs to be elucidated.

Increased C-reactive protein (CRP) levels are associated with coronary heart disease, stroke, and mortality. Physical activity prevents cardiovascular disorders, which can be partly mediated through reducing inflammation, including serum CRP levels. The association of different intensities of physical activity, sedentary behaviours, and C-reactive protein (CRP) levels in serum was examined after adjustment for markers of adiposity, including waist-circumference and body mass index (BMI), in a large population-based study. Using data of the SuRFNCD-2007 study, a large national representative population-based study in Iran, the relationship between quantitative CRP concentrations in serum and physical activity was examined in a sample of 3,001 Iranian adults. The global physical activity questionnaire (GPAQ) was used for evaluating the duration and intensity of physical activity. Total physical activity (TPA) was calculated using metabolic equivalents for the intensity of physical activity. Quantitative CRP concentrations in serum were measured with high-sensitivity enzyme immunoassay. The CRP levels in serum significantly correlated with TPA (r=-0.103, p=0.021 in men and r=-0.114, p=0.017 in women), duration of vigorous-intensity activity (r=-0.122, p=0.019 in men and r=-0.109, p=0.026 in women), duration of moderate-intensity activity (r=-0.107, p=0.031 in men and r=-0.118, p=0.020 in women), and duration of sedentary behaviours (r=0.092, p=0.029 in men and r=0.101, p=0.022 in women) after multiple adjustments for age, area of residence, BMI, waist-circumference, smoking, and diabetes mellitus. Physical activity (of both moderate and vigorous intensity) is inversely associated with the quantitative CRP levels in serum, independent of diabetes and body adiposity.

Given the long term benefits observed with metformin use in diabetes patients, a role in modulating oxidative stress is imputable. Effects of metformin on markers of oxidative stress, antioxidant reserve, and HDL-c associated antioxidant enzymes were investigated.In a clinical trial setting (Registered under Clinical Trials.gov Identifier no. NCT01521624) 99 medication-naïve, newly diagnosed type 2 diabetes patients were randomly assigned to either metformin or lifestyle modification. AOPP, AGE, FRAP, activities of LCAT, and PON were measured at baseline and after 12-weeks.Baseline values of the oxidative stress markers did not differ significantly between the two groups. In cases, after three months treatment, there was a significant reduction in AOPP (137.52 ± 25.59, 118.45 ± 38.42, p 0.001), and AGE (69.28 ± 4.58, 64.31 ± 8.64, p = 0.002). FRAP and PON increased significantly (1060.67 ± 226.69, 1347.80 ± 251.40, p 0.001 and 29.85 ± 23.18, 37.86 ± 27.60, p = 0.012 respectively). LCAT levels remained unchanged (45.23 ± 4.95, 46.15 ± 6.28, p = 0.439). Comparing the two groups in a final multivariate model, AOPP, FRAP, and AGE levels changed more significantly in metformin compared with lifestyle modification alone (p = 0.007, p 0.001 and p 0.001 respectively). Escalation in LCAT or PON activities did not differ between the two groups (p = 0.199 and 0.843 respectively).Use of metformin is more effective in reducing oxidative stress compared with lifestyle modification alone.

Purpose: Central fat distribution is significantly associated with an increased cortisol levels. We hypothesized that men with metabolic syndrome have a higher serum cortisol levels compared to women. The purpose of this study was to compare serum cortisol levels, and its correlation with serum leptin levels, between men and women with and without metabolic syndrome. Methods: A cross sectional study was performed with 120 untreated patients with metabolic syndrome and 165 healthy volunteers as controls. Serum lipid profile, fasting blood sugar, insulin, cortisol and leptin levels were measured for both groups. Results: Men with metabolic syndrome had a higher serum cortisol levels, while serum leptin levels were significantly higher in women. The higher serum cortisol level in men with metabolic syndrome was significant after multiple adjustments for age, BMI and waist circumference (17.74±5.1 vs 14.07±4.3; p < 0.05) using general linear model; however, these difference were no longer significant when the waist-to-hip ratio was added as one of the adjustment factors (16.7±1.2 vs. 14.9±0.5; p < 0.2). Serum cortisol levels was significantly correlated with serum leptin (r=0.33, p < 0.05), cholesterol (r=0.35, p < 0.05), triglyceride (r=0.25, p < 0.05), waist circumference (r=0.41, p < 0.01) and waist-to-hip ratio (r=0.32, p < 0.01) in women with metabolic syndrome, after controlling for age and BMI. Conclusion: Serum cortisol levels are significantly higher in men with metabolic syndrome. This effect is independent of waist circumference.

Background Despite ongoing findings on the relationship between elevated levels of alanine and aspartate aminotransferases (ALT and AST) and metabolic syndrome (MetS), this association in diabetic patients without a known cause for liver enzymes elevation other than diabetes, per se, remains unclear. In this study, we aimed to assess the relationship between circulating liver enzymes and MetS in a relatively large sample of patients with diabetes. Methods A total of 670 diabetic patients, without known causes of hepatocellular injury, were enrolled. Patients with ultrasonographic signs of fatty liver disease were not included. Fasting blood samples were obtained and biochemical characteristics were measured. MetS was defined according to the international diabetes federation criteria. Results Serum ALT and AST were significantly higher in patients with MetS (p < 0.001). High waist circumference and low HDL-cholesterol were significantly associated with elevated ALT (OR = 2.56 and 2.0, respectively) and AST (OR = 2.23 and 2.21, respectively). ALT and AST were significantly associated with MetS (OR = 2.17 and 2.31, respectively). These associations remained significant after multiple adjustments for age, sex, BMI, diabetes duration, HbA1c and medications. There was a significant (p < 0.01) positive association between the number of the MetS features and the level of ALT or AST. Conclusion In diabetic patients without ultrasonographic evidence of fatty liver, elevated aminotransferases are independently associated with MetS. Despite negative ultrasound results in diabetic patients with MetS, the serum level of liver aminotransferases may be elevated and should be more thoroughly monitored.

We read with interest Dr.Choi's comments on our article titled "Association of Vaspin with Metabolic Syndrome: The Pivotal Role of Insulin Resistance" published in Diabetes & Metabolism Journal [1]. Vaspin is a novel adipokine linking adipocytes and components of metabolic syndrome, although the exact role of vaspin remains unclear [2,3]. In our study, we found that central obesity, raised triglyceride, and raised fasting blood glucose are linked to higher vaspin concentrations; meanwhile, the relationship abolished after controlling for homeostasis model assessment of insulin resistance and high sensitivity C-reactive protein revealing the leading role of insulin resistance and chronic inflammation in this regard. Choi et al.'s reported a significant relationship between vaspin concentrations and metabolic syndrome component including obesity and raised triglyceride. However, they did not find any connection between raised fasting plasma glucose and vaspin, which is evident in our series of patients. Discrepancies observed between the two studies likely reflect the differences in glycemic status of the patients enrolled. Choi et al. included patients from a routine health examination center (Seoul National University Bundang Hospital, Seoul, Korea) whereas our sample comprised patients visited at a diabetes clinic of a teaching hospital (Valiasr Hospital, Tehran, Iran). The proportion of patients with diabetes in the Korean sample was low (16.0%). In our sample a significantly larger proportion of patients were diagnosed with type 2 diabetes (59.3%) and another 9.7% had impaired fasting glucose. We suggest the more prominent association observed between insulin resistance/chronic inflammation and vaspin is due to prolonged hyperglycemia and insulin insensitivity. It is hypothesized that the principal event for the development of metabolic syndrome is the deposition of fat in adipose tissue, liver, muscles, and pancreas in the face of impaired triglyceride/cholesterol metabolism and central obesity. This process in turn triggers the development of insulin resistance through various pathways including oxidative stress and chronic inflammation which, in a proportion of patients, lead to type 2 diabetes mellitus [4,5]. Chronic inflammation in turn could impair insulin signaling pathways in liver and other organs [6]. Vaspin is an adipocytokine involved in early as well as late stages of metabolic syndrome. In this view, results of the present study complement Choi et al. findings by showing the unflagging contribution of vaspin to the pathogenesis of metabolic syndrome. Further investigating the mechanisms by which vaspin promotes metabolic syndrome and resultant atherosclerosis is a focus of future research. The authors would like to thank Dr.Choi for thoughtful comments which put the findings of our study in perspective and postulate possible hypotheses for future research.