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.

The Impact of Mindfulness-Based Stress Reduction on Emotional Wellbeing and Glycemic Control of Patients with Type 2 Diabetes Mellitus.

OBJECTIVE: The aim of the study was to determine the effect of mindfulness-based stress reduction (MBSR) intervention on emotion regulation and glycemic control of patients with type 2 diabetes. MATERIALS AND METHODS: Sixty patients with type 2 diabetes were recruited for this randomized controlled trial from an outpatient clinic at Imam Hospital in Iran. The intervention group participated in 8 sessions of MBSR, and the control group continued the treatment as usual. Fasting blood sugar and HbA1c were measured as two indices of glycemic control. Overall mental health, depression, and anxiety were measured using the General Health Questionnaire (GHQ-28), Hamilton Depression Rating Scale (HDRS), and Hamilton Anxiety Rating Scale (HARS), respectively. All the assessments were performed at baseline and after 8 weeks and 3 months as follow-up. RESULTS: In comparison with the control group, the MBSR intervention group showed a significant reduction on all outcome measures including FBS, HbA1C, HARS, and HDRS scores (p < 0/05). CONCLUSION: MBSR had a remarkable improvement on emotional wellbeing and glycemic control of patients with type 2 diabetes.

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 synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat.

Protein glycation due to hyperglycemia resulting in misfolding and aggregation, which is known as one of the most important reasons of diabetes complications. We previously showed the beneficial effects of some antiglycating agents in diabetic rats. Here, the effect of MB-92, a combination of some amino acids and crocetin (Crt, a saffron carotenoid), was studied in the prevention of diabetic complications in diabetic-atherosclerotic rats. In addition, the inhibitory effect of these treatments on glycation intermediates, aggregation and misfolding of proteins was investigated both in vivo and in vitro. Thus, the streptozotocin-induced diabetic rats that underwent an atherogenic diet were treated with Crt, N-acetylcyctein and MB-92. Then, glycated products and markers of oxidation and inflammation, in addition to other markers of diabetes complications were studied. The results of the in vivo study indicated that the mentioned treatments prevented the atheromatos formation, reduced the increased blood glucose; inhibited the formation of various glycation products, induced glyoxalase system (I and II), diminished oxidation and inflammatory markers, and improved lipid profile and atherosclerotic index in the diabetic-atherosclerotic rats; but MB-92 was the most effective treatment. In vitro results also confirmed that MB-92 was the most effective treatment to inhibit protein glycation and misfolding in comparison with the other treatments. In conclusion, MB-92 showed the greatest potential for inhibition of glycation and oxidation products, atheromatose plaque formation and inflammation in diabetic-atherosclerotic rats, and to control protein glycation, misfolding and aggregation in high glucose concentration; thus, it can be suggested as a new drug to prevent diabetic complications.

Reduction in asymmetric dimethylarginine plasma levels by coenzyme Q10 supplementation in patients with type 2 diabetes mellitus.

AIM: According to many studies, supplementation with Coenzyme Q10 (CoQ10) yields beneficial results in terms of endothelial function in type 2 diabetes mellitus. Despite these promising results, data elucidating the effect of CoQ10 on plasma levels of asymmetric dimethylarginine (ADMA), as a recently discussed cardiovascular risk factor, is lacking. This study was designed to investigate the effect of CoQ10 supplementation on endothelial function, specifically by evaluating plasma ADMA levels. METHODS: Sixty-four type 2 diabetic patients were randomly assigned to two groups; either receiving 200mg/d oral dose of CoQ10 (N.=31) or receiving placebo (N.=33) for 12 weeks. Clinical and biochemical assessments were performed before and after the trial for evaluating ADMA, serum nitrite and nitrate (NOx), hemoglobin A1c and lipid profile. RESULTS: The intervention resulted in a significant improvement in ADMA, NOx , low-density lipoprotein and hemoglobin A1c levels in CoQ10 compared to placebo group. Interestingly, difference in changes of these parameters were also significant (P=0.01, 0.03, 0.04 and 0.03, respectively). CONCLUSION: Supplementation with CoQ10 yields beneficial effects on ADMA levels, leading to decreased diabetic cardiovascular events.

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.

Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics.

It is not known whether the association of serum 25-hydroxyvitamin D [25(OH)D] with glycemic measurements of individuals without diabetes is similar to those with diabetes or not. This study is aimed to investigate the association of serum 25(OH)D with glycemic markers of diabetics, nondiabetics, and prediabetics. A case-control study was conducted on age and sex matched 1,195 patients with type 2 DM, 121 prediabetics, and 209 healthy controls. Anthropometric variables, lipid profile, glycemic measurements, and serum 25(OH)D levels were recorded. Serum insulin and C-peptide levels were also measured. All glycemic measurements were compared between diabetics and nondiabetics and prediabetics at different vitamin D status. Patients with DM had lower serum 25(OH)D compared to prediabetics and healthy controls. Endogenous insulin production in response to food intake and in fasting was significantly lower in vitamin D deficient patients with DM compared to those with serum 25(OH)D>40 ng/ml. Diabetic women with serum 25(OH)D<20 ng/ml had lower beta cell function as estimated by lower HOMA-B compared to their counterparts with serum 25(OH)D>40 ng/ml. Healthy individuals with serum 25(OH)D<20 ng/ml had signs of insulin resistance as estimated by significant increase of HOMA-IR, HbA1c, and fasting plasma glucose (FPG). In addition, we found that serum 25(OH)D was inversely associated with insulin resistance. Vitamin D deficiency is associated with insulin resistance in nondiabetics, which is independent of obesity. Furthermore, vitamin D deficiency is associated with reduced insulin production in type 2 diabetics, which was mainly observed in men. Accordingly, a gender disparity also exists in association of serum 25(OH)D with glycemic measurements.

Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial.

PURPOSE: 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. METHODS: In a parallel-group, open-label, randomized trial setting (ClinicalTrials.gov Identifier No. NCT01521624), 84 newly diagnosed, medication-naïve 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. RESULTS: 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%). CONCLUSIONS: 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.

Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: associations with inflammatory and cardiometabolic markers in 4391 subjects.

AIM: This study aimed to compare concentrations of serum 25-hydroxy vitamin D and inflammatory markers in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and to determine whether the relationship between vitamin D levels and both cardiometabolic and inflammatory markers differs between MHO and MUO. METHODS: This cross-sectional study comprised 4391 obese subjects aged>18 years. A panel of cardiometabolic and inflammatory markers, including anthropometric variables, glycaemic indices, lipid profiles, liver enzymes, homocysteine, C-reactive protein (CRP), fibrinogen and serum 25-hydroxy vitamin D levels, was investigated. All cardiometabolic and inflammatory markers in MHO and MUO as well as in vitamin D deficiency were compared. RESULTS: Prevalence of MHO was 41.9% in our obese subjects using International Diabetes Federation criteria. Considering insulin resistance and inflammation, the prevalence of MHO was 38.4%. Individuals with MHO had significantly higher vitamin D concentrations compared with MUO, and this difference in vitamin D status persisted after accounting for BMI and waist circumference. Subjects with MHO had significantly better metabolic status, lower liver enzymes, lower inflammatory markers and higher serum 25-hydroxy vitamin D than those with MUO. Associations between vitamin D levels and inflammatory and cardiometabolic markers differed according to MHO/MUO status. Among MUO subjects, vitamin D deficiency was associated with higher liver marker and homocysteine levels. Serum vitamin D was negatively associated with fasting plasma glucose and HbA1c in MHO only. CONCLUSION: Serum 25-hydroxy vitamin D levels were lower in MUO vs MHO, and reduced vitamin D concentrations were more strongly associated with cardiometabolic and inflammatory markers in MUO than in MHO subjects. These findings suggest that a deficiency in vitamin D could be a key component of MUO.

Visit-to-visit blood pressure variability is related to albuminuria variability and progression in patients with type 2 diabetes.

Recent studies have suggested that visit-to-visit variability of blood pressure (BP) is correlated with microalbuminuria in patients with diabetes, independent of mean pressure. We investigated the contribution of BP variability to albuminuria progression in normoalbuminuric type 2 diabetes patients. BP and urinary albumin excretion of patients were assessed in each visit during a median follow-up of 31 months. Variability was assessed using standard deviation, coefficient of variation, standard deviation independent of mean, peak, average real variability, and average real variability independent of mean. Of 194 patients enrolled, 31 subjects (16.0%) developed microalbuminuria. Systolic blood pressure (SBP) variability indices (except for coefficient of variation and average real variability) were significant predictors of microalbuminuria in multivariate Cox regression models (hazard ratio ranging from 2.02 to 2.76). The same was not observed for diastolic blood pressure. Using linear regression, SBP variability significantly correlated with some but not all indices of albuminuria variability. Peak SBP was the strongest predictor of albuminuria variability in multivariate models (standardized beta ranging from 0.216 to 0.339). In conclusion, visit-to-visit variability of SBP is an independent risk factor for development of microalbuminuria in patients with diabetes, and is associated with an increased variability in albuminuria.

The effect of coenzyme Q10 supplementation on metabolic status of type 2 diabetic patients.

AIM: Increased oxidative stress and impaired antioxidant defense contribute to pathogenesis and progression of type 2 diabetes. Consistent with this fact, it has been shown that diabetic patients have reduced coenzyme Q10 level. In this study we sought to compare the effect of coenzyme Q10 versus placebo on glycemic control and lipid profile in type 2 diabetic patients. METHODS: In a randomized double-blind placebo-controlled trial, 64 type 2 diabetic patients were randomly assigned to receive either 200 mg Q10 or placebo daily for 12 weeks. Fasting blood samples were obtained and fasting plasma glucose (FPG), HbA1c, total cholesterol (TC), triglycerides (TG), LDL-C and HDL-C were measured. RESULTS: In this study no significant differences considering age, body mass index (BMI), diabetes duration, FPG, HbA1c, TC, TG, LDL-C and HDL-C were shown between two groups. Serum HbA1C concentration decreased in the Q10 treated group (8 ± 2.28 vs. 8.61 ± 2.47%) with no significant effect in the placebo group. Following intervention no differences have been shown regarding FPG, TG and HDL-C in Q10 treated group. Furthermore, mean differences of TC and LDL-C level were statistically altered between two groups (P value=0.027 and 0.039 respectively). CONCLUSION: In this study, Q10 treatment improved glycemic control, total and LDL cholesterol but these differences were associated with no favourable effects on TG and HDL-C.

Comparison of osteoprotegerin and vascular endothelial growth factor in normoalbuminuric Type 1 diabetic and control subjects.

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<0.01) and were positively correlated with glycemic indices (i.e. fasting plasma glucose and HbA1c, p<0.001). After controlling for possible confounding factors, odds ratios (confidence interval) of osteoprotegerin and VEGF for diabetes were 2.532 (1.003-6.392) and 1.021 (1.002-1.041), respectively (p<0.05). Further, linear regression analysis revealed that the association of osteoprotegerin with HbA1c is independent of VEGF and vice versa (p<0.001). CONCLUSION: Osteoprotegerin and VEGF are elevated in normoalbuminuric Type 1 diabetic subjects and are independently associated with glycemic indices and diabetes status.

Gender-dependent effects of metformin on vaspin and adiponectin in type 2 diabetes patients: a randomized clinical trial.

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-naïve, 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<0.001 in all cases). Vaspin and adiponectin concentrations were 23% and 26% higher in women compared with men. Vaspin dropped significantly after 3-month metformin therapy only in women (1.36 vs. 0.98, p=0.003 in women and 1.31 vs. 1.20, p=0.335 in men). Metformin therapy did not change adiponectin concentration in neither women nor men of the case group (12.66 vs. 12.44 p=0.699 in women and 10.13 vs. 10.94 p=0.253 in men). Comparing case and control groups, metformin decreased vaspin levels more significantly than lifestyle modification in the final multivariate model after controlling for potential confounders only in women (p=0.002) but not men (p=0.896). Conversely, adiponectin levels increased more significantly in the control group, again only in women (p=0.012 and 0.579 for women and men, respectively). Our findings suggest that metformin therapy reduces vaspin concentration in a gender-specific manner. Metformin exerts little benefit in increasing adiponectin levels in diabetes patients.

Effect of alendronate on early bone loss of renal transplant recipients.

INTRODUCTION: Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX. PATIENTS AND METHODS: We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years, mean body mass index of 23.6±3.73, and mean dialysis duration of 25.73±17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX. RESULTS: At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 (P<.01), while it decreased in the control group from 0.897±0.17 to 0.817±0.16 (P<.001). There was also a significant increase in radius BMD (P<.001) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD (P<.001) in the control group at 6 months. Upon multivariate analysis, there was a significant correlation between alendronate and spine BMD (r=.45, P<.001) but no linear regression between age, sex, BMI, dialysis duration of or iPTH with femoral, spine, or radius BMD changes at month 6. CONCLUSION: Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX.

Type 2 diabetes mellitus duration: an independent predictor of serum malondialdehyde levels.

INTRODUCTION: Patients with type 2 diabetes mellitus (DM) are subject to chronic oxidative stress. Lipid peroxidation of cellular structures is an important process in atherosclerosis and late complications of DM. Malondialdehyde (MDA) plays a major role in low-density lipoprotein modification. This study aimed to evaluate whether DM duration is an independent predictor of serum MDA levels. METHODS: A total of 120 patients with type 2 DM (60 with DM duration of 120 months or less and 60, with more than 120 months) and 45 gender- and body mass index (BMI)-matched healthy adults were studied. Fasting blood samples were obtained and the fasting plasma glucose (FPG), cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, creatinine, haemoglobin A1c (HbA1c), extracellular superoxide dismutase (EC-SOD) and MDA levels were measured. RESULTS: The MDA level was significantly higher in DM patients than in controls (p is less than 0.001), and in those with DM duration more than 120 months than those with DM duration of 120 months or less (p is less than 0.001). The level of MDA was significantly correlated with DM duration (correlation coefficient 0.254, p is less than 0.01) and the EC-SOD level (correlation coefficient 0.299, p is less than 0.001). In multivariate regression analysis, the association between MDA and DM duration remained significant after adjustments were made for age, gender, BMI, FPG, HbA1c, EC-SOD, plasma creatinine and anti-diabetic medications (p is less than 0.05). CONCLUSION: The results of this study suggest that in type 2 DM patients, DM duration is independently associated with increased levels of lipid peroxidation. Longitudinal studies are required to confirm these results.

ADMA is a correlate of insulin resistance in early-stage diabetes independent of hs-CRP and body adiposity.

OBJECTIVES: It has been shown that insulin resistance is associated with a state of chronic low-grade inflammation. Furthermore, depletion of nitric oxide (NO) or ineffectiveness of NO-mediated vasodilator mechanisms are associated with arterial stiffness and progression of insulin resistance to type-2 diabetes. In this study, we decided to evaluate the association between asymmetric dimethylarginine ([ADMA], an endogenous NO synthase inhibitor), high-sensitivity C-reactive protein ([hs-CRP]; a marker of chronic inflammation) and insulin resistance in early-stage type-2 diabetes. METHODS: A total of 40 diabetic patients and 40 age-, sex- and body mass index (BMI)-matched healthy adult volunteers were recruited in this case-control study. Diabetic patients were recently diagnosed and did not have a history of any diabetes-related complications. Fasting blood samples were obtained and fasting plasma glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, creatinine, insulin, ADMA and hs-CRP were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was also calculated. RESULTS: ADMA (0.9+/-0.2 vs 0.7+/-0.2 micromol/L; p<0.001) and hs-CRP (3.0+/-2.1 vs 1.3+/-1.0mg/L; p<0.001) were significantly higher in diabetic participants vs healthy controls. Age- and sex-adjusted ADMA values were significantly (p<0.05) correlated with hs-CRP (r=0.279) and HOMA-IR (r=0.288) in diabetic patients. These associations were not significant in healthy controls. The association between ADMA and HOMA-IR in diabetic patients remained significant (r=0.255; p<0.05), after adjustment for BMI, waist circumference, serum lipids, and hs-CRP. In multivariate regression analysis, ADMA and hs-CRP were independently correlated with diabetes. CONCLUSION: In early-stage type-2 diabetic patients, ADMA is an independent predictor of insulin resistance. Our results could possibly point to an independent mechanism for contribution of ADMA in development of insulin resistance.

Effect of renal transplantation on coronary artery calcification in hemodialysis patients.

OBJECTIVE: Vascular calcification is a strong predictor of cardiovascular and all-cause mortality. Coronary artery calcification is more frequent, more extensive, and progresses more rapidly among subjects with chronic kidney disease (CKD) than in the general population. It is also considered to be a marker of coronary heart disease, the main cause of increased morbidity and mortality among patients either on maintenance hemodialysis or after transplantation. The aim of this study was to evaluate the effect of renal transplantation on the calcium scores of coronary arteries among hemodialysis patients. PATIENTS AND METHODS: The study included 31 patients (17 males and 14 females) of age range 19 to 56 years (mean, 38.08 +/- 13.49 years) who had been hemodialyzed 3 times a week for 6 to 49 months (mean, 20 +/- 15.72 months) prior to renal transplantation. Homocysteine, intact parathyroid hormone (iPTH), calcium, phosphate, and indices of lipid metabolism such as total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were measured before and at 6 months after transplantation. To evaluate coronary artery calcification, all patients underwent multidetector coronary computed tomography (MDCT) using the Agatston technique for calcium scoring (CS) and color Doppler ultrasound for IMT before and at 6 months after the procedure. RESULTS: The prevalence of coronary artery calcifications among dialysis patients was 96% with a total CS ranging from 0 to 198. It affected more than 2 vessels in >50% of subjects with higher calcium scores in the left anterior descending artery (LAD). Mean total CS decreased significantly from pre- (39.82 +/- 63.05) to postoperation (24.34 +/- 39.55; P < .001). CS decreased from pre- to postprocedure in the left main artery (7.4 +/- 13.03 to 4.3 +/- 8.54; P < .01) and in LAD (15.76 +/- 23.53 to 10.23 +/- 15.81; P < .01 and in the circumflex (7.8 +/- 14.98 to 5.1 +/- 9.57; P < .001) and in the right coronary artery (9.2 +/- 17.18 to 4.7 +/- 8.18; P < .01). The CS before the procedure correlated significantly with age (r = .39; P < .005), P (r = .33; P < .05), Ca x P product (r = .39; P < .05), iPTH (r = .43; P < .001), and IMT (r = .56; P < .0001). There was a linear, meaningful correlation between CS and iPTH and Ca x P product reduction after renal transplantation. CONCLUSIONS: Renal transplantation significantly reduced coronary artery calcification among dialysis patients. It linearly correlated with a decrease in iPTH and Ca x P product at an early period after renal transplantation.

Changes in growth hormone and insulin-like growth factor-I levels in the acute stage after open heart surgery and at the time of discharge.

INTRODUCTION: Stress conditions are known to disturb the axis of growth hormone (GH)/insulin-like growth factor-I (IGF-I), but there is little data on this topic after open heart surgery. This study aimed to investigate changes in GH/IGF-I axis in adults undergoing open heart surgery. METHODS: A total of 162 adult patients admitted for elective major cardiac surgery were studied in a prospective setting. Serum concentrations of GH and IGF-I were measured at four time points: before operation as a baseline, 4 and 12 hours after operation in ICU, and at the time of discharge. Two to 4 venous blood samples were obtained from each patient. To study the changes of GH and IGF-I levels over time, general linear model for repeated measures was applied. RESULTS: Mean age of patients was 51.2+/-14.3 years. Compared with preoperative values (median 0.8, range 0.05-19.4 ng/mL), GH levels rose significantly at four (median 3.3, range 0.1-55 ng/mL) and twelve hours after surgery (median 5.45, range 0.55-61.2 ng/mL), and continued to remain high at the time of discharge (median 2.1, range 0.02-22.7 ng/mL) (p<0.05). Conversely, compared with preoperative levels (173.5+/-89.9 ng/mL), IGF-I decreased at four (140.9+/-66.9 ng/mL) and twelve hours after operation (135.9+/-59.9 ng/mL) and reached its nadir on the day of discharge (114.8+/-43.8 ng/mL) (p<0.01). The patterns of changes in GH and IGF-I over time were significantly different (p<0.01). CONCLUSION: Adult patients undergoing open heart surgery go through a state of GH resistance characterized by elevated GH and decreased IGF-I levels from the initial hours after operation.

Insulin resistance is an independent correlate of increased urine albumin excretion: a cross-sectional study in Iranian Type 2 diabetic patients.

AIMS: To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. METHODS: Three hundred and sixty-one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005-2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE >or= 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: HOMA-IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA-IR were 11.81 +/- 7.51 (mg/day) and 3.30 +/- 2.21 in normoalbuminuric and 75.36 +/- 55.57 (mg/day) and 4.98 +/- 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA-IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA-IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7-6.2)]. CONCLUSIONS: In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA-IR is an independent predictor of UAE.