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Purpose: Evidence suggests that changes in the composition of gut microbiota may be linked to metabolic disorders including type 2 diabetes (T2D). The present study aims to evaluate the compositional changes of the intestinal microbiota in patients with T2D as compared to healthy individuals., Methods: In this case-control study, there were 18 T2D patients and 18 healthy individuals who served as controls. To profile the gut microbiota in both groups, bacterial DNA was extracted from fecal samples and analyzed using quantitative real-time polymerase chain reaction (qPCR)., Results: The study discovered that diabetics had significantly greater frequencies of the genus Bacteroides and the phylum Bacteroidetes than did controls (P = 0.03 and P < 0.001, respectively). Conversely, the Actinobacteria and Firmicutes phyla were significantly more abundant in the controls ( P=0.01 for both). No significant differences were observed in the fecal populations of the genus Enterococcus , Clostridium clusters IV and XIVa , phylum Proteobacteria , and all bacteria between the studied groups ( P=0.88 , P=0.56 , P=0.8 , P=0.99 , and P=0.7 , respectively)., Conclusions: Our findings confirm that T2D may be associated with the gut microbiota fluctuations. These findings may be valuable for developing strategies to control or treatment T2D by restoring the intestinal microbiota through the strategic administration of specific probiotics/prebiotics and lifestyle and dietary modifications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: We aimed to assess the effect of air pollution on incident cardiovascular disease (CVD) in people with type 2 diabetes mellitus (T2DM)., Methods: We tracked 486 T2DM patients from 2012 to 2021. Cox regression models were applied to assess the hazard of exposure to particulate matter, carbon monoxide (CO), ozone, nitrogen dioxide, and sulfur dioxide (SO 2 ) on incident CVD, revealing hazard ratios (HRs)., Results: CVD incidents occurred in 73 individuals. Among men, each 1-ppm increase in CO levels raised the risk of CVD (HR: 2.66, 95% CI: 1.30-5.44). For women, a 5-ppb rise in SO 2 increased CVD risk (HR: 1.60, 95% CI: 1.11-2.30). No notable impact of particulate pollutants was found., Conclusions: Persistent exposure to gaseous air pollutants, specifically CO and SO 2 , is linked to the development of CVD in men and women with T2DM., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Background: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored., Methods: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans., Results: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001., Conclusion: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy., (© 2024. The Author(s).)

Purpose: Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED., Methods: Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2)., Results: The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65-0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy., Conclusion: Statin therapy could be a potential adjunctive modality for preventing and treating TED., Trial Registration: PROSPERO registration number: CRD42022315522., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the utility of point of care screening of diabetic retinopathy (DR) and the impact of a telemedicine program to overcome current challenges., Methods: This was a retrospective study on people with type 2 diabetes mellitus (T2DM) who were screened for DR using the single-field non-mydriatic fundus photography at the point of care during routine follow-up visits at endocrinology clinic. Retinal images were uploaded and sent to a retina specialist for review. Reports indicating retinopathy status and the need for direct retinal examination were transmitted back to the endocrinology clinic. All patients were informed about DR status and, if needed, referred to the retina specialist for direct retinal examination., Results: Of the 1159 individuals screened for DR, 417 persons (35.98%) were screen-positive and referred to the retina specialist for direct retinal examination. A total of 121 individuals (29.01%) underwent direct retinal examination by the specialist. Diabetes macular edema (DME) was detected in 12.1%. In addition, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were detected in 53.4% and 2.6% of the patients, respectively., Conclusion: Integrating DR screening program at the point of care at the secondary care services improves the rate of DR screening as well as detection of sight threatening retinopathy and provides the opportunity for timely intervention in order to prevent advanced retinopathy in people with T2DM., (© 2024. The Author(s).)

Objective: Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs., Methods: Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases., Results: In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151&#95;2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas., Conclusion: Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies., (© 2024. The Author(s).)

The rising prevalence of type 2 diabetes (T2D) is posing major challenges for the healthcare systems of many countries, particularly in the Asia-Pacific Region, in which T2D can present at younger ages and lower body mass index when compared with Western nations. There is an important role for insulin therapy in the management of T2D in these nations, but available evidence suggests that insulin is under-utilized and often delayed, to the detriment of patient prognosis. The authors of this article gathered as an advisory panel (representative of some of the larger Asia-Pacific nations) to identify their local barriers to insulin use in T2D, and to discuss ways in which to address these barriers, with their outputs summarized herein. Many of the key barriers identified are well-documented issues of global significance, including a lack of healthcare resources or of an integrated structure, insufficient patient education, and patient misconceptions about insulin therapy. Barriers identified as more innate to Asian countries included local inabilities of patients to afford or gain access to insulin therapy, a tendency for some patients to be more influenced by social media and local traditions than by the medical profession, and a willingness to switch care providers and seek alternative therapies. Strategies to address some of these barriers are provided, with hypothetical illustrative case histories., (© 2024. The Author(s).)

Background: Measures of insulin resistance (IR)/sensitivity (IS) are emerging tools to identify metabolic-associated fatty liver disease (MAFLD). However, the comprehensive assessment of the performance of various indicators is limited. Moreover, the utility of measures of IR/IS in detecting liver fibrosis remains unclear., Aims: To evaluate the predictive ability of seventeen IR/IS and two beta cell function indices to identify MAFLD and liver fibrosis., Methods: A cross-sectional study was conducted on individuals aged 25-75 years. Transient elastography was used to estimate liver stiffness and controlled attenuation parameter. The following measures were computed: homeostatic model assessment (HOMA/HOMA2) for IR, IS, and beta cell function; QUICKI; Bennett index; glucose/insulin; FIRI; McAuley index; Reynaud index; SPISE index; TyG; TyG-BMI; TyG-WC; TyG-WHtR; TG/HDL; and METS-IR. Subgroup analyses were performed according to age, gender, diabetes status, and body weight., Results: A total of 644 individuals were included in our analysis. MAFLD and significant liver fibrosis were detected in 320 (49.7%) and 80 (12.4%) of the participants, respectively. All measures of IR/IS identified MAFLD and liver fibrosis. However, TyG-WC, TyG-BMI, and TyG-WHtR were the top three indicators that identified MAFLD. Measures that include insulin level in their mathematical calculation, namely, Raynaud index, HOMA-IR, HOMA 2-IR, FIRI, and QUICKI had the best performance in identifying liver fibrosis in the entire population, as well as among the study subgroups., Conclusions: TyG-WC, TyG-BMI, and TyG-WHtR were the best predictors of MAFLD. Insulin-based measures had better performances in the detection of advanced fibrosis. This was independent of age, gender, obesity, or diabetes status., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Pharmacogenetics studies suggest that genetic variants have a possible influence on the inter-individual differences in therapeutic response to glucagon-like peptide 1 receptor agonists (GLP-1 RAs). We aimed to examine the potential role of genetic variability of glucagon-like peptide 1 receptor (GLP-1R) on glycemic response to GLP-1 RAs in a population of Iranian people with type 2 diabetes mellitus (T2DM)., Methods: In this study, we analyzed the data from participants in a non-inferiority randomized clinical trial between 2019 and 2020. Patients received liraglutide 1.8 mg/day subcutaneously for 24 weeks. They were stratified by the baseline hemoglobin A1c (HbA1c) into four categories: 7-7.99, 8-8.99, 9-9.99, and ≥ 10%. In each category, subjects with HbA1c reduction greater than the median ΔHbA1c value for that group were defined as optimal responders. The pooled number of optimal/suboptimal responders in the four groups was used for the comparison. We evaluated two genetic variants of GLP-1R, rs6923761 and rs10305420, using Sanger sequencing. Logistic regression analyses were performed to examine the associations of the GLP-1R variants with the glycemic response in different genetic models., Results: Out of 233 participants, 120 individuals were optimal responders. Median HbA1c reduction was - 2.5% in the optimal responder group compared with - 1.0% in the suboptimal responder group (P < 0.001). In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41-7.65, P = 0.006; codominant model: OR 2.52, 95% CI 1.03-6.13, P = 0.04). No significant association was found between rs6923761 variant and HbA1c reduction., Conclusion: GLP-1R rs10305420 polymorphism can explain some of the inter-individual differences in glycemic response to liraglutide in a population of Iranian people with T2DM., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Body composition is related to cardiometabolic disorders and is a major driver of the growing incidence of type 2 diabetes mellitus (T2DM). Altered fat distribution and decreased muscle mass are related to dysglycemia and impose adverse health-related outcomes in people with T2DM. Hence, improving body composition and maintaining muscle mass is crucial in T2DM. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering medications gaining popularity because of their cardiorenal-protective effects and weight-lowering characteristics. However, reports on myopathy secondary to SGLT2 inhibitor treatment raised a safety concern. The importance of maintaining muscle mass in people with T2DM necessitates further investigation to explore the impact of novel medications on body composition. In this review, we discussed current evidence on the impact of SGLT2 inhibitors on body composition in people with T2DM., (© 2023. The Author(s).)

Introduction: Liraglutide effectively controls blood glucose level and reduces body weight. The aim of this study was to compare the efficacy and safety of a biosimilar liraglutide (Melitide ® ; CinnaGen, Tehran, Iran) to the reference liraglutide (Victoza ® ; Novo Nordisk, Bagsvaerd, Denmark) in people with type 2 diabetes mellitus (T2DM)., Methods: In this phase 3 clinical noninferiority trial, adult patients with inadequately controlled T2DM and with hemoglobin A 1C (HbA 1C ) levels of 7-10.5% on at least two oral glucose-lowering drugs with stable doses for at least 3 months were randomized to receive Melitide ® (n = 150) or Victoza ® (n = 150) 1.8 mg/day for 26 weeks. The primary outcome was assessment of the noninferiority of Melitide ® to Victoza ® in terms of change in HbA 1C level with a prespecified margin of 0.4%. The secondary outcomes were the assessment of additional efficacy parameters (including the proportion of patients achieving HbA 1C levels of < 7%), the incidence of adverse events, and immunogenicity., Results: Of the 300 participants enrolled in this study, 235 were included in the per-protocol analysis (112 in the Melitide ® group and 123 in the Victoza ® group). The mean (standard deviation) changes in HbA 1C were - 1.76% (1.22) in the Melitide ® group and - 1.59% (1.31) in the Victoza ® group. The upper limit of the 95% one-sided confidence interval (CI) of the mean difference between Melitide ® and Victoza ® in lowering HbA 1C was lower than the predefined margin (mean difference - 0.18, 95% CI - 0.5 to 0.15). Similar findings were obtained with the intention-to-treat analysis. No statistically significant differences were observed between the two study arms regarding the proportion of patients achieving HbA 1C  < 7% (p = 0.210), other efficacy parameters (p > 0.05), and reported adverse events (p = 0.916). Furthermore, none of the patients developed anti-liraglutide antibodies., Conclusion: The biosimilar liraglutide (Melitide ® ) was noninferior in efficacy and comparable in safety when compared with the reference liraglutide., Trial Registration: NCT03421119., (© 2023. The Author(s).)

Introduction: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with type 2 diabetes mellitus (T2DM) and synergistically contributes to the development of atherosclerosis. Flow-mediated dilation (FMD) is a commonly used noninvasive test for assessing endothelial function. The main objective of this study was to explore FMD in patients with T2DM with and without NAFLD., Methods: In this cross-sectional study, conducted on people with T2DM, NAFLD was defined as controlled attenuation parameter (CAP) score > 302 dB/m. Endothelial dysfunction was detected when arterial FMD of brachial artery was equal or less than 0.7%. Regression analyses were applied to assess factors associated with impaired FMD., Result: A total of 147 patients (72 with NAFLD and 75 without NAFLD) were included in the final analysis. Patients with NAFLD were more likely to develop FMD ≤ 7% (77.8% vs. 58.7%, P = 0.01). In multivariate analysis, NAFLD (OR = 2.581, 95% CI (1.18-5.62), P = 0.017) and hypertension (HTN) (OR = 3.114, 95% CI (1.31-7.35), P = 0.010) were associated with an increased risk of impaired FMD. However, female sex was associated with a decreased risk of impaired FMD (OR = 0.371, 95% CI (0.15-0.87), P = 0.024)., Conclusion: NAFLD is associated with endothelial dysfunction in people with T2DM. This risk is comparable with the risk imposed by HTN, highlighting the importance of screening and management of NAFLD in these patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease., Methods: This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM)., Results: In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01., Conclusion: Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations., Trial Registration: This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Obesity is a serious chronic disease that adversely affects health and quality of life. However, a significant percentage of people do not participate in or adhere to weight loss programs. Therefore, a multidisciplinary approach is needed to identify critical barriers to effective obesity management and to examine health practitioners' attitudes and behaviors towards effective obesity treatment., Methods: This systematic review was conducted in accordance with PRISMA 2020. Eligible studies were identified through a systematic review of the literature using Medline, Scopus, Cochrane, Google Scholar, Web of Science, and Embase databases from January 1, 2011 to March 2, 2021., Results: A total of 57 articles were included. Data on 12663 physicians were extracted from a total of 35 quantitative articles. Some of the most commonly perceived attitude issues included "obesity has a huge impact on overall health", "obesity is a disease" and "HCPs are to blame". Health professionals were more inclined to believe in "using BMI to assess obesity," "advice to increase physical activity," and "diet/calorie reduction advice." The major obstacles to optimal treatment of obesity were "lack of motivation", "lack of time" and "lack of success"., Conclusion: Although the majority of health care professionals consider obesity as a serious disease which has a large impact on overall health, counseling for lifestyle modification, pharmacologic or surgical intervention occur in almost half of the visits. Increasing the length of physician visits as well as tailoring appropriate training programs could improve health care for obesity., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: Managing dietary glycemic index (GI) deserves further attention in the interplay between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). This study aimed to evaluate the relationship between dietary GI and the odds of NAFLD in patients with T2DM., Methods: A cross-sectional study was carried out between April 2021 and February 2022, including 200 participants with T2DM aged 18-70 years, of which 133 had NAFLD and 67 were in the non-NAFLD group. Cardiometabolic parameters were analyzed using standard biochemical kits and dietary intake was assessed using a validated food frequency questionnaire. Binary logistic regression was applied to explore odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD according to tertiles of dietary GI., Results: Highest vs. lowest tertile (< 57 vs. > 60.89) of energy-adjusted GI was not associated with the odds of having NAFLD (OR 1.25, 95% CI = 0.6-2.57; P-trend = 0.54) in the crude model. However, there was an OR of 3.24 (95% CI = 1.03-10.15) accompanied by a significant trend (P-trend = 0.04) after full control for potential confounders (age, gender, smoking status, duration of diabetes, physical activity, waist circumference, HbA1c, triglycerides, total cholesterol, dietary intake of total carbohydrates, simple carbohydrates, fat, and protein)., Conclusion: High dietary GI is associated with increased odds of NAFLD in subjects with T2DM. However, interventional and longitudinal cohort studies are required to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salavatizadeh, Soltanieh, Ataei Kachouei, Abdollahi Fallahi, Kord-Varkaneh, Poustchi, Mansour, Khamseh, Alaei-Shahmiri, Santos and Hekmatdoost.)

Introduction: Type 2 diabetes mellitus (T2DM) is a significant risk factor for the development of critical limb ischemia (CLI), the most advanced stage of peripheral arterial disease. The concurrent existence of T2DM and CLI often leads to adverse outcomes, namely limb amputation., Objective: To identify biomarkers for improving the screening of CLI in high-risk people with T2DM., Methods: We investigated metabolome profiles in serum samples of 113 T2DM people with CLI (n = 23, G2) and without CLI (n = 45, G0: no lower limb stenosis (LLS) and n = 45, G1: LLS < 50%), using hydrogen nuclear magnetic resonance ( 1 H NMR) approach. Principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to analyze 1 H NMR data., Results: Twenty potential metabolites that could discriminate people with T2DM and CLI (G2) from non-CLI patients without LLS (G0) were determined in serum samples. The correct percent of classification for the PLS-DA model for the test set samples was 85% (n = 20) and 100% (n = 5) for G0 and G2 groups, respectively. Non-CLI patients with LLS < 50% (G1) were projected on the PCA abstract space built using 20 discriminatory metabolites. Eleven people with T2DM and LLS < 50% were prospectively followed, and their ankle-brachial index (ABI) was measured after 4 years. A promising agreement existed between the PCA model's predictions and those obtained by ABI values., Conclusion: The findings suggest that confirmation of blood potential metabolic biomarkers as a complement to ABI for screening of CLI in a large group of high-risk people with T2DM is needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The aim of this study was to compare moderate- versus high-intensity statin therapy in patients with type 2 diabetes and low-density lipoprotein (LDL) cholesterol less than 130 mg/dL., Methods: This was a randomized, open-label, parallel design trial comprised of 79 patients randomly allocated into two groups receiving high-intensity [atorvastatin 40 mg (A40) or rosuvastatin 20 mg (R20) daily] or moderate-intensity [atorvastatin 20 mg (A20) or rosuvastatin 10 (R10) mg daily] statins for eight weeks. The variables investigated were lipid profile, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6)., Results: The percentage of decrease in LDL levels (±SD) for the high-intensity group (-35.5±25.5) was significantly greater than the moderate-intensity group (-24.6±23.5) ( P =0.04). While 38.1% (n:8) of patients receiving A20 and 55% (n:11) of those being on R10 achieved the targets of≥30% reduction in the LDL level, these figures were 63.2% (n=12) and 73.8% (n=14) for A40 and R20 subgroups, respectively. Subsequently, the likelihood of achieving LDL reduction≥30%, was significantly greater with high-intensity statin therapy (OR: 3.1, 95% CI: 1.09, 8.90, P =0.03). Logistic regression analysis also showed that for every 1 mg/ dL increase in the baseline LDL level, the odds of achieving the LDL reduction≥30% increased by 1.04 times [95% CI: (1.01, 1.07), P =0.003]., Conclusion: Despite the general conception, moderate-intensity statins are not adequate for the majority of patients with T2DM and mild hyperlipidemia and greater numbers of patients could reach the LDL cholesterol target with high-intensity statin therapy., (© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Cardiovascular diseases are the first leading cause of mortality in the world. Practical guidelines recommend an accurate estimation of the risk of these events for effective treatment and care. The UK Prospective Diabetes Study (UKPDS) has a risk engine for predicting CHD risk in patients with type 2 diabetes, but in some countries, it has been shown that the risk of CHD is poorly estimated. Hence, we assessed the external validity of the UKPDS risk engine in patients with type 2 diabetes identified in the national diabetes program in Iran., Methods: The cohort included 853 patients with type 2diabetes identified between March 21, 2007, and March 20, 2018 in Lorestan province of Iran. Patients were followed for the incidence of CHD. The performance of the models was assessed in terms of discrimination and calibration. Discrimination was examined using the c-statistic and calibration was assessed with the Hosmer-Lemeshow χ2 statistic (HLχ2) test and a calibration plot was depicted to show the predicted risks versus observed ones., Results: During 7464.5 person-years of follow-up 170 first Coronary heart disease occurred. The median follow-up was 8.6 years. The UKPDS risk engine showed moderate discrimination for CHD (c-statistic was 0.72 for 10-year risk) and the calibration of the UKPDS risk engine was poor (HLχ2 = 69.9, p < 0.001) and the UKPDS risk engine78% overestimated the risk of heart disease in patients with type 2 diabetes identified in the national diabetes program in Iran., Conclusion: This study shows that the ability of the UKPDS Risk Engine to discriminate patients who developed CHD events from those who did not; was moderate and the ability of the risk prediction model to accurately predict the absolute risk of CHD (calibration) was poor and it overestimated the CHD risk. To improve the prediction of CHD in patients with type 2 diabetes, this model should be updated in the Iranian diabetic population., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background & Objective: High prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus results in deleterious complications and morbidities related to both diseases. Thus, we aimed to investigate dietary and anthropometric risk factors for progression of Non-alcoholic Fatty Liver Disease (NAFLD) in diabetic people., Methods: Anthropometric, and dietary intakes, and hepatic steatosis and fibrosis were assessed in two hundred participants with type two diabetes (T2DM). Subjects with CAP score of more than 270 dB/m were considered to have NAFLD. Multivariable-adjusted ORs and 95% CIs were used to investigate the association between NAFLD and dietary inflammatory index (DII) score and anthropometric indices., Results: Participants in the highest tertile of DII had 2.41 (95% CI:1.16-4.97), 2,53 (95% CI: 1.04-6.16), 2.78 (95% CI: 1.09-7.13) times higher odds of developing NAFLD in comparison to the lowest tertile in crude, adjusted model 1 and 2, respectively. Among those with the highest relative to the lowest tertile of trunk-to-leg fat ratio (TLR), ORs and 95% CI were OR = 1.88, 95% CI = 0.9-3.91, and OR = 7.99, 95% CI = 2.43-26.26 in crude and full-adjusted models. Odds of NAFLD in the third tertile of metabolic score for visceral fat (METS-VF) was higher than the first tertile in crude (OR = 9.5, 95% CI = 4.01-22.46) and full-adjusted models (OR = 4.55, 95% CI = 1.46-14.2)., Conclusions: In conclusion, this study highlighted an association between greater DII (pro-inflammatory diet) and higher NAFLD risk. Moreover, TLR and METS-VF are known as novel estimators of central obesity as a risk factor for NAFLD in diabetes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Coronavirus disease (COVID-19) is an infectious disease caused by a new virus that causes respiratory illness. Older adults and individuals who have pre-existing chronic medical conditions are at higher risk for more serious complications from COVID-19. Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, cardiovascular events and associated comorbidities, which are the main causes of severe clinical complications in COVID-19 patients. Considering the defensive role of vitamin D, mediated through modulation of the innate and adaptive immune system as well as inhibition of the Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.

Background: This study was conducted to evaluate possible associations between Dietary Total Antioxidant Capacity (DTAC) and odds of non-alcoholic fatty liver disease (NAFLD) in people with type-2 diabetes mellitus (T2DM)., Materials and Methods: We recruited two hundred people with T2DM, and evaluated their liver steatosis using Fibroscan. Dietary intakes of participants were assessed using a validated food frequency questionnaire. DTAC was computed via ferric reducing antioxidant power (FRAP)., Results: In the crude model, no statistically significant association was found between DTAC and the odds of NAFLD in people with diabetes. However, after adjustment for potential confounders including age, gender, diabetes duration, smoking status, physical activity, BMI, waist circumference, and energy, the most reduced adjusted OR was indicated for the third tertile vs. the first one (OR: 0.28, 95% CI: 0.09-0.81, P = 0.02), meaning that diabetic patients in the third tertile of DTAC had 72% decreased risk of NAFLD in comparison to those in the first one. The relationship was remained significant after additional adjustment for HOMA-IR, HbA1c, serum Triglyceride (TG), and low-density lipoprotein-cholesterol (LDL) levels (OR: 0.29, 95% CI: 0.09-0.93, P = 0.03). Importantly, a dose-response pattern was demonstrated for DTAC and risk of NAFLD ( P = 0.04)., Conclusion: Higher DTAC was related with a decreased risk of NAFLD in individuals with diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salavatizadeh, Soltanieh, Poustchi, Yari, Shabanpur, Mansour, Khamseh, Alaei-Shahmiri and Hekmatdoost.)

Introduction: The purpose of this study was to determine the association between the postnatal umbilical coiling index (pUCI) and vascular endothelial growth factor A (VEGFA) and its receptor (VEGFR2) in parturients with and without gestational diabetes mellitus (GDM)., Methods: Within 24 h following birth, the umbilical cord and pUCI of 29 newborns with GDM and 28 neonates with non-GDM parturients were prospectively examined. Real-time PCR tests were used to determine the expression levels of the VEGFA and VEGFR2 genes, measured from the umbilical cord. The Mann-Whitney and Chi-squared tests were used to compare continuous and discrete variables with and without GDM., Results: The median (IQR) of maternal age was 30 (26-34) years. There were no differences in demographic features between GDM and non-GDM parturients. While there was a marginal difference in VEGFA expression levels between the GDM and non-GDM groups (P-values = 0.07), no difference was detected for VEGFR2 (P-values = 0.75). Comparing hyper- and hypocoiling cords revealed a small difference in VEGFA levels (P-values = 0.05), but no change in VEGFR2 (P-values = 0.50). Furthermore, in both GDM and non-GDM parturients, down-regulated VEGFA was the general rule among abnormal pUCIs., Discussion: The GDM and coiling state both are associated with the amount of VEGFA expression, but neither is related to VEGFR2. Furthermore, regardless of whether the patient has GDM or not, the abnormal coiling pattern appears to be related to the VEGFA down-regulation., Competing Interests: Declaration of competing interest The authors declare that there are no financial and non-financial conflicts of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Invasive non-functional pituitary adenomas (NFPAs) constitute 35% of NFPAs. Despite a relatively large body of molecular investigations on the invasiveness of NFPA, the underlying molecular mechanisms of invasiveness are yet to be determined. Herein, we aimed to provide an overview of gene/microRNA(miRNAs) expression alterations in invasive NFPA., Methods: This article describes a systematic literature review of articles published up to March 23, 2021, on the transcriptional alterations of invasive NFPA. Five digital libraries were searched, and 42 articles in total fulfilled the eligibility criteria. Pathway enrichment was conducted, and protein interactions among the identified deregulated genes were inferred., Results: In total 133 gene/protein transcriptional alterations, comprising 87 increased and 46 decreased expressions, were detected in a collective number of 1001 invasive compared with 1007 non-invasive patients with NFPA. Deregulation of CDH1, PTTG1, CCNB1, SNAI1, SLUG, EZR, and PRKACB, which are associated with epidermal-mesenchymal transition (EMT), was identified. Moreover, six members of the angiogenesis pathway, i.e., VEGFA, FLT1, CCND1, CTNNB1, MYC(c-MYC), and PTTG1, were detected. SLC2A1, FLT1, and VEGFA were also recognized in the hypoxia pathway. Physical interactions of CTNNB1 with FLT1, CCND1, and EZR as well as its indirect interactions with VEGFA, MYC, CCNB1, and PCNA indicate the tight interplay between EMT, angiogenesis, and hypoxia pathways in invasive NFPAs. In addition, Hippo, JAK-STAT, MAPK, Wnt, PI3K-Akt, Ras, TGF-b, VEGF, and ErbB were identified as interwoven signaling pathways., Conclusion: In conclusion, invasive NFPA shares very common deregulated signaling pathways with invasive cancers. A large amount of heterogeneity in the reported deregulations in different studies necessitates the validation of the expressional changes of the suggested biomarkers in a large number of patients with invasive NFPA., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The South Asian population is rapidly ageing and sarcopenia is likely to become a huge burden in this region if proper action is not taken in time. Several sarcopenia guidelines are available, from the western world and from East Asia. However, these guidelines are not fully relevant for the South Asian healthcare ecosystem. South Asia is ethnically, culturally, and phenotypically unique. Additionally, the region is seeing an increase in non-communicable lifestyle disease and obesity. Both these conditions can lead to sarcopenia. However, secondary sarcopenia and sarcopenic obesity are either not dealt with in detail or are missing in other guidelines. Hence, we present a consensus on the screening, diagnosis and management of sarcopenia, which addresses the gaps in the current guidelines. This South Asian consensus gives equal importance to muscle function, muscle strength, and muscle mass; provides cost-effective clinical and easy to implement solutions; highlights secondary sarcopenia and sarcopenic obesity; lists commonly used biomarkers; reminds us that osteo-arthro-muscular triad should be seen as a single entity to address sarcopenia; stresses on prevention over treatment; and prioritizes non-pharmacological over pharmacological management. As literature is scarce from this region, the authors call for more South Asian research guided interventions., Competing Interests: The authors declare no competing interests., (© 2022 The Korean Society of Osteoporosis. Publishing services by Elsevier B.V.)

Aim: To explore the association of visceral adipose tissue (VAT) area and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM)., Methods: This was a cross-sectional study comprising 100 patients with T2DM and 100 non-T2DM individuals, matched for age, sex, and body mass index (BMI). Transient elastography was used to assess hepatic steatosis and liver stiffness measurements (LSM). Controlled attenuation parameter (CAP) was used to quantify hepatic steatosis. To distinguish grades of hepatic steatosis, cutoff values were as follows: S1 ≥ 302, S2 ≥ 331, and S3 ≥ 337 dB/m. Moreover, VAT area was measured by dual-energy X-ray absorptiometry in accordance with validated protocols., Results: CAP score was significantly higher in participants with T2DM (294.61 ± 3.82 vs. 269.86 ± 3.86 dB/ m; P < 0.001). Furthermore, 42% of participants with T2DM had hepatic steatosis (S > S1: 302 dB/m), while this figure was 26% in non-T2DM group (P < 0.003). The mean liver stiffness measurement was also significantly higher in patients with T2DM (5.53 vs. 4.79 kPa; P < 0.001). VAT area was greater in patients with T2DM compared to non-T2DM individuals: 163.79 ± 47.98 cm 2 versus 147.49 ± 39.09 cm 2 , P = 0.009. However, total and truncal fat mass were not different between the two groups. Age, BMI, waist circumference, ALT, CAP, and LSM were significantly associated with VAT area. BMI and VAT area were the important determinants of steatosis in both groups of participants with and without T2DM. Moreover, the VAT area was associated with the severity of hepatic steatosis and liver stiffness, independent of anthropometric measures of obesity., Conclusion: VAT area is a major determinant of the severity of hepatic steatosis and liver stiffness in patient with T2DM., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Maintaining the pituitary function after surgery is highly important. The aim of this study was to investigate the relationship between preoperative magnetic resonance imaging (MRI) characteristics and pituitary function after surgery of non-functional pituitary macroadenoma., Methods: This retrospective study was performed between 2016 and 2018. Preoperative and postoperative MRI imaging data were retrieved from electronic registration system. The relationship between preoperative MRI characteristics and postoperative pituitary function as well as reconstruction of pituitary gland was investigated using regression models., Results: Complete data were available for 44 patients. Before surgery, invisible normal tissue was observed in 23 patients (53.5%). Suprasellar extension and cavernous sinus invasion were seen in 36 patients (each one 49.1%). There was a significant reverse relationship between preoperative tumor size and postoperative thyroid stimulating hormone (TSH) (odds ratio (OR): - 0.99 (- 0.18, - 0.003), p = 0.04). In addition, we found a significant positive correlation between prolactin level after surgery and tumor size before surgery, (OR: 5.29 (1.65, 8.92), p = 0006). Moreover, postoperative panhypopituitarism was observed in 25% of patients with complete morphologic reconstitution of pituitary tissue. While the rate was 50% in patients with no or partial morphologic reconstruction of pituitary tissue., Conclusion: Preoperative MRI characteristics predict TSH and prolactin level after operation. Furthermore, the adenoma size and volume prior to surgery are the main determinants of normal morphologic reconstruction of pituitary gland., (© 2022. The Author(s).)

Background: Acromegaly is a chronic disease significantly affects the physical, emotional, and health-related aspects of patients' life. This study aimed to validate the Acromegaly Quality of Life Questionnaire (AcroQoL) for the Persian-speaking population., Methods: This cross-sectional study recruited 73 Iranian patients with a confirmed diagnosis of acromegaly. The content validity of the scales was evaluated by an expert panel of eight endocrinologists applying content validity index (CVI) and content validity ratio (CVR). Construct validity was assessed by using confirmatory factor analysis. Internal consistency was assessed on the basis of Cronbach's alpha, and a goodness-of-fit (GoF) index was calculated to display whether the model fitted the data., Results: CVI and CVR yielded values of 0.85 and 0.80, respectively (Acceptable CVI: > 0.78 and CVR: > 0.75). The average variances extracted (AVE) from physical and psychological dimensions were 0.520 and 0.462, respectively, exceeding the minimum criterion of 0.40. Cronbach's alpha for physical and psychological dimensions equaled 0.868 and 0.866, respectively, indicating the adequate internal consistency of multiple items for each construct. The subscales' R square and path coefficient were greater than the recommended threshold as 0.75 (physical dimension: 0.778, psychological dimension: 0.873), demonstrating the suitability of this criterion. Finally, the GoF value of 0.29 indicated the model's moderate fit., Conclusions: The findings revealed that the Persian version of AcroQoL is of adequate validity and reliability for evaluating the quality of life of Iranian people with acromegaly., (© 2022. The Author(s).)

Background: Metabolic abnormalities are frequently seen in patients with acromegaly. However, it is not clear to what extent growth hormone/insulin-like growth factor-1 (GH/IGF-1) contributes to the development of these abnormalities., Objective: This study aimed to explore the impact of postoperative GH/IGF-1 on different aspects of metabolic abnormalities in patients with acromegaly., Methods: This retrospective, registry-based study conducted on 102 patients with acromegaly. The impact of GH/IGF-1 on the cardiometabolic risk factors at 3-12 months after surgery has been investigated using linear and logistic regression models., Results: In this study, each 1 ng/ml increase in the level of GH was significantly associated with a 2 mg/dl increase in the level of fasting blood glucose (FBG), a 0.5 mmHg increase in the level of systolic blood pressure (SBP), and a 0.9 mmHg increase in the level of diastolic blood pressure (DBP). Upon multivariate analysis, GH, but not IGF-1, significantly increased the odds of diabetes mellitus (DM) (OR; 1.2, 95% CI; 1.0-1.4, p = .025)., Conclusions: Our findings indicated at early postoperative stage, GH is significantly associated with the levels of FBG, SBP, and DBP. Moreover, GH, but not IGF-1, appears as a predictive factor for the presence of DM. However, neither GH nor IGF-1 could predict the presence of hypertension HTN , or dyslipidemia in this study., Abbreviations: CVD: Cardiovascular disease; GH: Growth hormone; IGF-1: Insulin-like growth factor 1; BMI: Body mass index; HTN: hypertension; IPTR: Iran Pituitary Tumor Registry; WC: Waist circumference; MRI: Magnetic resonance imaging; FBG: Fasting blood glucose; HbA1C: Glycated hemoglobin; TG: Triglyceride; LDL: Low density lipoprotein; HDL: High density lipoprotein; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Background: Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study., Methods: The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient's demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues., Results: Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient's age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group., Conclusions: According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence., (© 2021. The Author(s).)

Background: Type 2 diabetes (T2D) is a progressive disease that should be managed with insulin in case of oral glucose lowering drugs (OGLDs) failure. If basal insulin is not sufficient, rapid acting insulin will be added before the largest meal. We assessed the impact of adding one prandial insulin to a basal based regimen and insulin glargine in patients with type 2 diabetes to measure the percentage of subjects achieving the HbA1c target by the end of 24 weeks of treatment in routine clinical practice. Methods: This study was a 24-week observational study of patients with T2D not adequately controlled with OGLDs and basal insulin, for whom the physician had decided to initiate prandial insulin. The study endpoint was assessed at visit 1 (baseline), visit 2 at week 12 (±1 week) and visit 3 at week 24 (±1 week). The percentage of patients who achieved HbA1c targets was assessed at week 24. Statistical analyses were performed using IBM SPSS for Windows v 19 (IBM, Armonk, New York, USA). Logistic regression analysis was used to detect predicting factors of achieving the HbA1c target by week 24. P<0.05 was considered as significant level. Results : Four hundred and eighteen patients with a mean±SD age of 56.24±9.85 years and a mean±SD duration of diabetes of 12.50±7.16 years were included. The median total daily dose of basal insulin was 24 units, while prandial insulin was started with 6 (4, 10) U/day, titrating up to 10 (8, 18) U/day at week 24. The daily dose of prandial insulin was the only factor that could significantly predict achieving targeted HbA1c by week 24 [OR: 1.04; 95% CI: 1.007,1.079; p-value: 0.019]. At week 24, 96 (22.9%) subjects achieved the HbA1c target with one prandial insulin. Conclusion : The results of our study suggest that "basal plus therapy" can lead to good glycemic control with a low risk of hypoglycemia and weight gain in patients with type 2 diabetes., (© 2021 Iran University of Medical Sciences.)

Background: The triglyceride-glucose index (TyG), and TyG-driven parameters incorporating TyG and obesity indices have been proposed as reliable indicators of insulin resistance and its related comorbidities. This study evaluated the effectiveness of these indices in identifying hepatic steatosis in individuals with Type 2 diabetes (T2DM)., Methods: This was a cross-sectional study consisting of 175 patients with T2DM (122 with and 53 without NAFLD). TyG index, triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-waist-to-height ratio (TyG-WHtR) were determined using standard formulas. Controlled attenuation parameter (CAP) was measured by transient elastography (FibroScan)., Results: Among obesity parameters, CAP showed the strongest correlation with WHtR, followed by BMI and WC (all P < 0.001). Regression analyses demonstrated TyG-WHtR as a significant predictor of NAFLD with the highest odds ratio, reaching 10.69 (95% CI: 1.68-68.22) for the top quartile (Q4) compared to the first quartile (P = 0.01), followed by TyG-BMI (Q4: 6.75; 95% CI: 1.49-30.67) and TyG-WC (Q4: 5.90; 95% CI: 0.99-35.18). Moreover, TyG-WHtR presented the largest AUC for detection of NAFLD (0.783, P < 0.001) in ROC analysis, followed by TyG-BMI (AUC: 0.751, P < 0.001), TyG-WC (AUC: 0.751, P < 0.001), and TyG (AUC: 0.647, P = 0.002). TyG-WHtR value of 5.58 (sensitivity: 79%, specificity: 68%, P < 0.001) was the best cut-off point to identify hepatic steatosis in this population., Conclusions: This study confirmed that the TyG-related indices comprising TyG and obesity parameters can identify hepatic steatosis more successfully than TyG alone. Furthermore, our results highlighted TyG-WHtR as a simple and effective marker for screening fatty liver in patients with T2DM, which may be used practically in clinical setting., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Over the past decades prevalence of diabetes has increased in Iran and other countries. This study aimed to update the prevalence of diabetes and prediabetes in Iran and to determine associated sociodemographic risk factors, as well as diabetes awareness and control., Methods: This is a nationally representative cross-sectional survey that included 163,770 Iranian adults aged 35-70 years, from different ethnic backgrounds, between 2014 and 2020. Diabetes was diagnosed at fasting blood sugar of ≥ 6.99 mmol/L (126 mg/dL), or receiving blood glucose-lowering treatment. Multivariable logistic regression was applied to detect determinants associated with prevalence of diabetes and prediabetes, as well as predictors of diabetes awareness and glycemic control., Results: Sex- and age-standardized prevalence of diabetes and prediabetes was 15.0% (95% CI 12.6-17.3) and 25.4% (18.6-32.1), respectively. Among patients with diabetes, 79.6% (76.2-82.9) were aware of their diabetes. Glycemic control was achieved in 41.2% (37.5-44.8) of patients who received treatment. Older age, obesity, high waist to hip ratio (WHR), and specific ethnic background were associated with a significant risk of diabetes and prediabetes. Higher awareness of diabetes was observed in older patients, married individuals, those with high WHR, and individuals with high wealth score. Moreover, glycemic control was significantly better in women, obese individuals, those with high physical activity, educational attainment, and specific ethnic background., Conclusions: The prevalence of diabetes and prediabetes is increasing at an alarming rate in Iranian adults. High proportion of uncontrolled patients require particular initiatives to be integrated in the health care system., (© 2021. The Author(s).)

Background: Gestational diabetes mellitus (GDM) is a major pregnancy endocrine problem that has several confirmed risk factors and is associated with adverse pregnancy-related outcomes (PRO)., Objective: To evaluate the relationship between GDM diagnosis and the associated risk factors of PRO (maternal, intrapartum, perinatal, and neonatal) in accordance with International Association of Diabetes and Pregnancy Study Groups criteria., Materials and Methods: This prospective cohort study was performed with 531 singleton parturient (265 GDM and 266 non-GDM). They were selected consecutively from referral hospitals, and the maternal, intrapartum, perinatal, and neonatal outcomes were assessed., Results: The major risk factors influencing the GDM diagnosis were maternal age, obesity, family history of diabetes, previous history of GDM, and previous history of macrosomia. In the comparison of PRO between the groups, significant associations were detected for emergency cesarean delivery, preeclampsia, polyhydramnios, premature rupture of membrane, preterm delivery, and neonatal hyperbilirubinemia in the GDM group. In the multivariate logistic regression analysis, a previous history of stillbirth was significantly associated with maternal and perinatal outcomes. The odds ratios (CI 95%) of the PRO in the women with a GDM diagnosis were: maternal = 2.43 (1.51-3.90), intrapartum = 2.05 (1.35-3.11), perinatal = 2.00 (1.29-3.10), and neonatal = 1.68 (1.08-2.62). The PRO was significantly correlated with GDM diagnosis, but not with the risk factors., Conclusion: The adverse pregnancy outcomes were significantly correlated with GDM diagnosis, and the outcomes were not directly affected by the risk factors. Given the related adverse outcomes for mothers and offspring, early screening and management of GDM is necessary especially in Asians and in low-/middle-income countries., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2021 Kouhkan et al.)

Papillary Thyroid Carcinoma (PTC) accounts for approximately 85% of patients with thyroid cancer. Despite its indolent nature, progression to higher stages is expected in a subgroup of patients. Hence, genomic characterization of the early stages of PTC may help to identify this subgroup, leading to better clinical management. Here, we conducted a comprehensive mutational and somatic copy number alteration (SCNA) investigation on 277 stage one PTC from TCGA. SCNA analysis revealed amplification and deletion of several cancer related genes. We found amplification of 60 oncogenes (Oncs), from which 15 were recurrently observed. Deletion of 58 tumor suppressors (TSs) was also detected. MAPK, PI3K-Akt, Rap1 and Ras were the signaling pathways with large numbers of amplified Oncs. On the other hand, deleted TSs belonged mostly to cell cycle, PI3K-Akt, mTOR and cellular senescence pathways. This suggests that despite heterogeneity in SCNA events, the final results would be the activation/deactivation of a few cancer signaling pathways. Of note, despite large amounts of heterogeneity in stage one PTC, recurrent broad deletion on Chr22 was detected in 21 individuals, leading to deletion of several tumor suppressors. In parallel, the oncogenic/pathogenic mutations in the RTK-RAS and PI3k-Akt pathways were detected. However, no pathogenic mutation was identified in known tumor suppressor genes. In order to identify a potential subgroup of BRAF (V600E) positive patients, who might progress to higher stages, low frequency mutations accompanying BRAF (V600E) were also identified. In conclusion, our findings imply that SCNA have a substantial contribution to early stages of PTC. Experimental validation of the observed genomic alterations could help to stratify patients at the time of diagnosis, and to move toward precision medicine in PTC., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Adipokines play an important role in the development of type 2 diabetes mellitus (T2DM) and its complications like nephropathy. Asprosin is a newly discovered adipokine involved in glucose metabolism and inflammation process. The present study aimed to evaluate asprosin levels in patients with T2DM and T2DM + nephropathy (NP) compared to control subjects as well as investigating its relationship with insulin resistance, inflammation, and renal function markers., Methods: Serum levels of asprosin, adiponectin, IL-6, and TNF-α were measured in 55 control subjects, 54 T2DM, and 55 T2DM + NP patients using ELISA kits., Results: Asprosin was found to be higher in the T2DM (6.73 ± 1.67) and T2DM + NP (7.11 ± 1.54) patients compared to the controls (4.81 ± 1.09) (p < 0.001), while adiponectin indicated a lower concentration in both patient groups compared to the control group. Moreover, IL-6 and TNF-α indicated higher levels in the two patients group compared to the control group. Asprosin was observed to have a positive correlation with HbA1c, FBG, TC, LDL-C, IL-6, and TNF-α in the T2DM group. In the patients with T2DM + NP, asprosin was found to be positively correlated with BMI, HbA1c, insulin, HOMA-IR, Cr, UAE, IL-6, and TNF-α, and it was inversely correlated with eGFR., Conclusion: Higher concentrations of asprosin in the T2DM and T2DM + NP groups and its relationship with glucose and lipid metabolism and markers of renal function and inflammation suggested a possible role for this adipokine in the pathogenesis of both T2DM and nephropathy., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The Middle East and North Africa (MENA) is postulated to have the highest increase in the prevalence of diabetes by 2030; however, studies on the epidemiology of diabetes are rather limited across the region, including in Iran., Methods: This study was conducted between 2016 and 2018 among Iranian adults aged 20 to 65 years residing in Khuzestan province, southwestern Iran. Diabetes was defined as the fasting blood glucose (FBG) level of 126 mg/dl or higher, and/or taking antidiabetic medications, and/or self-declared diabetes. Prediabetes was defined as FBG 100 to 125 mg/dl. Multinomial logistic regression models were used to examine the association of multiple risk factors that attained significance on the outcome., Results: Overall, 30,498 participants were recruited; the mean (±SD) age was 41.6 (±11.9) years. The prevalence of prediabetes and diabetes were 30.8 and 15.3%, respectively. We found a similar prevalence of diabetes in both sexes, although it was higher among illiterates, urban residents, married people, and smokers. Participants aged 50-65 and those with Body Mass Index (BMI) 30 kg/m 2 or higher were more likely to be affected by diabetes [RR: 20.5 (18.1,23.3) and 3.2 (3.0,3.6)]. Hypertension [RR: 5.1 (4.7,5.5)], waist circumference (WC) equal or more than 90 cm [RR: 3.6 (3.3,3.9)], and family history [RR: 2.3 (2.2,2.5)] were also significantly associated with diabetes. For prediabetes, the main risk factors were age 50 to 65 years [RR: 2.6 (2.4,2.8)], BMI 30 kg/m 2 or higher [RR: 1.9 (1.8,2.0)], hypertension and WC of 90 cm or higher [RR: 1.7 (1.6,1.8)]. The adjusted relative risks for all variables were higher in females than males, with the exception of family history for both conditions and waist circumference for prediabetes., Conclusions: Prediabetes and diabetes are prevalent in southwestern Iran. The major determinants are older age, obesity, and the presence of hypertension. Further interventions are required to escalate diabetes prevention and diagnosis in high-risk areas across Iran.

Background: Atherosclerosis is the leading cause of death in patients with diabetes. We aimed to evaluate the association between ankle-brachial index (ABI) and toe-brachial index (TBI) with carotid intima-media thickness (CIMT) in patients with type 2 diabetes (T2DM)., Methods: This cross sectional study included 296 patients with T2DM who met the American Diabetes Association criteria for the assessment of peripheral arterial atherosclerosis. The ABI ≤ 0.9 and TBI ≤ 0.7 were considered as abnormal values. Linear and logistic regression analyses were performed to evaluate the association between TBI/ABI and CIMT., Results: Right CIMT was significantly greater in the low TBI group (p = 0.03) while, left CIMT did not show a significant difference. Each 0.1-unit decrease in TBI value was independently associated with 0.017 mm increase in the right CIMT (β ± SE; -0.017 ± 0.005, p = 0.002) and with odds of the presence of increased CIMT [odds ratio and 95% confidence interval: 1.21 (1.02, 1.44)] after adjustment with all traditional risk factors. There was not any significant association between ABI and increased CIMT., Conclusions: Beyond a suitable tool for the diagnosis of peripheral artery disease in patients with T2DM, TBI can be applied for prediction of subclinical carotid atherosclerosis., Competing Interests: The authors have declared that no competing interests exist.

Background: It remains unclear whether a specific chest CT characteristic is associated with the clinical severity of COVID-19. This meta-analysis was performed to assess the relationship between different chest CT features and severity of clinical presentation in COVID-19., Methods: PubMed, Embase, Scopus, web of science databases (WOS), Cochrane library, and Google scholar were searched up to May 19, 2020 for observational studies that assessed the relationship of different chest CT manifestations and the severity of clinical presentation in COVID-19 infection. Risk of bias assessment was evaluated applying the Newcastle-Ottawa Scale. A random-effects model or fixed-effects model, as appropriately, were used to pool results. Heterogeneity was assessed using Forest plot, Cochran's Q test, and I2. Publication bias was assessed applying Egger's test., Results: A total of 18 studies involving 3323 patients were included. Bronchial wall thickening (OR 11.64, 95% CI 1.81-74.66) was more likely to be associated with severe cases of COVID-19 infection, followed by crazy paving (OR 7.60, 95% CI 3.82-15.14), linear opacity (OR 3.27, 95% CI 1.10-9.70), and GGO (OR 1.37, 95% CI 1.08-1.73). However, there was no significant association between the presence of consolidation and severity of clinical presentation (OR 2.33, 95% CI 0.85-6.36). Considering the lesion distribution bilateral lung involvement was more frequently associated with severe clinical presentation (OR 3.44, 95% CI 1.74-6.79)., Conclusions: Our meta-analysis of observational studies indicates some specific chest CT features are associated with clinical severity of COVID-19., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC., Methods: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews., Results: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90 Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported., Conclusion: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events., Trial Registration: PROSPERO registration number: CRD42019125245 .

BMI does not reflect the location or amount of body fat. We aimed to investigate the role of general and central obesity measures in the prediction of incident gastrointestinal cancers. In this analysis of the Golestan Cohort Study, we included 47 586 cancer-free individuals followed for 12.3 years (IQR: 10.5-13.2). We investigated the association of obesity measures including BMI, waist circumference and waist-to-hip ratio (WHR) at enrollment and the incidence of esophageal, gastric, colorectal and pancreatic cancers. Cox proportional hazard models were used to estimate the association between covariates and gastrointestinal cancer risk. We observed no significant associations between obesity measures and incidence of the above-mentioned gastrointestinal cancers in men. In women, BMI, waist circumference and WHR were associated with significant reductions in the risk of esophageal squamous cell carcinoma (ESCC): hazard ratio (HR): 0.67 [95% confidence interval (CI): 0.56-0.81], HR: 0.71 (95% CI: 0.60-0.84) and HR: 0.80 (95% CI: 0.68- 0.94), respectively. In addition, WHR was associated with significantly increased risks for colorectal cancer (HR: 1.39, 95% CI: 1.08-1.78) and gastric cancer (HR: 1.24, 95% CI: 1.01-1.51) in women. In this study, statistically significant associations between obesity measures and incident esophageal, gastric and colorectal cancers were seen in women., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)