Regional fat distribution and hepatic fibrosis and steatosis severity in patients with nonalcoholic fatty liver disease and type 2 diabetes.

Background: Epidemiologic findings suggest that measures of body fat distribution predict health outcomes independent of the overall body fat assessed by body mass index (BMI). This study aimed to evaluate the associations of overall and regional body fat with the severity of hepatic steatosis and fibrosis in type 2 diabetic patients with non-alcoholic fatty liver disease. Methods: Bioelectric impedance analysis and two newly developed anthropometric indices, namely, A Body Shape Index (ABSI) and Body Roundness Index (BRI), were used to estimate the body fat. Based on fibroscan parameters, significant hepatic fibrosis and severe steatosis were defined as ≥F2 and >66%, respectively. Results: Higher total body fat (odds ratio [OR] 1.107, 95% confidence intervals (CI) 1.038-1.182, p = 0.002), trunk fat (OR 1.136, 95% CI 1.034-1.248, p = 0.008) and leg fat (OR 1.381, 95% CI 1.139-1.674, p = 0.001) were associated with liver fibrosis. However, in contrast to the total body fat (OR 1.088, 95% CI 1.017-1.164, p = 0.014) and leg fat (OR 1.317, 95% CI 1.066-1.628, p = 0.011), the trunk fat was not associated with severe hepatic steatosis. BRI performed better than trunk, leg and total body fat in predicting hepatic steatosis (OR 2.186, 95% CI 1.370-3.487, p = 0.001) and fibrosis (OR 2.132, 95% CI 1.419-3.204, p < 0.001). Moreover, the trunk to leg fat ratio and ABSI were not independent predictors of either steatosis or fibrosis (p > 0.05). Conclusion: BRI revealed a superior predictive ability for identifying the degree of hepatic steatosis and stiffness than other obesity indices. Additionally, higher levels of adiposity in the trunk, legs, and overall body were linked to an increased risk of developing liver fibrosis. Although trunk fat did not show an association with severe hepatic steatosis, an increase in leg and total fat was related to liver steatosis.

How Age, Sex and Transfusion Affects the Incidence of Endocrine and Bone Density Disorders in Major Thalassemic Patients.

Background: Beta-thalassemia major patients frequently have endocrinopathies. We tried to determine relation between demographic and transfusion factor and endocrinopathies. Methods: Major beta-thalassemia patients (n=114 cases), 3-38 yr of age, entered this study. Female to male ratio was 51/63. Children (less than 20 yr) formed 57% of participants. Information about bone mineral density (BMD) and hormonal and biochemistry blood evaluation including fasting blood sugar (FBS), ferritin, triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), testosterone (males), and estradiol (females) entered data sheet. Results: Sex and ferritin level showed no significant correlation with above disorders. Age significantly correlated to short stature, diabetes, low BMD at femur and neck (P, 0.031, 0.008, 0.009 and <0.001, respectively) . The risk of short stature had increased in 12 yr and older patients 7.71 times than younger patients (P= 0.008). The risk of diabetes had increased in 35 yr and older patients 26.25 times than younger patients (P= 0.03). The risk of Z-score ≤ -2 in femoral region has increased in 19 yr and older patients 5.84 times than younger patients (P= 0.002). The risk of Z-score ≤ -2 in spinal region has increased in 14 yr and older patients 17 times than younger patients (P= 0.007). Conclusion: The main factor related with endocrinopathies was age. The correlation between age and short stature, diabetes and low BMD was positive. Therefore, we recommend early monitoring of thalassemia patients (in their late childhood and early teenage) for these complications.

Hypoglycemia in non-diabetic in-patients at a teaching referral hospital in Iran.

Purpose: This study aims to investigate comorbidities, clinical features, laboratory values, and diagnoses in non-diabetic patients experiencing hypoglycemic episodes. Methods: A retrospective observational study was conducted at Shariati Hospital in Iran from 2016 to 2023. Seventy-four non-diabetic patients admitted with a diagnosis of hypoglycemia were included, while patients with diabetes were excluded. Demographic data, symptoms, and biochemical assessments were obtained from the hospital information system. Hypoglycemic episodes were identified based on low measured blood glucose, recorded medications for hypoglycemia treatment, or recorded codes indicating hypoglycemia. Hypoglycemia was defined as blood glucose below 70 mg/dL (3.9 mmol/L) along with two other criteria of the Whipple triad. Statistical analysis was performed using SPSS software (version 26). Results: Among the enrolled patients, 63.5% were female, and 13.5% were elderly (≥ 65 years). The most common comorbidities observed were cardiovascular disease (20.3%), psychological disorders (20.3%), hypothyroidism (14.9%), and hypertension (8.1%). The prevalent symptoms included weakness, loss of consciousness, sweating, palpitations, dizziness, and tremors. Non-diabetic hypoglycemia was caused by factitious disorders, insulinoma, organ failure, and infection, respectively. Conclusion: Due to the diverse range of clinical symptoms, hypoglycemia in non-diabetic patients may be diagnosed late, leading to misdiagnoses such as psychological disorders or seizures. It is crucial to consider the possibility of hypoglycemia in non-diabetic patients and determine its underlying cause. Given the poor prognosis associated with hypoglycemia, timely interventions are essential.

Design and implementation of a national quality registry of thyroid cancer in Iran: study protocol.

Purpose: Thyroid cancer is recognized as the predominant form of endocrine cancer. The likelihood of cancer recurrence and the development of distant metastases varies depending on the cancer's pathology and stage. Iran currently lacks country-specific data on thyroid cancer, which can potentially result in clinicians deviating from the optimal treatment. The primary objectives of establishing such a registry are to determine the incidence, identify risk factors, and evaluate treatment outcomes for thyroid cancer within the Iranian population. Ultimately, the overarching goal of this protocol study is to reduce mortality and morbidity rates among thyroid cancer patients by implementing appropriate interventions based on the findings derived from this registration system. Methods: The study will enroll all individuals aged 18 years and older who have received a diagnosis of primary thyroid carcinoma based on pathology criteria. Data will be collected from various thyroid clinic centers. The participating centers include the Endocrinology Clinic at Shariati Hospital, the Thyroid Clinic in the Nuclear Medicine Center at Shariati Hospital, as well as pathology and nuclear medicine centers in Kerman and Bushehr. Patient records comprise information on outpatient visits to the clinic. Conclusion: The registry aims to enhance treatment approaches and follow-up protocols while serving as a foundation for conducting clinical, epidemiological, and basic science studies based on robust evidence-based data.

Are resting metabolic rate and clinical symptoms affected by variation of serum thyroid stimulating hormone levels within the normal range in healthy and women with hypothyroidism? A case-control study.

BACKGROUND: It is unclear whether variation in thyroid stimulating hormone (TSH) levels within the reference range affect energy expenditure and clinical symptoms and even within the normal range of TSH levels, resting energy expenditure may alter. The aim of the present study was to determine whether treated hypothyroid subjects and healthy subjects with a low-normal TSH range (0.3-2.3 mIU/L) have better clinical outcomes and increased energy expenditure than those with a high-normal TSH range (2.3-4.3 mIU/L). METHODS: This was a case-control study of 160 overweight/obese women with TSH levels across the reference range of 0.3-4.3 mU/l. Subjects were paired in four groups: healthy subjects with low-normal target TSH (n = 40), healthy subjects with high-normal target TSH (n = 40), subjects with treated hypothyroidism with low-normal target TSH (n = 40), and subjects with treated hypothyroidism with high-normal target TSH (n = 40). Resting energy expenditure (RMR), dietary intake, body composition, physical activity, and biochemical markers were assessed. RESULTS: Subjects with low-normal (≤2.3 mU/L) and high-normal (>2.3 mU/L) TSH levels did not differ in terms of RMR, serum T3 levels, and clinical symptoms except fatigue (P = 0.013). However, serum fT4 levels were found to be significantly different between the study groups (P = 0.002). Serum fT4 concentration was the highest in subjects with treated hypothyroidism with low-normal target TSH. CONCLUSION: Variation in serum TSH levels within the reference range did not significantly affect REE and clinical symptoms except fatigue in healthy and women with hypothyroidism.

Fast-Track Pathway: An Effective Way to Boost Diabetic Foot Care.

Diabetes is a chronic disease that challenges global health issues in many aspects. Diabetic foot ulcer (DFU) is one of the most common causes of reduced quality of life and increased hospitalization, amputation, treatment costs, and mortality in patients. Improper patients' knowledge, unsatisfactory education and training of healthcare workers, and limited facilities are the major cause of delayed referral and downscale management in DFUs. The diabetic foot clinical pathway is pivotal in providing best practices based on the latest standards and patient preferences. In the diabetic foot clinical pathway provided by the Iran Ministry of Health, the common concepts and grading systems are well defined for diabetic foot specialists so that patients can be diagnosed correctly and referred properly. Based on clinical examination guidelines, patients with diabetes are classified into low-risk, moderate-risk, high-risk, and active diabetic foot ulcer groups. One of this Pathway's main objectives is to prevent the patient from getting the first ulcer, prevent frequent recurrence ulcers, and most importantly, prevent minor and major amputation.

Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population.

Polycystic ovary syndrome (PCOS) has significant metabolic sequelae linked to insulin resistance. This study aimed to compare clinical, metabolic, and hormonal characteristics of PCOS women with and without insulin resistance. The second aim was to compare the clinico-biochemical profiles of the various PCOS phenotypes. In this cross-sectional secondary analysis, we combined the baseline data from two separate randomized controlled trials (RCTs) in women diagnosed with PCOS. PCOS patients were categorized into the four Rotterdam PCOS phenotypes according to the presence of at least two criteria of oligomenorrhea/anovulation (O), hyperandrogenism (H), and polycystic ovary morphology (P): O-H-P, H-P, O-H, and O-P. Participants were categorized into two groups according to the homeostasis model assessment index of insulin resistance (HOMA-IR) levels: < 3.46, and ≥ 3.46. The correlation between the HOMA-IR and biometric, clinical, and biochemical variables was assessed in normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) PCOS women. Then, the association between PCOS phenotypes and insulin resistance was investigated using logistic regression analysis. A total of 125 PCOS patients aged 18-40 years were included in the present study. Based on our results, the HOMA-IR index was positively correlated with diastolic blood pressure, free androgen index, and triglycerides levels; and negatively correlated with sex hormone-binding globulin in overweight/obese PCOS women. In addition, the HOMA-IR index was found to be positively correlated with alanine transaminase and negatively correlated with diastolic blood pressure in normal weight PCOS women. Moreover, individuals with O-H-P phenotype (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.02-6.24) had about two-fold increased risk of insulin resistance. In conclusion, the full-blown PCOS (O-H-P) phenotype has an increased risk of insulin resistance. Accordingly, phenotype division may help physicians to predict adverse metabolic outcomes.

Adoption of IWGDF guidance on prevention and management of foot problems in diabetes for local use in Iran by ADAPTE methodology: a step toward best practice.

Purpose: Adoption of international working group on the diabetic foot (IWGDF) guidance on prevention and management of foot problems in patients with diabetes was the study aim. Methods: The ADAPTE process consisted of three main phases of set-up, adoption, and finalization with overall 24 steps was used. In set- up phase, organizing committee by a multidisciplinary approach was established. In adoption phase, comprehensive search in databases and guideline resources was done. According to the inclusion criteria, the 2015IWGDF guidance was selected for adoption process. Quality, currency, content and consistency of the guidance were assessed. Also, consensus on different level of agreement for each recommendation were reported. On finalization phase, the adopted version was reviewed by the guidance developer and the final guidance for local use in Iran was disseminated. Results: The 2015 IWGDF guidance with 77 recommendations was adopted after screening of 1760 documents retrieved from Jan. 2006 to Nov. 2016. An organizing committee was established according to a multidisciplinary approach including 73 members with endocrinology, orthopedic & vascular surgery, dermatology, infectious diseases, physical medicine and rehabilitation specialties, general practitioners and nurses. This guidance obtained a good quality in all six domains of AGREE II instrument (Score ≥ 80%), good currency, content, and consistency. Also, during the third round of Delphi, the consensus on the agreement level of each recommendation were greater than 80% and 77 recommendations of the original guidance were kept in the adopted version. Conclusion: The 2015 IWGDF guidance with 77 recommendations adopted for local use in different health care settings of Iran. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01121-0.

Design, synthesis, and cytotoxic evaluation of quinazoline derivatives bearing triazole-acetamides.

A novel series of quinazoline-based agents bearing triazole-acetamides 8a-l were designed and synthesized. All the obtained compounds were tested for in vitro cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was 8a (X = 4-OCH3 and R = H) with IC50 values of 10.72 and 5.33 µM after 48 and 72 h compared with doxorubicin with IC50 values of 1.66 and 1.21 µM, respectively. The same trend was seen in the HepG2 cancerous cell line in which 8a recorded the best results with IC50 values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that 8f with IC50 = 21.29 µM (48 h) exhibited the best activity, while compounds 8k (IC50 = 11.32 µM) and 8a (IC50 = 12.96 µM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC50 values of 1.15 and 0.82 µM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.

Factors related to hypermetabolism in individuals with type 2 diabetes mellitus and non-alcoholic fatty liver disease.

Considering the progressive prevalence and co-occurrence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD), as well as the current evidence suggesting the elevated levels of basal metabolic rate (BMR) among these individuals, the present study aimed to identify factors determining hypermetabolism in such subjects. This cross sectional study was conducted in 30 to 53-year-old individuals with concurrent T2DM and NAFLD (controlled attenuation parameter score ≥ 260 dB/m). Resting energy expenditure (REE) was determined by an indirect calorimetry device. Hypermetabolism was defined as an elevated measured REE > 110% of the predicted REE. The multivariate logistic regression test was used for detecting factors associated with hypermetabolism. Between September, 2017, and March, 2018, a total of 95 eligible participants (64.40% male) with both T2DM and NAFLD were included, while 32.63% of them were classified as hypermetabolic. Overall, the mean recruitment age ± standard deviation and median (interquartile range) body mass index were 44.69 ± 5.47 years and 30.20 (27.80-33.30) kg/m2, respectively. Demographic, anthropometric and biochemical variables did not vary significantly across two groups except for total body water, low-density lipoprotein cholesterol and dipeptidyl peptidase 4 (DPP-4) inhibitors (p < 0.05). According to the results of multivariable logistic regression analyses, hypermetabolism had a positive association with adiponectin (odds ratio [OR] 1.167, 95% confidence interval [CI] 1.015-1.342, p = 0.030), physical activity (OR 1.134, 95% CI 1.002-1.284, p = 0.046), alanine transaminase (OR 1.062, 95% CI 1.006-1.122, p = 0.031) and diastolic blood pressure (OR 1.067, 95% CI 1.010-1.127, p = 0.021). However, fat free mass was inversely related to hypermetabolism (OR 0.935, 95% CI 0.883-0.991, p = 0.023). Adiponectin, alanine transaminase, physical activity, diastolic blood pressure and fat free mass were independently associated with hypermetabolism in subjects with NAFLD and T2DM.

Ovarian volume, not follicle count, is independently associated with androgens in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is diagnosed based on chronic anovulation, androgen excess (clinical and/or biochemical), and polycystic ovaries in ultrasound. The aim of the present study was to evaluate which parameters in the transvaginal ultrasound (TVUS) of ovaries could be better associated with concurrent hormonal imbalance in the women with PCOS. METHODS: Using a cross-sectional design, this study focused on 61 subjects (18-40 years) with PCOS. Patients were recruited at three academic hospitals during the 2017-2019 period. PCOS was defined according to the Rotterdam criteria. The association of ovarian morphology with hormonal and metabolic feature was investigated using linear regression models, adjusted for a set of possible confounding variables including age, mensuration status and body mass index (BMI). RESULTS: The mean volume of both ovaries was positively associated with the total testosterone level (ß = 0.025, P value < 0.001), free androgen index (ß = 0.041, P value < 0.001) and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (ß = 0.032, P value = 0.004), even after adjustments made for age, mensuration status and BMI (fully-adjusted model). In contrast, in the fully-adjusted model, antral follicle count (AFC), follicle number per ovary (FNPO), ovarian area, stromal area, and ratio of stromal area to ovarian area (S/A) were not associated with androgen levels and LH/FSH ratio. In addition, after full adjustments, ovarian volume, AFC, FNPO, ovarian area, stromal area and S/A were not associated with insulin resistance, which was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSION: Increased ovarian volume is, thus, highly predictive of hyperandrogenemia and high LH/FSH ratio in PCOS patients.

Medical management of pancreatic neuroendocrine tumors in patients with MEN 1: case report.

Objectives: Multiple endocrine neoplasia type 1 (MEN-1) is a rare inherited autosomal dominant disease which manifests itself with at least one clinical scenario before 45 years of age. The value of somatostatin analogue therapy is unknown in the treatment of non-functioning pancreatic tumours and a few studies have been published in this field. Case presentation: We report a young patient with MEN-1 with multiple gastric and pancreatic neuroendocrine tumors that was treated with the monthly injection of Sandostatin LAR before and After Distal Pancreatectomy and partial gastrectomy. Conclusions: Now she is well after four years of treatment with Sandostatin LAR.

Diabetic foot workshop: A strategy for improving the knowledge of diabetic foot care providers.

BACKGROUND AND AIMS: Prevention and management of diabetic foot ulcer have essential effects on the quality of life of patients. Accordingly training the care providers can play an essential role in reducing complications foot ulcers and lead to an increase in the effectiveness and efficiency of patient health cares. We conducted a study to survey the impact of the diabetic foot workshop on the knowledge of nurses and physicians about diagnosis and managing diabetic foot. METHODS: The present study is a quasi-experimental which compare the knowledge of non-randomized group of nurses and physicians about diabetic foot care. The leaning objectives, agenda, contents and evaluation methods of the diabetic foot care workshop was designed by a multidisciplinary team members in form of 2 days workshop. Each topic of the workshop presented theoretically and practically using educational cases and real patient with diabetic foot ulcer. A valid and reliable questionnaire with 20 Multiple Choice Questions used for the evaluation of workshopin form of the pretest and posttest. RESULTS: In this study, 396 registered nurses and physicians participates in the diabetic foot workshop series. The results of this study showed that this increase in the level of knowledge was meaningful after the educational intervention since the mean of the posttest score increased more than 20% comparing with pretest. CONCLUSION: The promotion of knowledge of health care providers as shown in the study may almost be due to training by real patient, team-working, and using educational movies for the education of diabetic foot diagnosis, management and rehabilitation.

Psychotic Disorder as the First Manifestation of Addison Disease: A Case Report.

Introduction: Addison disease is a relatively uncommon endocrine disease resulting from adrenal insufficiency. Psychiatric symptoms are among its rare primary and particularly isolated clinical symptoms. This report presents a case with adrenal insufficiency manifested by the psychotic syndrome. Case Presentation: A 28-year-old Iranian female with a history of immune thrombocytopenic purpura (ITP) and asthma since childhood presented with a 13-month history of progressive depression with insomnia and nightmare symptoms. After being prescribed haloperidol, clomipramine, and clonazepam for eight months, abdominal pain and weight loss due to anorexia started. Her physical examination showed skin hyperpigmentation in the elbow, knee, ankle, and buccal mucosa. Physical examination and initial laboratory tests suggested adrenal insufficiency. Addison disease was confirmed according to the laboratory tests and abdominal CT. The symptoms were significantly improved using intravenous hydrocortisone treatment. The patient remained calm and had a normal sleep without depressive symptoms or psychosis after 72 hours of treatment. During one year of follow-up, the patient was in good general condition without psychological symptoms. Conclusions: This report shows that psychotic disorder can be the first manifestation of Addison disease. Therefore, physicians should be informed about the neuropsychiatric symptoms of adrenal insufficiency, especially when the patient lacks a family or personal history of psychiatric illness.

Diabetic Foot scientific activities in Endocrinology and Metabolism Research Institute.

INTRODUCTION: Diabetic Foot (DF) as a common complication of Diabetes should be intensive intervention for prevention, management and rehabilitation. In this regard, Diabetes Research Center of Endocrinology and Metabolism Research Institute (EMRI) of Tehran University of Medical Sciences (TUMS) considered DF as a priority research area to investigate multidimensional aspects of DF care. We are intended to summarize DF research studies affiliated to the EMRI for over the last two decades. METHODS: Three Electronic databases including Web of Science, PubMed, and Scopus were searched until January 2020 to find articles about DF published affiliated to EMRI. The main concepts of search strategies were "diabetes", "Foot". 115 documents retrieved from these databases which screened for inclusion and exclusion criteria. The visualization of the network of co-authorship of authors and co-occurrence of keywords was illustrated and documents were analyzed for content according to the Main areas of DF Research studies. RESULT: 64 related documents including original articles, reviews, letters, notes, and book chapter have included to this study. According to the objectives of the retrieved studies, DF documents and research studies categorized in the two main groups including DF prevention, classification and risk stratification in addition management of DF. CONCLUSION: Despite conducted research and educational activities in DF prevention and management, the following topics would be considered as well: effective offloading treatment, correcting the nutritional status for improving wound healing and novel educational strategies for diabetic foot multi-disciplinary team.

RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant.

BACKGROUND: The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14-16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed. RESULTS: Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients. CONCLUSION: RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.

Effect of resveratrol administration on ovarian morphology, determined by transvaginal ultrasound for the women with polycystic ovary syndrome (PCOS).

Intake of resveratrol has been associated with improved ovarian morphology under in vitro and in the animal models; however, this finding has not been confirmed in trials. The aim of our study was, therefore, to use a placebo-controlled approach with the detailed assessment of the ovarian morphology by applying transvaginal ultrasound to examine the effectiveness of this therapeutic approach in this group of women. The mean age of all participants was 28·61 (sd 4·99) years, with the mean BMI of 28·26 (sd 5·62) kg/m2. Resveratrol therapy, as compared with placebo, was associated with a significantly higher rate of improvement in the ovarian morphology (P = 0·02). Women who received resveratrol had a more dominant follicle than those getting placebo, with a significant reduction in the ovarian volume (P < 0·05). However, the number of follicle count per ovary (FNPO), stromal area (SA), ovarian echogenicity and distribution of follicles were not significantly altered (P > 0·05). Forty-one women with polycystic ovary syndrome (PCOS) were randomly assigned (1:1) to 3 months of daily 1000 mg resveratrol or placebo. Random assignment was done by blocked randomisation. Our primary endpoints were the change in the ovarian volume, SA and antral FNPO from the baseline to 3 months. Secondary endpoints were improvement in the distribution of follicles and ovarian echogenicity. Differences between the resveratrol and control groups were evaluated by Chi-square, Fisher's exact test and repeated-measures ANOVA. Treatment with resveratrol significantly reduced the ovarian volume and polycystic ovarian morphology, thus suggesting a disease-modifying effect in PCOS.

Effects of supplementation with main coffee components including caffeine and/or chlorogenic acid on hepatic, metabolic, and inflammatory indices in patients with non-alcoholic fatty liver disease and type 2 diabetes: a randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is much more frequent and more severe, including cirrhosis, hepatocellular carcinoma in patients with type 2 diabetes. Coffee is a complex beverage with hundreds of compounds whereas caffeine and chlorogenic acid are the most abundant bioactive compounds. The published epidemiological data demonstrating beneficial associations between all categories of coffee exposure and ranges of liver outcomes are rapidly growing; however, the main contributors and cause-effect relationships have not yet been elucidated. To address existing knowledge gaps, we sought to determine the efficacy and safety of 6 months chlorogenic acid and/or caffeine supplementation in patients with type 2 diabetes affected by NAFLD. METHODS: This trial was carried out at two Diabetes Centers to assess the effects of supplementation with daily doses of 200 mg chlorogenic acid, 200 mg caffeine, 200 mg chlorogenic acid plus 200 mg caffeine or placebo (starch) in patients with type 2 diabetes and NAFLD. The primary endpoint was reduction of hepatic fat and stiffness measured by FibroScan, and changes in serum hepatic enzymes and cytokeratin - 18 (CK-18) levels. Secondary endpoints were improvements in metabolic (including fasting glucose, homeostasis model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HBA1C), C-peptide, insulin and lipid profiles) and inflammatory (including nuclear factor k-B (NF-KB), tumor necrosis factor (TNF-α), high sensitive- C reactive protein(hs-CRP)) parameters from baseline to the end of treatment. RESULTS: Neither chlorogenic acid nor caffeine was superior to placebo in attenuation of the hepatic fat and stiffness and other hepatic outcomes in patients with diabetes and NAFLD. Except for the lower level of total cholesterol in caffeine group (p = 0.04), and higher level of insulin in chlorogenic acid plus caffeine group (p = 0.01) compared with placebo, there were no significant differences among the treatment groups. CONCLUSION: These findings do not recommend caffeine and/or chlorogenic acid to treat NAFLD in type 2 diabetes patients. TRIAL REGISTRATION: IRCT201707024010N21 . Registered 14 September 2017.

Effect of resveratrol on menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS.

AIM: The aim of this randomized trial was to find whether resveratrol could improve menstrual dysfunction, clinical signs (i.e., acne and hair loss), and the biochemical evidence of hyperandrogenism in the women with PCOS. METHODS: Women, in the age range of 18-40 years, diagnosed with PCOS, as defined by the Rotterdam criteria, and no other known cause of abnormal menstruation, were recruited. Participants were randomized based on a 1:1 ratio, to either 1000 mg resveratrol or 1000 mg placebo daily groups, for a period of 3 months. RESULTS: Seventy-eight patients were randomized: 39 to the resveratrol group and 39 to placebo. Results were analyzed according to the intention-to-treat principle. At the end of study, it was found that women who received resveratrol had a statistically higher regular menstruation rate, as compared to those who got placebo (76.47% vs. 51.61%; p = 0.03), and lower hair loss (32.10% vs. 68.00%; p = 0.009). We also found no significant differences between the two groups in terms of ovarian and adrenal androgens, sex hormone binding globulin (SHBG) levels, free androgen index (FAI), glycoinsulinemic metabolism and lipid profile. Moreover, the resveratrol treatment did not interfere with the thyroid, liver and kidney functions. The negative effect of resveratrol on the body composition was also observed, though not influencing changes in the weight, relative to the placebo group. CONCLUSION: Resveratrol improved menstrual cyclicity and hair loss, even though levels of androgens, insulin and lipids remained unchanged.