The effect of saffron (Crocus sativus L.) on glycemia, lipid profile, and antioxidant status in patients with type-2 diabetes mellitus: A randomized placebo-controlled trial.

In the current study, we aimed to investigate the effect of saffron supplementation on glycemic status, lipid profile, atherogenic indices, and oxidative status in patients with type-2 diabetes (T2DM). In a randomized, double-blind controlled trial, 70 patients were randomly allocated into two groups (n = 35, each) and received 100 mg/day of saffron or placebo for eight weeks. Dietary intake, weight, body mass index (BMI), waist and hip circumferences (WC and HC), waist to hip ratio (WHR), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, and Homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile, atherogenic indices, oxidative status, and liver enzymes were determined before and after the intervention. At the end of the eighth week, saffron intervention could significantly reduce FBS (7.57%), lipid profile (except high-density lipoprotein cholesterol [HDL-C]), atherogenic indices, and liver enzymes (p < .05). Moreover, saffron could improve oxidative status (nitric oxide [NO] and malondialdehyde [MDA] reduced by 26.29% and 16.35%, respectively). Catalase (CAT) concentration remained unchanged. Saffron supplementation may alleviate T2DM by improving glycemic status, lipid profile, liver enzymes, and oxidative status. Further investigation is necessary to assess possible side effects and confirm the positive effect of saffron as a complementary therapy in clinical recommendations for T2DM.

The role of bone turnover markers in screening low bone mineral density and their relationship with fracture risk in the postmenopausal period.

Background: Using bone turnover marker (BTM) monitoring to identify "quick losers" who may develop osteoporosis in the coming years is one of the main challenges in clinical practice. This study was implemented to examine the association of BTMs with bone mineral density (BMD) as well as to determine their relationship with the fracture risk assessment tool (FRAX) in women in the postmenopausal period. Materials and Methods: This study was observational cross-sectional research that was done on women between the ages of 50 and 65 who were in the postmenopausal period. A dual-energy X-ray absorptiometry was applied to select 120 eligible women with normal BMD and 120 women without normal BMD. BTMs were assessed using enzyme-linked immunosorbent assay. Osteoporosis's Odds Ratio (OR) was estimated using a confounder-adjusted logistic regression model. The area under curve was calculated for the differentiation of low BMD in the postmenopausal period through receiver-operator characteristic (ROC) curves. To assess the probability of major osteoporotic fracture and hip fracture for the future 10 years, FRAX was applied. Results: Higher serum osteocalcin (OC) (OR: 1.134, 95% confidence interval [CI]: 1.086-1.184), osteopontin (OP) (OR: 1.180; 95%CI: 1.105-1.261), and alkaline phosphatase (ALP) (OR: 1.007; 95%CI: 1.001-1.144) concentrations were potential risk factors for developing low BMD in women after menopause. The area under curve (AUC) (95%CI) for OC, OP, and ALP was 0.75 (0.668-0.8130), 0.75 (0.685-0.812), and 0.602 (0.524-0.670), respectively. ROC analysis indicated that at the cut-off point of 16.28 ng/mL, sensitivity and specificity were 70.3% and 70.9%, respectively, for OC. Furthermore, at the cut-off point of 28.85 ng/mL, the sensitivity of 70.3% and specificity of 66.6% were obtained for OP. The serum OC and OP were significantly related to hip and major osteoporotic fractures (P < 0.05). Conclusion: The higher serum concentration of OC, OP, and ALP had significant associations with lower BMD. These BTMs can be complementary tools and helpful in the postmenopausal period as measures for screening of bone loss and possible bone fracture.

The therapeutic effects and mechanisms of action of resveratrol on polycystic ovary syndrome: A comprehensive systematic review of clinical, animal and in vitro studies.

Polycystic ovary syndrome (PCOS) is one of the most important and common polygenic endocrine disorders among women of reproductive age. Resveratrol, a natural phenol, is involved in various biological activities, including antioxidant, antiseptic, anti-inflammatory, anti-ageing and anti-cancer effects. This systematic review aimed to investigate the therapeutic effects and mechanisms of actions of resveratrol in PCOS. The present study was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis statements. We searched PubMed, Science Direct, Google Scholar, Scopus, ISI Web of Science, ProQuest and Embase databases up to August 2021 by using the relative keywords. Original studies published in the English language that assessed the effects of resveratrol on PCOS and its associated complications were considered. Out of 417 records screened, only 24 articles met the inclusion criteria: 10 in vitro, 10 animal and 4 human studies. The results obtained in the present study showed that resveratrol supplementation might be effective in improving PCOS-related symptoms by reducing insulin resistance, alleviating dyslipidaemia, improving ovarian morphology and anthropometric indices, regulating the reproductive hormones and reducing inflammation and oxidative stress by affecting biological pathways. According to the available evidence, resveratrol may reduce the complications of PCOS. However, further studies are recommended for a comprehensive conclusion on the exact mechanism of resveratrol in PCOS patients.

The effect of saffron supplementation on glycemic parameters: An overview of systematic reviews.

Due to the widespread use of herbal medicine and evidence pointing to the health benefits of saffron supplementation, this review was performed to evaluate the effects of saffron supplementation on glycemic parameters and lipid profiles based on previous reviews. Relevant articles were retrieved from various databases, which included PubMed, Scopus, ProQuest, Web of Science, Embase, and Cochrane until 2020, with no date restrictions. The quality of the included reviews was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Finally, of 877 obtained articles, eight reviews meeting the inclusion criteria were included for analysis. Among the eight included reviews, seven articles were meta-analyses. In addition, one review had an average quality while seven had a good quality. A narrative description of the included reviews was performed, while a network meta-analysis was not conducted. A brief review of the results was reported according to the weighted mean difference and mean difference. Seven included reviews assessed the effects of saffron or crocin supplementation on glycemic parameters, and six examined these effects on lipid profile parameters. Almost half of the articles reported significant effects of these supplements on glycemic parameters and lipid profiles. Taken together, results suggest that saffron supplementation may improve glycemic and lipid profile parameters; however, further high-quality studies are needed to confirm the clinical efficacy of saffron on glycemic parameters and lipid profiles.

Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common noncommunicable diseases worldwide. The present study aimed to investigate the effects of oleoylethanolamide (OEA) supplementation combined with calorie restriction on inflammation, body composition, and hepatic fibrosis among obese patients with NAFLD. In this 12-week randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group. The weight-loss diet was also designed for both groups. Pre- and postintervention messenger RNA expression levels of the transcription factor nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and IL-10, body composition, and NAFLD fibrosis score were assessed. At the end of the study, the OEA group showed lower NF-κB and IL-6 expression levels compared to the placebo (p < .01). However, IL-10 expression level was approximately twofold higher in the OEA group compared to the placebo group (p = .008). A significant reduction was observed in the fat mass of the OEA group compared to the placebo (p = .044) postintervention. In addition, OEA supplementation led to a significant increase in fat-free mass in the OEA group compared to the placebo (p = .032). A remarkable increase was observed in resting metabolic rate (RMR) in the OEA group (p = .009); however, it was not found in the placebo group. There were no significant between-group differences in RMR postintervention. In addition, no significant within-and between-group differences were observed in the NAFLD fibrosis score at the end of the trial. Treatment with OEA along with weight-loss intervention could significantly improve inflammation and body composition in patients with NAFLD.

Serum neuregulin 4 (NRG-4) level and non-alcoholic fatty liver disease (NAFLD): A case-control study.

OBJECTIVE: The current case-control study aimed to examine the association of circulating neuregulin 4 (NRG-4), a brown fat-enriched endocrine factor, with non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 50 patients newly diagnosed with NAFLD with 50 age-matched and sex-matched subjects without NAFLD were recruited in the present study. Circulating NRG-4 levels were assessed with an enzyme-linked immunosorbent assay (ELISA) kit. SPSS version 23 was used for statistical analysis. RESULTS: Patients with NAFLD had lower levels of circulating NRG-4 than the control group (P < .001). Participants in the highest quartile of circulating NRG-4 had significantly lower body mass index (BMI), waist circumference (WC), triglyceride (TG) and homeostatic model assessment for insulin resistance (HOMA-IR) compared with those in the lowest quartile (all P < .01). The prevalence of NAFLD in the quartile 4 of the serum NRG-4 level was 38.46%, lower than the quartile 1 (62.50%, P = .006), quartile 2 (52.00%, P = .017) and quartile 3 (48.00%, P = .032). In multiple stepwise regression analysis, BMI (ß = -0.712, P = .016), WC (ß = -0.577, P = .023), TG (ß = -0.509, P = .001), high-density lipoprotein cholesterol (HDL-C) (ß = 0.489, P = .001) and HOMA-IR (ß = -0.609, P = .003) were independently related to serum NRG-4 level. The odds of NAFLD decreased by 41% per 1 SD increase in serum NRG-4 level (OR, 0.59; 95% CI, 0.35-0.78; P = .021), after adjustment for all potential confounders. CONCLUSION: The results of the present study demonstrate that circulating NRG-4 levels may play a protective role in NAFLD.

Saffron improves life and sleep quality, glycaemic status, lipid profile and liver function in diabetic patients: A double-blind, placebo-controlled, randomised clinical trial.

BACKGROUND: Type 2 diabetes (T2D) is a metabolic disorder that is related to hyperglycaemia, hyperlipidaemia and liver dysfunction and has detrimental effects on a patient's mental health. Hence, the current study investigated the effects of saffron supplementation on dietary intake, anthropometric measures, mood, sleep quality and metabolic biomarkers in overweight/obese patients with T2D. METHODS: In a double-blind, randomised controlled trial, 70 overweight/obese patients with T2D were randomly allocated to two groups and received 100 mg/day saffron or placebo for 8 weeks. Participants completed the Beck depression inventory-II (BDI-II), Hurlbert index of sexual desire (HISD), Pittsburgh Sleep Quality Index (PSQI) and Diabetes-specific Quality-of-Life Brief Clinical Inventory questionnaires (DQOL-BCI). Dietary intake, anthropometric measures, fasting plasma glucose (FPG), haemoglobin A1C (HbA1C), insulin, lipid profile and liver enzymes were determined at baseline and the end of the study. RESULTS: At the end of the eighth week, saffron supplementation significantly decreased FPG, triglyceride (TG), insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < .001). Moreover, significant improvements in BDI-II scores and total quality of life were observed in the intervention group (P < .001). The saffron group showed more significant improvements in PSQI scores than the placebo group, such that at the post-intervention analysis, only the saffron group achieved a "good" sleep band. At this relatively high dose, saffron supplementation improved glycaemic status, lipid profile and liver enzyme measures in patients with T2D while also improving sleep and overall quality of life. CONCLUSION: Our results indicate that saffron notably reduced hyperglycaemia and hyperlipidaemia and improved liver function in patients with T2D in an 8-week randomised clinical trial. Saffron also significantly improved depression, sleep quality and overall quality of life in diabetic patients. However, further investigation is necessary to confirm whether saffron is an effective complementary therapy for T2D.

The association of the steatosis severity, NAFLD fibrosis score and FIB-4 index with atherogenic dyslipidaemia in adult patients with NAFLD: A cross-sectional study.

OBJECTIVES: Obesity and dyslipidaemia are the major risk factors for non-alcoholic fatty liver disease (NAFLD), and are known to increase cardiovascular disease (CVD), which is the leading cause of death in NAFLD patients. The present cross-sectional study aimed to investigate associations among severity of hepatic steatosis, NAFLD fibrosis score and atherogenic lipid profile. METHODS: A total of 265 patients with NAFLD confirmed by ultrasonographic findings were included. The NAFLD fibrosis score and the fibrosis-4 (FIB-4) index were used to classify the probability of fibrosis as low, intermediate and high probability. Serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and then TC/HDL-C, LDL-C/HDL-C, TG/HDL-C and non HDL-C/HDL-C ratios were determined. Fasting blood sugar (FBS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also assessed. The homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. RESULTS: The severity of hepatic steatosis was positively correlated with TC/HDL-C (r = 0.29, P = .002), LDL-C/HDL-C (r = 0.32, P < .001), TG/HDL-C (r = 0.36, P < .001) and non-HDL-C/HDL-C (r = 0.24, P = .001) ratios. Similarly, these parameters were positively correlated with NAFLD fibrosis score and FIB-4 index (P < .05). In addition, alanine aminotransferase and aspartate aminotransferase levels were positively correlated with TG/HDL-C ratio (r = 0.31, P = .003; and r = 0.27, P = .001 respectively). With increasing the severity of hepatic steatosis and NAFLD fibrosis score, the mean of all lipid ratios increased significantly (P < .01 and P < .05, respectively). Importantly, after controlling for potential confounders including age, gender, physical activity level, body mass index, waist circumference and HOMA-IR, the severity of steatosis, NAFLD fibrosis score and FIB-4 index remained independent predictors of atherogenic lipid profile. CONCLUSIONS: Severity of hepatic steatosis, NAFLD fibrosis score and FIB-4 index were significantly correlated with atherogenic lipid profile. As NAFLD is high among patients with metabolic risk factors for CVD, their dyslipidaemia should be aggressively managed.

The impact of L-citrulline supplementation on glucose homeostasis, lipid profile, and some inflammatory factors in overweight and obese patients with type 2 diabetes: A double-blind randomized placebo-controlled trial.

This study investigated the impact of L-citrulline on glucose homeostasis, lipid profile, and inflammatory factors in overweight and obese patients with type 2 diabetes (T2D). In total, 54 participants with T2D were assigned to L-citrulline (3 g/day L-citrulline) or placebo groups and tested for 8 weeks. Serum levels of insulin, fasting glucose, hemoglobin A1c (HbA1c), lipid profile, tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and L-citrulline were measured pre- and post-intervention. Totally, 45 patients were enrolled in the research. L-citrulline supplementation decreased serum levels of insulin (p = .025), glucose (p = .032), HbA1c (p = .001), HOMA-IR (p = .037), TNF-α (p = .036), and hs-CRP (p = .027) significantly. At the end of the study, despite the significant decrease in serum levels of triglyceride (p = .027) and the increase in high-density lipoprotein cholesterol levels (p < .001) in the L-citrulline group, no significant differences were found for these parameters between the groups. Moreover, no significant inter- and intra-group changes were observed for dietary intakes, anthropometric indices, total and low-density lipoprotein cholesterol levels (p > .05). In conclusion, L-citrulline supplementation might improve glucose homeostasis, some lipid factors and inflammatory markers in overweight and obese patients with T2D.

Effect of pomegranate seed oil supplementation on the GLUT-4 gene expression and glycemic control in obese people with type 2 diabetes: A randomized controlled clinical trial.

Abnormality in glucose transporter type 4 (GLUT-4) function and insulin secretion are the main causes of type 2 diabetes mellitus (T2DM). Due to adverse effects of antidiabetic drugs, nowadays, nutraceuticals have been of much interest to investigators. The aim of the present study was to determine the effect of pomegranate seed oil (PSO) on the GLUT-4 gene expression and glycemic control in obese people with T2DM. This randomized clinical trial was conducted on 52 obese type 2 diabetic patients for 8 weeks in Tabriz, Iran, in 2018. Patients were divided into the intervention group (n = 26; who consumed daily three capsules containing 1 g PSO) and the placebo group (n = 26; the same amounts paraffin). GLUT-4 gene expression and glycemic indices were evaluated by standard methods. GLUT-4 gene expression was increased significantly in the PSO group. Within-group changes in fasting blood sugar (FBS) and quantitative insulin sensitivity check index were significant in the PSO group. After adjusting the age, gender, and baseline values, FBS was significantly decreased. Insulin concentration, HbA1C, HOMA-IR, and HOMA-ß did not manifest significant changes. PSO increased the GLUT-4 gene expression in diabetic patients without any side effects. However, future clinical studies are needed to confirm the obtained results.

The Effects of Choline and Magnesium Co-Supplementation on Metabolic Parameters, Inflammation, and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To our knowledge, no study has investigated the effects of choline and magnesium co-supplementation on metabolic parameters, inflammation, and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). The aim of this study was investigation of the effects of the choline and magnesium co-supplementation on metabolic parameters, inflammation, and endothelial dysfunction in patients with T2DM.Methods: A randomized double-blind placebo-controlled parallel clinical trial was carried out among 96 diabetic patients. Ninety-six patients were randomly assigned to either choline, magnesium, choline-magnesium, or placebo for 2 months. Anthropometric measurement; metabolic, inflammatory, and endothelial markers; dietary intake; and physical activity were assessed at baseline and after treatment.Results: There was a significant change in serum magnesium in both magnesium and choline-magnesium groups (p < 0.05). Also, significant changes were observed in interleukin (IL)-6 levels in magnesium and choline-magnesium groups (p < 0.05). Moreover, vascular cell adhesion molecule-1 (VCAM-1) levels decreased in choline and choline-magnesium groups (p < 0.05). When adjusted for potential confounders, inflammation and endothelial factors (IL-6 and VCAM-1) decreased significantly in the choline-magnesium group as compared to other groups (p < 0.05). Compared to baseline values there were no significant differences in all anthropometric measurements and metabolic factors among four groups (p > 0.05).Conclusions: Choline and magnesium co-supplementation was more effective in improving inflammation and endothelial dysfunction than supplementation with choline or magnesium alone.

Preparation of pH sensitive insulin-loaded nano hydrogels and evaluation of insulin releasing in different pH conditions.

In the recent years, temperature and pH-sensitive hydrogels were developed as suitable carriers for drug delivery. In this study, four different pH-sensitive nanohydrogels were designed for an oral insulin delivery modeling. NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction with 80:8:12 ratios respectively. Reactions were carried out in four conditions including 1,4-dioxan and water as two distinct solution under nitrogen gas-flow. The copolymers were characterized with FT-IR, SEM and TEM. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in pH 1.2 and pH 6.8 at 37 °C. For pH 6.8 and pH 1.2, 2 mg of the insulin loaded nanohydrogels was float in a beaker containing 100 mL of PBS with pH 6.8 and 100 mL of HCl solution with pH 1.2, respectively. Sample collection was done in different times and HPLC was used for analysis of samples using water/acetonitrile (65/35) as the mobile phase. Nanohydrogels synthesis reaction yield was 95 %, HPLC results showed that loading in 1,4-dioxan without cross-linker nanohydrogels was more than others, also indicated that the insulin release of 1,4-dioxan without cross-linker nanohydrogels at acidic pH is less, but in pH 6.8 is the most. Results showed that by opting suitable polymerization method and selecting the best nanohydrogels, we could obtain a suitable insulin loaded nanohydrogels for oral administration.

Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients.

The present study was aimed to evaluate the effects of Zingiber officinale on some biochemical parameters in type 2 diabetic (DM2) patients. In a randomized double-blind placebo controlled trial, 64 patients with DM2 were assigned to ginger or placebo groups (receiving 2 g/d of each). A 3 d diet record, anthropometric measurements and concentrations of fasting blood glucose (FPG), HbA1c, lipid profile (including total cholesterol, triglyceride, low density lipoprotein and high density lipoprotein) and also the homeostasis model assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI) were determined before and after 2 months of intervention. Ginger supplementation significantly lowered the levels of insulin (11.0 ± 2.3 versus 12.1 ± 3.3; p = 0.001), LDL-C (67.8 ± 27.2 versus 89.2 ± 24.9; p = 0.04), TG (127.7 ± 43.7 versus 128.2 ± 37.7; p = 0.03) and the HOMA index (3.9 ± 1.09 versus 4.5 ± 1.8; p = 0.002) and increased the QUICKI index (0.313 ± 0.012 versus 0.308 ± 0.012; p = 0.005) in comparison to the control group; while, there were no significant changes in FPG, TC, HDL-C and HbA1c (p > 0.05). In summary, ginger supplementation improved insulin sensitivity and some fractions of lipid profile in DM2 patients. Therefore it may be considered as a useful remedy to reduce the secondary complications of DM2.

The effect of bitter almond (Amygdalus communis L. var. Amara) gum as a functional food on metabolic profile, inflammatory markers, and mental health in type 2 diabetes women: a blinded randomized controlled trial protocol.

BACKGROUND: Using functional foods in the prevention and treatment of type 2 diabetes mellitus (T2DM) has increased across the world owing to their availability, cultural acceptability, and lower side effects. The present study will aim to examine the impact of bitter almond (Amygdalus communis L. var. Amara) gum as a functional food on metabolic profile, inflammatory markers, and mental health in women with T2DM. METHODS: We will conduct a randomized, triple-blind, placebo-controlled trial. A total of 44 women with T2DM will be randomly allocated into two groups: an intervention group (n = 20) and a placebo group (n = 20). Patients will receive either 5 g/d of bitter melon gum or a placebo for 8 weeks. Clinical and biochemical outcome parameters which include glycemic indices, lipid profile, inflammatory markers, oxidative stress indices, tryptophan (Trp), kynurenine (KYN), cortisol, glucagon-like peptide 1 (GLP-1), leptin, adiponectin, ghrelin, peroxisome proliferator-activated receptor (PPAR) gene expression, brain-derived neurotrophic factor (BDNF), endothelial cell adhesion molecules, plasminogen, cluster deference 4 (CD4), cluster deference 8 (CD8), anthropometric indices, blood pressure, dietary intake, and mental health will be measured at the baseline and end of the study. Statistical analysis will be conducted using the SPSS software (version 24), and P value less than 0.05 will be considered statistically significant. DISCUSSION: The present randomized controlled trial will aim to investigate any beneficial effects of bitter almond gum supplementation on the cardio-metabolic, immune-inflammatory, and oxidative stress biomarkers, as well as mental health in women with T2DM. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethical Committee of the Tabriz University of Medical Sciences (IR.TBZMED.REC.1399.726). TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.irct.ir/IRCT20150205020965N7 ).

The Possible Association of IL-6R Gene Polymorphisms in the Development of Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of type 2 diabetes (T2D). Chronic inflammation and a combination of environmental and genetic factors are involved in the pathogenesis and development of DN. OBJECTIVE: This case-control study aimed to determine the relationship between rs7529229 and rs2228145 polymorphisms of the IL-6R gene with the incidence of nephropathy among T2D patients. METHODS: Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals. METHODS: Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals. RESULTS: The frequencies of AC and CC genotype distributions of the rs2228145 polymorphism in DN patients were significantly higher than in healthy individuals (24.1 and 9.3% versus 10.7 and 6.7%, respectively, P= 0.02). Moreover, the frequency of allele C was higher in DN patients compared to healthy controls (21.30% versus 12%, P=0.025). However, genotype distribution and allele frequencies of the rs7529229 IL-6R polymorphism in DN patients were not statistically significant in comparison with diabetic patients and healthy individuals (P> 0.05). CONCLUSION: The results showed that the allele and genotype distribution frequencies of rs2228145 IL-6R gene polymorphism in patients with DN were significantly higher than in healthy individuals. Therefore, the presence of this polymorphism may be involved in the development of diabetic nephropathy in this population.

Effects of levothyroxine replacement therapy on insulin resistance in patients with untreated primary hypothyroidism.

OBJECTIVES: This study investigated the effects of levothyroxine replacement therapy on insulin resistance, lipid profile, and thyroid function in patients with untreated primary hypothyroidism. 105 patients with hypothyroidism with indication for levothyroxine replacement were enrolled in the present study. Insulin, fasting blood glucose and lipid profile were assessed at the beginning of diagnosis and three months after levothyroxine replacement. Insulin resistance was calculated by hemostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). RESULTS: Our data revealed a significant reduction in body mass index (27.18 ± 4.27 versus 26.81 ± 4.18 kg/m2, p = 0.028), cholesterol (199.79 ± 37.61 versus 178.10 ± 32.25 mg/dl, p < 0.001), triglyceride (160.41 ± 71.86 versus 146 ± 61.11 mg/dl, p = 0.012), low density lipoprotein-cholesterol (123.54 ± 30.7 versus 107.08 ± 26.98 mg/dl, p < 0.001), fasting insulin (8.91 ± 3.92 versus 8.05 ± 2.65 mIU/l, p < 0.001), and thyroid stimulating hormone (47.47 ± 3.4 versus 2.22 ± 1.84 µIU/ml, p < 0.001) levels before and after drug intervention. However, no statistical differences were observed in HOMA-IR, QUICKI, and high density lipoprotein-cholesterol. In conclusion, in patients with untreated primary hypothyroidism, levothyroxine replacement therapy based on HOMA-IR and QUICKI did not improve insulin resistance; however, lipid profile was significantly improved following levothyroxine administration. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20130610013612N10 on the date 2019-09-02.

Effects of vitamin D supplementation on metabolic parameters, serum irisin and obesity values in women with subclinical hypothyroidism: a double-blind randomized controlled trial.

Purpose: Subclinical hypothyroidism is an early, mild form of hypothyroidism that may progress to overt hypothyroidism if untreated. The current study aimed to assess the effects of vitamin D supplementation on hormonal (thyroid stimulating hormone [TSH], triiodothyronine, thyroxine, and free thyroxine) parameters, lipid profiles, serum irisin, and obesity indices in women with subclinical hypothyroidism. Methods: The present randomized, double-blind, placebo-controlled clinical trial was carried out on 44 women with subclinical hypothyroidism. The participants were allocated to two groups (22 patients in each group) that received vitamin D (50,000 IU/week) or placebo for 12 weeks. Fasting blood samples, anthropometric and body composition measurements, physical activity levels, and dietary intakes were collected at baseline and at the end of the study. Results: Vitamin D supplementation significantly decreased TSH, total cholesterol, and fat mass percentage, and significantly increased serum vitamin D and irisin levels and fat-free mass percentage compared to the control group (all, p<0.05). Changes in thyroid hormones, other lipid profiles, and anthropometric indices were not significantly different between the groups. Conclusion: Our study indicates that vitamin D administration improves serum TSH, total cholesterol, irisin, and body composition in women with subclinical hypothyroidism. More well-designed clinical trials are required to confirm these findings and clarify the effects of vitamin D supplementation on both genders of patients.Clinical trial registration: https://www.irct.ir/trial/57482, Identifier IRCT20100408003664N25.

The effect of the boron-based gel on the treatment of diabetic foot ulcers: A prospective, randomized controlled trial.

BACKGROUND: Chronic ulcers represent impaired healing capacity with high mortality in the elderly or patients with systemic disorders such as diabetes. Boron is an effective agent in wound healing by promoting cell migration and proliferation and reducing inflammation in the wound area. This study aimed to evaluate the therapeutic effect of a sodium pentaborate-based topical formulation compared to control on the treatment of diabetic foot ulcers. METHODS: A prospective, double-blind, randomized controlled trial was conducted to apply randomly the topical sodium pentaborate 3% gel or topical conventional remedy (control) by patients diagnosed with diabetic foot ulcers. The 171 eligible participants aged 18-75 years received the allocated medicines twice a day for a month with an allocation ratio of 3:1. Twenty-five days and two months after the end of the trial, participants were reinvestigated for their ulcer condition and any recurrence. Wagner's classification of diabetic foot ulcers was applied to this purpose (0-5). RESULTS: 161 participants (57 females, 104 males; mean age: 59.37) completed this study. After the intervention, most participants in the intervention group had a lower ulcer grade than the control group (adjusted mean difference (95% CI): - 0.91 (-1.1 to -0.73); p < 0.001). Moreover, most participants in the intervention group (n = 109 (90.8%)) were treated at a higher rate than the control group (n = 5 (12.2%)) after intervention (adjusted odds ratio (95% CI): 0.008 (0.002-0.029); p < 0.001). There was no case of recurrence in the intervention group while its rate was (n = 2 (40%)) in the control group (p < 0.001). CONCLUSION: The present study suggests that topical sodium pentaborate gel may help treat and decrease the grade of diabetic foot ulcers and prevent the recurrence of diabetic foot ulcers.

Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-ß genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). METHODS: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1α (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-ß between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. CONCLUSION: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".