Search

Background: The association between macronutrient consumption and the risk of type 2 diabetes (T2D) remains equivocal. Here, we investigated whether the quantity and quality of macronutrient intake are associated with T2D incidence in a West Asian population., Methods: T2D-free adults (n = 2457, mean age 38.5 ± 13.6 years, 54.2% women) who participated in the third examination cycle (2005-2008) of the Tehran Lipid and Glucose Study were followed for a median of 8.6 years. We estimated the macronutrient quality index (MQI), its individual sub-indices (carbohydrate quality index (CQI), fat quality index (FQI), and healthy plate protein quality index (HPPQI)), as well as the macronutrient quantity. The risk of T2D in relation to macronutrient quantity, quality, and their combined effects was examined using Cox proportional hazard models adjusted for known risk factors for T2D., Results: During the study follow-up, 257 incident cases of T2D were documented. Individuals in the highest tertiles of MQI and CQI had a 27% (HR = 0.73, 95% CI = 0.54, 0.98) and 29% (HR = 0.71, 95% CI = 0.51-0.99) lower T2D risk than those in the lowest tertiles. The T2D incidence was 35% lower in the middle HPPQI tertile than in the lowest (HR = 0.65, 95% CI = 0.47, 0.89). The multivariable adjusted model showed that individuals in the middle and highest tertiles of carbohydrate intake had 32% (HR = 0.68, 95% CI = 0.49-0.95) and 26% (HR = 0.74, 95% CI = 0.55-1.00) lower risks of T2D than individuals in the lowest tertile. A high-quantity, high-quality carbohydrate diet (≥ 58.5% of energy from carbohydrate with a CQI ≥ 13) and a low-glycemic index (GI), high-fiber diet (GI < 55 and fiber ≥ 25 g/d) were related to a reduced risk of T2D by 34% (HR = 0.66, 95% CI = 0.47, 0.93) and 42% (HR = 0.58, 95% CI = 0.38, 0.90), respectively., Conclusion: A diet with a higher carbohydrate quality may be associated with a lower T2D incidence, particularly when the carbohydrate quantity is also high., (© 2024. The Author(s).)

Type 2 diabetes (T2D) significantly increases the risk of vascular complications (12-32 %), which are a major cause of death (over 50 %) in T2D patients. In T2D, both endothelial (ET) and vascular smooth muscle (VSM) cells are impaired, which act as independent risk factors for cardiovascular disease. Thus, the question of this systematic review and meta-analysis is: Do ET-dependent and -independent VSM relaxation impair in T2D? We systematically searched PubMed and Scopus databases until March 2024; 44 eligible clinical trial studies (68, 16, 30, and 50 study arms for acetylcholine (ACh), methacholine (MTH), sodium nitroprusside (SNP), and glyceryl trinitrate (GTN)) published were included. ET-dependent VSM relaxation in response to ACh (overall ES = -28.9 %, 95 % CI: -35.2, -22.7; p<0.001) and MTH (overall ES = -55.3 %, 95 % CI: -63.6, -47.1; p<0.001) decreased in T2D patients compared to controls. ET-independent VSM relaxation in response to SNP (overall ES = -17.2 %, 95 % CI: -35.2, -22.7; p<0.001) and GTN (overall ES = -63.2 %, 95 % CI: -81.0, -45.5; p<0.001) decreased in T2D patients compared to controls. Our meta-analysis showed reductions in both ET-dependent (~40 %) and ET-independent (~25 %) VSM relaxation. The decrease was more pronounced for MTH (~55 %) compared to ACh (~30 %) and for GTN (~63 %) compared to SNP (~17 %). These findings suggest that dysfunction of both ET and VSM contributes to impaired VSM relaxation in T2D patients. See also the graphical abstract(Fig. 1)., (Copyright © 2024 Jeddi et al.)

Aim: We investigated the association of a 3-year change in body weight (BW) and regression to normal glucose regulation (NGR) among different phenotypes of pre-diabetes (Pre-DM), i.e., isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG) and combined IFG-IGT., Research Design and Methods: 1458 Pre-DM subjects (iIFG = 618, iIGT = 462, and IFG-IGT = 378) were assessed for 3-year change-percent in BW (2006-2008 to 2009-2011) and then followed up to 2015-2017, within the national cohort of Tehran Lipid and Glucose Study (TLGS). Binary logistic regression models were used to estimate the probability (odds ratio, ORs) of regression to NGR across categories of 3-year BW change (i.e., ≥5% BW loss, <5% BW loss, BW gain) in different phenotypes of Pre-DM., Results: The mean age of the participants was 53.0 ± 13.7, and 46.8% were men. Over a median of 6 years of follow-up, the rate of regression to normoglycemia was 50.6, 43.2, and 12.7% in iIGT, iIFG, and combined IFG-IGT, respectively. The baseline-adjusted mean of 3-year BW change was not significantly different across Pre-DM phenotypes (0.68 ± 0.19, 0.32 ± 0.22, and 0.23 ± 0.24 kg, in iIFG, iIGT, and IFG-IGT). Three-year BW loss ≥5% was associated with a greater NGR probability in iIGT than other phenotypes (OR = 4.29 vs. 3.90 and 2.84 in IFG-IGT and iIFG, respectively). A modest reduction (<5% of initial BW) resulted in an increased chance of Pre-DM regression among subjects with iIGT (OR = 1.61, 95% CI = 1.03-2.52) but not iIFG or IFG-IGT phenotypes., Conclusion: Short-term intensive BW loss (≥5% of initial BW) increased NGR probability in all Pre-DM phenotypes, with an order of iIGT > combined IFG-IGT > iIFG. Only iIGT takes advantage of moderate BW loss (<5% of initial BW) to increase the chance of Pre-DM regression., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: We assessed the possible effect of usual dairy consumption on pre-diabetes (Pre-DM) remission or progression to type 2 diabetes (T2D)., Methods: Pre-DM adults (n = 334, mean age of 49.4 years, and 51.5% men) were assessed for dairy intakes (2006-2008) and followed up to 9 years for incidence of T2D or normal glycemia (NG). All biochemical measurements were done at baseline and all subsequent examinations with 3-y follow-up intervals. Multinomial regression models with adjustment of confounding variables were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) of incident T2D and NG for each serving/d dairy consumption., Results: The odds of NG was significantly elevated by 69% (OR = 1.69, 95% CI = 1.00-2.86, P = 0.05) per 200 g/d increased high-fat dairy intake, while the amount of total dairy or low-fat dairy was not related to the outcomes. Higher intakes of yogurt were more likely to be associated with an increased odds of NG (OR = 1.82, 95% CI = 1.20-2.74, P = 0.01). Usual intakes of milk, cheese, or cream-butter were not associated to Pre-DM remission or progression to T2D., Conclusion: Regular dairy consumption may increase the chance of Pre-DM regression to NG., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) is a major cause of death worldwide, although limited data are currently available regarding the impact of consuming ultra-processed food (UPF) on its incidence. Given the increased consumption of UPF in Iran, we aimed to investigate the association between UPF intake and CVD risk., Methods: Individuals without CVD (n = 2050) aged ≥ 30 years old were recruited from the Tehran Lipid and Glucose Study (TLGS). Dietary data were collected using a validated food frequency questionnaire (FFQ) and UPF intakes were assessed based on the Nova food classification. Multivariable Cox proportional hazard models adjusted for potential confounders were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for the risk of CVD across tertiles of UPF intake., Results: A 10.1% incidence of CVD occurred over a median follow-up of 10.6 years, with a 22% increase in CVD risk per each 50 g/day UPF intake. Participants with the highest intake of UPF had a 68% greater incidence of CVD compared to those with the lowest intake (HR = 1.68, 95% CI=1.14-2.48) after controlling for potential confounders. Regarding sub-groups of UPF, participants in the 3rd tertile compared to the reference had a significantly increased risk of CVD (HR = 1.56, 95% CI=1.04-2.34). Nevertheless, intake of bread, fast food, sweetened beverages, sweets and desserts, high-fat dairy products, and other UPFs were not associated with greater CVD risk., Conclusion: Our findings support the hypothesis that the incidence of CVD is enhanced with the higher consumption of UPF in a representative sample of the Iranian population., (© 2024. The Author(s).)

Adipose organ, historically known as specialized lipid-handling tissue serving as the long-term fat depot, is now appreciated as the largest endocrine organ composed of two main compartments, i.e., subcutaneous and visceral adipose tissue (AT), madding up white and beige/brown adipocytes. Adipose organ dysfunction manifested as maldistribution of the compartments, hypertrophic, hypoxic, inflamed, and insulin-resistant AT, contributes to the development of type 2 diabetes (T2D). Here, we highlight the role of nitric oxide (NO·) in AT (dys)function in relation to developing T2D. The key aspects determining lipid and glucose homeostasis in AT depend on the physiological levels of the NO· produced via endothelial NO· synthases (eNOS). In addition to decreased NO· bioavailability (via decreased expression/activity of eNOS or scavenging NO·), excessive NO· produced by inducible NOS (iNOS) in response to hypoxia and AT inflammation may be a critical interfering factor diverting NO· signaling to the formation of reactive oxygen and nitrogen species, resulting in AT and whole-body metabolic dysfunction. Pharmacological approaches boosting AT-NO· availability at physiological levels (by increasing NO· production and its stability), as well as suppression of iNOS-NO· synthesis, are potential candidates for developing NO·-based therapeutics in T2D., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier Inc.)

Aim: The present study was conducted to analyze the publications of the Tehran Lipid and Glucose Study (TLGS) and assess its scientific productions during the last 23 years., Methods: The required data were retrieved from the Scopus database. The advanced search was chosen, and the search query included terms related to the TLGS. Search and retrieval of data were conducted on August 30, 2022. Bibliometric indicators have been used at three levels in this research including the level of documents, journals, and authors. Also, the knowledge structure of this set was analyzed at the level of social structure and the level of conceptual structure. Data analysis and visualizations was performed using Bibliometrix and VOSviewer software., Results: A total of 870 documents related to the TLGS have been indexed in the Scopus from 2000 to 2022, and 1148 authors have participated in the relevant studies. 66.4% of the TLGS documents were published in journals with Q1 subject area quartiles. There was an annual growth rate of 20% and average citations per document of 16.5. There was a co-authorship per document of 5.6 and an international co-authorship of 8.7%. According to the co-occurrence network for keywords, the most common areas in the TLGS published documents were nutrition, epidemiologic issues, cardiometabolic-related biomarkers, diabetes, hypertension, lifestyle variables and genetic studies., Conclusion: Over the past 23 years, the TLGS has successfully addressed a wide range of inquiries pertaining to cardiometabolic and nutritional issues in Iran. The remarkable achievements of the TLGS act as a catalyst, advocating for the planning and implementation of additional cohort studies that specifically focus on non-communicable diseases within the Iranian population., Competing Interests: Conflict of interestZB & DK are affiliated with Shahid Beheshti University of Medical Sciences which is the main executor of TLGS., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. 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.)

Introduction: We aimed to investigate the association between coffee drinking and total caffeine intakes with the chance of prediabetes (Pre-DM) regression and progression over 9-years of follow-up., Research Design and Methods: This cohort study included 334 Pre-DM individuals (mean age of 49.4 ± 12.8 years and 51.5% men) who participated in the third phase of the Tehran Lipid and Glucose Study (2006-2008). A validated food frequency questionnaire at baseline assessed habitual coffee consumption. All measurements were done at baseline and all subsequent examinations with 3-year follow-up intervals. The odds ratios (OR) and 95% confidence intervals (CIs) of Pre-DM regression to normal glycemia or progression to type 2 diabetes (T2D) in coffee drinkers/non-drinkers were estimated using multinomial logistic regression analysis., Results: During the study follow-up 39.8% of the study participants were progressed to T2D and 39.8% returned to normal glycemia. Coffee consumption nearly doubled the chance of returning to normal (OR = 2.26, 95% CI = 1.03-4.97). Total caffeine intake was not related to Pre-DM progression and regression. Compared to non-drinkers, coffee drinkers had significantly lower 2-hour serum glucose concentrations over time (152, 95% CI = 144-159 vs. 162, 95% CI = 155-169 mg/dL, P  = 0.05)., Conclusions: Habitual coffee drinking may increase the chance of returning to normal glycemia in Pre-DM subjects., Competing Interests: Competing interestsAll authors declare that they have no competing interests., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. 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: The association of prediabetes (Pre-DM) regression and progression with visceral adiposity index (VAI) and adipose tissue dysfunction (ATD) remains to be investigated., Methods: The present cohort study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 1458 Pre-DM cases (aged ≥ 21 years) who were followed for nine years. VAI was estimated based on waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. ATD status (i.e., absent, mild-moderate, and severe) was defined based on the age-stratified cutoff values of VAI. Multinomial logistic regression models with adjustment of potential confounders were used to estimate the chance of Pre-DM regression to normoglycemia or progression to T2D across ATD status., Results: During the study follow-up, 39.0% of the participants developed T2D, and 37.7% returned to normoglycemia. Compared to mild-moderate ATD, Pre-DM subjects with severe ATD had a higher risk of developing T2D by 45% (OR = 1.45, 95% CI = 11.08-1.93). Severe ATD was also associated with a decreased chance of returning to normoglycemia by 26% (OR = 0.74, 95% CI = 0.55-0.99). Participants with severe ATD had significantly higher fasting (overall mean = 111, 95% CI = 109-112 vs. 106, 95% CI = 105-108 mg/dL) and 2h-serum glucose (overall mean = 165, 95% CI = 161-168 vs. 153, 95% CI = 149-156 mg/dL) concentrations over time., Conclusion: Severe ATD was associated with an elevated risk of developing T2D and longitudinal poor-glycemic controls in Pre-DM subjects. ATD may be a simple and useful index for detecting subjects at a higher risk of Pre-DM progression to T2D, allowing for timely intervention strategies., (© 2024. The Author(s).)

Introduction: We aimed to track longitudinal changes of glycemic status in subjects with pre-diabetes (Pre-DM) in relation to their baseline levels of systemic nitric oxide (NO) production [i.e., measured as serum NO metabolites (NOx), crude and body weight (BW)-adjusted NOx to creatinine ratio (NOx-to-Cr)] over 9 years., Methods: This cohort study included 541 middle-aged Iranian men and women with Pre-DM, recruited in 2006-2008 and followed up to 2015-2017. The colorimetric Griess method was used to measure serum NOx concentration. Multinomial logistic regression analyses estimated the odds ratios (OR) of Pre-DM regression and progression across tertiles (tertile 3 vs. tertile 1 and tertile 2) of serum NOx, crude, and BW-adjusted NOx-to-Cr ratio., Results: Participants who regressed to normoglycemia (NG) had a higher BW-adjusted NOx-to-Cr ratio than those who developed type 2 diabetes (T2D) or those who remained Pre-DM (0.52±0.34 vs. 0.43±0.25 and 0.48±0.29, P =0.023). Higher BW-adjusted NOx-to-Cr increased chance of returning to NG (OR=2.05, 95% CI= 0.98-4.32, P =0.058) and decreased levels of 2h-serum glucose over time ( P time×group =0.025), as well as the decreased overall mean of fasting (106, 95% CI=103-109 vs. 110, 95% CI=108-112 mg/dL, P =0.008) and 2h-serum glucose (153, 95% CI=146-159 vs. 163, 95% CI=158-168 mg/dL, P =0.018)., Conclusion: A higher endogenous NO production (i.e., indirectly measured by BW- and Cr-adjusted serum NOx concentration) in Pre-DM subjects is associated with the chance of returning to NG., Competing Interests: The authors have no conflict of interest., (© 2024 The Author(s).)

Vascular nitric oxide (NO•) resistance, manifested by an impaired vasodilator function of NO• in both the macro- and microvessels, is a common state in type 2 diabetes (T2D) associated with developing cardiovascular events and death. Here, we summarize experimental and human evidence of vascular NO• resistance in T2D and discuss its underlying mechanisms. Human studies indicate a ~ 13-94% decrease in the endothelium (ET)-dependent vascular smooth muscle (VSM) relaxation and a 6-42% reduced response to NO• donors, i.e., sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), in patients with T2D. A decreased vascular NO• production, NO• inactivation, and impaired responsiveness of VSM to NO• [occurred due to quenching NO• activity, desensitization of its receptor soluble guanylate cyclase (sGC), and/or impairment of its downstream pathway, cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG)] are the known mechanisms underlying the vascular NO• resistance in T2D. Hyperglycemia-induced overproduction of reactive oxygen species (ROS) and vascular insulin resistance are key players in this state. Therefore, upregulating vascular NO• availability, re-sensitizing or bypassing the non-responsive pathways to NO•, and targeting key vascular sources of ROS production may be clinically relevant pharmacological approaches to circumvent T2D-induced vascular NO• resistance., (© 2023. The Author(s).)

The possible association of habitual physical activity (PA) and the risk of pre-diabetes (Pre-DM) progression to type 2 diabetes (T2D) or the chance of returning to normoglycemia was investigated. This cohort study included 1167 Pre-DM individuals (mean age of 53.5 years, and 45.3% men) who participated in the third phase of the Tehran Lipid and Glucose Study (2006 - 2008) and followed up to a median of 9 years. PA, including leisure time and job activities, was measured using a reliable and validated Iranian version of the Modifiable Activity Questionnaire and reported as metabolic equivalent (MET)-minutes per week. The odds ratios (ORs) and 95% confidence intervals (CIs) of incident T2D and returning to normoglycemia were estimated in relation to PA levels (i.e., per every 500 MET-minutes/week, or across categories of PA levels < 600 as a reference, 600 - 1500 and > 1500 MET-minutes/week). During the study follow-up, 39.0 % progressed to T2D, and 37.8% returned to normoglycemia. Compared to subjects with a PA < 600 MET-minutes/week, the chance of regression to normoglycemia increased by 58% [OR = 1.58, 95% CI = 1.03 - 2.40 ∼ relative risk (RR) = 1.32, 95% CI = 1.02 - 1.63] among the participants who had a PA > 1500 MET-minutes/week. We further noted that each 500 MET-min/week activity corresponded to an elevated chance of returning to normoglycemia by 5% (OR = 1.05, 95% CI = 1.01 - 1.11). The study's findings provided evidence that higher daily PA levels may facilitate Pre-DM regression to normoglycemia. The beneficial effect of PA in Pre-DM subjects needs to exceed the recommended levels (i.e., 600 MET-minutes/week)., 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.)

Background: The current prospective cohort study aimed to explore the potential associations between dietary sodium (Na), potassium (K), and sodium-to-potassium (Na-to-K) ratio with an incidence risk of cardiovascular disease (CVD) among Iranian adults., Methods: The participants of the Tehran Lipid and Glucose Study (men and women aged 30-84 years, n = 2050), free of CVD at baseline (2006-2008) were included. Dietary intakes were assessed using a validated food frequency questionnaire (FFQ), and incident CVD (i.e., coronary heart disease, stroke, and CVD mortality) were documented up to March 2018. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI) regarding the association between dietary Na, K, and Na-to-K ratio with CVD events., Results: During a median follow-up of 10.6 years, 10.14% of participants experienced CVD outcomes. A 41% increased risk of CVD in relation to each increase in 1000 mg/d of Na intake. In the fully-adjusted model, higher Na intake (> 4143 versus < 3049 mg/d) was significantly related to the increased risk of CVD (HR = 1.99, 95% CI = 1.06-3.74). Independent of the well-known risk factors, a 56% reduced risk of CVD was observed in the participants with a higher dietary K intake (HR = 0.44, 95% CI = 0.20-0.94). A Higher Na-to-K ratio was associated with an increased risk of CVD (HR = 1.99, 95% CI = 1.13-3.52)., Conclusion: Our study showed that the Na-to-K ratio might independently predict future risk of CVD events in adults., (© 2023. The Author(s).)

Objective: The association between consumption of dairy products and risk of chronic kidney disease (CKD) is under debate. We aimed to determine the potential effects of total and subtypes of dairy intake on the occurrence of CKD., Methods: This study was conducted within the Tehran Lipid and Glucose Study (TLGS) on 2416 CKD-free adults. At baseline, consumption of dairy products was estimated using a validated 168-items semiquantitative food frequency questionnaire. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CKD were calculated in tertile categories of dairy products. Also, the CKD risk was estimated with multivariable Cox regression to substitute total dairy with other dietary protein sources., Results: During 8.4 years of follow-up, the incidence rate of CKD was 21%. The participants' mean (±SD) age was 38 (±13) years and 46% were men. Dietary intakes of total dairy, low-fat dairy, and fermented dairy were not associated with CKD risk. There were significant lower risks of CKD in the highest compared to the lowest tertiles of high-fat dairy (HR = 0.76, 95% CI = 0.60-0.95) and high-fat milk (HR = 0.75, 95% CI = 0.59-0.96). However, no significant associations were found between other categories of dairy products and CKD incidence. Substitutions of total dairy with other dietary protein sources were not associated with CKD risk., Conclusions: In this study, higher intakes of high-fat dairy and high-fat milk were associated with lower risks of CKD. No significant associations were found between other dairy products and CKD. More prospective and clinical trials are needed to clarify the issue., (Copyright © 2022. Published by Elsevier Inc.)

Background: We aimed to assess potential associations of habitual dietary pattern scores in relation to the risk of pre-diabetes (Pre-DM) progression to type 2 diabetes mellitus (T2DM) or the chance of returning to normal glycemia., Methods: This cohort study included 334 Pre-DM individuals (mean age of 49.4 years, and 51.5% men) who participated in the third phase of the Tehran Lipid and Glucose Study (2006-2008) and followed up for a median of 9 years. A validated food frequency questionnaire at baseline assessed usual intakes of the participants. Major dietary patterns were identified using principal component analysis. The DASH score and Mediterranean diet score (MDS) were also calculated. Multinomial logistic regression analysis was used to estimate the odds ratios (95% confidence intervals (CIs)) of developing T2DM and returning to normal glycemia in relation to dietary pattern scores., Results: During the study follow-up, 39.8% progressed to T2DM, and 39.8% returned to normal glycemia. Three following major dietary patterns, including Western-style (with a higher load of red meats, hydrogenated fats, sodium, and total fat intakes), healthy pattern (with a higher load of whole grains, vegetables, and dairy products), and processed-foods pattern (with a higher load of processed-meats, fast-foods, salty snakes, and sweets and candies) were identified. The Western-style dietary pattern increased the risk of progressing to T2DM by 38% (OR = 1.38; 95% CI = 1.00 to 1.89, P = 0.050). Other dietary pattern scores were not related to regression or progression from Pre-DM., Conclusion: The Western-style dietary pattern (characterized by higher load of red meats, hydrogenated fats, sodium intake, and high-GI foods) may accelerate the progression of Pre-DM to T2DM., (© 2023. The Author(s).)

Scientific publishing, with about 350-year historical background, has played a central role in advancing science by disseminating new findings, generalizing accepted theories, and sharing novel ideas. The number of scientific journals has exponentially grown from 10 at the end of the 17th century to 100,000 at the end of the 20th century. The publishing landscape has dramatically changed over time from printed journals to online publishing. Although scientific publishing was initially non-commercial, it has become a profitable industry with a significant global financial turnover, reaching $28 billion in annual revenue before the COVID-19 pandemic. However, scientific publishing has encountered several challenges and is suffering from unethical practices and some negative phenomena, like publish-or-perish, driven by the need to survive or get a promotion in academia. Developing a global landscape with collaborative non-commercial journals and platforms is a primary proposed model for the future of scientific publishing. Here, we provide a brief history of the foundation and development of scientific journals and their evolution over time. Furthermore, current challenges and future perspectives of scientific publishing are discussed., Competing Interests: Conflict of Interests: We declare that two authors (A. Gh. and P. M.) are associate editors of the International Journal of Endocrinology and Metabolism., (Copyright © 2022, International Journal of Endocrinology and Metabolism.)

This systematic review and meta-analysis was conducted to pool findings of cohort studies that investigated hazards of type 2 diabetes mellitus (T2DM) in relation to intakes of SFAs. A systematic search was conducted in the PubMed, Scopus, and Embase databases up to June 2021 to find eligible studies. Review articles or commentaries, clinical trials, cross-sectional studies, studies on gestational or type 1 diabetes patients, animal studies, articles with no access to full-texts, articles published in non-English languages, and articles with missing critical data needed for the systematic review were excluded from the meta-analysis. A random-effects model was used to combine study-specific results. Thirteen cohort studies with 361,686 participants and 11,865 T2DM events were included. Dietary total SFA intake, as well as dietary palmitic acid (PA) or stearic acid (SA) were not associated with risk of T2DM when the highest was compared with the lowest intake category (HR = 0.99; 95% CI: 0.91, 1.09; n = 13 for total SFAs; HR = 0.96; 95% CI: 0.79, 1.15; n = 4 for PA; and HR = 1.08; 95% CI: 0.79, 1.49; n = 4 for SA). However, the risk of T2DM decreased by 11% in the highest compared with the lowest category of dietary lauric acid (HR = 0.89; 95% CI: 0.82, 0.97; n = 2), and by 17% in the highest compared with lowest category of dietary myristic acid (MA) (HR = 0.83; 95% CI: 0.74, 0.92; n = 3). There was evidence of publication bias among studies on dietary total SFAs and T2DM. Our results indicated no significant association between dietary total SFA and risk of T2DM. However, dietary intake of MA was negatively associated with developing T2DM., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The potential effects of dietary oxalate (Ox) intake on cardio-renal function have remained unestablished. We evaluated the effect of usual Ox intake and its interaction with dietary calcium (Ca) on incident hypertension (HTN) and chronic kidney disease (CKD)., Methods: Adult men and women, free of HTN and CKD at baseline (2006-2008), were recruited. Dietary intakes were assessed using a validated food frequency questionnaire, and the outcomes were documented up to 2014-2017. Multivariate Cox proportional hazard regression models were used to estimate the development of HTN and CKD in relation to Ox intakes. Repeated-measures generalized estimating equation (GEE) linear regression models were used to assess possible effect of Ox-intake on the estimated glomerular filtration rate (eGFR) and blood pressure levels over eight years., Results: Dietary Ox intakes were positively associated with incident CKD (HR = 2.59, 95% CI = 1.46-4.64) and HTN (HR = 1.79, 95% CI = 1.05-3.04). Compared to high-Ca consumers, subjects who had lower Ca intakes (< 990 vs. 1580 mg/d) had a higher incidence of CKD and HTN (HR = 2.43, 95% CI = 1.06-5.55, and HR = 1.72, 95% CI = 0.76-3.78). Participants with higher intakes of Ox (> 220 vs. < 150 mg/d) had lower eGFR values (75.3, 95% CI = 75.0-76.5 vs. 77.3, 95% CI = 76.6-78.1 mL/min/1.73m 2 , P time×group  = 0.004) and higher SBP levels (112, 95% CI = 111-113 vs. 109, 95% CI = 108-110 mmHg, P time×group  = 0.007) overtime., Conclusion: Higher dietary Ox intake may increase the risk of HTN and CKD. The relation between dietary Ox and risk of HTN and CKD seems to be varied by Ca intake, and subjects with lower Ca intakes may be more burdened by excessive amounts of dietary Ox., (© 2022. The Author(s).)

Inulin is a prebiotic and has beneficial effects on health, such as improving the immune function, lipid profile, and gut microbiota. Some previous studies have assessed the effects of inulin supplementation on cardiometabolic diseases, but the relationship between dietary inulin and these diseases has not been investigated yet. Thus, this survey was designed to assess the potential association between the dietary intake of inulin and the incidence of cardiometabolic diseases, including cardiovascular disease (CVD), hypertension (HTN), chronic kidney disease (CKD), and type 2 diabetes (T2D) among adults. The present prospective cohort study was conducted on participants in the third wave of the Tehran Lipid and Glucose Study (2006-2008) and was followed up until March 2018. The dietary intake of inulin was estimated using a special database that reports values of inulin and oligofructose in grams per 100 g of each food. Cox proportional hazards regression showed that higher consumption of inulin was associated with a lower risk of HTN (HR: 0.79, 95% CI: 0.63 to 0.99) and T2D (HR: 0.94, 95% CI: 0.89 to 1.00). We found no relationship between higher consumption of dietary inulin and the incidence of CKD and CVD in our population. According to our results, it seems inulin from foods had a preventive effect against HTN and T2D, which are major risk factors for cardiovascular and renal events. However, more investigations are warranted.

The literature review is an integral part of the research process, from developing research ideas to disseminating findings. It involves explaining, interpreting, and summarizing published materials around a topic to elaborate a research hypothesis/question, synthesize new concepts, identify knowledge gaps, develop new theories, and identify new research directions. Effective reading and processing of the literature (i.e., analyzing and synthesizing) and actual writing of the literature (verbal or non-verbal output, e.g., tables and figures) are essential stages of an effective literature review. This article provides a practical guide to conducting an effective literature review. In addition, literature search and evaluation are also briefly discussed., Competing Interests: Conflict of Interests: We declared that two of our authors (A.Gh and P.M) are editorial board members., (Copyright © 2022, International Journal of Endocrinology and Metabolism.)

Carbon monoxide (CO), a member of the multifunctional gasotransmitters family produced by heme oxygenases (i.e., HO-1 and HO-2), has received significant attention because of its involvement in carbohydrate metabolism. Experimental evidence indicates that both HO-2- and HO-1-derived CO stimulate insulin secretion, but the latter mainly acts as a compensatory response in pre-diabetes conditions. CO protects pancreatic β-cell against cytokine- and hypoxia-induced apoptosis and promotes β-cell regeneration. CO cross-talks with nitric oxide (NO) and hydrogen sulfide (H 2 S), other important gasotransmitters in carbohydrate metabolism, in regulating β-cell function and insulin secretion. These data speak in favor of the potential therapeutic application of CO in type 2 diabetes mellitus (T2DM) and preventing the progression of pre-diabetes to diabetes. Either CO (as both gaseous form and CO-releasing molecule) or pharmacological formulations made of natural HO inducers (i.e., bioactive components originating from plant-based foods) are potential candidates for developing CO-based therapeutics in T2DM. Future studies are needed to assess the safety/efficacy and potential therapeutic applications of CO in T2DM., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aim: The potential cardiovascular impact of usual intakes of oxalate (Ox) is uninvestigated. We evaluated the effect of dietary Ox and its interaction with dietary calcium (Ca) on incident cardiovascular disease (CVD)., Methods: We included 2966 adult men and women aged 19-84 y without known CVD during baseline enrollment (2006-2008) of the Tehran Lipid and Glucose Study. Dietary intakes were assessed using a validated FFQ, and incident CVD (i.e., coronary heart disease, stroke, and CVD mortality) were documented through March 2018., Results: A 7.1% incident of CVD occurred during a median follow-up of 10.6 y. After multivariable adjustment for traditional risk factors and key dietary nutrients, including total fat and fiber, Ox intakes ≥220 mg/d increased incident CVD (HR T3 vs. T1 = 1.47, 95% CI = 1.02-2.12). This association was potentiated (HR T3 vs. T1 = 2.42, 95% CI = 1.19-4.89) in subjects who had a lower intake of Ca (< 981 mg/d); in a low-Ca diet, an even lower amount of dietary Ox (second tertile, 148-220 mg/d) was related to increased CVD events by 92% (HR = 1.92, 95% CI = 1.00-3.70). No association was observed between dietary Ox and CVD events in the presence of medium- and high levels of Ca intakes. The critical cut-off point of Ox-to-Ca for predicting CVD events was 0.14, which was related to an increased risk of CVD by 37% (HR = 1.37, 95% CI = 1.02-1.84)., Conclusion: Higher dietary Ox intake appeared to be associated with a modestly elevated risk of incident CVD, especially in a diet with a lower amount of Ca., (© 2022. The Author(s).)

Background and Aim: Hydrogen sulfide (H 2 S), a signaling gasotransmitter, is involved in carbohydrate metabolism. Here, we aimed to assess the potential association between serum H 2 S and dysglycemia in the framework of a population-based study., Methods: Adults men and women with completed data (n = 798), who participated in the Tehran Lipid and Glucose Study (2014-2017) were included in the study. Medians of fasting serum H 2 S concentration were compared across the glycemic status of the participants, defined as type 2 diabetes mellitus (T2DM), isolated impaired fasting glucose (IIFG), isolated impaired glucose tolerance (IIGT), combined IFG-IGT, and normal glycemia [i.e., those with both normal fasting glucose (NFG) and normal glucose tolerance (NGT)]. Multinomial logistic regression was used to assess potential associations between serum H 2 S and the defined glycemic status., Results: Mean age of the participants was 45.1 ± 14.0 y, and 48.1% were men. Prevalence of T2DM, IIFG, IIGT, and combined IFG-IGT was 13.9, 9.1, 8.1, and 4.8% respectively. No significant difference was observed in serum H 2 S concentrations between the groups. Lower serum H 2 S (< 39.6 µmol/L) was associated with an increased chance of having IIGT (OR = 1.96, 95% CI = 1.15-3.34) in the adjusted model., Conclusion: Reduced serum H 2 S level may be associated with impaired glucose tolerance., (© 2022. The Author(s).)

Background: We aimed to estimate salt intake among an Iranian population using spot urine-based equations and a dietary-based method., Methods: Adult men and women (n = 2069) were recruited from the Tehran Lipid and Glucose Study (2014-2017). Urinary sodium (Na), potassium (K), and creatinine (Cr) concentrations were measured in the morning spot urine samples. The 24-h urinary Na excretion and predicted salt intake was estimated using five equations, i.e., Kawasaki, Tanaka, Intersalt, Toft, and Whitton. A validated food frequency questionnaire (FFQ) was used to obtain dietary intake of salt. The agreement of each urinary- and FFQ-based salt estimation with the overall mean of the methods, considered as the gold standard, was assessed using the Bland-Altman method., Results: Mean age of the participants was 45.6 ± 14.8 y, and 45.4% were men. Mean (SD) estimated salt intake, derived from the overall mean of the methods, was 9.0 ± 2.2 g/d (10.2 ± 2.1 and 7.9 ± 1.7 g/d in men and women, respectively). Mean bias of the estimations from the overall mean ranged from - 0.2.42 to 2.75 g/d, with the Tanaka equation having the least bias (mean bias = 0.13 ± 1.10, 95% CI - 2.37, 2.30 g/d). Tanaka estimated a mean salt intake of 8.9 g/d (range 2.1 to 18.7 g/d); accordingly, only 5.1% of participants adhered to the recommendation (< 5 g/d salt intake), whereas 26.8% and 2.4% exceeded the recommendation by 2- and threefold., Conclusion: The Tanaka equation could provide a more accurate mean-population estimated salt intake from casual urinary Na concentration in our population. About 95% of the Iranian population exceeded the current recommendations of salt intake., (© 2022. The Author(s).)

Aim: This study aimed to determine the association of urinary microalbumin concentrations with type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS), and its phenotypes. The optimum cut-off values of urinary microalbumin and microalbumin-to-creatinine ratio (MCR) for predicting the chance of having T2DM and MetS were also defined., Methods: Adult men and women (n = 1192) participated in the sixth phase (2014-2017) of the Tehran Lipid and Glucose Study (TLGS), with completed data, were included in the analyses. Odds ratios (ORs) (and 95% confidence intervals (CIs)) of T2DM, MetS, and its components across tertile categories of urinary microalbumin concentrations were estimated using multivariable logistic regressions. The optimal cut-off points of urinary microalbumin and MCR were determined using the receiver operator characteristic (ROC) curve analysis., Results: Participants' mean (±SD) age was 44.9 (±14.0) years, and 44.6% of the participants were men. The prevalence of microalbuminuria was 14.4%. Chance of having T2DM was significantly higher in the highest tertile of urinary microalbumin concentration (OR = 2.29, 95% CI = 1.43-3.67) and MCR (OR = 1.82, 95% CI = 1.15-2.89). Subjects with the highest urinary microalbumin concentration were more likely to have MetS (OR = 1.66, 95% CI = 1.17-2.35), hypertension (OR = 1.63, 95% CI = 1.16-2.30) and hyperglycemia (OR = 1.78, 95% CI = 1.24-2.56). No significant association was observed between urinary microalbumin concentrations and other components of MetS. The optimal cut-off points of urinary microalbumin for predicting the chance of having T2DM and MetS were 14.0 and 13.6 mg/L, respectively., Conclusions: Elevated spot urinary microalbumin, below the values defined as microalbuminuria, was associated with the chance of having T2DM and MetS., (© 2022. The Author(s).)

Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L -1 , is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. High UA concentrations decrease insulin-induced NO synthesis within the endothelial cells by interfering with insulin signaling at either the receptor or post-receptor levels (i.e., proximal and distal steps). At the proximal post-receptor level, UA impairs the function of the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in the insulin signaling pathway. At the distal level, high UA concentrations impair endothelial NO synthase (eNOS)-NO system by decreasing eNOS expression and activity as well as by direct inactivation of NO. Clinically, UA-induced endothelial insulin resistance is translated into impaired endothelial function, impaired NO-dependent vasodilation, and the development of systemic insulin resistance. UA-lowering drugs may improve endothelial function in subjects with hyperuricemia., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Getting feedback from the journals' editorial office upon the peer-review process, revising the manuscript, and responding to reviewers' comments are the essential parts of scientific publishing. The process of revising seems cumbersome and time-consuming as authors must be engaged probably with many comments and requested changes. Authors are advised to approach the reviewer as a consultant rather than an adversary. They should carefully read and understand comments and then decide how to proceed with each requested change/suggestion. In the case of serious disagreement with reviewer comments or misunderstanding, authors can defer the issue to the editor. Preparing a scientific and well-organized "response to reviews" and the revised version of the manuscript can increase the chance of acceptance. Here, we provide a practical guide on dealing with different types of comments (i.e., minor or major revisions, conflicting comments, or those that authors disagree with or cannot adhere to) and how to craft a response to reviews. We also provide the dos and don'ts for making a successful revision., Competing Interests: Conflict of Interests: The authors have no conflict of interest., (Copyright © 2022, International Journal of Endocrinology and Metabolism.)

Oral microbiota dysbiosis, concomitant with decreased abundance of nitrate (NO 3 - )-reducing bacteria, oral net nitrite (NO 2 - ) production, and reduced nitric oxide (·NO) bioactivity, is associated with the development of cardiometabolic disorders. Therefore, restoring the oral microbiome to a health-associated state is suggested as a therapeutic approach to potentiate the NO 3 - -NO 2 - -·NO pathway and provide a backup resource for insufficient NO production in conditions including cardiovascular disease and type 2 diabetes mellitus (T2DM). The current review discusses how inorganic NO 3 - can improve the oral microbial community in patients with T2DM and act as a prebiotic. Both animal and human experiments indicated that inorganic NO 3 - modulates the oral microbiome by increasing the abundance of health-associated NO 3 - -reducing bacteria (e.g., Neisseria and Rothia) and decreasing the plenty of species Prevotella and Veillonella, leading to oral NO 2 - accumulation and improved systemic ·NO availability. Supplementation with NO 3 - reduces caries- and periodontitis-associated bacteria and the pathogenic genus related to insulin resistance and glucose intolerance. In addition, inorganic NO 3 - may provide a more optimal environment for NO 3 - reductase activity in the oral cavity, as it increases salivary flow rate and prevents decreased pH by inhibiting acid-producing bacteria., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The association between dietary fats and the risk of cardiovascular disease (CVD) is under debate. We aimed to determine the potential effects of dietary saturated fats (SFA), mono-unsaturated (MUFA) and poly-unsaturated (PUFA) fatty acids on the occurrence of CVD in an adult Asian population., Methods: This study was conducted within the framework of the Tehran Lipid and Glucose Study on 2809 CVD-free adults, aged ≥ 19 years. Dietary intakes of fats were estimated using a validated 168-items semi-quantitative food frequency questionnaire, at baseline. Adjusted hazard ratios and 95% confidence intervals of CVD were calculated in tertile categories of dietary fats. The risk of CVD was estimated with multivariable Cox regression for the substitution of total fat or SFA with other macronutrients., Results: During 10.6 years of follow up, the incidence rate of CVD events was 7.1%. Mean (± SD) age of the participants was 39 (± 14) years and 43.9% were men. Total fat, animal and plant sources of fats were not associated with risk of CVD events. No significant associations were found between total SFA, lauric acid, myristic acid, stearic acid, palmitic acid as well as MUFA and PUFA and CVD incidence. Substitutions of total fats or SFA with other macronutrients were not associated with CVD risk., Conclusions: In this study, no significant associations were found between dietary fats and CVD risk. Considering the emerging body of literature that suggests no association between fats and CVD risk, reconsideration of dietary recommendations regarding low fat diets to prevent CVD, seems to be essential., (© 2021. The Author(s).)

Background and Aim: Considering the inconsistencies in the cardiovascular effects of dietary acid load and the impact of dietary acidity on the acid-base homeostasis within the body, we aimed to assess the association of dietary acid load and the risk of cardiovascular disease (CVD) in a prospective community-based study., Materials and Methods: Participants (n = 2369) free of CVD at baseline (2006-2008) were included from the Tehran Lipid and Glucose Study (TLGS) and followed up for a mean of 6.7 ± 1.4 years. Dietary intakes of the participants were assessed using a semi-quantitative food frequency questionnaire (FFQ). The dietary acid load was evaluated by Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) scores. Both scores have used the macronutrient and micronutrient data of the Food Frequency Questionnaires. Multivariate Cox proportional hazard regression models were used to estimate the 6-years incident risk of CVDs across tertiles of PRAL and NEAP scores., Results: Mean age and body mass index of participants were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m 2 at baseline. Within 6.7 ± 1.4 years of follow-up, 79 cases of cardiovascular events were reported. NEAP was significantly associated with the incidence of CVDs (HRs = 0.50, CI 0.32-0.96; P for trend = 0.032); however, after adjusting for potential confounders, no significant associations were observed between PRAL and NEAP scores and the risk of CVDs., Conclusions: This study failed to obtain independent associations between dietary acid load and the incidence of CVDs among an Asian population., (© 2021. The Author(s).)

A cover (covering) letter is a brief business letter introducing the scientific work alongside the submission process of a manuscript and is required by most scientific peer-review journals. A typical cover letter includes the name of the editor and the journal, date of submission, the characteristics of the manuscript, the importance of the work and its relevance to prospective audiences, declarations such as author agreements, conflicts of interest statement, funding source (s), and ethical statements. The letter also includes the contact information of the corresponding author (s) and may also include suggestions of potential reviewers. Spending enough time to draft an informative, comprehensive, and concise cover letter is quite worthwhile; a poorly drafted one would not persuade the editor that the submitted work is fit for publication and may lead to immediate rejection. Here, we provide a practical guide to draft a well-written, concise, and professional cover letter for a scientific medical paper., Competing Interests: Conflict of Interests: The authors have no conflict of interest., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Objectives: Ramadan intermittent fasting may affect whole-body metabolism by affecting appetite-related hormones. This systematic review and meta-analysis aimed to clarify the possible effects of Ramadan intermittent fasting on the main hormones regulating appetite and satiety, including leptin and adiponectin., Methods: All English language papers in the PubMed, Scopus, and Embase databases were searched using the keywords "Ramadan fasting", "adiponectin", and "leptin", up to 2020. Data extraction was conducted based on the main data of the studies; the primary outcomes of the analysis were mean changes of adiponectin and leptin levels during the holy month of Ramadan in fasted subjects., Main Results: Data of 16 eligible studies, conducted between 2003 and 2020, were included in the systematic review. Of these, 10 studies with complete data on leptin and adiponectin were included in the meta-analysis. A significant decrease in leptin levels was observed after Ramadan fasting (WMD = -2.28 ng/ml, 95% CI = -3.72, -0.84). Ramadan fasting had no significant effect on adiponectin levels (WMD = 2.19 ng/ml, 95% CI = -0.29, 4.67). Sub-group analysis demonstrated a greater decrease in leptin levels among normal-weight subjects compared to those of overweight/obese subjects (WMD = -4.67 ng/ml, 95% CI = -6.03, -3.31 vs. WMD = -3.43 ng/ml, 95% CI = -5.69, -1.17)., Conclusion: Ramadan fasting may decrease leptin levels, especially in normal-weight subjects. There was high heterogeneity, which may be explained by the differences between the wide ranges of study conditions.

Background: There are insufficient data in case of the potential association of habitual dietary L-arginine and the risk of type 2 diabetes mellitus (T2DM) incidence. Here we aimed to examine the potential effect of dietary L-arginine on the T2DM incidence., Methods: For this cohort study, 2139 T2DM-free adults from the participations of Tehran Lipid and Glucose Study (TLGS) were recruited. Follow up period was approximately 5.8 years. Daily intakes of protein and L-arginine were estimated using a validated food frequency questionnaire with 168 food item. Hazard Ratios (HRs) and 95% confidence intervals (CIs), adjusted for sex, age, smoking, diabetes risk score, physical activity levels, and total energy intakes as well as carbohydrate, fiber, fats and lysine, were calculated for L-arginine as both absolute intake and its ratio from total protein., Results: Mean (±SD) age of the participants was 38.9 (±12.6) years and 54.6% were women. Mean (±SD) intake of dietary protein and L-arginine was 77.2 (±22.4) and 4.05 (±1.50) g/d, respectively. An increased risk of T2DM (HR = 2.71, 95% CI = 1.20-6.09) was observed among participants with higher intakes of L-arginine (median intake of > 5.4 vs. 2.69 g/d). Total protein intake and the ratio of L-arginine to total protein intakes were not related to incidence of T2DM in both crude and adjusted models., Conclusion: We found that higher dietary L-arginine levels may increase risk of T2DM and it may have an independent role in T2DM development.

The evidence for a linkage between dietary intake of choline and betaine, a choline metabolism product, and the risk of hypertension (HTN) is limited. The current population-based cohort study was designed to investigate the possible association between dietary intake of choline and betaine with the risk of HTN in adults. This cohort study was conducted on the participants of the Tehran Lipid and Glucose Study (TLGS). Dietary intake of choline and betaine was calculated using the United States Department of Agriculture (USDA) database. Hypertension was diagnosed as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or used drugs to treat hypotension. In this study, 2865 subjects participated and followed-up for a median of 7.4 years. During the follow-up period, 623 patients with hypertension (22.1%) were detected. Our results revealed per every 100 mg increased dietary intake of choline, the risk of developing HTN decreased by 16% (0.84; 95% CI: 0.74 to 0.96, P for trend = 0.009). No significant association was observed between habitual dietary intake of betaine and the risk of HTN (1.10; 95% CI: 0.88 to 1.38, P for trend = 0.21). After stratification based on age, sex, and BMI, each 100 mg per d increase in dietary choline decreased the risk of HTN occurrence in subjects younger than 55 years old by 17% (0.83; 95% CI: 0.71 to 0.96) and men by 21% (0.79; 95% CI: 0.66 to 0.95). The current study's findings provide further support to confirm the protective properties of choline and choline-rich foods against HTN.

The progressive development of clinical and public health nutrition has long relied on dietary clinical trials (DCTs), investigating the causal relationship between diet and multiple risk factors of non-communicable and chronic diseases. DCTs are also hallmarks for establishing dietary requirements and promoting overall nutritional health among the population. Despite their critical importance in translation into public health strategies and practices, DCTs have several limitations and challenges for study design, implementation and finding interpretation. The complex nature of nutrition interventions, collinearity between diet components, multi-target effects of the interventions, diverse dietary behaviors, and food culture are the most challenging issues. Furthermore, baseline exposure and dietary status, appropriate control groups, blinding, randomization, and poor adherence undermine the effectiveness of DCTs in translation into practices. Disruptive factors will be minimized if researchers are committed to following good clinical practice (GCP) standards available for common designs of clinical trials. Planning DCTs, however, needs careful considerations for hypothesis generation, study design development, the definition of primary and secondary outcome measures, and target population., Competing Interests: Conflict of Interests: The authors declare that they have no competing interests., (Copyright © 2021, International Journal of Endocrinology and Metabolism.)

Beneficial metabolic effects of inorganic nitrate (NO 3 - ) and nitrite (NO 2 - ) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO 3 - to NO 2 - and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO 2 - to NO following ingestion of NO 3 - . In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO 3 - /NO 2 - supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO 2 - -to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO 3 - in patients with T2DM may be at least in part attributed to species differences in AA metabolism and also abnormal metabolism of AA in patients with T2DM. If this hypothesis is proved to be correct, then patients with T2DM may need supplementation of AA to attain the beneficial metabolic effects of inorganic NO 3 - therapy.

Both arginine (Arg) and its precursor citrulline (Cit) have received much interest in the past two decades because of their potential effects on whole-body nitric oxide (NO) production and augmentation of NO-dependent signalling pathways. However, the usefulness of Arg supplementation for NO production is questionable because of its high splanchnic first pass metabolism (FPM), which limits its systemic availability. Both hepatic- and extrahepatic arginases critically limit the availability of Arg for the NO synthase enzymes (NOSs) and therefore, a limited amount of oral Arg can reach the systemic circulation for NO synthesis. Arg also has some undesired effects including induction of arginase activity, an increase of urea levels, a decrease of cellular uptake of Cit and decrease of recycling of Arg from Cit. In contrast, Cit has more availability as an NO precursor because of its high intestinal absorption, low FPM and high renal reabsorption. At the cellular level, co-localization of Cit transport systems and the enzymes involved in the Cit-Arg-NO pathway facilitates channelling of Cit into NO. Furthermore, cells preferably use Cit rather than either intra- or extracellular Arg to improve NO output, especially in high-demand situations. In conclusion, available evidence strongly supports the concept that Cit leads to higher NO production and suggests that Cit may have a better therapeutic effect than Arg for NO-disrupted conditions., (© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Aim: In this randomized placebo-controlled clinical trial, effect of oral inorganic nitrate (NO 3 - ) on metabolic parameters was assessed in patients with type 2 diabetes mellitus (T2DM)., Methods: Seventy-four eligible patients with T2DM were randomly assigned to NO 3 - -rich beetroot powder (5 g/d contains ~250 mg NO 3 - ) and placebo groups to complete intervention over a 24-week period. Blood HbA1c, fasting serum glucose, insulin, C-peptide, as well as lipid profile were assessed at baseline and again at weeks 4, 12, and 24; indices of insulin resistance were also calculated. To assess safety of long-term oral NO 3 - , liver and renal function tests were measured. An intention-to-treat approach was used for data analysis. To compare effect of intervention over time between the groups (time×group), repeated measures generalized estimating equation (GEE) linear regression models were used., Results: Mean age of the participants was 54.0 ± 8.5 (47.9% were male) and mean duration of diabetes was 8.5 ± 6.1 years. A total of 64 patients (n = 35 in beetroot group and n = 29 in placebo group) completed at least two visits and were included in the analyses. No significant difference was observed between the groups for glycemic and lipid parameters over time. Liver and renal function tests, as safety outcome measures, showed no undesirable changes during the study follow-up., Conclusion: Supplementation with inorganic NO 3 - had no effect on metabolic parameters in patients with T2DM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Current evidence regarding the prognostic relevance of urinary sodium-to-potassium ratio (Na-to-K ratio), as an indicator of diet quality is limited. This study was conducted to investigate whether urinary Na-to-K ratio could be related to habitual dietary patterns, in a general population., Methods: This study was conducted in the framework of the Tehran Lipid and Glucose Study (2014-2017) on 1864 adult men and women. Urinary Na and K concentrations were measured in the morning spot urine samples. Dietary intakes of the participants were assessed using a validated 147-item Food Frequency Questionnaire (FFQ) and major dietary patterns were obtained using principal component analysis. Mediterranean dietary pattern and Dietary Approaches to Stop Hypertension (DASH) score, were also calculated. Multivariable-adjusted linear regression was used to indicate association of dietary patterns and urinary Na-to-K ratio., Results: Mean (± SD) age of participants was 43.7 ± 13.9 years and 47% were men. Mean (± SD) urinary Na, K and the ratio was 139 ± 41.0 and 57.9 ± 18.6 mmol/L, 2.40 ± 0.07, respectively. Higher urinary Na-to-K ratio (> 2.37 vs. < 1.49) was related to lower intakes of vegetables (282 vs. 321 g/day), low-fat dairy (228 vs. 260 g/day) and fruits (440 vs. 370 g/day). Western dietary pattern was related to higher urinary Na-to-K ratio (β = 0.06; 95% CI 0.01, 0.16). Traditional dietary pattern, Mediterranean and DASH diet scores were inversely associated with urinary Na-to-K ratio (β = - 0.14; 95% CI - 0.24, - 0.11, β = - 0.07; 95% CI - 0.09, - 0.01, β = - 0.12; 95% CI - 0.05, - 0.02, respectively)., Conclusions: Spot urinary Na-to-K ratio may be used as a simple and inexpensive method to monitor diet quality in population-based epidemiological studies.

Aim: In this study, we aimed to compare the pharmacokinetics of nitrate (NO 3 ) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO 3 was also assessed., Methods: Nine healthy adults and nine T2DM patients were recruited to consume a NO 3 -rich breakfast (~410 mg NO 3 ). Pharmacokinetics of NO 3 were examined using repeated measurements of NOx (nitrate+ nitrite) concentrations of serum and saliva over 8 hours and NO 3 concentrations of spot and 24-h urine samples. Cardiometabolic parameters, including serum levels of glucose, insulin, and triglycerides as well as blood pressure were also measured., Results: Compared to patients with T2DM, serum NOx concentration (Δ 1 = 16.7 vs. 4.4 μmol/L, P=0.057) of healthy subjects sharply increased within 1 hour after NO 3 loading. Healthy subjects had a higher NR activity index, and higher peak salivary NO 3 concentration with a lower time to peak. Diabetic patients with high- compared to low-NR values had a higher whole-body NOx exposure (103±31.4 vs. 58.9±22.1 μmol.h/L); they also showed a better glycemic response and more reduction of blood pressure following ingestion of a NO 3 -rich meal., Conclusion: T2DM may be associated with a different pattern of NOx pharmacokinetics (especially salivary NOx metabolism). Salivary NR activity may have a critical role in postprandial metabolism of NO 3 , and diabetic patients with higher NR activity may take more advantages from NO 3 supplementation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Publishing in peer-reviewed high-quality journals is a gold standard method for disseminating scientific work. Choosing the right journal is one of the most important and difficult aspects of publishing research results. Submitting to an inappropriate journal is one of the most common reasons for fast rejection of manuscripts, resulting in time wasted by the authors and journals' editors. Here, we discuss important factors that should be considered for choosing the right journal to get your work published successfully and effectively. The most important factors for journal targeting are: (1) The journal's characteristics, including its scientific prestige, performance, publishing model, acceptance possibility, and specialty; (2) the manuscript's characteristics, including its relevance to the journal's aim and scope, its intrinsic value, meaning the novelty of the research, soundness of the methodology, potential impact in the field, and its implication; and (3) authors' priorities and limitations., Competing Interests: Conflict of Interests: The authors have no conflict of interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Background: Considering the inconsistent available findings regarding the cardioprotective effect of dietary fatty acid composition, we prospectively examined the feasible association between the dietary fatty acids and the cardiovascular disease (CVD) incidence in framework of the population-based Tehran Lipid and Glucose Study., Methods: A total of 2369 participants (19-70 years, 43.5% men) without CVD at baseline (2006-2008) were included and followed-up for 6.7 years. Fatty acids' dietary intake was estimated using a 168-item semi-quantitative food frequency questionnaire. The CVD incidence risk across tertiles of dietary fatty acids was predicted via Cox proportional hazards regression models., Results: The average age and body mass index of the included population were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m 2 at baseline. Over 6.7 years of follow-up, 79 cases of CVD were detected. The risk of CVD was lower in upper tertile of monounsaturated fatty acids, oleic acid, and docosahexaenoic acid + eicosapentaenoic acid among the tertiles. No significant associations were found between total fat, saturated and polyunsaturated fatty acids' intake, and CVD., Conclusions: Our results suggest that the dietary fatty acid composition might affect the incidence risk of CVD within the Iranian population.

Results of animal experiments are used for understanding the pathophysiology of diseases, assessing safety and efficacy of newly developed drugs, and monitoring environmental health hazards among others. Systematic reviews and meta-analyses of animal data are important tools to condense animal evidence and translate the data into practical clinical applications. Such studies are conducted to explore heterogeneity, to generate new hypotheses about pathophysiology and treatment, to design new clinical trial modalities, and to test the efficacy and the safety of the various interventions. Here, we provide an overview regarding the importance of systematic reviews and meta-analyses of animal data and discuss common challenges and their potential solutions. Current evidence highlights various problems and challenges that surround these issues, including lack of generalizability of data obtained from animal models, failure in translating data obtained from animals to humans, poor experimental design and the reporting of the animal studies, heterogeneity of the data collected, and methodologic weaknesses of animal systematic reviews and meta-analyses. Systematic reviews and meta-analyses of animal studies can catalyze translational processes more effectively if they focus on a well-defined hypothesis along with addressing clear inclusion and exclusion criteria, publication bias, heterogeneity of the data, and a coherent and well-balanced assessment of studies' quality.

Evidence for potential effects of inorganic nitrate (NO 3 ) on body weight is limited to inconsistent findings of animal experiments. In this systematic review and meta-analysis, we aimed to quantify the overall effect of inorganic NO 3 , administered via drinking water, on body weight gain in rats. We searched PubMed, Scopus, and Embase databases, and the reference lists of published papers. Experiments on male rats, reported data on body weight in NO 3 -treated animals and controls, were included for quality assessment, meta-analyses, subgroup analyses, and meta-regressions. Of 173 initially obtained studies, 11 were eligible to be included in the analyses, which covered the years 2004 to 2019 and included a total of 43 intervention (n=395) and 43 control (n=395) arms. Overall, the final body weights were significantly lower in the NO 3 -supplemented groups compared to controls (WMD= -16.8 g, 95 % CI= -27.38, -6.24; P =0.002). Doses of NO 3 higher than the median (> 72.94 mg L -1 d -1 ) and longer NO 3 exposure (> 8 weeks) resulted in greater mean differences (WMD= -31.92 g, 95 % CI= -52.90, -10.94 and WMD= -23.16 g, 95 % CI= -35.64, -10.68 g). After exclusion of experiments using high doses of NO 3 (> 400 mg L -1 d -1 ), the overall mean differences in body weights between the groups decreased by approximately 37 % but remained statistically significant (WMD= -10.11 g, 95 % CI= -19.04, -1.19, P =0.026). Mean changes in body weight were affected by age, baseline values in body weight, and the duration of the studies. These preliminary experimental findings strongly support the hypothesis that NO 3 can be considered as a natural anti-obesity agent., (Copyright © 2020 Bahadoran et al.)

Nitric oxide (NO), a highly reactive gasotransmitter, is critical for a number of cellular processes and has multiple biological functions. Due to its limited lifetime and diffusion distance, NO has been mainly believed to act in autocrine/paracrine fashion. The increasingly recognized effects of pharmacologically delivered and endogenous NO at a distant site have changed the conventional wisdom and introduced NO as an endocrine signalling molecule. The notion is greatly supported by the detection of a number of NO adducts and their circulatory cycles, which in turn contribute to the transport and delivery of NO bioactivity, remote from the sites of its synthesis. The existence of endocrine sites of synthesis, negative feedback regulation of biosynthesis, integrated storage and transport systems, having an exclusive receptor, that is, soluble guanylyl cyclase (sGC), and organized circadian rhythmicity make NO something beyond a simple autocrine/paracrine signalling molecule that could qualify for being an endocrine signalling molecule. Here, we discuss hormonal features of NO from the classical endocrine point of view and review available knowledge supporting NO as a true endocrine hormone. This new insight can provide a new framework within which to reinterpret NO biology and its clinical applications., (© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Citation, the act of properly referring to others' ideas, thoughts, or concepts, is a common and critical practice in scientific writing. Citations are used to give credit to own work, to support an argument, to acknowledge others' work, to distinguish other authors' ideas from one's work, and to direct readers to sources of information. A good citation adds to the scientific prestige of the paper and makes it more valuable to the reader. The citation has three basic elements: quoting from others, an in-text reference to the source, and bibliographic details of the source. Beyond technical skills, the citation needs an in-depth knowledge of the field and should follow basic rules, including the selection of relevant and valid sources, stating information/facts from others' work, and referring to others' work accurately and ethically. Several systems and styles are used to cite scientific sources; however, the most commonly used systems in medical sciences are 'author-date' systems (e.g., Harvard system) and numerical systems (e.g., Vancouver system). Here, we discuss how to make an accurate, complete, and ethical citation, and provide simple and practical guides to organize references in a scientific medical paper., Competing Interests: Conflict of Interests: The authors have no conflict of interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Nitric oxide (NO) contributes to carbohydrate metabolism and decreased NO bioavailability is involved in the development of type 2 diabetes mellitus (T2DM). NO donors may improve insulin signaling and glucose homeostasis in T2DM and insulin resistance (IR), suggesting the potential clinical importance of NO-based interventions. In this review, site-specific roles of the NO synthase (NOS)-NO pathway in carbohydrate metabolism are discussed. In addition, the metabolic effects of physiological low levels of NO produced by constitutive NOS (cNOS) versus pathological high levels of NO produced by inducible NOS (iNOS) in pancreatic β-cells, adipocytes, hepatocytes, and skeletal muscle cells are summarized. A better understanding of the NOS-NO system in the regulation of glucose homeostasis can hopefully facilitate the development of new treatments for T2DM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

An abstract is a self-contained, short, powerful statement that describes a larger body of work. It may be incorporated as part of a published paper, book, grant proposal, thesis, research report, or a conference paper. An abstract of a scientific paper will be published online independently, so it should make sense when it is read alone. An abstract of a hypothesis-testing paper consists of at least four key elements, as follows: (1) study question/hypothesis/aim, (2) experiments/material and methods, (3) results, and (4) response to the question/conclusion(s). The abstract usually begins with a background and may end in applications, recommendations, implications, or speculations. The abstract is one of the many features of a manuscript that competes for the readers' attention; therefore, it should be informative, accurate, attractive, and concise. Since a huge amount of work must be compressed into a few sentences, writing an abstract may be a difficult task that needs professional skills. Here, we provide a practical guide to writing an abstract and selecting keywords for a hypothesis-testing medical paper., Competing Interests: Conflict of Interests: The authors have no conflict of interest., (Copyright © 2020, International Journal of Endocrinology and Metabolism.)

Red beetroot ( Beta vulgaris ), as a naturally occurring root vegetable and a rich source of phytochemicals and bioactive compounds, is known for its beneficial roles in the improvement of several clinical and pathologic outcome. Chronic and acute beetroot juice supplementation, as a cost-effective strategy, is proposed to hold promises in controlling diabetes and insulin hemostasis, blood pressure and vascular function, renal health and the possible effect on microbiome abundance. The secondary outcome and physiological response of microbiome abundance modulation included the non- significant fluctuation of systolic and diastolic blood pressures. Also, some studies have suggested a reno-protective property of beetroot juice that is associated with the reduction of mortality rate and favorable changes in kidney's functional parameters among patients with renal disorders. Similarly, it is shown that the persistent consumption of beetroot juice effectively postpones the postprandial glycemic response and decreases the blood glucose peak. The significant blood pressure lowering effect has been seen among normotensive subjects, which tend to be more considerable among hypertensive individuals and progressive among overweight adults. Within this context, this review aims to provide a comprehensive overview on the therapeutic applications of beetroot juice in metabolic disorders and theirs underlying mechanisms. Despite the inconsistencies in the set of results from the reviewed studies, there is no doubt that further contributing factors must be investigated more deeply in future studies., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

The title of a paper is "like a hat on a head or the front door to a house" and its initial impression. Writing a good and effective title makes the paper more retrievable by search engines and maximizes its impact in the scientific community. The paper's title presents what has been studied, how it has been done, and what are the major results. A well-written title is balanced for being informative and concise, as well as attractively conveying the main topic, highlighting the importance of the study. For writing a good title, it should be drafted correctly, accurately, carefully, and meticulously by the main study keywords. By removing extra and unspecific words, the final title should be unambiguous, memorable, captivating, and informative. Here, we provided an overview of the importance and function of the title as well as different types of titles in scientific medical writing. We also focused on the content and organization of the title of a hypothesis-testing paper. In addition, the features of a good title were discussed., Competing Interests: Conflict of Interests: The authors have no conflict of interest., (Copyright © 2019, International Journal of Endocrinology and Metabolism.)