Afsaneh Morteza

Contribution of Serum Leptin to Metabolic Syndrome in Obese and Nonobese Subjects

BACKGROUND AND AIMS 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. METHODS 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. RESULTS 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 (p <0.001). 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. CONCLUSIONS 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 dual behavior of heat shock protein 70 and asymmetric dimethylarginine in relation to serum CRP levels in type 2 diabetes

BACKGROUND Experimental evidence suggests that heat shock proteins (HSP) and asymmetric dimethylarginine (ADMA) are induced in the state of chronic inflammation and stress conditions. They are both inhibitors of nitric oxide synthase (NOS). The aim of this study was to evaluate the correlation between ADMA and HSP70, in patients with type 2 diabetes with respect to serum levels of C reactive protein (CRP). METHODS We quantified serum HSP70, ADMA and CRP in 80 newly-diagnosed patients with type 2 diabetes plus 80 age-, sex and BMI-matched healthy controls. The patients and controls were also stratified into groups of high and low CRP levels (cut-point: 2.5mg/ml). RESULTS Patients with type 2 diabetes had significantly higher serum HSP70 (0.52 [0.51-0.66] vs. 0.27 [0.26-0.36], p<0.001), ADMA (0.86 [0.81-0.92] vs. 0.72 [0.71-0.85], p<0.05) and CRP (2.9 [1.7-3.4] vs. 1.6[1.2-2.3], p<0.05) compared with healthy controls. Serum HSP70 and ADMA levels were significantly correlated in patients with high CRP levels (r=0.89, p<0.01), whereas there were no correlation in patients with low CRP (r=-0.37, p=0.07) and controls. This correlation was significant (r=0.77, p<0.001) in patients with high CRP and also in patients with low CRP levels (r=-0.51, p<0.05), after multiple adjustments for LDL and HDL levels. DISCUSSION We showed that, in a state of high inflammation; serum levels of ADMA parallel the HSP70 levels. However in low inflammation, they are negatively correlated. The duality in HSP70 and ADMA correlation may be related to the duality of NOS function in low and high CRP levels.

Physical activity is correlated with serum leptin independent of obesity: results of the national surveillance of risk factors of noncommunicable diseases in Iran (SuRFNCD-2007)

Reports on the relationship between leptin and physical activity (PA) at the population level are scarce. The present study examined the relationship between serum leptin concentrations and PA in a nationally representative sample of 3001 Iranian adults aged 25 to 64 years. Data of our third national surveillance of risk factors of noncommunicable diseases were analyzed. Using the Global Physical Activity Questionnaire, the duration and intensity of PA were evaluated in 3 domains: work, commuting, and recreation. Total PA was calculated using metabolic equivalents for PA intensity. Serum leptin was measured with an enzyme-linked immunosorbent assay. After adjustment for age, area of residence, smoking, body mass index, and waist circumference, total PA (r = -0.129, P = .038 in men and r = -0.226, P = .006 in women), the duration of vigorous-intensity activity (r = -0.120, P = .044 in men and r = -0.154, P = .019 in women), the duration of moderate-intensity activity (r = -0.114, P = .047 in men and r = -0.160, P = .018 in women), and time spent on sedentary behaviors (r = 0.194, P = .014 in men and r = -0.204, P = .007 in women) were significantly correlated with serum leptin. In both sexes, participants in higher categories of PA had significantly lower serum leptin levels. In conclusion, our results demonstrated an inverse association between leptin concentrations and PA independent of age, sex, smoking, and body adiposity. Our results point to the regulatory effects of PA on serum leptin.

Oxidized Low-Density Lipoprotein Is Negatively Correlated With Lecithin-Cholesterol Acyltransferase Activity in Type 2 Diabetes Mellitus

Introduction:It is now believed that the oxidative modification of plasma lipoproteins enhance their atherogenicity in patients with type 2 diabetes. Because a variety of highly reactive lipid peroxidation products can transfer from oxidized low-density lipoprotein (ox-LDL) to high-density lipoprotein -cholesterol, the authors evaluated the association between ox-LDL and lecithin-cholesterol acyltransferase (LCAT) activity, a key enzyme in reverse cholesterol transport and HDL remodeling. Methods:A total of 45 patients with diabetes and 45 age-, sex- and body mass index-matched healthy adult volunteers were enrolled. Fasting blood samples were obtained, and plasma glucose, lipid profile, creatinine, insulin, ox-LDL and LCAT activity were measured. Homeostasis model assessment of insulin resistance was also calculated. Results:Patients with diabetes, compared with healthy participants, had a significantly higher ox-LDL (17.16 ± 3.75 U/L versus 7.93 ± 1.92 U/L, P < 0.001) and lower LCAT activity (73.7 ± 9.1 &mgr;mol/L/hr versus 88.7 ± 4.5 &mgr;mol/L/hr, P < 0.001). The higher level of LCAT activity completely disappeared after adjustment for ox-LDL. LCAT activity had a significant (P < 0.001) inverse correlation with ox-LDL (r = −0.77) in patients with diabetes and healthy participants (r = −0.75). Conclusion:LCAT activity is significantly decreased in type 2 diabetes. The lower LCAT activity in type 2 diabetes might be through ox-LDL mechanism. Ox-LDL may adversely affect high-density lipoprotein -cholesterol metabolism by reducing LCAT activity.

The Value of Visfatin in the Prediction of Metabolic Syndrome: A Multi-Factorial Analysis

We describe the adipokine concentration in patients with metabolic syndrome, stressing the role of visfatin. A cross-sectional single center study on 70 patients with metabolic syndrome plus 76 controls was performed. Patients with metabolic syndrome had higher visfatin levels compared to controls, following adjustments for age, sex, waist/hip circumference, systolic, and diastolic blood pressure, fasting plasma glucose (FPG), HbA1c, body mass index, and homeostasis model assessment of insulin resistance (HOMA-IR) [(5.39 ± 0.29 vs. 3.88 ± 0.32); F(1, 129) = 10.8, P < 0.01]. A logistic regression analysis revealed that circulating visfatin levels and HbA1c were the top variables for predicating metabolic syndrome. In patients with metabolic syndrome, visfatin did not correlate with any of the measured variables, with the single exception of adiponectin; in patients without metabolic syndrome, circulating visfatin levels were significantly associated with FPG, HbA1c, insulin, HOMA-IR, HDL, and triglyceride. These findings may contribute to our current knowledge about visfatin in metabolic syndrome.

The role of Helicobacter pylori infection in gastro‐oesophageal reflux in Iranian children

Abstract Background: The relationship between Helicobacter pylori and gastro‐oesophageal reflux disease (GORD) in children is controversial. Aim: To determine the role of H. pylori infection and GORD in children living in a region which is endemic for H. pylori infection. Methods: A cross‐sectional study was undertaken in 263 children aged 3–18 years, all of whom had symptoms of GORD and underwent upper gastro‐intestinal endoscopy. H. pylori status was determined by conventional rapid urease test and Giemsa staining of antral and cardiac biopsies. Biopsies of the oesophagus and gastric mucosa were obtained from the lower oesophagus, the antrum and cardia according to standard protocol. Results: Of the 263 patients, 81 (31·5%) had GORD and 162 (61·5%) had gastritis. There were 59 H. pylori‐infected patients (22·4%) and 204 were uninfected. H. pylori infection was detected in 52 (88·1%) of the antral and 10 (1·9%) of the cardiac biopsies. Three (5·1%) of the biopsies revealed infection of both antrum and cardia and in seven (11·8%) only the cardia was infected. The prevalence of H. pylori infection among patients with GORD (13/83, 15%) was significantly lower than in those without GORD (46/180, 26%) (OR 0·54, CI 0·27–0·93, p<0·05). The prevalence of H. pylori infection among those with gastritis (48/162, 30%) was significantly higher than in those without gastritis (11/101, 10·8%) (OR 3·44, CI 1·69–7·015, p<0·001). Conclusion: H. pylori infection might protect against GORD.

Appearance of leptin-HSP70 correlation, in type 2 diabetes.

In vitro and in vivo studies have shown conflicting results regarding heat shock protein (HSP) and leptin correlation. More importantly both HSP70 and leptin are correlated with C reactive proteins. The purpose of the present study was to study the correlation between serum HSP70 and leptin levels in patients with type 2 diabetes stratified according to gender. We performed a cross sectional study on the established groups of patients with type 2 diabetes defined as 1: patients with long standing diabetes for more than 3 years; and 2: patients with newly diagnosed diabetes within recent 6 months who were not on any glucose lowering treatment other than by dietary means alone and 3: healthy controls. Patients with long standing diabetes had higher HSP70, HbA1c and triglyceride than controls. Serum leptin levels were significantly lower in patients with newly diagnosed diabetes. Women with type 2 diabetes had higher leptin levels compared to men, both before and after treatment. We showed a positive correlation between leptin and HSP70 levels in women with type 2 diabetes. The correlation was strongest in women with newly diagnosed diabetes (r = 0.59) and was attenuated in women who were on treatment (r = 0.3). The significance of this correlation was only observed in women with type 2 diabetes. There was no correlation between leptin and HSP70 in men. The positive correlation between leptin and HSP is observed in chronic inflammation such as type 2 diabetes. It could be hypothesized that the observed correlation between serum HSP70 and leptin implies a higher state of chronic inflammation.

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

Objective The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes. Methods We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial single-photon emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing. Results Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (P<0.001). The odds ratio of having ischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01–1.56] (P<0.05) in all studied populations, 0.79 [95% CI: 0.51–1.21] (P=0.14) in women, and 2.84 [95% CI: 1.68–4.79] (P<0.001) in men. We showed that diabetes duration, high-density lipoprotein, low-density lipoprotein, and hemoglobin A1c influence albuminuria in women, while diabetes duration, fasting blood sugar, and diastolic blood pressure influence albuminuria in men. Conclusions Men with albuminuria are at increased risk of ischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.

Metabolic syndrome is linked to a mild elevation in liver aminotransferases in diabetic patients with undetectable non-alcoholic fatty liver disease by ultrasound

BackgroundDespite 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.MethodsA 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.ResultsSerum 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.ConclusionIn 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.

Color Doppler ultrasound for evaluation of vasomotor activity in patients with carpal tunnel syndrome

BackgroundPatients with carpal tunnel syndrome (CTS) have a variety of vasomotor symptoms. Here, we aimed to study the vasomotor activity of the radialis indicis (RI) artery (median nerve territory) and the radial palmar digital (RPD) artery of the little finger (ulnar nerve territory) before and after sympathetic stimulation in CTS patients using color Doppler ultrasound.MethodsWe performed a cross-sectional study of 46 consecutive CTS patients plus 36 healthy controls. All patients underwent electromyography studies and were classified into mild and moderate/severe groups according to electrodiagnostic findings. Color Doppler examination of the RI artery and the RPD artery of the little finger were performed with the participants in a relaxed sitting position and after a deep breath followed by a cough (sympathetic stimulation). The pulsatility index (PI) was recorded at the point of maximal change in waveform, before and after this stimulus.ResultsThe PI of RI artery was significantly lower (p < 0.01) in CTS patients than healthy controls, both before and after stimulation. The changes in PI of RI artery after stimulation were significantly lower in CTS patients than healthy controls (1.18 ± 0.37 vs. 5.41 ± 0.87; p < 0.001). The same pattern was seen for PI of RI artery when comparing patients with mild vs. moderate/severe CTS. No difference was found in PI of RPD artery of the 5th finger between patients vs. controls and between patients with mild vs. moderate/severe CTS, both before and after stimulation.ConclusionsWe showed that color Doppler ultrasound can readily determine impaired vasomotor activity in CTS patients.