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1.  Utility of hypertriglyceridemic waist phenotype for predicting incident type 2 diabetes: The Isfahan Diabetes Prevention Study 
We evaluated the association between hypertriglyceridemic waist (HTW) phenotype and the risks of type 2 diabetes in an Iranian high‐risk population.
Materials and Methods
We analyzed 7‐year follow‐up data (n = 1,865) in non‐diabetic first‐degree relatives of consecutive patients with type 2 diabetes aged 30–70 years. The primary outcome was the diagnosis of type 2 diabetes based on repeated oral glucose tolerance tests. We used multiple logistic regressions to estimate the odds ratio (OR) for incident type 2 diabetes across four groups according to baseline fasting serum triglycerides (TG) level and waist circumference (WC): normal WC and normal TG, normal WC and high TG, enlarged WC and normal TG, and HTW (enlarged WC high TG).
The HTW phenotype at baseline was associated with the incidence of type 2 diabetes. Those with HTW were 2.4‐fold (OR 2.36, 95% confidence interval 1.61–3.44), those with normal WC high TG were 1.9‐fold (OR 1.87, 95% confidence interval 1.29–2.70) and those with enlarged WC but normal TG were 2.8‐fold (OR 2.84, 95% confidence interval 1.96–4.13) more likely to develop type 2 diabetes than those with normal WC and normal TG.
These data provide further evidence that the HTW phenotype is a robust predictor of type 2 diabetes in high‐risk individuals in Iran, and the predictive power is not higher than that of simple enlarged WC and normal TG, emphasizing the importance of enlarged WC to the development of type 2 diabetes.
PMCID: PMC5089948  PMID: 27180654
Hypertriglyceridemic waist; Risk factor; Type 2 diabetes
2.  The effect of hydroxychloroquine on glucose control and insulin resistance in the prediabetes condition 
Hydroxychloroquine can improve most underlying coronary risk factors; however, there are a few studies on the effects of hydroxychloroquine on blood glucose and insulin resistance. The current study aimed to assess the effects of hydroxychloroquine on blood glucose control status as well as on level of lipid profile and inflammatory biomarkers in prediabetic patients.
Materials and Methods:
In a randomized, double-blinded, controlled trial, 39 consecutive patients who were suffering from prediabetes and were referred to the Isfahan Endocrinology Center in January 2013 were randomly assigned to receive hydroxychloroquine (6.5 mg/kg/day) (n = 20) or placebo (n = 19) for 12 weeks. The biomarker indices and anthropometric parameters were tested before and after completion of treatment.
In both groups of patients receiving hydroxychloroquine and placebo, except for serum level of insulin that was significantly elevated after treatment by hydroxychloroquine, the changes in other parameters remained insignificant. Both groups experienced increase of insulin level, but this change was considerably higher in those groups receiving hydroxychloroquine. The group receiving hydroxychloroquine experienced reduction of glucose at 60 min of Oral Glucose Tolerance Test (OGTT) test after intervention, while the placebo group experienced increase of blood glucose at the same time.
The use of hydroxychloroquine may increase the serum insulin level in patients with prediabetic states who are at risk of developing diabetes mellitus.
PMCID: PMC5025914  PMID: 27656614
Hydroxychloroquine; insulin resistance; prediabetes condition
3.  Predictors of all-cause and cardiovascular-specific mortality in type 2 diabetes: A competing risk modeling of an Iranian population 
In Asian population, diabetes mellitus is increasing and has become an important health problem in recent decades. In Iran, cardiovascular disease (CVD) accounts for nearly 46% of the total costs spent for diabetes-associated diseases. Because individuals with diabetes have highly increased CVD risk compared with normal individuals, it is important to diagnosis factors that may increase CVD risk in diabetic patients. The study objective was to identify predictors associated with CVD mortality in patients with type 2 diabetes (T2D) and to develop a prediction model for cardiovascular (CV)-death using a competing risk approach.
Materials and Methods:
The study population consisted of 2638 T2D (male = 1110, female = 1528) patients aged ≥35 years attending from Endocrine and Metabolism Research Center in Isfahan for a mean follow-up period of 12 years; predictors for different cause of death were evaluated using cause specific Cox proportional and subdistribution hazards models.
Based on competing modeling, the increase in blood pressure (BP) (spontaneously hypertensive rats [SHR]: 1.64), cholesterol (SHR: 1.55), and duration of diabetes (SHR: 2.03) were associated with CVD-death. Also, the increase in BP (SHR: 1.85), fasting blood sugar (SHR: 2.94), and duration of diabetes (SHR: 1.68) were associated with other death (consist of cerebrovascular accidents, cancer, infection, and diabetic nephropathy).
This finding suggests that more attention should be paid to the management of CV risk in type 2 diabetic patients with high cholesterol, high BP, and long diabetes duration.
PMCID: PMC4879860  PMID: 27274497
Cardiovascular disease; cause-specific hazard model; competing risks; subdistribution hazard model; type 2 diabetes
4.  The Direct Medical Costs of Outpatient Cares of Type 2 Diabetes in Iran: A Retrospective Study 
Diabetes mellitus is a chronic disease which many factors are involved and is developing considerably worldwide. Increasing aging population and obesity in the societies has improved the scale of the type 2 diabetes significantly. The aim of this study was to determine the direct medical costs of outpatient cares of diabetes in Iran.
Active patients of Isfahan Endocrinology and Metabolism Research Center (IEMRC) by the end of March 2011 were employed for data extraction. Type 2 diabetics were classified into 4 groups based on their therapeutic regimens. Type and frequency of health care services were extracted from the patients’ profiles manually. The incidence of major diabetes complications were also examined from the subjects’ profiles. The numbers of services used by the patients in different treatment groups were multiplied by the desired medical tariffs to calculate the direct medical costs.
2898 number of cases was reviewed in this study; 63.8 % women and 36.2% men. 4.3% of the patients were placed group I; 50.1% in group II, and 34.6% and 11% in groups III and IV respectively. The age distribution of the patients varied widely from 30 to 90 years; 5.8% between 30 and 39 years, 62.3% between 40 and 59, and 31.9% at 60 and over. Nephropathy (72.4%), and neuropathy (39%) were the most frequent adverse effect between the type 2 diabetics in Isfahan. The group III with spending $192.3 in total was absorbed the highest amount of the resources between the patients’ groups. The average direct medical cost of outpatient cares of diabetics per year was 155.8 US $.
The direct medical cost of diabetes management is progressed sharply in past years in Iran. Pharmaceutical expenditures was the main cost component of outpatient cares for diabetes. It is estimated that the Iranians directly spend approximately $4.05 milliard annually to manage 5.2 million diabetics in the country.
PMCID: PMC4872475  PMID: 27217937
Diabetes complications; direct medical costs; Iran; type 2 diabetes
5.  Effect of the co-administration of glucose with morphine on glucoregulatory hormones and causing of diabetes mellitus in rats 
Morphine is related to dysregulation of serum hormone levels. In addition, addict subjects interest to sugar intake. Therefore, this study investigated the effect of co-administration of glucose with Mo on the glucoregulatory hormones and causing of diabetes mellitus in rats.
Materials and Methods:
Male rats were randomly divided into four groups including, control, morphine, Morphine-Glucose and diabetes groups. Morphine was undergone through doses of 10, 20, 30, 40, 50, and 60 mg/kg, respectively on days 1, 2, 3, 4, 5, and 6. Then, dose of 60 mg/kg was used repeated for 20 extra days. The Morphine-Glucose group received the same doses of morphine plus 1 g/kg glucose per day. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. At the end of experiment, the serum insulin, glucagon, growth hormone (GH), cortisol, and glucose levels were measured. The homeostasis model assessment (HOMA) indexes concluding the HOMA-insulin resistance (HOMA-IR) and HOMA-β were evaluated.
Morphine insignificantly induced a hyperglycemia condition and insulin resistance. Whereas, the beta-cell functions significantly (P < 0.05) decreased only in morphine group. The co-administration of glucose slightly increased the GH, and increased insulin and cortisol levels significantly (P < 0.05 and P < 0.01; respectively) in the Morphine-Glucose group. Furthermore, the co-administration of glucose with morphine could nearly modulate the morphine effects on body weight, glucose, and glucagon levels.
It is probable that the co-administration of glucose with morphine modulate the serum glucose levels by stimulating the beta-cell functions and to increase insulin secretion.
PMCID: PMC4770615  PMID: 26962523
Cortisol; diabetes mellitus; glucagon; growth hormone; insulin; morphine
6.  Efficacy of bromocriptine on glycemic and metabolic control of prediabetic patients 
It is suggested that bromocriptine could be effective in treatment of prediabetic patients and, consequently, in preventing type 2 diabetes (T2DM). In this study, we investigated the effectiveness of bromocriptine on glycemic and metabolic control of prediabetic patients.
Materials and Methods:
In this double-blind, placebo controlled trial study, prediabetic patients diagnosed during Isfahan Diabetes Prevention Project (IDPP) were enrolled. They randomized in two bromocriptine (2.5 mg) and placebo-treated groups, for 12 weeks. After physical examination, fasting plasma glucose (FPG), HbA1c, Insulin, cholesterol, HDL-c, and triglyceride were measured and glucose tolerance test (OGTT) was performed. HOMA-IR and LDL-c were calculated. The mean of the data were compared in the bromocriptine and placebo treated groups, before and after intervention by intention to treat analysis using mixed effect model. P values < 0.05 were considered, statistically, significant.
In this study, 53 prediabetic patients (27 in the bromocriptine group and 26 in the placebo group) were treated. There were no differences between data of two groups at baseline (P > 0.05). The mean body mass index, systolic blood pressure, fasting plasma glucose and glucose of 30 min, 60 min, 120 min of post OGTT, HbA1c, insulin, HOMA-IR, lipid profile did not change, significantly, in both bromocriptine and placebo-treated groups after 12 weeks (P > 0.05). However, diastolic blood pressure (P = 0.02) and the area under the curve of glucose (P = 0.045) were decreased in the bromocriptine-treated group.
Bromocriptine did not have significant effect on glycemic control of prediabetic patients. Further studies, with bigger sample size are recommended.
PMCID: PMC4746945  PMID: 26918235
Bromocriptine; prediabetics; type 2 diabetes
7.  Current status of glucose, blood pressure and lipid management in type 2 diabetes clinic attendees in Isfahan, Iran 
To estimate the prevalence of meeting American Diabetes Association clinical practice recommendations for hemoglobin A1c (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) among Iranian type 2 diabetes clinic attendees, and to identify the factors associated with therapeutic target achievement.
Materials and Methods
A total of 2,640 patients with type 2 diabetes (944 men and 1,696 women) from Isfahan Endocrine and Metabolism Research Center outpatient clinics, Iran, were examined. The main outcome measures were HbA1c, BP and LDLC, in accordance with the American Diabetes Association recommendations. The mean (standard deviation) age of participants was 49.6 years (9.3 years) with a mean (standard deviation) duration of diabetes of 5.0 years (4.9 years) at initial registration.
The percentages of patients who had HbA1c <7%, BP <140/90 mmHg and LDLC <100 mg/dL was 37.4% (95% confidence interval [CI] 35.6–39.3), 35.3% (95% CI 33.5–37.3) and 48.9% (95% CI 47.0–50.8), respectively. The proportion of patients meeting all three goals was 7.7% (95% CI 6.7–8.8). Lower BP, cholesterol level and higher education at registration, and higher follow up but lower number of follow-up visits affected achievement of all three goals.
The present study highlights that a substantial proportion of Iranian type 2 diabetes clinic attendees did not meet the American Diabetes Association clinical practice recommendations, and shows the difficult challenges physicians face when treating patients with type 2 diabetes.
PMCID: PMC4627550  PMID: 26543547
Clinical practice guidelines; Diabetes; Diabetes control
8.  Trends of diabetic nephropathy prevalence in Isfahan, Iran, during 1992-2010 
Diabetes mellitus is a metabolic disorder and its subsequent complications such as retinopathy, nephropathy, ulcers, disability, and amputation increase the burden of the disease. Patient knowledge-improving programs are employed to prevent disease progression and to improve the quality of life of the patients. In this way, we need to characterize the groups of patients in urgent need for more and rich-in-content programs. In the present study, we used piecewise regression to evaluate the trends of diabetic nephropathy prevalence in patients registered in the Sedigheh-Tahereh Research Center and to identify patients who were in need of more attention.
Materials and Methods:
Piecewise regression, used in this study, is a statistical method to identify change points, if any, in the trends of mortality rates, prevalence of a disease, or any other trends. Available information for 1,935 patients were retrieved from the database. Joinpoint program 3.5.3 and Statistical Package for the Social Sciences (SPSS) 20 was used to fit piecewise regression and obtain descriptive statistics, respectively.
We assessed the trend of diabetic nephropathy in different groups of diabetic patients with respect to sex, blood pressure status, education, family history of diabetes, and age. The results showed an increasing trend in females, patients without family history of diabetes, and eover th recent years. The prevalence of diabetic nephropathy in patients with academic education was high.
The groups with high prevalence or increasing trends need more preventive intervention and detailed assessment of the present trends. Exploring high-risk groups is beneficial for better policy-making in the future. However, discovering the reasons for the increased trend of the disease is really helpful in controlling diabetes complications.
PMCID: PMC4746867  PMID: 26929758
Diabetic nephropathy; piecewise regression; prevalence; trend
9.  Impacts of insulin infusion protocol on blood glucose level and outcomes in acute coronary syndrome patients with diabetes mellitus 
Acute coronary syndrome is the most common disease in the world. Several studies suggest that hyperglycemia is associated with poor clinical outcomes in patients with coronary artery disease. The aim of this study was to investigate the impact of insulin infusion protocol and conventional therapy on the blood glucose level and outcomes in acute coronary syndrome patients with diabetes mellitus.
Materials and Methods:
We studied 64 patients (32 in each group) with acute coronary syndrome and acute myocardial infarction, who were admitted to the coronary care unit in a hospital in Isfahan, Iran in 2012. Inclusion criterion was blood sugar (BS) of more than 180 mg/dl on admission. Patients in the intervention group received insulin with East Jefferson insulin infusion protocol for at least 4 h, and in the control group, the subjects received subcutaneous insulin (conventional therapy) for at least for 48 h. Independent t-test, Student's t-test, and Chi-square test were used to analyze the data.
Groups were matched for baseline characteristics. Blood glucose was significantly reduced in the two groups (P < 0.001), and the mean blood glucose level in the interaction group was significantly less than in the control group (P = 0.0002).
Hypoglycemia was 31.2% and 25% in the intervention and control groups, respectively. The frequency of hypoglycemia did not differ significantly between the two groups (P = 0.75). Time to reach target insulin level differed between the two groups (4.75 h in the intervention group and 36.93 h in the control group; P < 0.001).
Our research showed that use of insulin infusion protocol is better in maintaining glycemia control compared to subcutaneous sliding scale method. The protocol allows nurses to commence and maintain the infusion more effectively and safely compared to the traditional method.
PMCID: PMC4462053  PMID: 26120328
Acute coronary syndrome; diabetes mellitus; insulin infusion systems; Iran; nursing
10.  Adherence to statin therapy in patients with type 2 diabetes: An important dilemma 
Despite the importance of patients’ adherence to their drug treatments for achieving desired therapeutic goals and the proven role 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) for the health status of patients with cardiovascular diseases, there is not enough information regarding diabetic patients’ adherence to statin therapy in developing countries. In this clinical study we aimed to assess the adherence of diabetes type 2 patients to statin therapy in a research based community clinic in Iran.
Materials and Methods:
In this prospective clinical study which was done at Isfahan Endocrinology and Metabolism Research Center, 204 diabetic type 2 patients under treatment with statin were interviewed twice and their demographic data (age, gender, body mass index, education), statin information (type, dose) and their serum lipid profile were recorded. Three months after the initial visits, patients were assessed using pill counting method and according to patients’ self-reporting and also assessed low-density lipoprotein (LDL) cholesterol goal attainment <100 mg/dl.
Adherence rate was 79.7% and 69% according to pill counting and self-reporting among study population. Moreover, 68.4% of patients achieved their LDL cholesterol goal of <100 mg/dl and adherent patients reached therapeutic goal significantly more than those who were considered non-adherence to statin therapy (P < 0.01).
Adherence to statin therapy, as reflected by pill count method, is significantly related to LDL cholesterol goal achievement in patients with diabetes and dyslipidemia. Pill count method can be used to identify patients who are nonadherent to statin therapy and at high risk for failure to attain LDL cholesterol goals.
PMCID: PMC4400702  PMID: 25983760
Diabetes; drug adherence; pill count method; statins
11.  Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial 
The people with prediabetes have insulin resistance (IR). IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people.
Materials and Methods:
In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43) and placebo (n = 46) treated groups. Serum thyroid stimulating hormone (TSH) was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study.
Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 μU/ml) and high-normal (2.6-5.5 μU/ml) ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01). Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03). In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed) nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01).
In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 μU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume.
PMCID: PMC4310072  PMID: 25657744
Insulin resistance; metformin; prediabetes; thyroid; thyroid nodule; thyroid volume
12.  Evaluation of Peripheral Arterial Disease in Prediabetes 
The prevalence of prediabetes in the world continues to increase. These patients have elevated the risk of atherosclerosis. The current study was designed to assess the prevalence of peripheral arterial disease (PAD) and its related risk factors in prediabetes patients.
This was the case-control study in which 135 adults in three groups: Diabetes, prediabetes, and normal were studied. We evaluated the prevalence of PAD through the measurement of ankle-brachial index (ABI). All the patients were interviewed about demographic and medical data, including age, sex, disease duration, body mass index, hypertension (HTN), fasting blood glucose, hemoglobin A1C (HbA1C), lipid profile, and medication use.
The prevalence of PAD in diabetes patients was higher than the normal group (8.5%vs. 0.0%) (P < 0.05), but the differences between prediabetes compared with diabetes and normal group were not significant. The mean level of ABI in normal, prediabetes, and diabetes group was (1.11 ± 0.11), (1.09 ± 0.12), and (1.05 ± 0.03) respectively (P < 0.1). There were marginally significant differences of ABI observed between the normal group and the diabetes group. The observed differences between groups in the ABI were significant after adjusting the effects of age and sex (P < 0.05). There was an association observed between ABI and HbA1C in diabetes patients (r = 0.249, P < 0.01) and a significant association seen between PAD and HTN in the prediabetes group (P < 0.01).
Peripheral arterial disease is common in asymptomatic diabetes and prediabetes patients. Management of hypertensive prediabetes patients and early detection of PAD in this group as well as in asymptomatic patients is important.
PMCID: PMC4192770  PMID: 25317291
Ankle-brachial index; diabetes; peripheral arterial disease; prediabetes
13.  Retinopathy risk factors in type II diabetic patients using factor analysis and discriminant analysis 
Diabetes is one of the most common chronic diseases in the world. Incidence and prevalence of diabetes are increasing in developing countries as well as in Iran. Retinopathy is the most common chronic disorder in diabetic patients.
Materials and Methods:
In this study, we used the information of diabetic patients’ reports that refer to endocrine and metabolism research center of Isfahan University of Medical Sciences to determine diabetic retinopathy risk factors. We used factor analysis to extract retinopathy's factors. Factor analysis is using to analyze multivariate data, in which a large number of dependent variables summarize into the fewer independent factors. Factor analysis is applied, in both diabetic and nondiabetic patients, separately. To investigate the efficacy of factor analysis, we used discriminant analysis.
We investigated 3535 diabetic patients whose prevalence of retinopathy was 53.4%. Six factors were extracted in each group (i.e. diabetic and nondiabetic groups). These six factors were explained 69.5% and 69.6% of total variance in diabetic and nondiabetic groups, respectively. Using original variables such as sex, weight, blood sugar control method, and some laboratory variables, the correct classification rate of discriminant analysis was identified as 67.4%. However, it decreased to 49.5% by using extracted factors.
Retinopathy is one of the important disorders in diabetic patients that involves a large number of variables and can affect its incidence. By the method of factor analysis, we summarize diabetic retinopathy risk factors. Factor analysis is applied separately, in two diabetic and nondiabetic group. In this way, 10 variables were summarized into the six factors. Discriminant analysis was used to investigate the efficacy of factor analysis.
Although factor analysis is a powerful way to reduce the number of variables, in this study did not worked very well.
PMCID: PMC4165112  PMID: 25250351
Factor analysis; retinopathy; type II diabetic
14.  Vitamin C may have similar beneficial effects to Gemfibrozil on serum high-density lipoprotein-cholesterol in type 2 diabetic patients 
Type 2 diabetes mellitus (DM-T2) is commonly associated with increased triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels. Fibrates like gemfibrozil are frequently used in diabetic patients to decrease TG and increase HDL-C levels. We compared the efficacy of Vitamin C, an antioxidant vitamin, with gemfibrozil on serum HDL-C in diabetic patients.
Type 2 diabetic patients, referred to our out-patient clinic were randomly divided into three groups. After 1 month of lifestyle and diet modifications, groups A, B, and C were prescribed 1000 mg Vitamin C, 600 mg gemfibrozil and combination of both, respectively. Before the study initiation and after 6th week of drug prescription, the blood samples were taken and analyzed for total cholesterol (Total-C), HDL-C, TG, fasting blood sugar (FBS), and hemoglobin A1c (HbA1c) levels.
Sixty-seven patients entered, and 50 patients (18 male, 32 female) finished the study. Overall, serum HDL-C increased significantly from 39.8 to 45.2 mg/dL in the participants (P = 0.001). HDL-C increased 6.3, 4.4 and 5.0 mg/dL in groups A, B and C, respectively (related significances were 0.017, 0.022 and 0.033, respectively). Significant decrease of serum TG and Total-C occurred in gemfibrozil and combination groups, but not in Vitamin C group. Changes in serum HDL-C between three groups were not significant (P = 0.963). We found a significant decrease in TG and Total-C in the groups B and C (P < 0.05), but no significant changes of TG, Total-C, LDL-C, FBS and HbA1c in group A (P > 0.05).
The results demonstrated that Vitamin C may have beneficial effects on HDL-C in diabetic patients without significant effects on plasma glucose or other lipid parameters; however, its role for the treatment of low HDL-C patients should be evaluated in larger studies.
PMCID: PMC4199195  PMID: 25328896
Diabetes mellitus; Gemfibrozil; high-density lipoprotein cholesterol; Vitamin C
15.  Serum uric acid level and its association with cardiometabolic risk factors in prediabetic subjects 
Excess serum uric acid (UA) accumulation can lead to various diseases. Increasing evidences reveal that UA may have a key role in the pathogenesis of metabolic syndrome. Little is known about the associations of UA levels with cardiometabolic risk factors in prediabetic individuals. This study was designed to evaluate the association between UA and cardiometabolic risk factors in prediabetic subjects with family history of diabetes compared with those with normal glucose tolerance (NGT).
Materials and Methods:
In a cross-sectional setting, a sample containing 643 (302 prediabetic subjects and 341 normal) of the first-degree relatives of diabetic patients aged 35-55-years old were investigated. Samples were assessed in prediabetic and normal groups using glucose tolerance categories. Prediabetes was defined based on American Diabetes Association (ADA) criteria. Body weight and height, systolic and diastolic blood pressure (SBP and DBP), UA, creatinine (Cr), albumin (Alb), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and lipid profiles were measured and compared between two groups.
Prediabetic persons were older and obese than normal persons. Also, prediabetic persons (5.2 ± 1.3 mg/dl) had significantly higher UA than normal persons (4.9 ± 1.4 mg/dl) (P < 0.05). FBG after 0, 30, 60, and 120 min in prediabetic were higher than normal persons (P < 0.001). With respect to metabolic parameters, the patients in the higher UA quartiles exhibited higher levels of body mass index (BMI), SBP, FBG and triglycerides (TG). The higher quartiles of UA tended to be associated with higher BMI and higher total cholesterol (TC) in females prediabetic persons. Based on logistic regression analysis in different models, UA was positively (odds ratio (OR) >1, P < 0.05) associated with glucose tolerance categories. This association remained statistically significant after adjusting the effects of age and BMI. Also, the association between glucose tolerance categories and UA were positively significant in both genders.
High UA level was associated with some cardiometabolic risk factors in prediabetic individuals compared with normal person. UA level was also a significant predictor for prediabetes condition.
PMCID: PMC4061650  PMID: 24949036
Cardiometabolic; glucose tolerance; prediabetic; uric acid
16.  Executive functions and information processing in patients with type 2 diabetes in comparison to pre-diabetic patients 
Diabetes is associated with cognitive decline or dementia. The purpose of this study was to assess the executive functions and information processing in patients with type 2diabetes in comparison to pre-diabetic patients and normal subjects in Endocrine and Metabolism Research Center of Isfahan City from April to July 2011.
The sample consisted of 32 patients with type 2 diabetes, 28 pre-diabetic patients and 30 healthy individuals. Executive functions were assessed by Wisconsin Card Sorting Test (WCST). Information processing was assessed by Paced Auditory Serial Addition Test (PASAT) and sub tests of Wechsler Adult Intelligence Scale-Revised (WAIS-R).
There was a significant difference among 3 groups, after the variables of age, sex and academic status were controlled (p ≤ 0.001). The pairwise comparisons of executive functions among three groups suggest a significant difference between diabetic and normal groups in WCST (perseveration) p = 0.018, and significant difference between diabetic and pre-diabetic patient in WCST (perseveration) p = 0.019. But there was no difference between three groups in WCST (category) and WCST (conceptual responses). The pairwise comparisons of information processing among three groups, suggest a significant difference between diabetic and normal groups in PASAT3". PASAT2", and Symbol coding (P = 0.003, P = 0.009, and P = 0.001, respectively). There was a significant correlation between demographic variable (FBS, HbA1c) and Symbol coding p = 0.05, p = 0.01 respectively) and significant correlation between (cholesterol) and WCST (conceptual responses) p = 0.05. The other variables were not correlated.
There were significant differences in executive function and information processing in patients with type 2 diabetic and normal individuals. Thus, monitoring neuropsychological status besides controlling levels of blood sugar in these patients is important.
PMCID: PMC3938133  PMID: 24495302
Executive functions; Information processing; Type 2 Diabetes; Pre-diabetic patients
17.  Association of Polymorphism of Ser311cys Paraoxonase-2 Gene with Type 2 Diabetes Mellitus in Iran 
It is believed that paraoxonase-2 gene polymorphism is associated with type 2 diabetes. This study is aimed to investigate the association between paraoxonase-2 gene polymorphism and type 2 diabetes in an Iranian population.
This study was performed on 200 individuals including 100 diabetics and 100 healthy subjects. Genomic DNA was extracted from peripheral blood leukocytes, and PCR-RFLP was carried out. Palindromic sequence in PON2 gene was recognized by Dde1 restriction endonuclease. In order to visualize restriction products, electrophoresis was carried out using polyacrylamide gel (8%) and ethidium bromide staining.
The expected PCR product of 331 bp was obtained. Digestion of this product with DdeI showed four Ser homozygotes, three Cys homozygotes, and five Ser311 Cys heterozygotes. The gene frequency of Cys (C) in diabetic subjects was significantly higher than in healthy subjects.
This study suggests that an association exists between Ser311 Cys polymorphism and type 2 diabetes mellitus.
PMCID: PMC3733181  PMID: 23930161
Iranian population; paraxonase-2 gene; polymorphism; type 2 diabetes
18.  Association between PRO12ALA polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in Iranian patients 
Indian Journal of Human Genetics  2013;19(2):239-244.
Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. It has been shown that an association exists between Proline 12 alanine (Pro12Ala) polymorphism of PPAR-GAMMA2 (PPAR-γ2) gene and increased risk of type 2 diabetes mellitus (T2DM) in different populations. Therefore, the present study was designed to investigate the association between Pro12Ala polymorphism of PPAR-γ2 gene and T2DM in an Iranian population.
Two hundred unrelated people, including 100 healthy controls and 100 diabetic patients were recruited diagnosed based on American Diabetes Association criteria. Blood samples were used for isolation of genomic deoxyribonucleic acid (DNA). Having extracted the genomic DNA from human blood leukocytes by means of High Pure polymerase chain reaction (PCR) Template preparation kit, we carried out polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on each blood sample. Then, Genomic DNA was digested by BstU-I restriction enzyme. Thereafter, restriction products were analyzed by means of Polyacrylamide gel electrophoresis and stained by Ethidium Bromide.
We found that the frequency of Ala allele in healthy subjects was significantly higher than in diabetic subjects (P = 0003). Moreover, the genotype frequency of Ala/Ala in healthy subjects was significantly higher than in diabetic subjects (P < 0.001). However, the genotype frequency of Ala/Pro in diabetic subjects was significantly higher than in healthy subjects (P < 0.001).
The present study suggests that polymorphism of PPAR-γ2 gene is associated with T2DM. Furthermore, Ala allele is significantly found in non-diabetic individual’s Iranian population.
PMCID: PMC3758733  PMID: 24019628
Polymorphism; peroxisome proliferator-activated receptor-GAMMA 2 gene; type 2 diabetes mellitus
19.  Prevalence of stomach cancer in Shiraz, Southern Iran 
Worldwide, cancer of stomach is still the fourth common cancer and the second cause of mortality among all cancers affecting annually 870,000 subjects. This study aims to determine the frequency and the characteristics of gastric cancer in southern Iran.
Materials and Methods:
10,800 of all cancers registered in Fars Hospital-based Cancer Registry were surveyed among which 574 cases were gastric cancer in both genders and all age groups. From January 2002 to December 2007, all hospital-based data were recorded according to International Classification of Disease for Oncology (ICD-O) and registered cases included all invasive cancers in ICD-10 categories of C-00 to C-80 and all duplicate cases were eliminated.
Among all registered cancers, there were 574 cases of gastric cancer including 69.3% males. The mean age of patients was 58.1 ± 14.8 years, 25.4% with a history of in their first relatives and most of them were smokers (50.9%) and from low socioeconomic class (45.5%). Metastasis was visible in 182 patients and majority of them underwent surgery (64.3%). The majority of gastric cancer patients were older than 50 years, smokers, low socioeconomic class, and female in favor of adenocarcinoma.
Our results showed that in our area, treatment programs and health plans should focus on men, patients older than 50 years and with adenocarcinoma, smokers, and those in a low income level.
PMCID: PMC3793381  PMID: 24124433
Epidemiology; Iran; prevalence; stomach cancer
20.  Growth and Specialized Growth Charts of Children with Congenital Hypothyroidism Detected by Neonatal Screening in Isfahan, Iran 
ISRN Endocrinology  2013;2013:463939.
Objectives. The aim of the current study was to investigate the growth status of CH, generate specialized growth charts of CH infants, and compare them with their counterparts of regional normal infants. Methods. In this prospective cohort study, 760 (345 girls and 415 boys) neonates born in 2002–2009 diagnosed by neonatal CH screening program in Isfahan were followed up from the time of diagnosis. 552 healthy children were recruited as a control group. The empirical 3rd, 15th, 50th, 85th, and 97th percentiles for height, weight, and head circumference of both sexes were determined and compared with their counterpart values of the control group. The relative frequency of patients with impaired growth for each studied variable was determined. Also, specialized growth charts of CH patients were generated. Results. The percentiles of weight, height, and head circumference of studied patients are significantly different from regional healthy children (P < 0.001). The relative frequency of impaired head circumference was decreased to less than 3% at the 3rd year of age and for height it reached gradually 3% and 9% at the 5th year of age for boys and girls, respectively (P < 0.05); however for weight still it was statistically more than 3% in both sexes. Conclusion. CH patients had impaired growth development which was improved during follow up, but the catch-up time was earlier for head circumference and later for weight.
PMCID: PMC3582096  PMID: 23476799
21.  Evaluating the efficacy of Salsalate on prediabetic and diabetic patients with fatty liver: A randomized clinical trial 
Nearly two-third of the patients with type 2 diabetes have degrees of fatty liver; this may induce some side effects in them. This study aimed to find effect of salsalate on treatment of steatohepatitis and correlation of fatty liver with metabolic syndrome in the setting of impaired glucose metabolism.
In a double-blind randomized trial within two distinct groups, i.e., recently diagnosed diabetics and prediabetic cases allocated in two arms of the intervention to receive 3 g salsalate or placebo. All cases underwent glucose and lipid level studies and liver ultrasound study.
Out of 46 patients with diabetes, 34 (74%) had fatty liver in ultrasound; this ratio was 75% in 113 prediabetic cases. Relative frequency of fatty liver stages did not differ between diabetics and prediabetics. Within diabetics, mean aspartate aminotransferase (AST) level of fatty liver cases (23 ± 7 IU/dl) was higher than others (18 ± 3 IU/dl) (P < 0.05). Changes in transaminase levels following intervention did not significantly differ, comparing drug and placebo arms in two subgroups.
According to the findings, if diabetes could be assumed as the logical consequence of prediabetic state, it seems that fatty liver did develop before this preliminary status. In this study, salsalate could not change biochemical markers of fatty liver significantly.
PMCID: PMC4076898  PMID: 24991603
Diabetes; fatty liver; salsalate
22.  Patterns and Predictors of Long-Term Glycemic Control in Patients with Type 2 Diabetes 
ISRN Endocrinology  2012;2012:526824.
Aims/Introduction. To describe patterns of long-term glycemic control among patients with type 2 diabetes in Isfahan, Iran and identify factors associated with glycemic control. Methods. During the mean (standard deviation (SD)) follow-up period of 8.4 (4.2) (range 1–18) years, 4,582 patients with type 2 diabetes have been examined to determine glycemic changes. Their glycated hemoglobin (GHb) at the last clinic visit was compared with the initial visit data. The mean (SD) age of participants was 49.3 (9.6) years with a mean (SD) duration of diabetes of 5.0 (5.1) years at initial registration. Results. Mean (SD) GHb was 8.7% (2.3) at baseline and 7.9% (1.9) at the study end and decreased by mean of 0.8% (95% confidence interval (CI) 0.74, 0.87; P < 0.001) and varied by the severity of baseline GHb. 74.6% at the initial visit versus 64.4% at the last clinic visit had GHb values above the target level of 7.0%. Using a stepwise multiple regression models, age, higher GHb, FPG, follow-up period, and number of follow-up visits increased and higher systolic BP and female gender significantly decreased the percent glycemic change. Conclusions. This study highlights that more than 64.4% of the patients have GHb values higher than 7.0% at last clinic visit andindicatesthe difficult challenges physicians face when treating their patients with type 2 diabetes. Clinical efforts should focus on more effective methods for glycemic control in diabetic patients.
PMCID: PMC3479977  PMID: 23119180
23.  Impact of exercise on affective responses in female adolescents with type I diabetes 
Adolescent is a time of profound biologic, intellectual, psychological, and socioeconomic change that they will face a crisis. Therefore, compatibility may be exposed to many hazards, such as depression, anxiety, and other emotional problems. Nevertheless, a planned regular exercise enhances physical and mental health of adolescent female with diabetes. The aim of this study was to determine the effect of exercise on emotional reactions of female adolescents with type I diabetes.
Materials and Methods:
This study was a quasi-experimental research conducted in Endocrine and Metabolism Research Centre. A total of 72 patients were randomly allocated in the two groups. The intervention group did aerobic exercise for 45 minutes, while the control group did not aerobic exercise. Data were collected using a Symptom Checklist (SCL)-90 questionnaire. Data were analyzed and using descriptive and inferential statistics methods and SPSS software.
The results showed that the mean score for physical symptoms, depression, obsession-compulsion, interpersonal sensitivity, aggression, phobia, paranoid ideation, psychosis, and anxiety in the test group significantly decreased after intervention than before intervention. The average score in the control group did not differ. The average total score of emotional reactions in the test group after the intervention decreased before the intervention significantly (P = 0.001). However, in the control group, the mean scores did not differ (P = 0.97).
The findings showed that regular exercise is effective on affective responses of adolescent females with type I diabetes.
PMCID: PMC3733289  PMID: 23922585
Aerobic exercise; affective symptoms; female adolescents; Iran; type I diabetes mellitus
24.  Incidence of Metabolic Syndrome and Its Risk Factors among Type 2 Diabetes Clinic Attenders in Isfahan, Iran 
ISRN Endocrinology  2012;2012:167318.
Aim. At present, little data exist about incidence and the risk factors associated with metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (T2DM). The objectives of present study were to assess the incidence and risk factors of MetS in people with T2DM. Methods. During the mean (SD) follow-up period of 11.7 (4.8) years, 3,047 patients with T2DM and free of MetS at baseline have been examined to determine incidence and predictors of progression to MetS. A modified the National Cholesterol Education Program—Adult Treatment Panel III definition with body mass index (BMI) instead of waist circumference was used for the MetS. Results. The prevalence of MetS was 63.2% (95% CI: 62.3, 64.1). The incidence of MetS was 28.5 (95% CI: 26.8, 30.2) (25.9 men and 30.9 women) per 1,000 patient-years based on 35,677 patient-years of follow-up. Multivariate analysis revealed that higher BMI and education, lower HbA1c and treatment with oral agent or insulin were associated with MetS. Conclusion. These are the first estimate of incidence and risk factors of MetS in patients with T2DM in Iran. These findings showed that the natural course of MetS is dynamic. The clinical management of patients with T2DM will contribute significantly to MetS prevention.
PMCID: PMC3313686  PMID: 22474593
25.  Sleep Apnea Symptoms in Diabetics and their First Degree Relatives 
Sleep apnea is associated with increased risk of diabetes mellitus. However, no studies have compared sleep apnea symptoms in diabetic patients and their first degree relatives. The purpose of our study was to investigate high risk for sleep apnea syndrome, in diabetics and their first degree relatives for prevention of diabetes in family.
As a part of a cohort study, all of diabetic and their first degree relatives who came for glucose control in diabetes clinic were invited to take part in the survey. Two thousand, four hundred and sixty-two individuals (82% of invited) agreed to fill out the Berlin and Epworth sleep questionnaire. Participants consisted of 2462 subjects of 15–70 years of age, both males and females with diabetes and family history of type 2 diabetes mellitus. A total of 1234 participants had diabetes and 11,231 were relatives of diabetic patients. High risk for sleep apnea regarding Berlin questionnaire and Epworth sleepiness scale, diabetic and relative were analyzed.
Prevalences of high risk for sleep apnea were higher among diabetics than relatives (P-value<0.001). In a multiple regression analysis, “age, body mass index, education, high blood pressure” were risk factor for sleep apnea symptoms while isolated blood glucose level was not by Berlin questionnaire. By Epworth sleep scale only education level was a risk factor for sleep apnea symptoms while isolated blood glucose level was not risk factor.
Sleep apnea symptoms may not have significant difference between diabetics and their relatives. We need more study on sleep apnea in the family of diabetic patients. We hope that more studies on mentioned field may help prevention of diabetes in their family.
PMCID: PMC3278886  PMID: 22347605
Diabetes; first degree relatives; Iran; sleep apnea

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