Severity of adipose tissue dysfunction is associated with progression of pre-diabetes to type 2 diabetes: the Tehran Lipid and Glucose Study.

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.

Dietary pattern scores in relation to pre-diabetes regression to normal glycemia or progression to type 2 diabetes: a 9-year follow-up.

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.

Dietary sodium to potassium ratio is an independent predictor of cardiovascular events: a longitudinal follow-up study.

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.

High-Fat Dairy Products May Decrease the Risk of Chronic Kidney Disease Incidence: A Long-Term Prospective Cohort Study.

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.

Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection.

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.

Spot urinary microalbumin concentration, metabolic syndrome and type 2 diabetes: Tehran lipid and glucose study.

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.

Association between serum hydrogen sulfide concentrations and dysglycemia: a population-based study.

BACKGROUND AND AIM: Hydrogen sulfide (H2S), a signaling gasotransmitter, is involved in carbohydrate metabolism. Here, we aimed to assess the potential association between serum H2S 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 H2S 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 H2S 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 H2S concentrations between the groups. Lower serum H2S (< 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 H2S level may be associated with impaired glucose tolerance.

Dietary oxalate to calcium ratio and incident cardiovascular events: a 10-year follow-up among an Asian population.

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.

Inorganic nitrate: A potential prebiotic for oral microbiota dysbiosis associated with type 2 diabetes.

Oral microbiota dysbiosis, concomitant with decreased abundance of nitrate (NO3-)-reducing bacteria, oral net nitrite (NO2-) 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 NO3--NO2--·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 NO3- can improve the oral microbial community in patients with T2DM and act as a prebiotic. Both animal and human experiments indicated that inorganic NO3- modulates the oral microbiome by increasing the abundance of health-associated NO3--reducing bacteria (e.g., Neisseria and Rothia) and decreasing the plenty of species Prevotella and Veillonella, leading to oral NO2- accumulation and improved systemic ·NO availability. Supplementation with NO3- reduces caries- and periodontitis-associated bacteria and the pathogenic genus related to insulin resistance and glucose intolerance. In addition, inorganic NO3- may provide a more optimal environment for NO3- reductase activity in the oral cavity, as it increases salivary flow rate and prevents decreased pH by inhibiting acid-producing bacteria.

Effect of inorganic nitrate on metabolic parameters in patients with type 2 diabetes: A 24-week randomized double-blind placebo-controlled clinical trial.

AIM: In this randomized placebo-controlled clinical trial, effect of oral inorganic nitrate (NO3-) on metabolic parameters was assessed in patients with type 2 diabetes mellitus (T2DM). METHODS: Seventy-four eligible patients with T2DM were randomly assigned to NO3--rich beetroot powder (5 g/d contains ~250 mg NO3-) 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 NO3-, 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 NO3- had no effect on metabolic parameters in patients with T2DM.

Habitual intake of dietary L-arginine in relation to risk of type 2 diabetes: a prospective study.

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.

Dietary acid load and risk of cardiovascular disease: a prospective population-based study.

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/m2 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.

Lost-in-Translation of Metabolic Effects of Inorganic Nitrate in Type 2 Diabetes: Is Ascorbic Acid the Answer?

Beneficial metabolic effects of inorganic nitrate (NO3-) and nitrite (NO2-) 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 NO3- to NO2- 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 NO2- to NO following ingestion of NO3-. 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 NO3-/NO2- supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2--to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO3- 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 NO3- therapy.

Association of dietary fatty acids and the incidence risk of cardiovascular disease in adults: the Tehran Lipid and Glucose Prospective Study.

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/m2 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.

Circulating nitric oxide metabolites and the risk of cardiometabolic outcomes: a prospective population-based study.

Aim: This study was conducted to investigate whether serum NO metabolites (NOx) could predict the occurrence of type 2 diabetes (T2DM), hypertension (HTN) and metabolic syndrome (MetS). Methods: We measured serum NOx 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 NOx 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 NOx values. Results: The optimal cut-off points of serum NOx levels for predicting T2DM, HTN and MetS were 26.5, 25.5 and 25.5 µmol/L, respectively. Participants with serum NOx 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 NOx 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 NOx was associated with development of MetS.

Elevated serum levels of aminotransferases in relation to unhealthy foods intake: Tehran lipid and glucose study.

BACKGROUND: Abnormal levels of liver enzymes, particularly aminotransferases, are prognostic features of non-alcoholic fatty liver disease (NAFLD). Considering the important role of dietary intakes in development of NAFLD, we aimed to determine possible association of unhealthy foods (fast foods, soft drinks, sweet and salty snacks) consumption with elevated levels of aminotransferases. METHODS: This cross-sectional study was conducted within the framework of sixth phase of the Tehran Lipid and Glucose Study (2014-2017), on 187 adult men and 249 adult women (19-70 y). Usual intakes of unhealthy foods (kcal/week) were measured using a validated semi-quantitative 147-items food frequency questionnaire. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) were measured. Multivariable logistic regression models were used to estimate the odds of elevated aminotransferases in each tertile of energy-dense unhealthy foods. RESULTS: Mean age of participants was 44.44 ± 15.09 years, 43% of participants were men. Higher consumption of fast foods (> 11.39% kcal/week) was associated with elevated ALT to AST ratio (OR: 3.27; 95% CI: 1.90-5.63) and elevated ALT (OR: 2.74; 95% CI: 1.57-4.76). Also, each 1 SD increased energy intakes from fast foods was related to increased chance of having elevated ALT and ALT to AST ratio by 35% (OR: 1.35; 95% CI: 1.08-1.68, OR: 1.35; 95% CI: 1.10-1.66, respectively). There was no significant association between consumption of soft drinks, sweet or salty snacks and elevated aminotransferases. CONCLUSIONS: Higher intakes of energy from fast foods seems to be associated with an elevated serum levels of ALT and ALT to AST ratio, as indicators of development of NAFLD.

Effects of Ramadan intermittent fasting on lipid and lipoprotein parameters: An updated meta-analysis.

AIMS: This systematic review and meta-analysis aimed to clarify several aspects of intermittent fasting during the month of Ramadan on lipid and lipoprotein levels in apparently healthy subjects. DATA SYNTHESIS: We searched PubMed, Scopus, and Embase databases and the reference lists of previous reviews, up to Feb 2019 for studies that investigated the effects of Ramadan fasting on fasting levels of triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C, and VLDL-C among healthy subjects including pregnant women and athletic subjects. Studies were selected for quality assessment, meta-analyses, subgroup analyses, and meta-regressions; data of 33 eligible studies, conducted between 1978 and 2019, were included in the analysis. RESULTS: Intermittent fasting showed no significant effect on circulating TG (WMD = -0.38 mg/dl, 95% CI = -5.33, 4.57), TC (WMD = -1.58 mg/dl, 95% CI = -6.04, 2.88), and LDL-C levels (WMD = 1.85 mg/dl, 95% CI = 0.77, 2.92). Overall, HDL-C (WMD = -2.97 mg/dl; 95% CI = -6.43, 0.48 mg/dl) and VLDL-C (WMD = -1.41 mg/dl; 95% CI = -2.73, -0.10 mg/dl) significantly decreased after Ramadan fasting. A significant increase in LDL-C levels was observed in athletic subjects (WMD = 2.97 mg/dl; 95% CI = 0.80, 5.13) and apparently healthy subjects (WMD = 1.81 mg/dl; 95% CI = 0.55, 3.07). Change in TG levels was associated with age (ß = -0.94, P = 0.043), its baseline values (ß = -0.44, P = 0.001), and weight change during the fasting period (ß = -0.57, P = 0.032). CONCLUSION: Ramadan fasting may be accompanied by a moderate improvement of lipid and lipoprotein parameters, especially HDL-C levels; fasting appears to be more beneficial for men and athletic subjects.

Serum nitric oxide metabolites and hard clinical endpoints: a population-based prospective study.

Objective. Limited data are available regarding prognostic value of nitric oxide metabolites (NOx) for clinical hard end points. In this study, we defined optimum cut-off values of serum NOx for predicting all-cause and cardiovascular disease (CVD) mortality events and prospectively investigated their hazards in the presence of traditional risk factors. Design. Serum NOx concentrations were measured at baseline (2006-2008) and 3520 adult men and women were followed during 7.7 years for all-cause and cardiovascular disease (CVD) mortality. To determine the optimal cut-off points of serum NOx, the receiver operator characteristic (ROC) curve analysis was used. Multivariate Cox proportional hazard models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of all-cause and CVD mortality below and above the defined optimal cut-off points of serum NOx. Results. Mean age of participants was 44.5 ± 16.0 years at baseline and 40.2% were male. Median (inter-quartile range) of serum NOx levels was 25.0 µmol/L (19.0-37.0), at baseline. The optimal cut-off points of serum NOx levels for predicting CVD and all-cause mortality were 30.5 and 32.5 µmol/L, respectively. In the presence of age, sex, body mass index, smoking, type 2 diabetes, hypertension, and history of CVD, a significant increased risk of CVD mortality (HR = 1.98, 95% CI = 1.10-3.58) and all-cause mortality (HR = 1.52, 95% CI = 1.05-2.21) was observed for serum NOx values higher than their cut-offs. Conclusion. Serum NOx level may be predictor of CVD mortality and death, in general populations.

Dietary sodium to potassium ratio and the incidence of hypertension and cardiovascular disease: A population-based longitudinal study.

OBJECTIVE: There is an interaction between dietary sodium/potassium intake in the pathogenesis of hypertension (HTN) and cardiovascular disease (CVD). The aim of this study was to investigate the association of dietary sodium to potassium (Na/K) ratio and the risk of HTN and CVD in a general population of Iranian adults. METHODS: In this prospective cohort study, adults men and women with complete baseline data were selected from among participants of the Tehran Lipid and Glucose Study and were followed up for 6.3 years for incidence of HTN and CVD outcomes. Dietary sodium and potassium were assessed using a valid and reliable 168-item food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between dietary sodium, potassium and their ratio and risk of outcomes. RESULTS: During the study follow-up, 291 (15.1%) and 79 (5.0%) new cases of HTN and CVD were identified, respectively. No significant association was observed between usual intakes of sodium, potassium and dietary Na/K ratio with the incidence of HTN. There was no significant association between dietary intakes of sodium and potassium per se and the risk of CVD, whereas when dietary sodium to potassium ratio was considered as exposure in the fully-adjusted Cox regression model, and participants in the highest compared to lowest tertile had a significantly increased risk of CVD (HR = 2.19, 95% CI = 1.16-4.14). CONCLUSIONS: Our findings suggest that high dietary Na/K ratio could contribute to increased risk of CVD events.

Vitamin C intake modify the impact of dietary nitrite on the incidence of type 2 diabetes: A 6-year follow-up in Tehran Lipid and Glucose Study.

BACKGROUND: There is no epidemiological study on the association between dietary nitrate (NO3) and nitrite (NO2) and intakes and the risk of type 2 diabetes (T2D). OBJECTIVE: The aim of this study was therefore to examine the potential effect of dietary NO3 and NO2 on the occurrence of T2D. DESIGN: This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 2139 T2D-free adults, aged 20-70 years, followed for a median of 5.8 y. Dietary intakes of NO3 and NO2 were estimated using a 168-food items validate semi-quantitative food frequency questionnaire, at baseline. Multivariate Hazard Ratios (HR) and 95% confidence intervals (CI), adjusted for diabetes risk score (DRS), and dietary intakes of fat, fiber and vitamin C, were calculated for residual energy-adjusted NO3 and NO2 intakes. Since significant interaction (P = 0.024) was found between NO2 and vitamin C intakes in the multivariable model, stratified analyses were done for < and ≥ median vitamin C intakes. RESULTS: Median (inter quartile range; IQR) daily intake of NO3 and NO2 were 410 mg/d (343-499) and 8.77 mg/d (7.53-10.2). An increased risk of T2D was observed among participants who had higher intake of total and animal-based NO2 in participants who had low vitamin C intake (HR = 2.43, 95% CI = 1.45-4.05, HR = 1.88, 95% CI = 1.12-3.15, respectively). We found no significant association between NO3 in overall, and plant- and animal sources as well, with the risk of T2D. Plant-derived NO2 was also unrelated to incidence of T2D. CONCLUSION: Our findings indicated that higher intakes of total and animal-based NO2 may be an independent dietary risk factor for development of T2D in subjects with lower vitamin C intakes.