Publications by authors named "Ashraf Aminorroaya"

86 Publications

A 16-year prospective cohort study to evaluate effects of long-term fluctuations in obesity indices of prediabetics on the incidence of future diabetes.

Sci Rep 2021 Jun 2;11(1):11635. Epub 2021 Jun 2.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

This study aimed to evaluate the patterns of changes in obesity indices over time in prediabetic subjects and to classify these subjects as either having a low, moderate, and high risk for developing diabetes in the future. This study was conducted among 1228 prediabetics. The patterns of changes in obesity indices based on three measurements including first, mean values during the follow-up period, and last visit from these indices were evaluated by using the latent Markov model (LMM). The mean (standard deviation) age of subjects was 44.0 (6.8) years and 73.6% of them were female. LMM identified three latent states of subjects in terms of change in all anthropometric indices: a low, moderate, and high tendency to progress diabetes with the state sizes (29%, 45%, and 26%), respectively. LMM showed that the probability of transitioning from a low to a moderate tendency to progress diabetes was higher than the other transition probabilities. Based on a long-term evaluation of patterns of changes in obesity indices, our results reemphasized the values of all five obesity indices in clinical settings for identifying high-risk prediabetic subjects for developing diabetes in future and the need for more effective obesity prevention strategies.
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http://dx.doi.org/10.1038/s41598-021-91229-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172923PMC
June 2021

Bacterial Profile and Antimicrobial Resistance Patterns of Infected Diabetic Foot Ulcers in Iran: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

Int J Low Extrem Wounds 2021 Apr 28:15347346211002715. Epub 2021 Apr 28.

Isfahan Endocrine and Metabolism Research Center, 48455Isfahan University of Medical Sciences, Isfahan, Iran.

Since infectious foot ulcers represent one of the major causes of lower-limb amputation, it calls for an appropriate action for early detection and sufficient treatment of diabetic foot infection (DFI). The present study aimed at investigating the bacterial epidemiology and antimicrobial resistance (AMR) patterns of DFIs in Iran. We have conducted a systematic search in PubMed, Embase, Web of Science, Scopus, Google Scholar, and Scientific Information Database to identify all articles reporting the proportion of different kinds of bacteria isolated from Iranian DFI samples. Quality was assessed using Joanna Briggs Institute tool. A pooled estimate of proportion with a corresponding 95% confidence interval (95% CI) was calculated using the random effect method. Fifteen studies were eligible, of which 1970 bacterial isolates were obtained from 1316 patients. The most predominant isolates recovered from DFIs was with a pooled proportion of 24.29% (95% CI: 20.25%, 28.57%) from which 55% (95% CI: 38%, 72%) were methicillin-resistant (MRSA). Among Gram-negative strains, had the highest proportion (17.19%; 95% CI: 13.96%, 20.68%) followed by , 7.54% (95% CI: 4.56%, 11.14%). The highest pooled estimates of resistance against cotrimoxazole and ciprofloxacin were found in 66% (95% CI: 48%, 82%) and isolates 68% (95% CI: 51%, 84%), respectively. Our study revealed that AMR is at a high level in Iran and clinicians should be aware of bacterial resistance patterns to prescribe appropriate antibiotic regimens.
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http://dx.doi.org/10.1177/15347346211002715DOI Listing
April 2021

Alleviating neuropathy of diabetic foot ulcer by co-delivery of venlafaxine and matrix metalloproteinase drug-loaded cellulose nanofiber sheets: production, in vitro characterization and clinical trial.

Pharmacol Rep 2021 Jun 7;73(3):806-819. Epub 2021 Apr 7.

Isfahan University of Medical Sciences, Isfahan, Iran.

Background: The objective of the present study was co-delivery of venlafaxin (VEN) and doxycycline (DOX), a matrix metalloproteinase inhibitor drug, for alleviating inflammation and neuropathy in diabetic foot ulcer (DFU).

Methods: Bacterial cellulose nanofiber sheets (BCNS) were loaded with DOX and VEN and categorized by their loading efficiency, release profiles and ex vivo permeation throughrat skin. The optimized nanofibers were used in patients with DFU to compare with the standard wound care regimen during a 12-week trial. Wound area was measured every 2 weeks. Biochemical parameters and microscopic studies of the skin were examined prior and at the end of the treatment. The Michigan Neuropathy Screening Instrument (MNSI) questionnaire was utilized to assess diabetic neuropathy.

Results: The optimum formulation showed loading efficiency of 37.8 ± 1.6% for DOX and 48 ± 1.9% for VEN. Rat skin permeation was 40% for DOX after 7-29 h and 83% for VEN during 105 h. Patients treated with BCNS showed no significant difference in their biochemical parameters before and after intervention. The ulcer size showed faster reduction after 12 weeks in the treatment group compared to the control group. The abnormal responses in the MNSI questionnaire decreased and pain-free walking distance increased significantly in the treatment group compared with the control group (p < 0.001). Microscopic studies of the skin after using nanofibers showed a large number of polymorphonuclear chronic inflammatory cells and formation of new capillary beds.

Conclusions: The BCNS loaded with DOX and VEN may expedite healing and reduce neuropathy in the DFU of diabetic patients.
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http://dx.doi.org/10.1007/s43440-021-00220-8DOI Listing
June 2021

Patterns of changes in fasting plasma glucose, hemoglobin A1c and the area under the curve during oral glucose tolerance tests in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

Acta Diabetol 2021 Mar 21;58(3):371-381. Epub 2020 Oct 21.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Aim: This study aimed to identify the patterns of changes in glycemic indices over time in prediabetics and to classify these subjects as either having a high or low risk for developing diabetes in future.

Methods: This prospective 16-year cohort study was conducted among 1228 prediabetic subjects. Three measurements including first visit, mean values during the follow-up period, and last visit from fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1), and area under the curve during an oral glucose tolerance test (OGTT AUC) were used to evaluate the patterns of changes by using the latent Markov model (LMM).

Results: The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The LMM identified 2 latent states of subjects in terms of changes in FPG, HbA1c, OGTT AUC, and the combination of these glycemic measures: a low tendency to progress diabetes and a high tendency to progress diabetes with the latent state sizes (87, 13%), (94, 6%), (57, 43%), and (84, 16%), respectively. The LMM showed that the probability of transitioning from a low tendency to a high tendency to progress diabetes was higher than the probability of transitioning in the opposite direction.

Conclusion: Based on a long-term evaluation of patterns of changes in glycemic indices, we classified prediabetic subjects into 2 groups (high or low risk to progress diabetes states in future). Also, the method used enabled us to estimate the transition probabilities from low- to high-risk states and vice versa. Our results reemphasized the values of all 3 glycemic measures in clinical settings for identifying prediabetic people with a high risk of progressing diabetes and the need for more effective prevention strategies, which should be conducted as urgently in prediabetic life as high-risk subjects.
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http://dx.doi.org/10.1007/s00592-020-01622-5DOI Listing
March 2021

Patterns of changes in serum lipid profiles in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

Lipids Health Dis 2020 Aug 23;19(1):193. Epub 2020 Aug 23.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Lipid abnormality pervasively is associated with the risk of type 2 diabetes mellitus. To the best of our knowledge, there is no study that has examined the longitudinal changes in a wide range of serum lipid profiles in prediabetic subjects in association with the risk of developing type 2 diabetes mellitus in the future. This study aimed to identify the patterns of changes in lipid profiles over time in prediabetic patients and to classify these subjects in order to highlight which patients are at high risk for future diabetes.

Methods: This prospective 16-year (2003-2019) cohort study was conducted among 1228 prediabetic subjects. The study subjects were followed, and the changes in their lipid profiles, including triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, were evaluated. The latent Markov model was used for data analysis.

Results: The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The latent Markov model identified two latent states of subjects in terms of changes in lipid profiles: a low tendency to progress diabetes / high tendency to progress diabetes (74, 26%). The latent Markov model showed that the transition probability from a "low tendency to progress diabetic" state to a "high tendency to progress diabetic" state was lower than the transition probability from "high tendency to progress diabetic" state to "low tendency to progress diabetic" state.

Conclusions: The present study showed that more than half of the first-degree relatives of T2DM had approximately normal lipid profiles and that these patients are more inclined to transition from a higher- to a lower-tendency diabetic state. These findings confirm the value of regular screening of first-degree relatives of T2DM. Moreover, preventive intervention strategies are recommended to reduce their risk of developing T2DM.
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http://dx.doi.org/10.1186/s12944-020-01371-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444073PMC
August 2020

Association of Lipid Profile with Type 2 Diabetes in First-Degree Relatives: A 14-Year Follow-Up Study in Iran.

Diabetes Metab Syndr Obes 2020 5;13:2743-2750. Epub 2020 Aug 5.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Purpose: Dyslipidemia is claimed to be associated with an increased risk of type 2 diabetes mellitus (T2DM). However, first-degree relatives (FDRs) of patients with T2DM are reported to be at higher risk. The aim of this study was to evaluate the association between serum lipid profile and T2DM incidence in FDRs.

Patients And Methods: Information on 1222 T2DM FDRs during 14 years of follow-up was retrieved. All individuals were examined for diabetes status and dyslipidemia once a year. We used a Bayesian joint longitudinal-survival model to assess the association.

Results: Our data showed that a 10 mg/dL increase in triglycerides (TG), very-low-density lipoprotein (VLDL), and non-high-density lipoprotein (non-HDL) cholesterol levels during the follow-up period was associated with an increased risk of diabetes by 5%, 29%, and 6.6%, respectively. Moreover, for every one-unit increase in the TG to HDL ratio, the T2DM incidence increased by 35%. Subgroup analysis also showed that the increased risk of diabetes was significant only in female FDRs, so that a 10 mg/dL increase in TG and VLDL cholesterol level and a one-unit increase in TG to HDL ratio in female FDRs resulted in an increased risk of diabetes by 7.8%, 46%, and 64%, respectively. However, analysis of HDL, low-density lipoprotein (LDL), total cholesterol (TC), TC to HDL, and LDL to HDL cholesterol levels/ratios did not find any statistically significant associations.

Conclusion: Increases in TG, VLDL, non-HDL cholesterol level, and TG to HDL ratio are associated with an increased risk of T2DM in FDRs, especially in female FDRs.
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http://dx.doi.org/10.2147/DMSO.S259697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415448PMC
August 2020

The effects of 6 mo of supplementation with probiotics and synbiotics on gut microbiota in the adults with prediabetes: A double blind randomized clinical trial.

Nutrition 2020 Nov - Dec;79-80:110854. Epub 2020 May 19.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Objectives: The evidence of 16S rRNA genes in the gut microbiota distinguished a higher Firmicutes-to-Bacteroidetes ratio in individuals who were obese and had diabetes than in a healthy cohort. So, it seems that the modulation of intestinal microbial ecology by pro-/pre-/synbiotics may contribute to the progression and prevention of metabolic diseases. The aim of this study was to assess the effects of probiotics and synbiotic supplementation on the modification of the intestinal microbiome in adults with prediabetes.

Methods: In a randomized, double-blinded, placebo-controlled clinical trial, 120 patients with prediabetes were randomly assigned to consume 6 g/d of either a placebo containing maltodextrin (control) or multispecies probiotic or inulin-based synbiotic for 6 mo. Fecal samples were obtained at baseline and after 6 mo of supplementation. Dietary intake was assessed throughout the study (at baseline and after 3 and 6 mo). Total energy, macronutrients, and dietary fiber were calculated using a dietary program Nutritionist 4. DNA was extracted from fecal samples and the numbers of Clostridium perfringens (the represent of phylum Firmicutes), Bacteroides fragilis (the representative of Bacteroidetes) and Escherichia coli (as universal bacteria) were determined by quantitative real-time polymerase chain reactions (qPCR). The changes in the relative abundance of the two fecal bacteria before and after supplementation were analyzed and compared within and between groups.

Results: There were no significant changes in dietary intake during the study. Six mo of supplementation with probiotics resulted in a statistically significant increase in the abundance of the B. fragilis-to-E.coli ratio (mean difference [MD] ± SE 0.47 ± 0.37, P = 0.04) and decrease of the relative proportion of Firmicutes-to-Bacteroidetes representatives (MD ± SE -118.8 ± 114.6, P = 0.02). Synbiotic had no significant effect on the changes in the bacteria. There were no significant differences between the three groups.

Conclusion: The results of this study suggest that manipulation of the human gut microbiome by using probiotics could provide a potential therapeutic approach in the prevention and management of obesity and metabolic disorders such as diabetes.
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http://dx.doi.org/10.1016/j.nut.2020.110854DOI Listing
May 2020

Multistate Models to Predict Development of Late Complications of Type 2 Diabetes in an Open Cohort Study.

Diabetes Metab Syndr Obes 2020 28;13:1863-1872. Epub 2020 May 28.

Department of Biostatistics, Physiotherapy Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Increase in the prevalence of type 2 diabetic mellitus (T2DM) as a complex disease, its complications, and spread has become a dominant global health threat in recent decades.

Objective: The aim of the current study was to investigate the impact of risk factors and transition probability on the development and progression of the late complications of T2DM.

Methods: This study was an open cohort one which was conducted at Isfahan Endocrine and Metabolism Research Center (IEMRC). The data were collected from 1993 to 2018. The sample size consisted of 2519 adults diagnosed with type 2 diabetes. We applied the homogeneous multistate models including no complication, retinopathy alone, coronary artery disease (CAD), microalbuminuria, retinopathy and CAD, and the final absorbing mortality states.

Results: Based on our results, time-varying hypertension strongly intensified the hazard of transition to mortality in CAD, no complication, CAD and retinopathy, and retinopathy patients by 4.99, 4.09, 3.42, and 2.65 times, respectively. Hypertension seemed to be a potential factor for the transition of microalbuminuria to no complication in diabetic patients. One-unit increase in LDL increased the hazard ratio of transition from CAD, and retinopathy and CAD to mortality by 1.8% and 2.4%, respectively. Moreover, one level increase in time-varying HbA1c increased the hazard ratio of transition to retinopathy and mortality among no complication diabetic patients by 30% and 67%, respectively. One level increase in time-varying HbA1c also intensified the hazard ratio of transition from retinopathy to mortality by 45%. The same level of increase in time-varying HbA1c also intensified the hazard ratio of transition from CAD alone to CAD and retinopathy, and microalbuminuria to retinopathy by 26% and 50%, respectively.

Conclusion: In addition to glycemic control, our study indicates that controlling hypertension and hyperlipidemia is more effective in reducing mortality and the diabetic macro- and microvascular complications.
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http://dx.doi.org/10.2147/DMSO.S234563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266524PMC
May 2020

Severity of the metabolic syndrome as a predictor of prediabetes and type 2 diabetes in first degree relatives of type 2 diabetic patients: A 15-year prospective cohort study.

World J Diabetes 2020 May;11(5):202-212

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.

Background: Type 2 diabetes mellitus (T2DM) has high morbidity and mortality worldwide, therefore there is of paramount importance to identify the risk factors in the populations at risk early in the course of illness. A strong correlation between severity of metabolic syndrome (MetS) and HbA1c, fasting insulin and insulin resistance has been reported. Accordingly, the MetS severity score (or MestS Z-score) can potentially be used to predict the risk of T2DM progression over time.

Aim: To evaluate the association the of MestS Z-score in first degree relatives (FDRs) of T2DM with the risk of prediabetes and type 2 diabetes in future.

Methods: A prospective open cohort study was conducted between 2003-2018. At baseline, the sample comprised of 1766 FDRs of patients with T2DM who had a normal glucose tolerance test. Relative risk (RR) and 95% confidence interval were calculated based on logistic regression. The receiver-operator characteristic analysis and area under the curve based on MetS Z-score were used to evaluate the risk of prediabetes and diabetes among the FDR population.

Results: Baseline MetS Z-scores were associated with the its latest values ( < 0.0001). Compared with individuals who were T2DM free at the end of follow up, those who developed T2DM had higher MetS Z-score at baseline ( < 0.001). In multivariable logistic regression analyses for every unit elevation in MetS Z-score at the baseline, the RR for developing future T2DM and prediabetes was (RR = 1.94, RR = 3.84), (RR = 1.5, RR = 2.17) in total population and female group, respectively ( < 0.05). The associations remained significant after adjusting the potential confounding variables. A cut off value of 0.97 and 0.94 was defined in the receiver-operator characteristic curve based on the MetS Z-score for differentiating female patients with diabetes and prediabetes from the normal population, respectively.

Conclusion: The MetS Z-score was associated with an increased risk of future T2DM. Appropriate interventions at earlier stages for preventing and attenuating MetS effects may be considered as an effective strategy for FDR as at-risk population.
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http://dx.doi.org/10.4239/wjd.v11.i5.202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243485PMC
May 2020

Prevalence and predictors of prediabetes and its coexistence with high blood pressure in first-degree relatives of patients with type 2 diabetes: A 9-year cohort study.

J Res Med Sci 2020 18;25:31. Epub 2020 Mar 18.

Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Prediabetes is strongly associated with high blood pressure; however, a little is known about prediabetes and high blood pressure comorbidity in the high-risk individuals. This is the first study in the world to assess the long-term effects of risk factors associated with high blood pressure and prediabetes comorbidity in the first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) patients.

Materials And Methods: The longitudinal data obtained from 1388 nondiabetic FDRs of T2DM patients with at least two visits between 2003 and 2011. We used univariate and bivariate mixed-effects logistic regressions with a Bayesian approach to identify longitudinal predictors of high blood pressure and prediabetes separately and simultaneously.

Results: The baseline prevalence of high blood pressure, prediabetes, and the coexistence of both was 27.4%, 19.1%, and 29.8%, respectively. The risks of high blood pressure and prediabetes were increased by one-unit raise in the age (odds ratio [OR] of high blood pressure: 1.419 (95% credible intervals [CI], 1.077-1.877), prediabetes: 1.055 (95% CI: 1.040-1.068)) and one-unit raise in remnant-cholesterol (OR of high blood pressure: 1.093 (95%CI, 1.067-1.121), and prediabetes: 1.086 (95% CI, 1.043-1.119)). Obese participants were more likely to have high blood pressure (OR: 2.443 [95% CI, 1.978-3.031]) and prediabetes (OR: 1.399 [95% CI, 1.129-1.730]) than other participants.

Conclusion: We have introduced remnant-cholesterol, along with obesity and age, as a significant predictor of prediabetes, high blood pressure, and the coexistence of both in the FDRs of diabetic patients. Obesity index and remnant-cholesterol showed the stronger effects on high blood pressure and prediabetes comorbidity than on each condition separately.
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http://dx.doi.org/10.4103/jrms.JRMS_472_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213002PMC
March 2020

Thyroid volume and nodular and diffuse thyroid diseases by ultrasonography in pregnant women: A case-control study.

J Res Med Sci 2020 20;25:13. Epub 2020 Feb 20.

Department of Medicine, Southend University Hospital, Southend-on Sea, United Kingdom, Southend University Hospital, Westcliff-on-Sea, England, UK.

Background: Currently, it is shown that pregnancy may have an impact on the thyroid that can be leading to pregnancy complications such as abortion, preeclampsia, and preterm delivery. The objective was to compare the thyroid volume, number and characteristics of thyroid nodules, and prevalence of diffuse thyroid diseases in a sample of Iranian pregnant women in the first trimester to nonpregnant women.

Materials And Methods: This case-control study was conducted on 298 pregnant and 290 nonpregnant women. Thyroid volume, maximum diameter of thyroid nodules and prevalence of moderate to highly suspicious thyroid nodules, Hashimoto's appearance and goiter were assessed using thyroid ultrasonography. Antithyroperoxidase (TPO) antibodies were measured if the sonographic features were highly suggested for Hashimoto's thyroiditis.

Results: The mean of total thyroid volume in pregnant and nonpregnant women was 6 and 6.5 ml, respectively ( = 0.053), and the median (interquartile range) was 6.2 and 5.5, respectively. Nodules were observed in 16.4% of pregnant and 16.6% of nonpregnant women ( = 0.845). Hashimoto's thyroiditis was detected in 6.7% of pregnant and 12.4% of nonpregnant women ( = 0.013). Anti-TPO antibodies were detected in 5% of pregnant and 9.3% of nonpregnant women ( = 0.034).

Conclusion: The thyroid volume and nodule characteristics in the first trimester of pregnancy were similar to nonpregnant women. Hashimoto's thyroiditis and anti-TPO antibodies in pregnant women were significantly lower than in nonpregnant women.
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http://dx.doi.org/10.4103/jrms.JRMS_42_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053162PMC
February 2020

Diabetes and all-cause mortality, a 18-year follow-up study.

Sci Rep 2020 02 21;10(1):3183. Epub 2020 Feb 21.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical sciences, Isfahan, Iran.

This study compared mortality rates and decline in life expectancy of Iranian patients with type 2 diabetes (T2DM) with the general population. A retrospective study of 2451 patients with T2DM was conducted in the Isfahan Endocrine and Metabolism Research Center, Iran, between 1992 and 2010. The mean (SD) of diabetes duration and median (Q1,Q3) of follow-up period were 15.5(8.0) and 8(5, 10) years. The main outcome was all-cause mortality. 732(29.87%) of patients died during the follow-up. Overall mortality rates (95%CI) per 1000 person-years in men and women were 56.3(52.0-62.1) and 27.3(24.5-30.4), respectively. The relative risks (95%CI) of all-cause mortality in males vs. females with T2DM aged 45-49, 50-54, 55-59, 60-64, 65-69, 70-74 were [3.02(1.49-6.11) vs. 2.09(0.96-4.57)], [4.05(2.73-6.01) vs. 2.29(1.52-3.45)], [4.13(3.26-5.24) vs. 1.70(1.23-2.35)], [2.42(1.90-3.07) vs. 1.82(1.46-2.27)], [2.36(2.02-2.76) vs. 1.49(1.25-1.78)] and [1.71(1.50-1.95) vs. 1.04(0.88-1.23)] times more than the general population, respectively. Men and women living with diabetes lost an average of 13.2(6.3) and 13.9(6.0) life-years from the year of diagnosis, respectively (p = 0.101). The estimated life-years lost were greater in younger patients and a gradual decline was observed with increasing the age at diagnosis. In conclusion, Iranians with diabetes had higher risk of death and lower life expectancy compared to the general population.
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http://dx.doi.org/10.1038/s41598-020-60142-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035261PMC
February 2020

Cause-Specific Risk Factors of Death in Individuals with Diabetes: A Competing Risks Modeling.

Int J Endocrinol Metab 2019 Jul 3;17(3):e69419. Epub 2019 Jun 3.

Medical Education Research Center, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: Diabetes is on the rise worldwide.

Objectives: This study aimed to evaluate the risk factors of various causes of death in people with type 2 diabetes (T2D).

Methods: In this cohort study on 2638 people with T2D, we applied cause-specific and sub-distribution hazards models to assess the impact of various factors on the risk of death. Moreover, we plotted a cumulative incidence curve to summarize cumulative failure rates over time.

Results: About 75% of individuals with T2D died from cardiovascular disease (CVD) and cerebrovascular accidents (CVA). Death from CVD was associated with the increased risk of hypertension (hazard ratio (HR) = 1.83, 95% CI: 1.37 - 2.46), hypercholesterolemia (HR = 1.58, 95% CI: 1.17 - 2.14), and diabetes duration. The risk of death from CVA was related to hypertension (HR = 2.76, 95% CI: 1.67 - 4.55) and hyperglycemia (HR = 4.34, 95% CI: 1.75 - 10.79). The CVA risk in patients with diabetes duration of 10 - 20 years was higher than the risk in patients with diabetes duration > 20 years (diabetes duration of ≤ 10 years as the reference category). Diabetes duration of longer than 20 years was associated with a higher risk of death from cancer (HR = 2.65, 95% CI: 1.05 - 6.68). The risk of death from foot infection and diabetic nephropathy increased in patients with longer diabetes duration after adjustment for sex, age, and body mass index.

Conclusions: Regardless of the cause, death rates in people with T2D increase over time and risk factors have different impacts on death from each cause. This should be acknowledged in risk management in individuals with T2D.
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http://dx.doi.org/10.5812/ijem.69419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678678PMC
July 2019

Cross-sectional and longitudinal assessments of risk factors associated with hypertension and moderately increased albuminuria comorbidity in patients with type 2 diabetes: a 9-year open cohort study.

Diabetes Metab Syndr Obes 2019 15;12:1123-1139. Epub 2019 Jul 15.

Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Moderately increased albuminuria (MIA) is strongly associated with hypertension (HTN) in patients with type 2 diabetic mellitus (T2DM). However, the association between risk factors and coexisting HTN and MIA remains unassessed.

Objectives: This study aimed to determine both cross-sectional and longitudinal associations of risk factors with HTN and MIA comorbidity in patients with T2DM.

Methods: A total of 1,600 patients with T2DM were examined at baseline and longitudinal data were obtained from 1,337 T2DM patients with at least 2 follow-up visits to assess the presence of HTN alone (yes/no), MIA alone (yes/no) and the coexistence of both (yes/no) in a 9-year open cohort study between 2004 and 2013. Bivariate mixed-effects logistic regression with a Bayesian approach was employed to evaluate associations of risk factors with HTN and MIA‎ comorbidity in the longitudinal assessment.

Results: After adjustment for age and BMI, patients with uncontrolled plasma glucose, as a combined index of the glucose profile, were more likely to have HTN [odds ratio (OR): 1.73 with 95% Bayesian credible intervals (BCI) 1.29-2.20] and MIA [OR: 1.34 (‎95% BCI 1.13-1.62)]. The risks of having HTN and MIA were increased by a one-year raise in diabetes duration [with 0.89 (95% BCI 0.84-0.96) and 0.81 (95% BCI 0.73-0.92) ORs, respectively] and a one-unit increase in non-high-density lipoprotein-cholesterol (Non-HDL-C) [with 1.30 (95% BCI 1.23-1.34) and 1.24 (95% BCI 1.14-1.33) ORs, respectively].

Conclusions: T2DM patients with HTN,‎ MIA, and the coexistence of both had uncontrolled plasma glucose, significantly higher Non-HDL-C, and shorter diabetes duration than the other T2DM patients. Duration of diabetes and uncontrolled plasma glucose index showed the stronger effects on HTN and MIA comorbidity than on each condition separately.
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http://dx.doi.org/10.2147/DMSO.S189726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646050PMC
July 2019

Different metabolic/obesity phenotypes are differentially associated with development of prediabetes in adults: Results from a 14-year cohort study.

World J Diabetes 2019 Jun;10(6):350-361

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.

Background: The risk of developing prediabetes based on the metabolic/obesity phenotypes has been poorly investigated.

Aim: To examine the association of baseline metabolic/obesity phenotypes and their changes over time with the risk of prediabetes development.

Methods: In a population-based cohort study, 1741 adults (aged > 19 years) with normal blood glucose were followed for 14 years. Anthropometric and biochemical measures were evaluated regularly during the follow-up period. According to body mass index and metabolic health status, participants were categorized into four groups: Metabolically healthy normal weight (MHNW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy obese (MUO). Multivariable Cox regression analysis was used to measure the risk of prediabetes according to the baseline metabolic/obesity phenotype and their changes during the follow-up.

Results: In the whole population with a mean (95CCI for mean) follow up duration of 12.7 years (12.6-12.9), all three MUNW, MHO, MUO groups were at higher risk for developing prediabetes compared to the MHNW group ( = 0.022). The MUNW group had the highest risk for developing prediabetes (hazard ratio (HR): 3.84, 95%CI: 1.20, 12.27). In stratified analysis by sex, no significant association was found in men, while women in the MUNW group were at the greatest risk for prediabetes (HR: 6.74, 95%CI: 1.53, 29.66). Transforming from each phenotype to MHNW or MHO was not related to the risk of prediabetes development, whereas transforming from each phenotype to MUO was associated with an increased risk of prediabetes (HR > 1; < 0.05).

Conclusion: Our findings indicate that MHO is not a high risk, unless it transforms into MUO over time. However, people in the MUNW group have the greatest risk for developing prediabetes, and therefore, they should be screened and treated.
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http://dx.doi.org/10.4239/wjd.v10.i6.350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571483PMC
June 2019

Effects of somatostatin analog treatment on cardiovascular parameters in patients with acromegaly: A systematic review.

J Res Med Sci 2019 26;24:29. Epub 2019 Apr 26.

Max-Planck-Institute of Psychiatry, Internal Medicine/Endocrinology and Clinical Chemistry, Munich, Germany.

Background: There is a belief that in patients with acromegaly, first-generation somatostatin analogs (SSAs) might improve cardiovascular (CV) structure and function. However, most published clinical trials involved only a few patients and their results are rather variable. We aimed to conduct a systematic review on available studies on the impact of these drugs on CV parameters.

Materials And Methods: A literature search was conducted in MEDLINE (OVID), EMBase, Cochrane, and ISI Web of Science for citations published until April 30 2018 to identify studies on our objective that considered changes in CV parameters. For this search, we established a Boolean search strategy using keywords related to "acromegaly," "Somatostatin analog," and "cardiovascular diseases and parameters." All study types except for case reports or conference abstracts were included. Twenty-four studies ( = 558) fulfilled the inclusion criteria and were selected for final analysis.

Results: In 12 studies ( = 350), decrease in heart rate (HR) and in 4 studies ( = 128), decrease in blood pressure (BP) was significant. In 15 studies ( = 320), left ventricular mass index (LVMi) changes were significant. In 9 studies ( = 202), the early diastole to peak velocity flow in late diastole (E/A ratio) was evaluated, and in 5 of them ( = 141), the improvement was significant. Eighteen studies ( = 366) examined changes in left ventricular ejection fraction (LVEF), 5 of which ( = 171) reported that these changes were significant. Decrease of left ventricular end-diastolic diameter was reported in only 2 studies ( = 27).

Conclusion: We found that first-generation SSAs have a beneficial effect on cardiac parameters such as HR and LVMi. For other parameters such as LVEF, BP, LV diameter, and E/A ratio, we were not able to draw a firm conclusion.
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http://dx.doi.org/10.4103/jrms.JRMS_955_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521613PMC
April 2019

Assessment of the Early and Late Complication after Thyroidectomy.

Adv Biomed Res 2019 27;8:14. Epub 2019 Feb 27.

General Surgery, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: The complications in thyroid surgery have been reported variable in literature. The aim of this study was to evaluate the early and late (3 months after surgery) complication rates of thyroidectomy in a cohort of patients undergoing thyroid surgery at two hospitals of Isfahan University of Medical Science, Iran.

Materials And Methods: This study included 204 patients who candidates for thyroidectomy presenting at Medical Educational Centers of Al-Zahra and Kashani hospitals in Isfahan between March 2016 and March 2017. Clinical data are collected for all patients by continuous enrollment. The patients examined before and after thyroid surgery and the findings were recorded.

Results: The highest prevalence of thyroidectomy was in women (81.9%). The most frequent thyroid surgery was total thyroidectomy and the most common indication for thyroid surgery was suspicious fine-needle aspiration for thyroid malignancy. Hypocalcemia was the most common complication with a frequency of 54.4%. The odds ratios for early complications were 2.375 and 2.542 for intermediate- and low-volume surgeons, respectively, compared to high-volume surgeons.

Conclusions: According to the results of this study, the high level of surgeon's skill is effective to reduce the likelihood of late and early complications; furthermore, the chance of late complications increases with age.
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http://dx.doi.org/10.4103/abr.abr_3_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425745PMC
February 2019

Thyroid-stimulating hormone (TSH) serum levels and risk of spontaneous abortion: A prospective population-based cohort study.

Clin Endocrinol (Oxf) 2019 07 15;91(1):163-169. Epub 2019 Apr 15.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Objective: Thyroid dysfunction, a common complication of pregnancy, is associated with adverse obstetric and neonatal consequences. This study aimed to determine the effect of TSH levels on early pregnancy outcome in a prospective population-based cohort study.

Design And Methods: The serum TSH, free thyroxine, free triiodothyronine, thyroid peroxidase antibody levels and urinary iodine concentration of 418 pregnant women in their first trimester of pregnancy were measured. According to the American Thyroid Association (ATA) and the local reference ranges for TSH, women were divided into two groups of 0.1-2.5, >2.5 mIU/L and 0.2-4.6, >4.6 mIU/L. The risk of spontaneous abortion (SA) was calculated for each group.

Results: Spontaneous abortion was detected in 7.2% (n = 30) of total 418 pregnancies. Women with TSH levels > 2.5 mIU/L had an increased risk of SA, compared to women with TSH levels of 0.1-2.5 mIU/L (relative risk [RR] 3.719, 95% confidence interval [CI]:1.713-8.074). The risk of SA was increased in women with TSH levels > 4.6 mIU/L (RR 5.939, 95% CI: 1.711-20.620). The rate of SA was increased by 78% for every unit increase in standard deviation of TSH concentration (RR 1.35, 95% CI: 1.09-1.70). The rate of miscarriages in the treated group by levothyroxine was 9.8% (n = 6) compared to 28.6% (n = 8) in the untreated group (P = 0.024).

Conclusions: Our finding suggests that the upper limit for the TSH normal range should be redefined to <2.5 mIU/L during the first trimester of gestation. The local upper limit was 4.6 mIU/L, consistent with 4.0 mIU/L cut-off value recommended by the ATA.
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http://dx.doi.org/10.1111/cen.13979DOI Listing
July 2019

The prevalence of comorbid depression in patients with type 2 diabetes: an updated systematic review and meta-analysis on huge number of observational studies.

Acta Diabetol 2019 Jun 22;56(6):631-650. Epub 2019 Mar 22.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Aims: Depression is a common co-morbidity in patients with type 2 diabetes mellitus (T2DM). Untreated depression in these patients adversely affects self-care activities and other diabetes complications. The aim of this study is to estimate the prevalence of depression among patients with T2DM by conducting a meta-analysis of observational studies.

Methods: MEDLINE, Web of Science, Science Direct, and Google Scholar databases were searched for all observational studies that assessed depression in T2DM. Relevant articles were searched using the combination of Medical Subject Heading (MeSH) terms of "depression", "depressive disorder", and "diabetes mellitus" published between January 2007 and July 2018. Random effects model was used to estimate the weighted prevalence rates and 95% CI using "metaprop program in STATA 11".

Results: In total, the 248 included studies (with 273 reported prevalence) identified 83,020,812 participants; of them, 23,245,827 (28%; 95% CI 27, 29) suffered from different severity levels of depressive disorders. The prevalence of depression was separately reported in 137,372 males and 134,332 females. Of them, 31,396 males (23%, 95% CI: 20, 26) and 45,673 females (34%, 95% CI: 31, 38) were depressed. Compared with global estimate, depression prevalence was lower in Europe (24%) and Africa (27%), but higher in Australia (29%) and Asia (32%). The prevalence in America was equal to the estimated prevalence in the world (28%). Depression was more common in subjects younger than 65 compared with elderlies (31% vs. 21%).

Conclusion: Our findings demonstrated that almost one in four adults with T2DM experienced depression. Given the high prevalence of depressive disorders in diabetic patients, screening these patients for co-morbid depression and its relevant risk factors is highly recommended.
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http://dx.doi.org/10.1007/s00592-019-01295-9DOI Listing
June 2019

Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level.

Horm Metab Res 2019 Mar 12;51(3):165-171. Epub 2019 Mar 12.

Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

The physiological changes during pregnancy modulate the endocrine system. Therefore, both the American and the European thyroid associations recommend the use of local trimester-specific reference intervals. The purpose of this study was to establish the first trimester reference intervals for thyroid function tests in the central area of Iran. We examined 436 pregnant women in their first trimester of pregnancy, and 444 non-pregnant women in a cross sectional study. Serum levels of thyroid stimulating hormone (TSH), free thyroxin (FT), free triiodothyronine (FT), thyroid peroxidase antibody, urinary iodine concentration (UIC), and thyroid volume were measured for all subjects. The first trimester-specific reference intervals (2.5th-97.5th percentile) were determined for 185 pregnant women and 256 non-pregnant women with negative TPOAb, adequate iodine level (UIC≥150 μg/l in pregnant and UIC≥100 μg/l in non-pregnant women), and normal thyroid examination. We calculated multiples of the median (MoM) for TFTs to normalize the obtained data. The first trimester-specific reference intervals of serum TSH, FT, and FT for pregnant women were 0.20-4.60 mIU/l, 9.0-18.02 pmol/l, and 3.40-5.64 pmol/l, respectively, while the corresponding figures for non-pregnant women were 0.59-5.60 mIU/l, 9.52-19.30 pmol/l, and 3.70-5.55 pmol/l, respectively. The first and 99th percentile MoM of TSH in pregnant women in their first-trimester was 0.06-4.62. The local normal reference ranges for the first trimester of pregnancy in central region of Iran were different from the ranges suggested by the ATA.
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http://dx.doi.org/10.1055/a-0855-7128DOI Listing
March 2019

Thyroid function test reference ranges in the first trimester of gestation and pregnancy outcomes: Protocol and preliminary results for cohort population-based study Isfahan, Iran.

J Res Med Sci 2018 28;23:99. Epub 2018 Nov 28.

Isfahan Endocrine and Metabolism Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: This paper presents the protocol and primary findings of pregnancy cohort population-based study in Isfahan, Iran.

Materials And Methods: In this cohort, 418 pregnant and 438 nonpregnant women were enrolled. In the first phase, serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, and urinary iodine concentration (UIC) were measured. Furthermore, the thyroid ultrasound was also performed. According to the results of thyroid function tests in the first phase, local reference range for TSH, FT4, and FT3 in pregnant and nonpregnant women are determined. The 2.5 and 97.5 percentiles are determined as limits of the reference ranges. In the second phase, all pregnant women underwent prenatal care visits in each trimester and they followed for 7 days after delivery and the pregnancy outcomes data are reported.

Results: The mean ± standard deviation for TSH, FT4, FT3, and UIC in the first trimester of gestation was 1.84 ± 1.32 mIU/L, 1.01 ± 0.15 ng/dL, 4.50 ± 0.64 pmol/L, and 172.0 ± 90.29 μg/L, respectively. In nonpregnant women, these values for TSH, FT4, FT3, and UIC were 2.58 ± 1.77 mIU/L, 1.10 ± 0.21 ng/dL, 4.49 ± 0.57 pmol/L, and 190.0 ± 109.6 μg/L, respectively.

Conclusion: The results of the present study could contribute to establish a local thyroid function tests reference ranges in the first trimester of pregnancy. It could possibly be effective on making a local reference value to prevent of thyroid disease misdiagnosis during pregnancy and adverse pregnancy outcomes.
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http://dx.doi.org/10.4103/jrms.JRMS_197_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282545PMC
November 2018

Alendronate improves fasting plasma glucose and insulin sensitivity, and decreases insulin resistance in prediabetic osteopenic postmenopausal women: A randomized triple-blind clinical trial.

J Diabetes Investig 2019 May 23;10(3):731-737. Epub 2018 Oct 23.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Aims/introduction: Postmenopausal women receive bisphosphonates for osteoporosis treatment. The effect of these medications on developing diabetes mellitus in prediabetic patients is yet to be investigated. We aimed to determine the effect of alendronate on plasma glucose, insulin indices of postmenopausal women with prediabetes and osteopenia.

Materials And Methods: The present triple-blind randomized controlled clinical trial included 60 postmenopausal women, aged 45-60 years. All patients were vitamin D sufficient. They were randomly enrolled in intervention (70 mg/week alendronate for 12 weeks) and control (placebo tablet per week for 12 weeks) groups. The morning 8-h fasting blood samples were collected at the baseline and follow-up visits to measure the fasting plasma glucose (mg/dL), insulin and hemoglobin A1c (HbA1c). Plasma glucose and insulin concentration were measured 30, 60 and 120 min after the glucose tolerance test. The Matsuda Index, homeostasis model assessment of insulin resistance, homeostasis model assessment of β-cell function and the area under the curves of glucose and insulin were calculated.

Results: The mean (standard deviation) fasting plasma glucose (102.43 [1.46] mg/dL vs 94.23 [1.17] mg/dL, P = 0.001), 120-min insulin concentration (101.86 [15.70] mU/L vs 72.60 [11.36] mU/L, P = 0.026), HbA1c (5.60 [0.06]% vs 5.40 [0.05]%, P = 0.001), homeostasis model assessment of insulin resistance (3.57 [0.45] vs 2.62 [0.24], P = 0.021) and Matsuda Index (7.7 [0.41] vs 9.2 [0.4], P = 0.001) significantly improved in the alendronate-treated group. There were more statistically significant reductions in fasting plasma glucose (-8.2 [8.63] mg/dL vs -2.5 [14.26] mg/dL, P = 0.002) and HbA1c (-0.2 [0.23]% vs -0.09 [0.26]%, P = 0.015) observed in the alendronate-treated group than the placebo group during the study course, respectively.

Conclusions: Administration of 70 mg/week alendronate improves fasting plasma glucose, HbA1c and insulin indices in postmenopausal women.
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http://dx.doi.org/10.1111/jdi.12944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497594PMC
May 2019

DEXAMETHASONE STRESS TEST: A PILOT CLINICAL STUDY FOR IDENTIFICATION OF INDIVIDUALS HIGHLY PRONE TO DEVELOP TYPE 2 DIABETES.

Endocr Pract 2018 Oct 7;24(10):894-899. Epub 2018 Aug 7.

Objective: We examined whether the "Dexamethasone Stress Test" exhibits the requisite high predictive ability to identify individuals highly prone to develop type 2 diabetes mellitus (T2DM).

Methods: Seven years ago, we administered an oral glucose tolerance test (OGTT) to 33 individuals without T2DM and repeated the OGTT 24 hours after a single oral dose of 8 mg dexamethasone (Dex); all participants had a first-degree relative with T2DM, and close to half had prediabetes. We calculated receiver operating characteristic (ROC) curves for all parameters derived from the OGTT before and after Dex in individuals who subsequently developed diabetes compared to individuals who did not.

Results: At 7 years of follow-up, 9 individuals had developed T2DM, while 24 remained without diabetes. None of the OGTT-derived parameters before administration of Dex had an area under the ROC curve of >0.8. However, 24 hours after Dex, three parameters, including fasting plasma insulin, homeostatic model assessment-insulin resistance, and 2-hour plasma glucose level, exhibited areas under the ROC curves of 0.84, 0.86, and 0.92, respectively.

Conclusion: The Dexamethasone Stress Test appears to be a good to excellent test in identifying individuals highly prone to develop T2DM.

Abbreviations: AUC = area under the curve; Dex = dexamethasone; HOMA-IR = homeostatic model assessment-insulin resistance; NGT = normal glucose tolerance; OGTT = oral glucose tolerance test; PreDiab = prediabetes; ROC = receiver operating characteristic; T2DM = type 2 diabetes mellitus.
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http://dx.doi.org/10.4158/EP-2018-0188DOI Listing
October 2018

Probiotic and synbiotic supplementation could improve metabolic syndrome in prediabetic adults: A randomized controlled trial.

Diabetes Metab Syndr 2019 Sep - Oct;13(5):2991-2996. Epub 2018 Jul 30.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Aims: Modulation of the gastrointestinal microbiome is suggested to contribute to the progression of metabolic syndrome associated diseases. This study was designed to assess the effects of probiotics and synbiotics on metabolic syndrome in individuals with prediabetes.

Methods: 120 adults with prediabetes were enrolled in a double-blind, placebo-controlled randomized parallel-group clinical trial. Participants were randomized to a multi-species probiotic or inulin-based synbiotic or placebo. Blood samples and anthropometric measures were collected at baseline, 12 and 24 weeks after treatment. The primary outcome measures were the changes between groups in metabolic syndrome and its components' prevalence.

Results: A significant trend for a reduction in the prevalence of hyperglycemia in probiotic and synbiotic groups (p = 0.01 and 0.005 respectively), and hypertension in probiotic group (p = 0.04) was found. The decreases in metabolic syndrome prevalence were significant after taking probiotic and synbiotic supplementation as compared with placebo (p = 0.02). Also, the prevalence of low HDL-cholesterol level was decreased during the study in the probiotic group compared with placebo (p = 0.02).

Conclusions: The potential benefits of using probiotic and synbiotic for metabolic syndrome management in prediabetes have been supported by the results in the current study which might provide an important strategy to combat metabolic syndrome-associated diseases.
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http://dx.doi.org/10.1016/j.dsx.2018.07.016DOI Listing
February 2020

Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients.

Adv Biomed Res 2018 25;7:96. Epub 2018 Jun 25.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Tehran, Iran.

Background: Sulfonylureas are important drugs of choice for treatment of type 2 diabetes mellitus (T2DM). It is suggested that differential response to sulfonylureas from T2DM patients is under influence of single nucleotide polymorphisms in some of the target genes. In spite of favorable therapeutic effects, sulfonylureas are associated with some adverse side effects such as microvascular complications and stroke, especially in older patients. Therefore, for T2DM patients who are getting less benefit, sulfonylureas should be avoided. Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene variation is reported to be associated with sulfonylureas effectiveness. Due to the inconsistency of available data regarding association of rs7754840 in CDKAL1 gene with sulfonylureas response in T2DM patients, the present study is conducted.

Materials And Methods: Fifty-one diabetic patients sensitive to sulfonylureas and 51 patients resistant to sulfonylureas treatment were recruited to this study. After extraction of DNA from patients' peripheral blood samples, rs7754840 single-nucleotide polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism assay using restriction enzyme.

Results: Frequency of G allele in resistant group was more than sensitive group (71, 6% vs. 57, 8%). Regression analysis was shown significant association between GG genotype and higher risk of resistance to sulfonylureas treatment (odds ratio = 2.250 [95% confidential intervals: 1.010-5.012]; = 0.046).

Conclusion: Our data confirmed that genotypes of rs7754840 are significantly associated with sulfonylureas treatment response. rs7754840 in CDKAL1 gene in combination with other clinicopathological findings would help to move towards personalized therapy of T2DM patients.
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http://dx.doi.org/10.4103/abr.abr_144_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036778PMC
June 2018

The effects of probiotics and synbiotic supplementation on glucose and insulin metabolism in adults with prediabetes: a double-blind randomized clinical trial.

Acta Diabetol 2018 Oct 22;55(10):1019-1028. Epub 2018 Jun 22.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Sedighe Tahere Research Complex, Khoram St., Isfahan, Iran.

Aims: Probiotics and/or prebiotics could be a promising approach to improve metabolic disorders by favorably modifying the gut microbial composition.

Objectives: To assess the effects of probiotics and synbiotic on glycemic indices in prediabetic individuals who are at risk of type 2 diabetes and its complications.

Methods: In a double-blind, randomized, placebo-controlled parallel-group clinical trial, 120 prediabetic adults participated and were randomly allocated to receive either probiotics or synbiotic or placebo supplements for 24 weeks. Anthropometric measurements, food record, physical activity and glycemic biomarkers including glycated hemoglobin (HbA1C), fasting plasma glucose (FPG), fasting insulin levels (FIL), homoeostasis model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and β-cell function (HOMA-B) were assessed at baseline and repeated at 12 and 24 weeks and compared within and between three groups using repeated measure ANOVA.

Results: Compared with the placebo, synbiotic supplementation resulted in a higher significant reduction in FPG (- 6.5 ± 1.6 vs. - 0.82 ± 1.7 mg/dL, P = 0.01), FIL (- 2.6 ± 0.9 vs. - 0.8 ± 0.8 µIU/mL, P = 0.028), and HOMA-IR (- 0.86 ± 0.3 vs. - 0.16 ± 0.25, P = 0.007), and a significant elevation in the QUICKI (+ 0.01 ± 0.003 vs. + 0.003 ± 0.002, P = 0.006). In addition, significant decreases in HbA1C was seen following the supplementation of probiotics and synbiotic compared with the placebo (- 0.12 ± 0.06 and - 0.14 ± 0.05 vs. +0.07 ± 0.06%, P = 0.005 and 0.008, respectively). HOMA-B was not found to be different between or within the three groups.

Conclusion: Glycemic improvement by probiotics and particularly synbiotic supplements in prediabetic individuals has been supported by current study. However, further studies are required for optimal recommendations in this important area of patient treatment.

Trial Registration: Iranian Registry of Clinical Trials: IRCT201511032321N2, Date registered February 27, 2016.
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http://dx.doi.org/10.1007/s00592-018-1175-2DOI Listing
October 2018

Low-density lipoprotein cholesterol and risk of type 2 diabetes: The Isfahan diabetes prevention study.

Diabetes Metab Syndr 2018 Sep 21;12(5):715-719. Epub 2018 Apr 21.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Iran.

Background: Studies reported that lipid-lowering treatment may increase the risk of diabetes, support the hypothesis that low-density lipoprotein cholesterol (LDLC) may be associated with type 2 diabetes (T2D).

Objective: The aim of this study was to assess the association between the LDLC levels and the incidence of T2D in an Iranian high-risk population not treated with lipid-lowering medications.

Methods: Mean 10-year follow-up data (1819) in non-diabetic first-degree relatives (FDR) of consecutive patients with T2D 30-70 years old, who were not treated with lipid-lowering drugs at baseline were examined. The diagnosis of T2D based on serial oral glucose tolerance test was the primary outcome. Cox proportional hazard model was used to estimate the hazard ratio (HR) for the incidence of T2D within tertiles of LDLC.

Results: A higher LDLC concentration was significantly associated with higher risk of T2D. Compared with the first tertile, the adjusted risk of T2D increased for the second (HR 1.20, 95% CI: 1.07, 1.35, P < 0.01) and third (HR 1.22, 95% CI: 1.08, 1.37, P < 0.01), tertiles of LDLC.

Conclusions: While these results await confirmation, a higher LDLC level was significantly associated with higher risk of T2D, independent of age, gender, fasting plasma glucose, waist circumference or blood pressure, in high-risk individuals in Iran.
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http://dx.doi.org/10.1016/j.dsx.2018.04.019DOI Listing
September 2018

Risk modeling in prospective diabetes studies: Association and predictive value of anthropometrics.

Diabetes Metab Syndr 2018 Jul 3;12(4):563-567. Epub 2018 Apr 3.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Aims: This study aimed to introduce and apply modern statistical techniques for assessing association and predictive value of risk factors in first-degree relatives (FDR) of patients with diabetes from repeatedly measured diabetes data.

Methods: We used data from 1319 FDR's of patients with diabetes followed for 8 years. Association and predictive performance of weight (Wt), body mass index (BMI), waist and hip circumferences (WC and HC) and their ratio (WHR), waist-height ratio (WHtR) and a body shape index (ABSI) in relation to future diabetes were evaluated by using Cox regression and joint longitudinal-survival modeling.

Results: According to Cox regression, in total sample, WC, HC, Wt, WHtR and BMI had significant direct association with diabetes (all p < 0.01) with the best predictive ability for WHtR (concordance probability estimate = 0.575). Joint modeling suggested direct associations between diabetes and WC, WHR, Wt, WHtR and BMI in total sample (all p < 0.05). According to LPML criterion, WHtR was the best predictor in both total sample and females with LPML of -2666.27 and -2185.67, respectively. However, according to AUC criteria, BMI had the best predictive performance with AUC-JM = 0.7629 and dAUC-JM = 0.5883 in total sample. In females, both AUC criteria indicated that WC was the best predictor followed by WHtR.

Conclusion: WC, WHR, Wt, WHtR and BMI are among candidate anthropometric measures to be monitored in diabetes prevention programs. Larger multi-ethnic and multivariate research are warranted to assess interactions and identify the best predictors in subgroups.
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http://dx.doi.org/10.1016/j.dsx.2018.03.027DOI Listing
July 2018

Incidence, risk factors, and pregnancy outcomes of gestational diabetes mellitus using one-step versus two-step diagnostic approaches: A population-based cohort study in Isfahan, Iran.

Diabetes Res Clin Pract 2018 Jun 10;140:288-294. Epub 2018 Apr 10.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Aims: To study the incidence, risk factors, and pregnancy outcomes associated with gestational diabetes mellitus (GDM) diagnosed with one-step and two-step screening approaches.

Methods: 1000 pregnant women who were eligible and consented to participate underwent fasting plasma glucose testing at the first prenatal visit (6-14 weeks). The women free from GDM or overt diabetes were screened at 24-28 weeks using the 50-g glucose challenge test (GCT) followed by 100-g, 3-h oral glucose tolerance test (OGTT) (two-step method). Regardless of the GCT result, all women underwent a 75-g, 2-h OGTT within one-week interval (one-step method).

Results: GDM incidence using the one-step and two-step methods was 9.3% (95% CI: 7.4-11.2) and 4.2% (95% CI: 2.9-5.5). GDM significantly increased the risk of macrosomia, gestational hypertension, preeclampsia, and cesarean section and older age and family history of diabetes significantly increased the risk of developing GDM in both approaches. In two-step method, higher pre-pregnancy body mass index and lower physical activity during pregnancy along with higher earlier cesarean section also increased significantly the risk of developing GDM.

Conclusions: Despite a higher incidence of GDM using the one-step approach, more risk factors for and a stronger effect of GDM on adverse pregnancy outcomes were found when using the two-step approach. Longer follow-up of women with and without GDM may change the results using both approaches.
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http://dx.doi.org/10.1016/j.diabres.2018.04.014DOI Listing
June 2018

Relationship Between Serum Uric Acid and Incident Hypertension in Patients with Type 2 Diabetes.

Rev Diabet Stud 2018 10;14(4):354-363. Epub 2018 Mar 10.

Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Little is known about the relationship between high baseline serum uric acid (SUA) and incident hypertension in patients with type 2 diabetes (T2D).

Objectives: To evaluate the ability of baseline SUA to predict the incidence of hypertension in non-hypertensive patients with T2D.

Methods: The association between SUA and mean 20-year incidence of hypertension was examined in 1,666 non-hypertensive patients with T2D from Isfahan Endocrine and Metabolism Research Center outpatient clinics, Iran. The primary outcome was incident hypertension defined as systolic blood pressure (BP) of 140 mmHg or higher and/or diastolic BP 90 mmHg or higher and/or use of antihypertensive medications. The mean (standard error (SE)) age of participants was 49.4 years (0.25 years) with a mean (SE) duration of diabetes of 6.1 years (0.15 years) at initial registration. We used multiple logistic regression to estimate the odds ratio (OR) for the incidence of hypertension across quartiles of SUA, and plotted a receiver operating characteristic (ROC) curve to assess discrimination.

Results: The highest quartile of SUA was not associated with hypertension compared with the lowest quartile in multivariable adjusted models (OR: 1.22, 95% CI: 0.87, 1.73). The area under the ROC curve for SUA was 51.7% (95% CI: 48.9, 54.5).

Conclusions: High initial SUA levels are not a predictor of incident hypertension in an Iranian T2D population.
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http://dx.doi.org/10.1900/RDS.2017.14.354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230447PMC
May 2019