Iranian Journal of

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Background: All contemporary methods of insulin administration are non-physiological. The euglycemia that is achieved in at the expense of the adverse effects of systemic hyper-insulinemia, emphasize the importance of devising methods to deliver insulin physiologically and directly into the portal circulation. The aim of the present study was to evaluate the oral absorption of insulin from gastrointestinal tract, using novel oral drug delivery system delivery based on superporouse hydrogel (SPH) and SPH composite (SPHC) in combination with insulin.
Methods: This study has been done based on interventional clinical trial in healthy volunteers. Capsules containing insulin and SPH &SPHC in various combination were administered orally, to 15 non-diabetics subjects in order to assess this biological effects and safety. Serum glucose, insulin and C - peptide levels were determined, at predetermined timed intervals up to 4 h.
Results: An increase in serum insulin level was demonstrated in all subjects that used polymer plus insulin. The nadir of serum glucose level appeared after 60 - 120 min following the ingestion of polymer plus insulin. Serum C - peptide levels were suppressed while exogenous insulin was absorbed at the same time. No adverse effects were detected during the trial and several weeks following the trial using SPH based drug delivery system.
Conclusions: Insulin in combination with novel delivery agents, SPH & SPHC, given orally was partially absorbed through the GI tract in a biologically active form. This was demonstrated by serum glucose lowering effect of the delivery system as well as a suppression of plasma C-peptide which also represented a decrease in endogenous insulin secretion.

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Background: Elevated total plasma Homocysteine, is an independent risk factor for cardiovascular disease. Folate and vitamin B12 have not only a protective effect on cardiovascular disease but also an essential effect on total Homocysteine concentrations (tHcy). This survey has been conducted to evaluate the determinants of tHcy in 1191 healthy Iranian adults.
Methods: This study which was a part of the Cardiovascular Risk Factors Survey in the Population Lab Region, has been designed and conducted based on MONICA/WHO project. A total of 1191 people have been recruited and assessed on serum Homocysteine, Folic acid and vitamin B12, triglycerides, cholesterol, HDL-C, LDL-C, FBS, BMI, BP and smoking, with interview, questionnaires, examination and blood sampling. Blood samples were analyzed according to standard methods.
Results: The variables were assessed in 1191 participants include 416 men (34.9%) and 775 women (65.1%). Prevalence of hyperhomocysteinemia was correlated significantly with male sex and aging. Hcy levels were inversely related to serum Folate and vitamin B12 concentrations. After further adjustments, we detected a positive correlation between tHcy and age, male sex, smoking and BMI, and a negative one with LDL-C and diabetes. Although there was a correlation between tHcy and blood pressure, after age, sex, BMI and smoking adjustment, it just remained significant in women and with systolic blood pressure.
Conclusion: We found that dietary and lifestyle parameters such as Folate intake and smoking habit are the main determinants of distribution of plasma Homocysteine in an apparently healthy population. We assumed that lifestyle changes could have considerable subsequences in public health. Our findings confirm the potential advantages of dietary improvements and increased intake of nutrients along with smoking cessation in order to prevent cardiovascular diseases in high-risk patients.

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Background: Cardiovascular diseases are described as the most important health problems in developing countries which are developed in parallel with industrialization of communities. Based on the high morbidity and mortality of cardiovascular disease, this study was performed for examining the population lab inhabitants’ knowledge and practice.
Methods: In this cross – sectional study, 1576 inhabitants of the Population Lab Region were studied by cluster random sampling in 2002. 181 persons were selected from this population. The frequency of each cardio- vascular diseases risk factor such as hyperlipidemia, smoking, obesity, hypertension, Diabetes, family history of heart attack, being man, stress and excitement, sedentary life style, salty food, vegetables fruits, fatty food and red meat consumption, were assessed. In addition, the population study's practice regarding controlling the risk factors of cardiovascular diseases was determined, as well. Moreover, specific questionnaire and direct interview were used for collecting data and then the gathering data was analyzed by SPSS and EPI – Info soft wares.
Results: In this study, 71.8% of people were women while 28.2% of them were men. Besides, there was a significant relationship between the people’s knowledge about cardiovascular disease and the level of their education (P < 0.001). According to the results, 65.2% of population believed that heart attack was the most prevalent cause of death in comparison with 44% of them considered car accident and 13.3% agreed with cancers. On the other hand, 74% of people used liquid oil in their food and 77.9% of them knew the side effects of unhealthy foods such as salty food as one of the cardiovascular risk factors.
Conclusion: The inhabitants' knowledge regarding to the risk factors of cardiovascular diseases was approximately acceptable. However, there was a significant different between their knowledge and practice. Therefore, providing suitable educational programs for improving people’s nutrition, physical activity and the other relevant factors for preventing cardiovascular risk factors would be mentioned.

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Background: Glucokinase serves as a glucose sensor in pancreatic β-cells and plays a key role in glucose homeostasis and glucose-stimulated insulin secretion (GSIS). In the present study we examined the effect of glucosamine, a glucokinase inhibitor, on the pancreatic glucokinase and hexokinase activities and on insulin secretion from freshly rat pancreatic islets of Langerhans. Insulin concentration was measured by rat insulin ELISA kit. Methods: The pancreatic islets from normal and type 2 diabetic (nSTZ) rats were isolated by collagenase digestion method. Glucose phosphorylation was quantitated by measuring the rate of glucose-6-phosphate formation in the fluorometric assay. Insulin secretion from hand-picked islets was evaluated in static incubation system. Insulin concentration was measured by rat insulin ELISA kit. Results: Our findings demonstrate that glucosamine in a dose dependent manner, reduced glucokinase activity in islet extract, but had no effect on hexokinase activity. The glucose-stimulated insulin secretion, was inhibited by glucosamine but it had no effect on the basal insulin secretion. In diabetic rats glucokinase was decreased while the basal insulin secretion and the activity of hexokinase were higher than normals. Conclusion: Based on results obtained from the present study, the assumption could be made that the decrease in the activity of glucokinase of pancreatic islets could be related to the impaired glucose stimulated insulin secretion. The increase in basal insulin secretion of diabetic rats may be due to an increase in pancreatic hexokinase activity.

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Background: Diabetes is a common endocrine disease in human kind. In most type II diabetic patients, obesity and overweight status account as the serious health problems worldwide and variety of endocrine factors well known that have regulatory role in weight balance and body composition including Leptin and IGF-I factor. The aim of this study was to examine the correlation between Leptin and IGF-I in type II diabetics and controls.
Methods: As a case- control study, 38 type 2 diabetics (20 males and 18 female with mean age 49.22) and 46 healthy controls (16 males and 30 females with mean age 49.52) are recruited. We measured the concentrations of FPG, IGF-I, HbA1C and IGFBP-3 in both groups. FPG was measured by enzymatic glucose oxidase method and Hb Gold analyzer HPLC was used to measure HbA1C. Determination of Leptin, IGF-I, IGFBP-3 and Insulin concentrations were carried out using ELIZA method. P< 0.05 was considered as statistically significant.
Results: The mean of BMI and age were not significantly different in both groups. The mean serum levels of IGF-I, Leptin, Insulin, FPG and HbA1c concentrations in type II diabetics were significantly higher than controls (P< 0.05). In males, the mean serum levels of Leptin were statistically lower than in females in both groups. There was a strong correlation between IGF-I and IGFBP-3, Leptin and insulin, IGF-I and age, and BMI with FPG in both patients and controls (P< 0.05). A reverse correlation was observed between IGF-I and HbA1c in patients and controls (P< 0.05).
Conclusion: It is speculated that based on this findings, Leptin and IGF-I system could have regulatory roles in body composition and fat content particularly in obese and overweight diabetic patients and have significant correlation with Insulin, glucose, BMI and age.

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Background: Although there is increasing evidences that vitamin D is related to the occurrence of diabetes mellitus, its relation to glucose metabolism in pregnancy is not well studied. This study investigated 25-hydroxyvitamin D deficiency status in GDM pregnant women.
Methods: As a cross sectional study we recruited 741 pregnant women referred to five university educating hospital clinics. The universal screening was performed with a GCT-50g and those with plasma glucose level ≥130mg/dl, were diagnosed as GDM, if they had an impaired GTT-100g based on Carpenter and Coustan criteria. The levels of insulin was studied during OGTT-100g. Serum concentrations of 25-hydroxy vitamin D was measured too.
Results: Univeriate analysis revealed that 25 (OH) vit D concentrations were positively correlated with HOMA and ISOGTT index. Subjects with hypovitaminosis D (<12.5nmol/dl) had greater prevalence of GDM than others.
Conclusion: The results reveal a positive association between 25(OH) vit D concentrations and insulin sensitivity. Vit D deficiency is more prevalent in patients with GDM than normal pregnant women, So vit D supplementation may control glucose levels and improves outcome of pregnancy.

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Background: Dyslipidemia accounts as a major risk factor for cardiovascular diseases. The aim of this survey was to determine the prevalence of dyslipidemia among relatives of patients with premature coronary artery disease (PCAD).
Methods: As a cross-sectional study 232 first degree relatives of patients with PCAD were recruited. A questionnaire was filled out by all of the participants all of them undergone physical examination and blood sampling. Lipid profile was categorized according to the NCEP: ATPIII criteria.
Results: Total Cholesterol>200 in 29.7%, LDL>160 in 10.3%, HDL<40 in 12.9%, TG>200 in 32.8%, ApoB100>130 in 14.2%, Apo A1<90 in 1.7% and LP(a)>30 in 47% of participants were seen. Serum levels of TG were significantly higher in men than women levels of HDL and ApoA1 were lower in men than women. The Prevalence of dyslipidemia among relatives was 59.6%.
Conclusion: In view of high prevalence of Dyslipidemia among relatives of PACD patients, active interventions in order to primary prevention of cardiovascular diseases via exact screening is recommended.

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Medicine and ethics have increasingly more links caused by considerable progresses in biotechnology in different fields of medical diagnosis, treatment and prevention. The issue of research ethics is one of the most important subjects which have been emphasized by international and regional organizations, policy-makers, medical and religious professions, scientists and researchers in different countries in recent decade. It is widely understood that research ethics committees typically play an important role in evaluating the ethical aspects of medical research. A ‘Research Ethics Committee’ (REC) is defined as a multidisciplinary, independent, body charged with reviewing research involving human participants to ensure that their dignity, rights and welfare are protected. Research ethics committees protect the welfare and rights of participants involved in research through reviewing research proposals, monitoring the conduct of research and dealing with complaints that arise from research. This manuscript will introduce you to the concepts underlying research ethics committees worldwide and in Iran. This paper will begin with a brief history of research ethics, continues with a concise overview of ethics committee situation and responsibilities, and ends with an outline of the national activities. We hope the manuscript could enhance awareness of biomedical researchers about status and duties of research ethics committees and consequently strengthen the RECs in our country.

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Background: Gestational diabetes mellitus is a common metabolic disorder in pregnancy. Low levels of sex hormone–binding globulin level (SHBG) is associated with increased insulin resistance and hyperinsulinemia. The aim of this study was comparison of SHBG levels between gestational diabetic pregnant women and normal ones.
Methods: Serum SHBG concentration were measured in 38 women with gestational diabetes and in 143 women with normal pregnancy. The levels of Insulin, C-peptide and testosterone were measured and Insulin resistance was estimated via HOMA Index. Insulin sensitivity was estimated via QUIKE Index.
Results: Serum SHBG concentrations was significantly lower in the diabetic group (P=0.015). In a logistic regression model after adjustment of age, body mass index (BMI) and number of gravid, lower than 25 percentile of SHBG was independently effective in prediction of gestational diabetes mellitus.
Conclusion: SHBG concentrations are lower in gestational diabetic pregnant women and low levels account as a predictor of gestational diabetes mellitus.

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Background: Diabetes mellitus is an insidious disease which can affect different organs. One of the problems is resistant vaginitis, which is related to factors such as high blood glucose levels, allergy and atopia. One of the most common pathogens associated with this condition is Candida Albicans. Thus most physicians begin anti-fungal therapy in first visit even without documented evidence of fungal origin.
Methods: This descriptive analytical cross-sectional study was performed on 160 non-pregnant diabetic women in diabetes clinic of Shariati Hospital during a period of three years (2002-2005). Fasting and 2 hours postprandial blood glucose levels and HbA1C were measured and culture of vaginal discharge was performed. Fisher's exact test was used for statistical analysis.
Results: 71% of women had clinical vaginitis (fungal or bacterial) and 12.5% were diagnosed with Candida vaginitis. Microscopic findings were positive in 1.3 % of patients who had Candida vaginitis (16.7% of all patients). Culture of vaginal discharge revealed that the Candida was responsible of 4.4% of Candida vaginitis. Overlay, the prevalence of Candida vaginitis based on positive culture was 8.8 % in this study. There was significant statistical relationship between mean FBS and infectious vaginal culture. However, the difference was not significant between positive culture of Candida and age, controlled blood glucose, history of allergy, genital hygiene, occupation, level of education, kind of treatment , and type or duration of diabetes.
Conclusion: We suggest in the patients with positive signs of vaginitis, especially Candida vaginitis (even with positive smear) culture of vaginal discharge be carried out.

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In the field of health care and medical practice, gain sharing plans should be carefully examined to be sure they reflect the codes of ethics. Ethical principles involved in gain sharing include informed consent and conflict of interest. Physicians must discharge their responsibilities to patients with loyalty, honesty and good faith, all the while avoiding conflict of interest. Conflict of interest rules usually focus on financial gain. This may raise some important issues, including kickbacks, fee-splitting and self-referral. These practices can potentially distort professional judgment. Some countries have rules of professional conduct governing these issues. In this article, we intend to describe importance of the issues of kickbacks, fee-splitting and self-referral in the field of clinical medicine and discuss some ethical issues that should be considered by physicians.

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Background: Sulfonylurea agents such as Glibenclamide (Glyburide) have been widely prescribe in treatment of type 2 diabetic patients for decades, but controversy remains about their precise mechanism of action. On the other hand, glucokinase serves as a glucose sensor in pancreatic β-cells and plays a key role in the regulation of insulin secretion and glucose homeostasis. The aim of the present study was to evaluate the effect of Glibenclamide on insulin secretion and glucokinase activity in the rat isolated pancreatic islets of Langerhans.
Methods: The islets from normal and type 2 diabetic rats were isolated by collagenase digestion method. Glucokinase activity was measured via determination the rate of glucose-6-phosphate formation in the fluorometric assay. Insulin secretion from hand-picked islets was evaluated by static incubation technique. Insulin concentration was measured by rat insulin ELISA kit.
Results: Our findings obtained from incubation of Glybenclamide with pancreatic islets revealed that this agent increases basal insulin secretion (at 2.8 mM glucose) in both normal and diabetic rats as compared it with control islet (without drug). However, the increase of insulin secretion in response to 16.7 mM glucose was not significant. On the other hand, Glybenclamide had no activating and/or inhibiting effect on pancreatic glucokinase activity in both diabetic and normal Rats. But reduced activity of this enzyme in diabetic rats was significant in comparison with normal.
Conclusion: These data show that increasing effect of Glybenclamide on insulin secretion is through a mechanism other than affecting Glucose Mediated Insulin Release. Moreover, the regulation of pancreatic glucokinase does not depend on glybenclamid.

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Background: Many researches have been conducted on islet cells' transplantation for a definitive treatment of diabetes mellitus type1. As the viability of the islets is the most important factor in predicting the transplantation prognosis, we have designed a study to isolate rat's islets. The aim of the study was to assess the viability of the islets at different stages and suggest the best transplantation time.
Methods: Pancreatic islets were isolated from male rats (250-300gr) by standard surgical procurement followed by intraductal HBSS distension, chopping and digestion with collagenase (type V). After being centrifuged for 3 times, the islets were then hand-picked and incubated in 37oC with RPMI 1640 media for 6 days. Each well contained 35-45 islets. Viability of islets was assessed by 2 independent investigators, giving score 0-2 to the color of islets under florescent microscope after Propidium iodide/Acridine orange staining at 6 times: just after the incubation, 24h, 48h, 3rd day, 5th and 6th day.
Results: The viability of the islet cells was gradually increased after the incubation as we had the most viability rate after the second day, while it decreased after this period and reached the least rate on the 5th and 6th day.
Conclusion: The islets' viability increased following the cell culture after the isolation procedure, as they have the best condition for transplantation after 48 hours. As the islets’ viability is the most critical point in transplantation, further studies evaluating the effects of different interventions on viability is needed.

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Background: Overweight is one of the most worldwide health problems particularly in industrial and developed communities. Obese subjects are at high risk for developing various disorders such as diabetes and especially cardiovascular diseases. It has been well established that life style modification plays an important role in reducing these complications, particularly weight reduction and caloric restriction (CR) as a non- pharmacological approach. In the present study the possible effects of caloric restriction on Nitric Oxide production and blood pressures in rat were investigated.
Methods: Four groups of rats were selected as control(C), caloric restriction (CR), diabetic (D), and caloric restriction diabetic (CRD). Control animals fed freely with standard pellet but caloric restricted animals fed an every other day diet for 4 weeks. The systolic blood pressure (SBP) was measured in all groups using the tail-cuff method under the light general anesthesia induced by ether. Nitric oxide (NO x) concentrations were determined in serum using a colorimetric non- enzymatic NO assay kit .
Results: In CR experimental groups (CR&CRD) SBP was significantly decreased as compared to control: (P<0.001) and diabetic (P<0.01) rats , while the serum NO x was significantly increased (P<0.01) in both groups as compared to control and diabetic rats.
Conclusion: On the basis of obtained results, it could be concluded that caloric restriction may reduce blood pressure and increase nitric oxide in diabetic and non-diabetic rats. Increase nitric oxide is the likely mechanism for decreasing blood pressure .

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Background: Few studies have investigated maternal leptin concentrations in women with pregnancies complicated by gestational diabetes mellitus (GDM), and these published results are conflicting. We examined the association between plasma leptin concentration and GDM risk.
Methods: As a cross-sectional study 741 pregnant women that referred to five university hospital clinics were recruited. The universal screening was performed with a GCT-50g and those with plasma glucose level ≥130mg/dl, were diagnosed as GDM if they had an impaired GTT-100g based on Carpenter and Coustan criteria. The level of insulin was measured during OGTT-100g. Also maternal plasma leptin concentrations were measured.
Results: GDM patients had higher age, parity, BMI, and serum leptin concentration as compare with normal pregnancies. In logistic regression model serum leptin levels were independent factor for GDM.
Conclusion: Serum leptin concentrations can predict GDM.

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Medical ethics has a long history worldwide, and the move towards a trans-cultural ethics must be based on an appreciation of the civilizations’ history. It is often thought that medical ethics history has begun by Hippocrates, however it is much older. It is clear that various cultures such as Babylonia, ancient Egypt, Greece, and the Persians have attempted to regulate medicine and to protect patients' rights in the known ancient world. One of the earliest written provisions in this field, which comes back to about 1750 BC, is the code of Hammurabi written by Babylonian. In this paper we aimed to explore the roots of medical ethics in Persian history, particularly, after adherence of Iranians to Islam. In this article, we used related books of great Iranian and non-Iranian historians, and examined some authentic articles collected through searches of databases such as Medline and Ovid and search engines such as Google Scholar. History of medicine in Iran has begun about fourth century BCE. Great Iranian physicians had paid special attention to ethics in their practices, teachings and manuscripts. There was a gap between the ancient civilizations and the Renaissance era in Europe, commonly called the dark ages (Medieval). The immense strides have been made by the Persians in that long interval which is briefly reviewed.

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Background: Pancreatic islet transplantation has been reported as an appropriate method for treatment of type I diabetes patients, however there are strong indications that cytokine and chemokines secreted from transplanted islets play an important role in islet graft rejection in different stage post-transplantation. The NF-kB signaling pathway is activated in response to the stress resulted from isolation and purification process of pancreatic islets. Secretion and release of inflammatory mediators, including MCP-1, result from activation of this pathway which plays important part in activation of inflammatory processes accelerating graft rejection.
Methods: This study was performed to examine the effect of curcumin on secretion of inflammatory mediators and function of pancreatic islets.
Results: We observed that curcumin significantly decreased MCP-1 release from mouse islets compared to the control group and had no effect on function of pancreatic islets. Conclusion: Investigating the stimulatory signals leading to production and secretion of inflammatory mediators from pancreatic islets and discovering their underlying mechanisms will be useful in finding new therapeutic interventions for blocking inflammatory pathways and improvement in outcome of islet cell transplantation.

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Background: Fetal hyperinsulinemia correlated with large birth weight and impaired glucose tolerance test and obesity in second decades of life. In this study we compared the correlation between fetal insulin production (as estimated by amniotic fluid (AF) C-peptide concentration) and AF insulin with macrosomia (as estimated by neonatal birth weight 4000 gr).
Methods: Thirty eight neonates were studied. Ten infants were macrosom and 28 were normal (birth weight < 4000 gr). Amniontic fluid C-peptide and insulin concentration and mother and fetal blood C-peptide and insulin were measured during delivery with radioimmunoassay and mother and fetal glucose were measured at the same time and correlated with neonatal macrosomia within first hour of birth.
Results: There was a significant correlation between infant serum C-peptide level and macrosomia. Amniotic fluid insulin level was higher in the macrosom infants but this correlation was not significant. AF C-peptide was higher in the macrosom group. Also there was a significant correlation between maternal serum C-peptide and macrosomia. Infant and mother serum insulin was higher in the macrosom group.
Conclusion: Our results suggest that fetal insulin (as estimated by AF C- peptide) and mother insulin and C- peptide production, can influence fetal weight and induce fetal macrosomia.

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Background: Adiponectin and leptin are hormones which are related to body fat tissues and body weight. In pregnant women, conflicting associations have been reported between the role of serum concentrations of adiponectin and leptin with infant birth weight. The aim of this study was to determine the association between maternal and cord blood adiponectin and leptin concentrations with birth weight. Methods: As a cross-sectional study 86 pregnant women referred to university hospital clinics were recruited. Maternal and umbilical cord blood samples were obtained in delivery room just after birth. The maternal and umbilical cord serum samples were analyzed for adiponectin and leptin. Their birth weight and height were measured at labor.
Results: The mean of maternal BMI, birth weight, and gestational age was 23.8±4.8 kg/m2, 3.13±0.14 kg, and 38.15±2.6 week, respectively. No correlation between adiponectin and birth weight were found. Birth weight positively correlates with leptin.
Conclusion: leptin concentrations in cord blood may be reflected the alternation of body fat tissue in infant and independently associated with infant birth weight.

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Background: Plasma concentration of adiponectin was found to play an important role in regulation of glucose metabolism, insulin resistance and conditions commonly associated with obesity. The aim of this study was to assess adiponectin level and its relation with percent of body fat mass and insulin sensitivity in over-weight men.
Method: This study was conducted on two groups of type 2 diabetic (n=20) and non-diabetic (n=20) overweight adult men. Serum level of adiponectin (ELIZA), FBS (GOD-PAP), fasting insulin (immunoreactive assay) and body fat mass (Bio-electric impedance) were measured. Insulin sensitivity was calculated using QUICKI.
Results: Diabetics had significantly higher mean of fat mass% than non-diabetics (26.55± 2.87% vs. 22.93±2.64 p< 0.05), despite fairly similar BMIs (27.7 kg/m2). Adiponectin concentration was lower in diabetics (7.77 ±3.53µg/ml) than non-diabetics (8.13 ± 0.03µg/ml) however, this difference was not statistically significant. The negative correlation between adiponcetin and fat mass didn't reach statistical significance. Adiponectin positively related with insulin sensitivity in non-diabetics (r= +0.5 p= 0.04).
Conclusion: Lower level of adiponcetin in diabetics than their non-diabetic counterparts. As well as the positive association of adiponectin with insulin sensitivity confirm the suggested role of decreased level of adiponectin in conditions such as insulin resistance and diabetes.