The hypoglycemic effects of Juglans regia L. internal septum in type 2 diabetic patients: A double-blind, randomized, placebo-controlled clinical trial.

Introduction: The internal septum of J.regia is traditionally used to control diabetes, and its effectiveness has been shown in animal studies. Accordingly, human clinical trials are needed to confirm its effectiveness on hemoglobin A1c (HbA1c), fasting blood sugar (FBS), blood insulin level, and insulin resistance as a complementary for better control of type 2 diabetes. Methods: This study was a randomized, double-blinded, controlled trial. The lyophilized powder of extract of the internal septum of J.regia was used to fill the capsules. Sixty type 2 diabetic patients were randomly divided into two groups. 500 mg capsules three times daily before meal was added to their routine drug regimen, and HbA1c, FBS, and blood insulin level were checked at the baseline and after three months. Results: Sixty patients completed the study. The mean(±SD) age of patients was 49.1(10.2) and 50.9(12.7) years in the placebo and J.regia groups, respectively. We observed that J.regia internal septum increases the level of HbA1c by about 0.02 units, but this effect was not significant (MD=0.02,95%CI=-0.36 to 0.40, P=0.93). Regarding the impact of capsules on insulin level, it seems that J.regia-containing capsules can raise insulin level by one unit. However, it was not significant (MD=1.01,95%CI=-0.86 to 2.88, P=0.28). As for FBS, it can cause a decrease of four units, but this effect is also not significant (MD=-3.98,95%CI=-18.33 to 10.37, P=0.58). Conclusion: Based on our study, the internal septum of J.regia has no significant effect on HbA1c, FBS, and insulin resistance. Moreover, no specific adverse reaction was observed in any of the patients.

The approach of Iranian clinical pharmacists in the treatment of dyslipidemia based on international guidelines.

Introduction: Optimal treatment of dyslipidemia is a top priority in the prevention of cardiovascular diseases. For this purpose, clinicians in Iran usually refer to four current international guidelines. The aim of this study was to assess the approach of Iranian clinical pharmacists in the treatment of dyslipidemia based on international guidelines. Methods: A structured questionnaire was prepared. Questions (n=24) included the demographics (n=7), dyslipidemia references (n=3), dyslipidemia general knowledge of respondents (n=10), and questions (n=4) designed based on the difference among the latest version of guidelines participants stated they use in their practice. After validity conformation, the questionnaire was distributed to 120 clinical pharmacists, electronically from May to August 2021. Results: Response rate was 77.5% (n=93). The majority of participants (80.6%, n=75) claimed to have used the 2018 ACC/AHA guideline. The Median (interquartile range [IQR]) score of the general knowledge questions was 5.0 (2.0) out of 10. The Median (IQR) score of questions designed based on the difference among guidelines was calculated 3(1) out of 4. There was no significant (P=0.25) difference in score among participants according to their guideline selection. Moreover, the gender and length of experience as a clinical pharmacist had no significant (P>0.05) effect on the score of participants. Conclusion: In this study, Iranian clinical pharmacists answered half of the dyslipidemia general knowledge questions correctly. Also, Participants were up-to-date on 75% of the questions designed based on the latest version of the guideline they had been using in their practice.

Evaluation of important human CYP450 isoforms and P-glycoprotein phenotype changes and genotype in type 2 diabetic patients, before and after intensifying treatment regimen using Geneva cocktail.

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ± 0.93 versus 2.68 ± 0.87), CYP2C19 (0.420 ± 0.360 versus 0.687 ± 0.558) and CYP3A4/5 (0.487 ± 0.226 versus 0.633 ± 0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ± 0.037 versus 0.069 ± 0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ± 0.085 versus 0.136 ± 0.065), CYP2D6 (1.17 ± 0.56 versus 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL-1ß and IL-6), genotypes, diabetes and demographic-related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.

Preventive effect of probiotics supplementation on occurrence of gestational diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

Background: Gestational diabetes mellitus (GDM) is a health challenge during pregnancy and is associated with adverse effects. Dysbiosis of the gut microbiota may play a role in developing inflammation and insulin resistance observed in GDM. Probiotics are supposed to be influential in preventing GDM since they can alter the composition of microbiota in the intestine. Despite the existing studies on the therapeutic effects of probiotics in women with GDM, in this study we aim to systematically review and meta-analyze the results of randomized control trials (RCTs) on the beneficial effects of probiotics supplements on the prevention of GDM in healthy pregnant women. Methods: Web of science, Scopus and PubMed databases were searched via a precise strategy to gather RCTs related to our study. Duplication removal, screening and data extraction were conducted by two researchers, independently. Quality assessment of eligible studies was conducted by Cochrane risk of bias tool. Meta-analysis was conducted using the random effects model due to substantial heterogeneity among studies. Results: Ten articles met our eligibility criteria from our initial search of 451 articles. Two thousand nine hundred and twenty-one participants without previously diagnosed glucose disturbance were included in our analysis. Probiotics reduced GDM incidence by 33% (RR = 0.67, 95% CI: 0.47, 0.95), while greater effect was detected in trials using multiple-strains probiotics (RR = 0.65, 95% CI: 0.42, 0.99). We did not detect any significant benefits or harms related to probiotics supplements on secondary outcomes including GDM related infantile and maternal complications including preeclampsia, caesarian section, mothers' weight gain during pregnancy, prematurity, macrosomia, hypoglycemia, NICU admission, and birth weight. Conclusion: Probiotics supplementation may reduce the incidence of GDM and help control glucose parameters in pregnant women. Further studies are warranted regarding the GDM-related maternal and infantile complications. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022315550, identifier: CRD42022315550.

Microbiome alterations in women with gestational diabetes mellitus and their offspring: A systematic review.

Aims: Gestational diabetes mellitus (GDM) is a metabolic disorder that might predispose pregnant women to develop type 2 Diabetes Mellitus or lead to severe adverse outcomes in their offspring. One of the factors that have been thought to be involved in the pathology behind this disorder is the microbiome. In this systematic review, we comprehensively review the documents regarding the microbiota alterations in different tracts of pregnant women with GDM and their offspring. Methods: A comprehensive search was conducted in major databases including MEDLINE (PubMed), Scopus, and Web of sciences up to August 2021. Data on the demographics, methodology, and microbiome alterations were extracted and classified according to the type of microbiome in pregnant women with GDM and their offspring. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: In 49 articles which were retrieved, the findings were variable on the level of changes in alpha and beta diversity, enrichment or depletion in phyla, genera, species and OTUs, in each microbiome type. Although there were some inconsistencies among the results, a pattern of significant alterations was seen in the gut, oral, vaginal microbiome of women with GDM and gut, oral, and placental microbiome of their offspring. Conclusion: Even though the alteration of the microbiome of the different tracts was seen in the cases of GDM, the inconsistency among the studies prevents us from identifying unique pattern. However, the results seem promising and further studies that overcome the confounding factors related to the demographics and methodology are needed.

Serum Prooxidant-Antioxidant Balance and hs-CRP in Patients with Clinical and Subclinical Hypothyroidism.

Background: Oxidative stress (OS) is caused by an imbalance between prooxidant substance production and antioxidant defense. OS is involved in physiologic interactions in the body and the pathogenesis of various disorders. This study aimed to evaluate serum prooxidant-antioxidant balance (PAB) as a selective prooxidant, antioxidant defense, and acute phase reactant protein in patients with subclinical and clinical hypothyroidism. Methods: This case-control study was conducted in three groups including clinical hypothyroidism (32 patients), subclinical hypothyroidism, (42 cases), and healthy controls (32 individuals). This study was performed in the Endocrine Clinic of Arash Training and Research Hospital, Tehran, 2017. In the study groups, thyroid hormones including T4 and Thyroid Stimulating Hormone (TSH), fasting blood glucose (FBG), lipid profile, PAB, and hs-CRP as inflammatory markers were measured and compared between the groups. Results: Among 106 participants, 95.3% were females, the gender balance was similar across groups and mean age was 30.79 ± 7.65 years. FBG and lipid profile except for cholesterol level were not significantly different between the three study groups. However, cholesterol level in the clinical hypothyroid group was significantly higher than the other two groups. PAB was higher in subclinical hypothyroidism compared to healthy controls after adjustment for age and TSH levels (P value: 0.04) but there was no significant difference in the clinical hypothyroid group in comparison with healthy controls. In addition, there was no significant difference in high-sensitivity C-reactive protein (hs-CRP) between the three study groups. Conclusions: This study suggests that that subclinical hypothyroidism increases PAB in comparison to healthy control which could indicate OS response in patients with subclinical hypothyroidism, respectively.

The association between advanced glycation end products (AGEs) and ABC (hemoglobin A1C, blood pressure, and low-density lipoprotein cholesterol) control parameters among patients with type 2 diabetes mellitus.

BACKGROUND: Diabetes-induced chronic hyperglycemia results in the formation and aggregation of advanced glycation end-products (AGEs), which are products of non-enzymatic glycosylation of lipids or proteins. The development of diabetic complications can be accelerated by AGEs. In the current study, we aimed to explore the relationship between AGEs levels and ABC goals of diabetes control (A: Hemoglobin A1C < 7.0%, B: Blood pressure < 140/90 mmHg, and C: low-density lipoprotein cholesterol [LDL] < 100 mg/dL). METHODS: In the current cross-sectional study, 293 patients with type 2 diabetes mellitus (T2D), were enrolled. Demographic and clinical characteristics of the individuals were collected. AGEs levels were measured using quantitative fluorescence spectroscopy. Finally, the association of AGEs levels with patients' characteristics and ABC goals was assessed. RESULTS: Higher serum AGEs concentration was detected in older age, smoking patients and those with higher diastolic blood pressure, lower high-density lipoprotein (HDL) level, lower body mass index (BMI) and retinopathy. Moreover, the T2D patients who achieved higher numbers of ABC goals of diabetes were younger age (P-value = 0.003), with lower hemoglobin A1C (P-value = 0.001), fasting blood sugar (P-value = 0.002) diastolic blood pressure (P-value = 0.001), systolic blood pressure (P-value = 0.001), cholesterol (P-value = 0.001), LDL (P-value = 0.001), and AGEs (P-value = 0.023) levels. Diabetic patients with AGEs levels above 73.9% were about 2.2 times more likely to achieve none of ABC treatment goals (95% CI 1.107-3.616). CONCLUSION: Our results revealed the relationship between AGEs and ABC goal achievement, and microvascular diabetic complications, and imply that AGEs measurement may be valuable in the monitoring of diabetic patients' complications and treatment adjustment.

Diabetes-related distress and its association with the complications of diabetes in Iran.

Purpose: Diabetes-related distress (DRD) has negative emotional effects on the patients' quality of life. This is while the condition often goes undiagnosed despite it being common among diabetic patients. This study investigated the prevalence of DRD and its association with diabetes complications among a group of Iranian type 2 diabetic patients (T2DM). Methods: This descriptive-analytical cross-sectional study was conducted on 186 T2DM patients referred to a diabetes clinic in a teaching hospital from the beginning of May 2019 to the end of April 2020. Two questionnaires on disease-related information and diabetes distress screening scale (DDS) were filled out for each patient. The latter was divided into four domains, emotional burden (EB), diabetes-related interpersonal distress (ID), physician-related distress (PD), and regimen-related distress (RD). In addition to the frequency of DRD and its association with age, sex, body mass index (BMI), hypertension, hemoglobin A1C, duration of disease, and type of medication regimen (oral, insulin, or mix) along with the history of cardiovascular disease (CVDs), retinopathy, nephropathy, and diabetic foot were assessed. Results: DRD was reported in 47% of the patients. Being female, old age, hypertension, high hemoglobin A1C levels, nephropathy, and retinopathy were significantly associated with DRD (P-value = < 0.001, 0.013, 0.014, 0.007, 0.001, and 0.004, respectively). The history of the diabetic foot had a significant relationship with PD and ID (P-value = 0.007 and < 0.001, respectively). Multivariate regression showed gender and the existence of complications to have a direct effect on the development of DRD. Conclusion: DRD prevalence is relatively high and requires screening to identify and treat high-risk patients. Further studies are needed to study diabetes, its complications and their relation with DRD to help reduce such conditions and improve the patient's quality of life.

Aspirin versus placebo on estrogen levels in postmenopausal women: a double-blind randomized controlled clinical trial.

BACKGROUND: Estrogen is involved in the pathogenesis of breast and gynecological cancers. Regular use of aspirin reduces estrogen levels. The present study aimed to evaluate the effect of aspirin on estrogen levels in postmenopausal women. METHODS: This double-blind, placebo-controlled parallel-group trial was conducted on postmenopausal women referred to an outpatient clinic at a women's hospital in Tehran. Volunteers were randomly assigned to receive aspirin 100 mg/day or placebo for 6 weeks. Estradiol, sex hormone-binding globulin (SHBG), and testosterone levels at baseline and at the end of the intervention were measured by ELISA. Data were analyzed using SPSS 20, Kolmogorov-Smirnov test, independent samples t-test, and Mann-Whitney U test. RESULTS: Twenty-seven and 28 participants were finally analyzed in the aspirin and placebo groups, respectively. There was no significant difference between the two groups in body mass index (BMI), age, or menopausal years. There was a statistically significant difference (p = 0.002) in the amount of  change in estradiol levels of the intervention group (median=- 3.5 pg/ml) compared to the control group (median=1.5 pg/ml). In contrast, there were no significant differences between the two groups regarding testosterone and SHBG levels (p = 0.58, p = 0.32). CONCLUSIONS: Since low doses of aspirin may decrease estradiol levels, it could be considered a promising adjunctive therapeutic candidate in postmenopausal women to decrease BC incidence. However, further studies with larger sample sizes, measurements of estrogen levels and its related compounds in different time points accompanied by long-term follow-ups are needed to better elucidate the potential mechanisms by which nonsteroidal anti-inflammatory drugs (NSAIDs) negatively affect breast cancer. TRIAL REGISTRATION: IRCT201012195397N1. Date of first registration: 03/01/2011.

Effect of daily consumption of probiotic yoghurt on albumin to creatinine ratio, eGFR and metabolic parameters in patients with type 2 diabetes with microalbuminuria: study protocol for a randomised controlled clinical trial.

INTRODUCTION: To alleviate clinical symptoms of diabetic nephropathy (DN), several dietary and non-dietary strategies have been suggested. Probiotic-enriched foods, through their effects on modulating microflora, might help these patients control the adverse effects. The current study will be done to examine the effects of probiotic yoghurt consumption on albumin to creatinine ratio, estimated glomerular filtration rate (eGFR) and metabolic parameters in patients with type 2 diabetes with nephropathy. METHODS AND ANALYSIS: Sixty patients with DN will be recruited in this study. After block matching for sex, body mass index and age, patients will be randomly assigned to receive 300 g/day probiotic yoghurt containing 106 CFU/g Lactobacillus acidophilus and Bifidobacterium lactis strains or 300 g/day plain yoghurt daily for 8 weeks. Weight, height and waist circumference will be measured at study baseline and after the intervention. Biochemical indicators including glycaemic measures (haemoglobin A1c (HbA1c), fasting blood sugar (FBS)), inflammatory markers (high sensitivity-C reactive protein), lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL)) and finally renal makers (creatinine, albumin to creatinine ratio, eGFR) will be assessed at study baseline and at the end of the trial. DISCUSSION: Improving the condition of a person with DN is a serious clinical challenge. The use of probiotic supplements has been considered in these people, but the use of probiotic-enriched foods has received less attention. TRIAL REGISTRATION NUMBER: Iranian Registry of Clinical Trials (www.irct.ir) (IRCT20201125049491N1).

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.

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.

Pretreatment serum GH levels and cardio-metabolic comorbidities in acromegaly; analysis of data from Iran Pituitary Tumor Registry.

BACKGROUND: Acromegaly is a rare chronic disabling disorder, in which growth hormone (GH) excess is associated with a range of clinical features and systemic complications. The present study aims to evaluate the association between pretreatment basal GH levels as well as GH levels after oral glucose tolerance test (OGTT) and cardio-metabolic comorbidities, including diabetes mellitus (DM), left ventricular hypertrophy (LVH) and hypertension (HTN) in patients with active acromegaly. METHODS: A retrospective study of the medical records regarding 113 patients with acromegaly registered at two main centers of Iran Pituitary Tumor Registry during 2011-2018. RESULTS: The mean age of the patients was 42.76 ± 11.6 (range: 21-72) years. Mean GH level at baseline was 21 ng/ml while nadir GH levels at 60 and 120 min after glucose were 6.95 and 9.05 ng/ml, respectively. There was a negative correlation between age and basal serum GH level (r= -0.196, p = 0.038). Hypertension and diabetes mellitus were detected in 26.8% and 19.7% of the patients. A positive correlation was detected between serum GH values and systolic blood pressure. There was not any significant difference in basal GH and GH post OGTT regarding DM, Diastolic blood pressure and LVH. CONCLUSIONS: Our findings suggest that pretreatment basal GH levels are higher in younger patients with acromegaly. Furthermore, higher GH values (0, 60 and 120 min) during OGTT are associated with higher systolic blood pressure. A comprehensive evaluation of this population regarding comorbidities should be performed.

Evaluating the effect of type 2 diabetes mellitus on CYP450 enzymes and P-gp activities, before and after glycemic control: A protocol for a case-control pharmacokinetic study.

Cytochrome P450s (CYP450) family is one of the most critical factors in the metabolism process. Hence, the present study aims to characterize the activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, and P-glycoprotein (P-gp) pump in patients with type 2 diabetes (T2DM). This characterization was performed before and after good glycemic control versus non-diabetic subjects following the administration of a substrate probe drug cocktail. This single-center clinical study proposes the characterization of T2DM impacts on major CYP450 drug-metabolizing enzyme and P-glycoprotein (P-gp) activities. The main propose of the present study is evaluating any alternation in major CYP450 enzymes and P-gp activities in patients with T2DM, before (A1C>7%) and after (A1C≤7%) good glycemic control along with comparing the activities versus non-diabetic subjects. The phenotypes will be assessed following the oral administration of a drug cocktail containing caffeine (CYP1A2), bupropion (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A4/5), and fexofenadine (P-gp) as probe substrates. Furthermore, the influence of variables such as glycemia, genetic polymorphisms, and inflammation on the metabolism process will be evaluated. The first patient has entered the study in Dec 2018.

The effect of synbiotics supplementation on anthropometric indicators and lipid profiles in women with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Different therapies have been suggested for polycystic ovary syndrome (PCOS), but changes in lifestyle and diet have been considered. Diet and dietary factors can be very effective in modifying the disease. The positive effects of probiotic and synbiotics supplementation on improving lipid profiles and anthropometric indices have been examined in various diseases. This study was conducted to evaluate the effects of synbiotics supplementation on lipid and anthropometric profiles in infertile women with PCOS. METHODS: PCOS patients aged 19-37 years old were randomized to receive either synbiotics supplement (n = 50) or placebo (n = 49) for 12 weeks. RESULTS: Consumption of synbiotics compared to the placebo, resulted in a significant decrease in Low-density lipoprotein cholesterol (LDL) value (Change Mean Difference (CMD): 4.66, 95%CI: 0.20, 9.13) and a significant increase in high-density lipoprotein cholesterol (HDL) (CMD: 1.80, 95%CI: 0.34, 3.26). Although we failed to find a significant effect of synbiotics consumption on total cholesterol (TC) and triglyceride (TG) levels. We did not find differences in anthropometric indices between groups. CONCLUSIONS: Overall, 12 weeks of synbiotics supplementation among PCOS women resulted in beneficial effects on LDL and HDL, although it is not yet clear how much our findings are clinically significant and more clinical studies with larger sample sizes are still needed. TRIAL REGISTRATION: Iranian Registry of clinical Trial, IRCT.ir, ID: IRCT2014110515536N2. Registered on 19 December 2015.

The Effect of Oligopin Supplementation on Hormonal and Metabolic Profiles in the Polycystic Ovary Syndrome: A Randomized Controlled Trial.

Background: A double blind clinical trial was performed to evaluate whether the polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in the women with PCOS during the three-month administration of oligopin. Methods: In this double-blind multicenter trial, we randomly assigned 80 PCOS women, based on a 1:1 ratio, to receive oligopin (n= 40) or maltodextrin as placebo (n = 40) for up to 3 months. As PCOS-specific outcomes, we investigated the changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from the baseline to the end of treatment. We investigated serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. Results: The first participant was enrolled on April 18, 2018, and the last study visit took place on May 14, 2019. PCOS-specific serum parameters did not change during the three-month administration of oligopin (p > 0.05), except for a small increase in the FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels was significantly increased in placebo group, as compared with oligopin (p=0.01). Conclusion: Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in the women with PCOS. Clinical Trial Registration: www.irct.ir, identifier IRCT20140406017139N3.

Our Little Friends with Big Roles: Alterations of the Gut Microbiota in Thyroid Disorders.

BACKGROUND: The thyroid gland influences the metabolic processes in our body by producing thyroid hormones, and thyroid disorders can range from a harmless goiter to life-threatening cancer. A growing number of evidence support the link between gut microbiota composition and thyroid homeostasis. Gut dysbiosis can disrupt the normal gut barrier function, leading to immunologic and metabolic disorders. OBJECTIVE: The aim of this review was to discuss the main features of gut dysbiosis associated with different thyroid disorders. RESULTS: Gut microbiota contributes to thyroid hormone synthesis and hydrolysis of thyroid hormones conjugates. It has been shown that microbial metabolites may play a role in autoimmune thyroid diseases via modulating the immune system. Intestinal microbiota can contribute to the thyroid malignancies via controlling DNA damage and apoptosis and influencing inflammatory reactions by the microbiota- derived metabolites. However, the pathogenic role of altered gut microbiota in different thyroid disorders has not yet fully elucidated. CONCLUSION: Further research is needed to assess the role of alterations of the gut microbiota in disease onset and development in order to achieve novel strategies for the prevention and treatment of these diseases.

Diabetes mellitus and cancer incidence: the Atherosclerosis Risk in Communities (ARIC) cohort study.

PURPOSE: To assess the association between diabetes mellitus (DM) and the incidence of cancer at different sites. METHODS: Data from the baseline and first three follow-up visits of the Atherosclerosis Risk in Communities (ARIC) study, an ongoing cohort study of adults from four American communities, were used in this study. Of 15,792 persons aged 45-64 years old who participated in the baseline visit, the data of 15,118 participants were available for this study. For each cancer site, a conditional stratified Poisson regression model was fitted to estimate the adjusted relative rate and 95% confidence interval (adj. RR, 95% CI) of its incidence in diabetics compared to non-diabetics. RESULTS: We excluded 850 participants with a history of cancer at baseline and 149 participants who developed cancer during 2 years after enrollment, leaving a total of 14,119 participants of whom 1721 were diabetics. Independent of age, body mass index, alcohol consumption, and physical activity, DM decreased the risk of all cancers combined (adj. RR: 0.77, 95% CI: 0.60, 0.98) and the risk of prostate cancer (adj. RR: 0.51, 95% CI: 0.27, 0.97) and increased the risk of colorectal cancer in non-menopausal women (adj. RR: 12.08, 95% CI: 2.06, 70.94). CONCLUSIONS: In conclusion, DM may be associated with an increased risk of colorectal cancer in non-menopausal women and a decreased risk of prostate cancer and all cancers combined.

Effects of synbiotic supplementation on metabolic parameters and apelin in women with polycystic ovary syndrome: a randomised double-blind placebo-controlled trial.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women of reproductive age. Insulin resistance is a main pathophysiologic feature in these patients. According to some studies, the intake of probiotic bacteria may improve glucose homoeostasis. The aim of this study was to investigate the effect of synbiotics on metabolic parameters and apelin in PCOS patients. This randomised double-blind placebo-controlled trial was conducted on eighty-eight PCOS women aged 19-37 years old. The participants were randomly assigned to two groups receiving (1) synbiotic supplement (n 44), and (2) placebo (n 44) for 12 weeks. Fasting blood samples were taken at baseline and after 12 weeks. The two groups showed no difference in fasting blood sugar (adjusted mean difference: 0·60; 95 % CI -3·80, 5·00, P=0·727), plasma glucose fasting 2-h (adjusted mean difference 2·09; 95 % CI -9·96, 14·15, P=0·134), HbA1c (adjusted mean difference 0·06; 95 % CI -0·09, 0·22, P=0·959), homoeostatic model assessment-insulin resistance (HOMA-IR) (adjusted mean difference: 0·02; 95 % CI -0·99, 1·03, P=0·837), quantitative insulin sensitivity check index (QUICKI) (adjusted mean difference: -0·02; 95 % CI -0·33, 0·29, P=0·940) and C-reactive protein (CRP) (adjusted mean difference: 0·24; 95 % CI -1·61, 2·08, P=0·141) by the end of the intervention. A significant difference was observed in the mean apelin 36 before and after the intervention between synbiotic and placebo groups (adjusted mean difference: -4·05; 95 % CI -7·15, -0·96, P=0·004). A 12-week synbiotic supplementation has no significant beneficial effects on HOMA-IR and CRP in PCOS patients, whereas the level of apelin 36 significantly decreased.