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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).)

Background: Adequate evidence supports beneficial effects of plant-derived phytochemicals against type 2 diabetes (T2D). Among phytochemicals, dietary flavonoids is one of the superb candidates. The whole studies are carried out in Western populations, so it is needed to investigate the risk of T2D by dietary flavonoid intakes in ethnic origins and other regions to confirm these relations. This study was conducted to investigate whether the daily consumption of total flavonoid and its subclasses can affect the incidence of type 2 diabetes (T2D) in the Iranian population. Methods: Eligible adults ( n This study was conducted on 2882 men and 3665 women, aged 41.3±14.6 and 39.0±13.4 years, respectively. After adjustment for several potential confounders (age, sex, diabetes risk score, physical activity, energy, fiber and total fat intakes), risk of T2D decreased from tertiles 1 to 3 for flavonols (HR (95% CI): 1.00, 0.86 (0.64-1.16), 0.87 (0.63-0.93), P Results: =0.01) and isoflavonoids (HR (95% CI): 1.00, 0.84 (0.62-1.13), 0.64 (0.46-0.88), P trend =0.01) and isoflavonoids (HR (95% CI): 1.00, 0.84 (0.62-1.13), 0.64 (0.46-0.88), P trend =0.02), whereas non-significant results were found for total flavonoid and other subclasses of flavonoid. Conclusion: These results emphasize the potential protective role of flavonols and isoflavonoids rich food (e.g. apple, tea, soy, and dark chocolate) in the prevention of T2D.

The present prospective cohort study aimed to determine whether dietary antioxidants were associated with incident type 2 diabetes mellitus (T2DM). Another objective was to find out whether such associations could be modified by the BMI status. A total of 2188 Tehranian adults aged 21-84 years, free of T2DM with the validated FFQ, was entered in the study. Multivariable Cox proportional hazards models adjusting for confounders were used to assess the association between dietary antioxidants and incident T2DM in total population, as well as in subjects with various BMI statuses. During 8·9 (8·1-9·6) years of follow-up, dietary vitamin E significantly decreased the incident T2DM, after adjustment for confounders. However, other dietary antioxidants were not shown to be significantly associated with incident T2DM. The interaction between dietary vitamin E, Mg and BMI status was found to influence the risk of T2DM ( P for interaction < 0·05). After stratification of subjects based on BMI status, it was found that vitamin E and Mg decreased the risk of T2DM only among normal-weight individual. Also, an inverse association was found among dietary vitamin C, dietary Zn and the risk of T2DM in individuals with normal weight but not in overweight and obese individuals; however, the interaction test tended to be significant for these dietary variables. Dietary antioxidants including vitamin E, vitamin C, Zn and Mg when accompanied by healthy weight, may bring benefits to the prevention of T2DM.

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).)

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.)

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).)

Background: Our knowledge for the possible link between choline and betaine and the risk of type 2 diabetes (T2D) is very limited and contradictory. This study aimed to investigate the prospective association of dietary choline and betaine intakes with the risk of T2D in a group of Tehranian adults. Methods: In this prospective study, 6022 eligible subjects aged ≥18 years were chosen from the participants of the Tehran Lipid and Glucose Study in a secondary analysis. Diet was assessed based on a valid and reliable semiquantitative food frequency questionnaire. At baseline and follow-up examinations, biochemical and anthropometric variables were assessed. Multivariable Cox proportional hazard regression models was used to estimate the new onset of T2D concerning choline and betaine intake. Results: The mean age ± SD of 2707 men and 3315 women were, respectively, 41.4 ± 14.2 and 39.1 ± 13.1. During a median follow-up of 6.63 years, 528 cases of T2D incidence were diagnosed. Participants with a higher intake of choline had a higher intake of protein, fiber, and B12 and a lower intake of energy and carbohydrates. After controlling of confounders a significant positive association was observed between choline intake and the hazard ratio (HR) of T2D across quartiles of choline intake [HR (CI) in the fourth quartile: 1.25 (1.14-1.38), P trend = 0.01], but this significant finding was not reported for betaine intake. For every 100 milligram increase in choline consumption, the HR of T2D increased significantly in all age, sex, and BMI subgroups. Conclusions: Choline consumption increased the risk of T2D in total population and subgroups. No statistically significant association was found between dietary betaine intake and the risk of T2D in total population and subgroups.

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).)

Background: The Dietary diabetes risk reduction score (DDRRS) has recently been considered by researchers as a diet quality index to predict the risk of chronic diseases, such as type 2 diabetes (T2D). In this study, we aimed to assess the association of DDRRS with T2D risk in Iranian adults., Methods: Subjects aged ≥ 40 years without T2D (n = 2081) were selected for the current study from participants of the Tehran Lipid and Glucose Study (2009-2011) and followed for a mean of 6.01 years. We used the food frequency questionnaire to determine the DDRRS that is characterized by eight components, including higher consumption of nuts, cereal fiber, coffee, and polyunsaturated to saturated fat ratio and lower consumption of red or processed meats, trans fats, sugar-sweetened beverages, and high glycemic index foods. The multivariable logistic regression analysis was used to determine the odds ratio (ORs) and 95% confidence interval (CI) of T2D across the DDRRS tertiles., Results: The mean ± SD age of individuals was 50.4 ± 8.2 years at baseline. The Median (25-75 interquartile range) DDRRS of the study population was 24(22-27). During the study follow-up, 233(11.2%) new cases of T2D were ascertained. In the age and sex-adjusted model, the odds of T2D were decreased across tertiles of DDRRS (OR = 0.68; 95%CI: 0.48-0.97, P for trend = 0.037). Based on the multivariable-adjusted model, after controlling all potential confounders, the risk of T2D is reduced across tertiles of DDRRS (OR = 0.66; 95%CI: 0.44-0.98, P for trend = 0.047). Also, higher scores (lower consumption) of red and processed meat (OR = 0.59; 95%CI: 0.39-0.88, P = 0.012) and sugar-sweetened beverages (OR = 0.49; 95%CI: 0.32-0.76, P = 0.002) as DDRRS components were associated with decreased T2D incident., Conclusions: Our findings suggested that a diet with a higher score of DDRRS may be related to reducing the risk of T2D in Iranian adults., (© 2023. The Author(s).)

This study aimed at investigating the association of acrylamide consumption with the incidence of type 2 diabetes (T2D) in adults. The 6022 subjects of the Tehran lipid and glucose study participants were selected. The acrylamide content of food items were summed and computed cumulatively across follow up surveys. Multivariable Cox proportional hazard regression analyses were performed to estimate the hazards ratio (HR) and 95% confidence interval (CI) of incident T2D. This study was done on men and women, respectively aged 41.5 ± 14.1 and 39.2 ± 13.0 years. The mean ± SD of dietary acrylamide intake was 57.0 ± 46.8 µg/day. Acrylamide intake was not associated with the incidence of T2D after adjusting for confounding variables. In women, a higher acrylamide intake was positively associated with T2D [HR (CI) for Q4: 1.13 (1.01-1.27), P trend: 0.03] after adjusting for confounding factors. Our results demonstrated that dietary intake of acrylamide was associated with an increased risk of T2D in women., (© 2023. The Author(s).)

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).)

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.)

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.

Background: Among candidate genes related to type 2 diabetes (T2DM), one of the strongest genes is Transcription factor 7 like 2 (TCF7L2), regarding the Genome-Wide Association Studies. We aimed to conduct a systematic review of the literature on the modification effect of TCF7L2 on the relation between glycemic parameters and lifestyle factors., Methods: A systematic literature search was done for relevant publications using electronic databases, including PubMed, EMBASE, Scopus, and Web of Science, from January 1, 2000, to November 2, 2021., Results: Thirty-eight studies (16 observational studies, six meal test trials, and 16 randomized controlled trials (RCTs)) were included. Most observational studies had been conducted on participants with non-diabetes showing that TCF7L2 modified the association between diet (fatty acids and fiber) and insulin resistance. In addition, findings from meal test trials showed that, compared to non-risk-allele carriers, consumption of meals with different percentages of total dietary fat in healthy risk-allele carriers increased glucose concentrations and impaired insulin sensitivity. However, ten RCTs, with intervention periods of less than ten weeks and more than one year, showed that TCF7L2 did not modify glycemic parameters in response to a dietary intervention involving different macronutrients. However, two weight loss dietary RCTs with more than 1-year duration showed that serum glucose and insulin levels decreased and insulin resistance improved in non-risk allele subjects with overweight/obesity. Regarding artichoke extract supplementation (ALE), two RCTs observed that ALE supplementation significantly decreased insulin concentration and improved insulin resistance in the TT genotype of the rs7903146 variant of TCF7L2. In addition, four studies suggested that physical activity levels and smoking status modified the association between TCF7L2 and glycemic parameters. However, three studies observed no effect of TCF7L2 on glycemic parameters in participants with different levels of physical activity and smoking status., Conclusion: The modification effects of TCF7L2 on the relation between the lifestyle factors (diet, physical activity, and smoking status) and glycemic parameters were contradictory., Prospero Registration Number: CRD42020196327., (© 2022. The Author(s).)

Purpose: The current study aimed to investigate the effects of legumes inclusion in the hypocaloric dietary approaches to stop hypertension (DASH) diet on fasting plasma glucose (FPG) and cardiometabolic risk factors in overweight and obese patients with type 2 diabetes over 16 weeks. Also, the modulatory effects of rs7903146 variant in the transcription factor 7 like 2 (TCF7L2) gene that is associated with the risk of diabetes, were assessed on these cardiometabolic risk factors., Methods: This study was a randomized controlled trial. Three-hundred participants, aged 30-65 years, whose TCF7L2 rs7903146 genotype was determined, were studied. The participants were randomly assigned to receive either the hypocaloric DASH diet or a hypocaloric legume-based DASH diet. The primary outcome was the difference in FPG change from baseline until the 16-week follow-up between the two dietary interventions. The secondary outcomes were differences in insulin resistance and lipid profile changes between the dietary intervention diets., Results: A reduction in FPG, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) was observed at week 16 in both hypocaloric dietary interventions. Compared to the DASH diet, the legume-based DASH diet decreased the FPG and HOMA-IR. There is no interaction between rs7903146 and intervention diets on glycemic parameters., Conclusion: The DASH diet, enrich in legumes, could improve the glycemic parameters in participants with type 2 diabetes, regardless of having rs7903146 risk or non-risk allele., Registration Number of Clinical Trial: Iranian Registry of Clinical Trials (IRCT) (code: IRCT20090203001640N17)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: The aim of this study was to assess the prospective association between diet quality and risk of type 2 diabetes (T2D)., Research Design and Methods: Eligible adults (n=7268) were selected from among participants of the Tehran Lipid and Glucose Study with an average follow-up of 6.6 years. Dietary intakes were assessed using a valid and reliable semiquantitative Food Frequency Questionnaire. Anthropometrics and biochemical variables were evaluated at baseline and follow-up examinations. Dietary pattern scores were calculated for the Healthy Eating Index 2015, Mediterranean diet and the Dietary Approaches to Stop Hypertension diet. Multivariate Cox proportional hazards regression models were used to estimate the development of T2D in relation to diet quality., Results: This study was conducted on 3265 men and 4003 women aged 42.4±14.6 and 40.6±13.5 years, respectively. After adjustment for potential confounders, all three diet quality scores were not associated with risk of T2D. Among individual components of the examined dietary patterns, risk of T2D increased from quartiles 1 to 4 for sodium intake (HR (95% CI) 1.00, 0.97 (0.75 to 1.25), 1.17 (0.92 to 1.49), 1.28 (1.01 to 1.62), P trend <0.01) and decreased from quartiles 1 to 4 for red meat intake (HR (95% CI) 1.00, 0.91 (0.72 to 1.14), 0.75 (0.58 to 0.95), 0.85 (0.67 to 1.08), P trend <0.01)., Conclusion: This study emphasizes a potentially protective relationship of moderate red meat intake against development of T2D; also higher intake of sodium is related to risk of T2D., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 & Aims: In the current study, we aimed to assess the effect of dried Ziziphus jujube on blood glucose, lipid profiles, anthropometric indices, and inflammatory factors in type 2 diabetic(T2D) patients., Methods: In this randomized controlled clinical trial, 48 patients, aged 30-65 years, were randomly assigned to two intervention(n = 24) and control(n = 24) groups. The subjects in the intervention group received 30 g Ziziphus jujube daily for 12 weeks. At baseline and the end of the 12th week, 10 ml of blood was taken from each patient after a 12- to 14-h overnight fasting. Plasma levels of fasting plasma glucose (FPG), triglycerides(TGs), total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C), high-sensitivity C-reactive protein(hs-CRP), and interleukin-6(IL-6) were measured. Anthropometric indices were determined., Results: Plasma FPG, TG, TC, and LDL-C decreased significantly up to -11.36%, -13.59%, -7.46%, -7.65% in the Ziziphus jujube group at the end of week 12 compared to baseline, respectively (P < 0.05), and this reduction was significant in comparison with the control group (P < 0.05). The plasma hs-CRP reduced significantly up to -24.46% in the Ziziphus jujube group at the end of week 12 compared to baseline (P < 0.05), however, this reduction was not significant in comparison with the control group (P < 0.05). Also, there were no significant differences between the two groups in mean changes of body mass index, plasma HDL-C, and IL-6., Conclusions: The current study showed that daily consumption of Ziziphus jujube may have beneficial effects on the lipid profiles and blood glucose levels in T2D., Clinical Trial Registration Number: T his clinical trial was registered at the Iranian registry of clinical trials (IRCT registration number: IRCT20181210041913N1)., Competing Interests: Declaration of Competing Interest The authors declared there is no conflict of interest., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

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).)

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).)

Background: The combined roles of lifestyle factors in the risk of type 2 diabetes (T2D) are not fully investigated. In the present study, we aimed to assess the relationship between a healthy lifestyle score (HLS) and the risk of T2D in Tehranian adults., Methods: A total of 3859 individuals without T2D were recruited from participants of the Tehran Lipid and Glucose Study (2009-2011) who were followed up for a mean period of 6 years. A food frequency questionnaire was used to collect individuals' dietary intakes at baseline. HLS scores was calculated based on three pre-defined methods with focusing on 4 lifestyle factors including, no current smoking, no obesity, high physical activity, and greater adherence to the healthy diet[determined using the alternate healthy eating index-2010(AHEI-2010), modified French Programme National Nutrition Santé-Guideline Score(mPNNS-GS), and healthy diet pattern score(HDP)]., Results: Mean ± SD age of participants(44.4% men) was 41.1 ± 12.3 years. After 6-year follow-up of study, 295(7.6%) new cases of T2D were reported. Based on the age and sex-adjusted model, an inverse association was observed between the higher score of HLS-AHEI-2010 (OR = 0.24;95%CI:0.10-0.60), HLS-mPNNS-GS (OR = 0.28;95%CI:0.15-0.50), and HLS-HDP (OR = 0.39;95%CI:0.24-0.64) and the risk of T2D (P for trend < 0.05). Also, the fully-adjusted model showed that after controlling the effects of various confounders, this invers association between the higher score of HLS-AHEI-2010 (OR = 0.25;95%CI:0.10-0.61, P for trend:0.001), HLS-mPNNS-GS (OR = 0.29;95%CI:0.15-0.55,P for trend:0.001), and HLS-HDP (OR = 0.36;95%CI:0.22-0.61,P for trend < 0.001) and risk of T2D was remained significant., Conclusion: The results of this study suggested that higher score of HLS, characterized by no smoking, normal body weight, vigorous physical activity, and healthy diet, is related to decreased risk of T2D incidence., (© 2022. The Author(s).)

Aims: There is still controversy on optimal percentage of macronutrient intakes especially carbohydrate on prevention of type 2 diabetes (T2D). The aim of the current study was to evaluate the iso-energetic substitution of dietary macronutrients in relation to incidence of T2D., Methods: This prospective study was conducted on 6547 subjects who were followed for 3.0 ± 1.6 years. Dietary intakes were evaluated using a valid and reliable semi-quantitative food frequency questionnaire. Biochemical variables and anthropometrics were evaluated at baseline and follow-up examinations. Multivariate Cox proportional hazard regression models were used to estimate the hazards ratio (HR) of T2D., Results: A one unit higher proportion of carbohydrate from whole grain at the expense of carbohydrate from non-whole grain (HR = 0.82, 95% CI = 0.71-0.95), protein (HR = 0.75, 95% CI = 0.60-0.94), total fat (HR = 0.79, 95% CI = 0.67-0.93), saturated fatty acid (HR = 0.79, 95% CI = 0.65-0.96), poly-unsaturated fatty acid (HR = 0.81, 95% CI = 0.68-0.96) and mono-unsaturated fatty acid (HR = 0.75, 95% CI = 0.60-0.94) was associated with decreased risk of T2D. The substitution of protein and fats was not associated with diabetes. Risk of T2D increased from quartiles 1-4 for trans-fatty acid (HR: 1.00, 1.27, 0.95, 1.97, P trend = 0.01)., Conclusions: A higher proportion of carbohydrate from whole grain in replacement of refined grain, and other macronutrients was associated with decreased risk of T2D. Also our study suggests a positive association between trans-fatty acid intake and risk of T2D., (Copyright © 2021. Published by Elsevier Ltd.)

Background: People with prediabetes can postpone or even reverse progression to type 2 diabetes (T2D) by making dietary changes. This study aimed to examine the association of changes in consumption of total and specific types of dairy products with the subsequent risk of incident T2D among individuals with prediabetes., Method: This cohort study included 639 individuals (50% female, mean age 47.3 years) of the Tehran Lipid and Glucose Study (TLGS) who had prediabetes at baseline. We assessed 3-year changes in the consumption of dairy products using a food frequency questionnaire. Using multivariable logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated for the association of changes in intake of total and subtypes of dairy products during a 3-year interval with the risk of incident T2D in the subsequent 3 years., Results: After almost 9 years of follow-up, the incidence of T2D was 25.2%. Compared with individuals whose intake remained relatively stable over 3 years, those who decreased consumption of total dairy (> 0.5 servings/day) had a higher T2D risk (OR = 1.56; 95% CI: 1.02 to 2.41). Increasing low-fat dairy consumption by 0.50 serving/d was associated with a lower risk of T2D (OR = 0.56; 95% CI: 0.35 to 0.90) compared with stable consumption. Those who increased consumption of low-fat milk (OR = 0.59; 95% CI: 0.37 to 0.92) and low-fat yogurt (OR = 0.55; 95% CI: 0.33 to 0.93) had a lower risk of T2D than those who were relatively stable in their consumption. Replacing low-fat milk and yogurt with regular cheese was associated with 66 and 47% higher risk of T2D, respectively., Conclusion: In individuals with prediabetes, increasing consumption of low-fat dairy, low-fat milk, and low-fat yogurt had reduced risk of subsequent T2D. These data suggest a role of low-fat dairy products in the prevention of T2D among prediabetes patients., (© 2021. The Author(s).)

Purpose: This study aimed to investigate the effects of vitamin K 2 supplementation in the form of menaquinone-7 (MK-7) on glucose, insulin, and lipid metabolism in patients with type 2 diabetes mellitus (T2DM)., Methods: In this double-blinded, placebo-controlled, randomized trial, 68 insulin-independent people with diabetes received either 180 µg MK-7 twice a day or placebo for 12 weeks. We assessed fasting plasma glucose (FPG) and insulin concentrations (primary outcomes), glycated hemoglobin (HbA1c), insulin sensitivity indices, and lipid profiles (secondary outcomes) at baseline and end of the trial., Results: At the end of the trial, FPG (effect size (ES) = - 0.68; p-adjusted = 0.031) and HbA1c (ES = - 0.36; p-adjusted = 0.004) were significantly lower in the vitamin K 2 group compared with the placebo at the end of the trial. The number of participants achieved the target levels of glycemic control based on FPG, and HbA1c concentrations were significantly higher in the vitamin K 2 group compared to the placebo group. Insulin concentrations (ES = - 0.29; p = 0.019) and homeostatic model assessment for insulin resistance (HOMA-IR) significantly decreased in the vitamin K 2 group (ES = - 0.29; p = 0.019) compared to baseline, but their values were not significantly different compared to the placebo group at the end of the trial. No significant variation was observed in lipid profiles., Conclusion: Daily intake of 360 µg Vitamin K 2 in the form of MK-7 for 12-weeks reduces FPG and HbA1c in patients with T2DM but does not have a lipid-lowering effect., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

The objective of this study was to determine the effects of Nigella sativa oil extract on cardiometabolic risk factors in people with type 2 diabetes (T2D). A randomized, controlled, clinical trial was conducted on 43 patients with T2D (23 women and 20 men; aged 53.5 ± 7.4 years). The intervention group (N = 23) received two 500-mg per day soft gel capsules containing Nigella sativa oil extract and the control group (N = 20) received two identical placebo soft gel capsules containing sunflower oil per day for the same period, 8 weeks. Pre- and post-intervention cardiometabolic risk factors were measured. Compared with the placebo, the N. sativa oil significantly decreased FBS (p = .03(, HbA1c (p = .001), total cholesterol (p = .04), TG (p = .003), LDL-c (p = .001), BMI (p < .001), waist circumference (p < .001), SBP (p = .001), and DBP (p = .002). HOMA-IR (p = .51) and HDL-c (p = .91) did not change significantly following Nigella sativa supplementation. Nigella sativa oil exerted beneficial effects on glycemic control, serum lipid profile, blood pressure, and body weight among people with T2D. Further long-term trials in the future may help confirm the current therapeutic benefits of Nigella sativa in T2D., (© 2021 John Wiley & Sons, Ltd.)

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.

Background: This study was aimed to examine the effects of vitamin K2 supplementation on atherogenic status, assessed by insulin resistance (IR)-related indexes, in patients with type 2 diabetes mellitus (T2DM)., Methods: In this double-blind, controlled trial, 68 patients with T2DM on the oral glucose-lowering medications were randomly allocated into two groups receiving daily intakes of 360 μg MK-7 or placebo for 12 weeks. Eight different IR-related indexes were calculated at the baseline and end of the trial., Results: At the end of the study, atherogenic coefficient (mean ± SD: - 0.21 ± 0.45 vs. 0.02 ± 0.43; p = 0.043), triglyceride-glucose index (8.88 ± 0.55 vs. 9.23 ± 0.69; p = 0.029), and atherogenic index of plasma (0.37 ± 0.27 vs. 0.51 ± 0.24; p = 0.031) were significantly lower in the vitamin K2 group, compared to the placebo. However, after accounting for their baseline values, the differences were no more significant. No significant differences were observed in Castelli's Ӏ and ӀӀ risk indexes, the ratio of triglycerides to high-density lipoprotein cholesterol, lipoprotein combine index, and the metabolic score for insulin resistance index between the two groups at the end of the study., Conclusions: Daily intakes of 360 μg vitamin K2 in the form of MK-7 for 12 weeks could not improve the IR-related indexes of Cardiovascular Diseases risk., Trial Registration: The trial was registered on Iranian Registry of Clinical Trials registry (Trial ID. IRCT20190824044592N1) on 22 December 2019. The record can be found at https://en.irct.ir/trial/41728 .

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.

Background: We aimed to assess the associations between insulinemic potential of diet and lifestyle and the risk of diabetes incident, using four empirical indices including the empirical dietary index for hyperinsulinemia (EDIH), the empirical dietary index for insulin resistance (EDIR), empirical lifestyle index for hyperinsulinemia (ELIH), and empirical lifestyle index for insulin resistance (ELIR)., Methods: A total of 3734 individuals, aged ≥ 20 years old, who were free of diabetes at baseline (2008-2011), were followed for 6.2 years (2015-2018) to ascertain incident diabetes. The food frequency questionnaire was used to collect dietary intakes at baseline. Odds ratio (OR) of diabetes were calculated across quartiles of EDIH, EDIR, ELIH, and ELIR using logistic regression, which controlled for confounding factors., Results: The mean ± SD age and BMI of individuals (45.1 % male) were 40.9 ± 12.0 years and 27.1 ± 4.1 kg/m 2 , respectively. At the end of follow-up, 253 (6.8 %) diabetes cases were identified. In the multivariable-adjusted model, individuals in the highest quartile of EDIR (1.58;95 %CI:1.03-2.44, P for trend = 0.025), ELIH (1.89;95 %CI:1.20-2.97, P for trend = 0.004), and ELIR (1.74; 95 %CI:1.11-2.72, P for trend = 0.031) had increased the risk of diabetes. However, no significant associations were found between the score of EDIH and diabetes incident., Conclusions: Higher adherence to EDIR, ELIH, and ELIR scores were associated with increased risk of diabetes, while no significant association was found between EDIH score and diabetes incident.

Background and Aim: The aim of this study was to investigate the association of dietary insulin index(II), insulin load(IL), glycemic index(GI), and glycemic load(GL) with risk of developing diabetes among the Tehranian adults., Methods: This study was conducted within the framework of the Tehran Lipid and Glucose Study on 1149 subjects, aged ≥30 years, who were followed-up for a mean of 8.04 years. Food frequency questionnaire was used to calculate the dietary GI, GL, II, IL at the baseline. Multivariate Cox proportional hazard regression models, adjusted for the potential confounders, were used to estimate the risk of diabetes based on the dietary indices., Results: Mean age of the study population was 44.8 ± 10.4 years and 46.3% of them were men. During a mean of 8.04 ± 2.1 years of follow-up, 76 (6.6%) new cases of diabetes were identified. The mean ± SD of the II, IL, GI, and GL of the participants were 52.4 ± 6.5, 234.9 ± 88.8, 61.8 ± 7.9, and 200.6 ± 74.5, respectively. After adjusting for age, sex, smoking, physical activity, daily energy intake, and body mass index, higher dietary scores of the II[HR = 1.33 (95%CIs = 1.06-1.68)], IL[HR = 1.70(95%CIs = 1.10-2.60)], GI[HR = 1.28(95%CIs = 1.03-1.60)], and GL[HR = 1.84 (95%CIs = 1.19-2.84)] were found to be associated with the increased risk of diabetes incidence per each ones SD increment in the scores. Considering the tertiles of the dietary scores, the risk of developing diabetes was increased significantly from tertile 1 into 3 of the GL, and after adjusting for all the potential covariates (p-trend = 0.002); the diabetes risk was 3.40 (95%CI:1.48-7.83) in those with highest tertile of GL compared to those in the lowest tertile of GL., Conclusion: Our findings suggest that the diet with high GL, GI, II, and IL can increase the incidence of diabetes. The glycemic and insulin load can strongly predict the risk of diabetes rather than the glycemic index and insulin index., Competing Interests: Conflict of Interest The authors declared there is no conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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.)

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.)

This study aims to assess the effects of a community-based lifestyle intervention program on the incidence of type 2 diabetes (T2D). For this purpose, three communities in Tehran were chosen; one community received a face-to-face educational session embedded in a long-term community-wide lifestyle intervention aimed at supporting lifestyle changes. We followed up 9,204 participants (control: 5,739, intervention: 3,465) triennially from 1999 to 2015 (Waves 1-5). After a median follow-up of 3.5 years (wave 2), the risk of T2D was 30% lower in the intervention community as compared with two control communities by (Hazard-ratio: 0.70 [95% CI 0.53; 0.91]); however, the difference was not statistically significant in the following waves. After a median follow-up of 11.9 years (wave 5), there was a non-significant 6% reduction in the incidence of T2D in the intervention group as compared to the control group (Hazard-ratio: 0.94 [0.81, 1.08]). Moreover, after 11.9 years of follow-up, the intervention significantly improved the diet quality measured by the Dietary Approaches to Stop Hypertension concordance (DASH) score. Mean difference in DASH score in the intervention group versus control group was 0.2 [95% CI 0.1; 0.3]. In conclusion, the intervention prevented T2D by 30% in the short-term (3.5 years) but not long-term; however, effects on improvement of the diet maintained in the long-term.Registration: This study is registered at IRCT, a WHO primary registry ( https://irct.ir ). The registration date 39 is 2008-10-29 and the IRCT registration number is IRCT138705301058N1.

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.)

Background and Objectives: NF-kB, SIRT1 and systemic inflammation factors including hs-CRP, IL-6 and TNF-α accelerate atherosclerosis pathogenesis. Our purpose was to evaluate the effect of daily supplementation of three-gram cinnamon on plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α among type 2 diabetes patients., Subjects and Methods: A randomized, double blind, and controlled clinical trial was performed with 44 adult patients who were 25 to 70 years old with type 2 diabetes, randomized to two intervention (n = 22) and control (n = 22) groups differing by daily three grams cinnamon supplementation and placebo for 8 weeks, respectively. The plasma levels of NF-kB, SIRT, hs-CRP, IL-6 and TNF-α were measured by ELISA assay at the beginning and end of the study., Results: After 8-week intervention, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) ended up the trial. It was not observed significant difference in levels of hs-CRP (P = 0.29), TNF-α (P = 0.27), IL-6 (P = 0.52), and Sirtuin-1 (P = 0.51) in between group comparison. While, the result showed significant difference in levels of NF-kB (P = 0.02) between groups. As well as, in among group comparison, there was not observed significant differences except in hs-CRP (P = 0.008) in placebo group., Conclusions: This study elucidated that cinnamon supplementation has no beneficial effects in reduction of NF-kB, SIRT1, hs-CRP, IL-6 and TNF-α levels in type 2 diabetes patients which have a considerable role in development of atherogenesis.

Background: More than 1% of urban Iranians aged >20 years develop type 2 diabetes annually. A major contributing factor is overweight due to energy imbalance and poor quality diet. Even though there are reports on the beneficial effects of some isolated foods on glucose metabolism, researchers are increasingly focusing on dietary patterns versus single foods., Aims: The aim of this study was to evaluate the association between adherence to a Mediterranean diet and risk of type 2 diabetes., Methods: The current study was a case-control study nested in the cohort of the Tehran Glucose and Lipid Study. Among participants who met the study criteria, 187 incident cases of diabetes were identified and matched with 374 healthy controls according to sex, age, date of data collection, and previous history of lifestyle intervention., Results: In the highest Mediterranean Diet Scale (MDS) category there were higher intakes of energy, fibre, glycaemic load, carbohydrate, total fat, and olive oil. However saturated fatty acid and monounsaturated fatty acid intakes decreased in higher MDS categories. The multiple adjusted odds ratios (ORs) for type 2 diabetes among individuals with medium (score 3-4) and high (score 5-8) adherence to MDS were 0.79 (95% CI:0.38-1.65) and 0.93 (95% CI:0.44-1.96), respectively, compared to individuals with low adherence (score 0-3)., Conclusion: Adherence to the Mediterranean dietary pattern was not associated with type 2 diabetes. Increased rates of type 2 diabetes in the Islamic Republic of Iran might be accounted for by the cultural and traditional differences between the Iranian and the Mediterranean dietary patterns., (Copyright © World Health Organization (WHO) 2019. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Soluble forms of vascular adhesion molecules, ICAM-1 and VCAM-1, accelerate atherosclerosis pathogenesis. The present study was conducted to evaluate the effect of daily supplementation of 3 g cinnamon on the plasma levels of ICAM-1 and VCAM-1 among patients with type 2 diabetes. This randomized double-blind placebo-controlled trial was performed on 44 adult patients with type 2 diabetes aged 25-70 years. The patients were randomized to two groups of intervention (n = 22) and control (n = 22), differing by daily cinnamon supplementation or placebo (3 g) for 8 weeks. Plasma levels of ICAM-1 and VCAM-1 were measured at the beginning and end of the study. After 8 weeks, 39 subjects (n = 20 in the cinnamon and n = 19 in the placebo groups) completed the trial. There was a significant reduction in the mean levels of ICAM-1 and VCAM-1 within cinnamon and placebo groups (P < 0.001). But there was no significant difference in ICAM-1 (P = 0.75) and VCAM-1 (P = 0.72) between the groups at the end of the trial. According to the results, cinnamon supplementation has no beneficial effect on the reduction of ICAM-1 and VCAM-1 levels in patients with type 2 diabetes, which have a role in the development of atherogenesis.

Aim: This study was conducted to investigate whether serum NO metabolites (NO x ) could predict the occurrence of type 2 diabetes (T2DM), hypertension (HTN) and metabolic syndrome (MetS). Methods: We measured serum NO x concentrations in the Tehran Lipid and Glucose Study participants (aged ≥19 years) and followed them for a median of 7.7 years for the incidence of outcomes. To determine the appropriate cut-off points of serum NO x for predicting clinical events, a random sampling method (50:50 ratio) was used for the population and for analysis, receiver operator characteristic curve was used. Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of T2DM, HTN and MetS in response to serum NO x values. Results: The optimal cut-off points of serum NO x levels for predicting T2DM, HTN and MetS were 26.5, 25.5 and 25.5 µmol/L, respectively. Participants with serum NO x levels ≥25.5 µmol/L had increased risk of MetS (HR = 1.31, 95% CI = 1.01-1.72). No evidence was found for any association of serum NO x with incidence of T2DM and HTN (HR = 1.03, 95% CI = 0.83-1.77 and HR = 1.09, 95% CI = 0.88-1.35). Conclusion: In this prospective population-based investigation, a higher circulating NO x was associated with development of MetS.

Type 2 diabetes (T2DM) is now considered an independent risk factor for the development of some types of cancers, including liver, pancreas, endometrium, colon, rectum, breast, and bladder cancers. Several underlying mechanisms have been proposed that connect T2DM and cancer: hyperglycemia, hyperinsulinemia, increased levels of free steroid and peptide hormones, oxidative stress, and proinflammatory cytokines. Because nitric oxide (NO), a multifunctional gaseous signaling molecule, plays a critical role in carcinogenesis and tumor growth progression, undesirable changes of the NO system in T2DM may be an important missing link between these two pathogenic conditions. Increased inducible NO synthase (iNOS) activity is seen in T2DM (due to inflammatory cytokines, mitochondrial dysfunction, hyperglycemia and hypoxia), where detrimental amounts of NO can result in the initial carcinogenic transformation of normal cells and progression to malignancy. The uncoupling of endothelial NO synthase (eNOS) and increased generation of free radicals in hyperglycemic conditions can also lead to the formation of highly reactive nitrogen species such as peroxynitrite, which can lead to DNA damage, carcinogenic mutations, and activation of critical pathways involved in cell proliferation and apoptosis. In this review, we focused on the hypothesis that the imbalanced NO metabolism in pathologic conditions such as T2DM may contribute to the development of cancer. Overall, current evidence strongly suggests that an imbalanced NO metabolism in T2DM may contribute to the development of cancer.

Background/objectives: Type 2 diabetes (T2D) is fast increasing in recent decades. Limited prospective studies are available on Mediterranean diet protective effect against T2D development. We assessed longitudinal association of the Mediterranean diet with T2D risk in Iranian men and women., Subjects/methods: Diet was measured using a 168-item food frequency questionnaire in 2139 adults (free of T2D), aged 20-70 years. All individuals, based on the traditional Mediterranean diet score (MDS), received scores between 0 and 8 points. Multivariate hazard ratio (HR) and 95% confidence interval (CI) were reported for the association of T2D and the MDS, with adjustment of diabetes risk score (DRS) and dietary energy intakes., Results: During follow-up, a total of 143 events occurred. Individuals who had higher intakes of fish/sea foods, legumes, nuts, and monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) ratio had a decreased risk of T2D. After adjustment for confounders, an inverse association was found between adherence to the MDS and T2D (HR = 0.48; 95% CI 0.27-0.83)., Conclusions: Our findings demonstrated an inverse association between the Mediterranean diet score and incidence of T2D.

Background and Objective: This randomized crossover clinical trial investigated the effects of substituting legumes for meat consumption in the therapeutic lifestyle change (TLC) diet on leptin and adiponectin concentrations among type 2 diabetic patients., Material and Methods: Thirty-one type 2 diabetic patients (24 women, age: 58.1±6.0 years) were randomly assigned to groups designated to consume a legume-free TLC diet or a legume-based TLC diet for 8 weeks. Both diets were similar except for the replacement of two servings of red meat with legumes 3 days per week in the legume-based TLC group. Leptin and adiponectin concentrations were measured at baseline and after the 8-week intervention., Results: The legume-based TLC diet significantly increased adiponectin concentrations in comparison with the legume-free TLC diet. There was no significant change in leptin concentrations after both intervention diets., Conclusions: Legumes increased serum adiponectin concentrations in type 2 diabetic patients. Registration number: IRCT201202251640N7., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: The role of gut microbiota in the pathogenesis of diabetes is increasing; this study investigates the effect of multi-strain probiotics on fasting plasma glucose (FPG), plasma insulin and lipid profile among patients., Methods: This randomized double blind controlled trial was performed among 60 patients; individuals were randomly assigned into 2 groups of 30 participants in order to take either probiotic supplements or placebo for 6 weeks. The probiotic supplement consisted of 7 viable strains Lactobacillus, Bifidobacterium and Streptococcus. Nutrient intakes were estimated using a 3-day and 24 hour-dietary recall at the beginning and end of study. Fasting blood samples were taken before and after intervention to measure the levels of FPG, plasma insulin and lipid profiles., Results: Within group comparisons showed significant decrease and increase in the levels of FPG (P = 0.001) and HDL-C (P = 0.002) in probiotic group, respectively. No significant alterations were observed for within and between group comparisons in the levels of insulin, triglycerides, total cholesterol, insulin resistance and anthropometric measurements, including weight, waist circumference and body mass index (all P > 0.05)., Conclusions: This study showed a significant decrease in FPG level by multi-strain probiotic supplements in within group comparison; though, further studies are needed to confirm results. (IRCT Code: IRCT2013100714925N1)., (Copyright © 2018. Published by Elsevier Ltd.)

In 1976, an animal model of type 2 diabetes (T2DM) was described by Cameron et al. using injection of monosodium glutamate (MSG) in KK mice during the neonatal period. Some years later, similar models have been developed by various doses and durations and the main of these models exhibited obesity and features of diabetes mellitus, including glycosuria, hyperglycemia, hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. Studies indicated that MSG treatment of newborn animals generates necrosis of neuronal cells of the hypothalamic ventromedial nucleus and arcuate nucleus. Neonatal MSG-treatment was related to normoglycemic-normoinsulinemic state at young ages and development of obesity and hyperinsulinemia at adult ages. Following observation of a severe hypertrophy of pancreatic islets due to the proliferation of β-cells in MSG-treated mice, this model has been proposed as a useful animal model of human T2DM. A higher dose of MSG (≥4 mg/g body weight) accompanied by a longer follow-up duration (>6 months) are needed to establish a typical animal model of T2DM.

Epidemiological studies have demonstrated an association between type 2 diabetes (T2DM) and the development of different types of cancer including those of the liver, pancreas, endometrium, colon and rectum, breast, and bladder. The association between T2DM and cancers may partly be due to shared common risk factors of these pathologic conditions and/or anti-diabetic treatments. Hyperglycemia and hyperinsulinemia, two important features of T2DM, are more clinically relevant factors in cancer development. Other factors, including the increased levels of insulin-like growth factor, steroid and peptide hormones, oxidative stress, and inflammatory markers, are also involved in the connection between T2DM and cancer. This review provides a brief overview of the epidemiological evidence supporting the association of T2DM and cancer and discusses the most important potential causes.

Background: Type 2 diabetes is a multifactorial disorder influenced by both genetic and environmental factors and is rising dramatically throughout the world. Recently, consideration to dietary acid-base load has been raised as a nutritional indicator that could have metabolic effects., Objective: The aim of this study was to systematically investigate the associations of dietary acid load indices with glucose/insulin homeostasis and type 2 diabetes in a patent based review., Methods: Systematic literature review was conducted using PubMed, Scopus and Google Scholar, from inception up to 10 January 2018. All human studies publications investigated the association of dietary acid load indices (PRAL or NEAP or Pro:K) and incidence of diabetes or glucose/insulin metabolism were included., Results: In all, 174 studies were included for the title and abstract screening. A total of 164 articles were excluded because they did not meet the inclusion criteria. Finally, 10 articles (five crosssectional studies and five cohort studies) in accordance with our inclusion criteria were chosen for further evaluations that were published between 2008 and 2017., Conclusion: Although there are some evidence of an association between dietary acid load and type 2 diabetes, definitive declarations in this regard will be needed to intervention human studies modifying acid-base dietary intake., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Previous studies indicate that the risk for diabetes associated with high consumption of potato differs in various populations. We aimed to investigate the associations between total, boiled and fried potato intake and the risk for incident diabetes in Tehranian adults., Methods: This cohort study was conducted in 1,981 adults, aged 19 to 70 years, who participated in the Tehran Lipid and Glucose Study and were followed up for 6 years. Usual dietary potato intakes were assessed using a valid and reliable food-frequency questionnaire. Anthropometric, biochemical and blood pressure data were determined, and diabetes was defined according to the criteria of the American Diabetes Association., Results: The mean (± SD) age and potato intake of participants was 38.9±13.4 years and 30.2±30.7 g/day, respectively. The risk for incident diabetes in participants was 6.7% after 6 years of follow up. After adjusting for age, sex, body mass index, physical activity, smoking, family history of diabetes, hypertension, serum triglyceride levels, high-density lipoprotein cholesterol levels, energy intakes and consumption of saturated fat, fruit, whole grains, vegetables, nuts and legumes, the risk for incident diabetes was lower in subjects with higher intakes of total potato (OR=0.46; 95% CI 0.25 to 0.84) and boiled potato (OR=0.47; 95% CI 0.26 to 0.85) in comparison with those who had the lowest intakes (p for trend <0.05). However, there was no significant association between fried potato intake and risk for diabetes (OR=0.50; 95% CI 0.25 to 1.07; p for trend >0.05)., Conclusions: Our findings indicate that, in Tehranian adults, a moderate intake of dietary total and boiled, but not fried, potatoes may be associated with a lower risk for incident diabetes., (Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Here, we examined the potential effect of coffee consumption and total caffeine intake on the occurrence of pre-diabetes and T2D, in a population with low coffee consumption., Methods and Results: Adults men and women, aged 20-70 years, were followed for a median of 5.8 y. Dietary intakes of coffee and caffeine were estimated using a 168-food items validate semi-quantitative food frequency questionnaire, at baseline. Cox proportional hazards regression models, adjusted for potential cofounders, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between coffee and caffeine intakes and incidence of pre-diabetes and T2D. The total population was 1878 adults (844 men, 1034 women) and 2139 adults (971 men, 1168 women) for analysis of pre-diabetes and T2D, respectively. During the follow-up period the incidence of pre-diabetes and T2D was 30.8% and 6.6%, respectively. Forty-three percent of our subjects were no coffee drinker whereas 51.4% consumed 1 cup of coffee/week and 6.0% consumed more than 1 cup of coffee/week. A lower risk of pre-diabetes (HR = 0.73, 95% CI = 0.62-0.86) and T2D (HR = 0.66, 95% CI = 0.44-1.00) was observed in coffee drinkers compared to non-drinkers, in the fully adjusted models. Higher dietary intake of caffeine (≥152 vs. <65 mg/d) was accompanied with a borderline (P = 0.053) reduced risk of pre-diabetes (HR = 0.45, 95% CI = 0.19-1.00)., Conclusion: Our findings indicated that coffee drinking may have favorable effect in prevention of pre-diabetes and T2D., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aim: Studies suggest that fatty acid intake may be an important determinant of type 2 diabetes mellitus (T2DM). This study aims to prospectively examine the association between fatty acid quantity and quality with risk of T2DM in adults., Methods: In this community-based prospective sample, 2139 adults, free of T2DM, aged 20-70y-old were followed for a median of 5.8 y. Diet information was collected with the use of a validated questionnaire at baseline. Cox regression and 95% confidence intervals (CI), adjusted for age, diabetes risk score (DRS), and dietary intakes of energy, fiber and magnesium, were used to evaluate the association of fatty acid intakes with incident T2DM., Results: During follow-up, we identified 143 incident T2D cases. In multivariable analyses, when extreme quintiles were compared, cholesterol (HR = 0.40; 95% CI: 0.20-0.82; P-trend, 0.02), monounsaturated fatty acids (HR = 0.30; 95% CI: 0.13-0.70; P-trend, 0.02), polyunsaturated fatty acids (HR = 0.45; 95% CI: 0.24-0.93 P-trend = 0.04) and ω-3 fatty acids (HR = 0.55; 95% CI: 0.31-0.88; P-trend = 0.02) were associated with T2DM. The ratio of ω-6 to total ω-3 intake was associated with a higher risk of T2D (HR = 1.65; 95% CI: 1.05-2.86; P-trend, 0.04). We also found positive associations between the ratios of total fat to ω-3 (HR = 1.65; 95% CI: 1.02-2.46; P-trend = 0.05)., Conclusions: Our findings indicate that diets with high cholesterol, monounsaturated, polyunsaturated and ω-3 fatty acids are associated with a lower risk of T2DM. Also the ratios of ω-6/ω-3 and total fat/ω-3 were positively associated with T2DM., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to investigate the effect of barberry juice (BJ) on cardiovascular risk factors in patients with type 2 diabetes (T2DM)., Methods: 46 diabetic Patients were randomly allocated to either the BJ group (n = 23) who consumed 200 ml of BJ daily for eight weeks, or the control group (n = 23) with no intervention. At the baseline and the end of 8-week intervention, blood pressure and biochemical markers were measured., Results: forty-two Patients completed the study. After intervention systolic blood pressure (SBP), diastolic blood pressure (DBP), Fasting Blood Sugar (FBS) Total Cholesterol significantly decreased (P < 0.05 for treatment effect) also Triglyceride (TG) decrease significantly in BJ group. Paraoxonase-1(PON1) concentrations significantly increased in Bj group and have a significant difference (P < 0.0001 for treatment effect) compared with control group., Conclusions: This study revealed that BJ might decrease the risk of cardiovascular diseases in patients with diabetes., (Copyright © 2018. Published by Elsevier Ltd.)

The objective of this study was to investigate whether a diet rich in legumes are associated with oxidative stress among type 2 diabetic patients. In a randomized, controlled, crossover clinical trial, 31 type 2 diabetic patients were randomly assigned to receive 2 diets, each for a period of 8 weeks: (1) The legume-free therapeutic lifestyle change (TLC) diet and (2) the legume-based TLC diet. Both diets were similar except that 2 servings of red meat were replaced by different types of legumes 3 days per week in the legume-based TLC diet. Oxidative stress biomarkers were measured at baseline and after 8 weeks. Compared to the legume-free TLC diet, the legume-based TLC diet significantly decreased malondialdehyde (-0.22 versus -0.68 μmol/l; P=0.002), oxidized-LDL (-0.9 versus -2.3 mU/l; P=0.05) and increased nitric oxide (0.40 versus 0.96 mM/l; P=0.03) and catalase activity (1.2 versus 2.1 Iu/ml; P=0.05).