Dietary fatty acid patterns and risk of metabolic syndrome: Tehran lipid and glucose study.

BACKGROUND: The association between individual dietary fatty acids (FAs) and risk of metabolic syndrome (MetS) has been investigated in previous studies. However, synergistic or additive effects of multiple FA have received less attention. Hence, we aimed to determine the major dietary FA patterns and evaluate the association between FA patterns and risk of MetS. METHODS: Dietary intakes of 1713 MetS-free adults who participated in the third phase of the Tehran Lipid and Glucose Study (TLGS) were assessed using a validated 168-items food frequency questionnaire. FA patterns were obtained by principal component analysis (PCA). Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were calculated for the association of MetS incident with the extracted FA patterns. RESULTS: Four major FA patterns were identified through PCA of the 24 FAs consumed: "short- and medium-chain saturated fatty acid (SFA) pattern", "long-chain FA pattern", "omega-3 PUFA pattern", and "long-chain SFA pattern". There was no significant association between dietary FA patterns and risk of MetS incidence. CONCLUSIONS: We found no significant association between FA patterns and risk of MetS. More prospective cohort studies and clinical trials are needed to clarify the issue.

Snack consumption patterns and their associations with risk of incident metabolic syndrome: Tehran lipid and glucose study.

AIM: Few studies considered the association between snack patterns and metabolic abnormalities. Here we aimed to characterize the major snack patterns among Iranian adults and determine their association with the risk of metabolic syndrome (MetS). METHODS: This study was conducted on 1713 MetS-free adults who participated in the third phase of the Tehran Lipid and Glucose Study (TLGS). At baseline, dietary intake of snack was assessed using a validated 168-items food frequency questionnaire, and snack patterns were obtained by principal component analysis (PCA). Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were calculated for the association of incident MetS with the extracted snack patterns. RESULTS: PCA identified five major snack patterns, defined as "healthy pattern", "low-fructose pattern", "high-trans pattern", "high-caffeine pattern" and "high-fructose pattern". Participants in the highest tertile of the "high-caffeine pattern" had lower risk of MetS (HR = 0.80, 95% CI = 0.65-0.99, P for trend = 0.032). Other snack patterns have not shown any significant association with MetS incidence. CONCLUSIONS: Our findings suggest that consuming a snack pattern with high loads of caffeine, defined as "High-caffeine pattern" in the present study, could reduce the risk of MetS in healthy adults. Further prospective studies are needed to more fully determine the association between snack patterns and MetS incidence.

The effects of curcumin-containing supplements on inflammatory biomarkers in hemodialysis patients: A systematic review and meta-analysis.

In the past decade, the effect of curcumin or turmeric supplementation on many aspects of health status in different populations has been evaluated. In the present study, a systematic review and meta-analysis were conducted to estimate the effect of curcumin administration on inflammatory markers in hemodialysis (HD) patients. A systematic search was performed in MEDLINE, EMBASE, Scopus, and Clarivate Analytics Web of Science databases from 1997 until June2022 for terms related to curcumin/turmeric and hemodialysis (HD). Randomized, double-blind/single-blind studies examining the effects of curcumin/turmeric on the inflammation of HD participants older than 18 years were considered eligible for inclusion. Data were pooled using the weighted mean difference (WMD) and 95% CI as the summary statistic, considering a random-effects analysis model. The data that were pooled from nine studies with 472 patients indicated that curcumin-containing supplement had significant effect on serum C-reactive protein (CRP) levels (WMD = -3.3 mg/L; 95% CI: -5.4 to -1.3; p < 0.001, I2  = 76.7%, 8 studies, 467 participants), and interlukine-6 (IL-6) levels (SMD: -0.4; 95% CI: -0.8 to -0.07; p = 0.02, I2  = 31.6%, 3 studies, 153 participants) compared control group. Although curcumin intervention could not change tumor neurosis factor-α (TNF-α) concentration (SMD = -0.3; 95% CI: -0.7 to 0.04; p = 0.08, I2  = 25.3%, 3 studies, 153 participants), when compared with the placebo group. Our study's main limitations were small number of studies, overall high risk of bias in the included trials, and high heterogeneity in some results. The present meta-analysis suggested that intervention with curcumin-containing supplements was associated with a significant reduction in serum hs-CRP and IL-6 concentrations in HD patients. The curcumin intervention in the reduction of hs-CRP levels was greater than the minimal clinically important difference (MCID) for CRP (0.5 mg/L), which can be helpful in physicians' clinical decisions.

Effects of supplementation of vitamins D, C and E on Idiopathic Pulmonary Fibrosis (IPF): A clinical trial.

BACKGROUND & AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a growing prevalence. We aimed to evaluate the effects of co-supplementation with vitamins C, E, and D on respiratory, inflammatory, and oxidative stress outcomes in IPF patients. METHODS: Thirty-three patients participated in this quasi-experimental study and were supplemented with vitamins E, C, and D with 200 IU/daily, 250 mg/every other day and 50000 IU/Weekly, respectively for 12 weeks. Anthropometric indices, dietary recall, physical activity, Saint George questionnaire were assessed along with the biochemical measures of inflammation and oxidative stress, and respiratory parameters. Data were analyzed by SPSS version 21, and P-value ≤ 0.05 was considered significant. RESULTS: Results of spirometry and plethysmography tests showed a significant increase in FEV1 (P-value = 0.016), IRV (P-value = 0.001), RV (P-value = 0.002) and TLC (P-value = 0.003). But no significant change was observed in FVC, VC, FEV1/FVC, and ERV. We also found that ESR, hs-CRP, TGFß, and PrC remarkably reduced after the supplementation (P-value ≤ 0.05), while the GPx level remained unchanged. CONCLUSIONS: It is concluded that three months of supplementation with a combination of D, C, and E vitamins in IPF patients may positively affect the respiratory function and alleviate the inflammation and oxidative stress.

The effects of saffron supplementation on the measures of renal function indicators: a systematic review and meta-analysis.

CONTEXT: Saffron (Crocus sativus L.) has been proposed as a potential agent to improve renal function in animal studies. But, due to insufficient evidence in human research, further investigation is needed. OBJECTIVE: To fill this knowledge gap, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of saffron supplementation on the measures of renal function indicators in adults. Renal function was assessed based on serum urea, blood urea nitrogen, and creatinine levels. METHOD AND MATERIALS: A systematic search in PubMed/Medline, Scopus, Web of Science, Embase, and Google Scholar databases was done until March 2021 using relevant keywords. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine RCTs were included in the meta-analysis, and their quality was assessed using the Cochrane risk of bias tool. RESULTS: The pooled analysis showed that saffron supplementation had no significant effect on serum urea concentrations (WMD: - 1.05 mg/dl; 95% CI - 5.1 to 3; P = 0.6, I2 = 93%, P < 0.001) and serum creatinine levels (WMD: - 0.006 mg/dl; 95% CI - 0.08 to 0.06; P = 0.8, I2 = 79%, P < 0.001) when compared to the placebo group. In the dose-response analysis, we observed a significant non-linear relationship between the duration of saffron supplementation and serum urea and creatinine levels. CONCLUSIONS: Based on our findings, Saffron supplementation had no significant effect on renal function markers, including urea and creatinine. However, further trials are required to determine the actual effect and safety of saffron intervention in human studies. PROSPERO SUBMISSION ID: 248081.

E4orf1-induced reduction in endogenous insulin level is independent of pancreas endocrine function.

BACKGROUND: Obesity is often associated with hyperinsulinemia due to insulin resistance. In mice models of hyperinsulinemia, adenovirus-derived E4orf1 protein promotes glucose disposal via insulin-independent pathway, and reduces insulin response to glucose load, described as its "Insulin Sparing Action". This is likely because less insulin is needed for disposing glucose in presence of E4orf1, however, there are other potential possibilities. This study determined if E4orf1 reduces insulin response to glucose load because it a) suppresses the ability of pancreatic ß-cells to secret insulin, or b) upregulates glucagon production by the pancreas. METHODS: C57BL/6J wild type (control) and transgenic C57BL/6J (E4orf1) mice that express E4orf1 protein in adipose tissue upon doxycycline feeding, were used. Post-doxycycline feeding, insulin and glucagon secretion in response to glibenclamide or phenylephrine were compared between the two groups. The pancreases were examined for histological changes. RESULTS: In response to glibenclamide, E4orf1 mice secreted more insulin and exhibited lower blood glucose compared to control (47.4 ± 4.4 vs 27.4 ± 3.7 mg/dl, p < 0.003), but showed no difference in glucagon secretion. Post-phenylephrine injection, no differences were observed between the two groups for glucagon or insulin, except E4orf1 mice had a lower blood glucose rise after 10-min of injection compared to the control (39.7 ± 4.7 vs. 58.3 ± 7.5 mg/dl, p < 0.05). E4orf1 mice had significantly larger pancreatic islets and higher number of islets per mm2 tissue area. Neither the size nor the number of islets met the criteria of hypertrophy or hyperplasia. CONCLUSIONS/INTERPRETATION: E4orf1 retains and may enhance the ability of the pancreases to secret insulin in response to insulin secretagogue. Glucagon does not seem to play a role in the Insulin Sparing Action of E4orf1. Overall, the histology studies support better pancreatic islet health in presence of E4orf1, compared to that in control mice. The "insulin-independent" role of E4orf1 has potential therapeutic implications in addressing hyperinsulinemia in obesity.

The association between dietary patterns and quality and duration of sleep in children and adolescents: A systematic review.

BACKGROUND: Dietary pattern has been represented as a contributor to the duration and quality of sleep. This study aimed to review the evidence on this relation among children and adolescents. STUDY DESIGN: This was a systematic review on the association of dietary pattern and sleep. METHODS: A literature search was conducted for all articles published between 1980 and August 2020 using the terms "diet" AND "sleep" in PubMed/Medline, Scopus, Web of Science, Cochrane, and Embase databases. Screening and selection of eligible studies were performed by two separate investigators. Studies reporting the impact of different dietary patterns and indices on sleep duration or quality were included. RESULTS: Fourteen publications (12 cross-sectional, 1 cohort, and 1 clinical trial) were identified. Findings from most studies suggested that long sleep duration was consistently associated with healthy dietary patterns, such as "Vegetables & Healthy Proteins", "Traditional", "Fruit & Vegetables", etc. Results were more mixed and inconclusive regarding the quality of sleep, with 2 studies supporting, 2 studies disapproving, and one study neutral about the association between better sleep quality and healthier dietary patterns. The association between diet and sleep seemed to be affected by confounders and covariates, including sex, physical activity, screen time, etc. CONCLUSIONS: Longer sleep duration appears to be associated with healthier dietary pattern. However, various results in regard to the relation between dietary patterns and sleep quality preclude definitive conclusions. Further research with standard measures of sleep quality and experimental study designs are needed to better define the causal relationship between sleep and diet.

The effect of beetroot inorganic nitrate supplementation on cardiovascular risk factors: A systematic review and meta-regression of randomized controlled trials.

OBJECTIVES: Inorganic nitrate is one of the most effective compounds in beetroot for improving cardiovascular function due to its conversion to nitric oxide in the body. This review and meta-analysis aimed to investigate the role of beetroot inorganic nitrate supplementation on adults' cardiovascular risk factors. METHODS: We conducted a systematic literature review of articles published without time limitation until November 2020 in PubMed, Embase, ISI Web of Science, Scopus, Cochrane Library, and gray literature databases. We included the original randomized clinical trials (RCTs) in which the effect of beetroot inorganic nitrate supplementation on endothelial function, arterial stiffness, and blood pressure was studied. RESULTS: 43 studies were included for qualitative synthesis, out of which 27 were eligible for meta-analysis. Beetroot inorganic nitrate supplementation significantly decreased Arterial Stiffness (Pulse Wave Velocity (-0.27 m/s, p = 0.04)) and increased Endothelial function (Flow Mediated Dilation: 0.62%, p = 0.002) but did not change other parameters (p > 0.05). CONCLUSION: Beetroot inorganic nitrate supplementation might have a beneficial effect on cardiovascular risk factors. Further high-quality investigations will be needed to provide sufficient evidence.

Nanoparticle-mediated in vitro delivery of E4orf1 to preadipocytes is a clinically relevant delivery system to improve glucose uptake.

OBJECTIVE: Impaired glycemic control is a common comorbidity of obesity. E4orf1(E4), an adenovirus-derived protein, reduces the activity of insulin receptor substrate (IRS), yet activates Akt and promotes the membrane translocation of GLUT4, resulting in better glycemic control in mice. To develop a clinically suitable delivery system, here we constructed and tested liposome nanoparticles (NP), to deliver E4 to preadipocytes. METHODS: Glutathione-S-transferase (GST)-tagged E4 was encapsulated in Rhodamine-phosphatidylethanolamine (PE)-tagged soy-phosphatidylcholine-NP. The NP were characterized. Preadipocytes were treated with free E4, E4 containing NP (E4 NP) or E4-free NP (void NP). RESULTS: For void and E4 NP, the average size was ~150 and 130 nm, PDI was ~0.25 and 0.27, and Zeta potential was -23 and -25, respectively. The average encapsulation efficiency (EE) was ~50%. Cells treated with E4 showed maximum GST expression and Rhodamine signals at 24 h. The presence of E4 in cells was confirmed at 24, 48, and 72 h. At 72 h after exposure, E4 NP significantly decreased pTyr-IRS, yet increased pAkt protein abundance, membrane translocation of GLUT4, and glucose uptake, compared with cells treated with void NP. Free E4 (without NP) had no effect. CONCLUSIONS: NP-mediated delivery of E4 promotes glucose uptake in preadipocytes. The next step is to test the efficacy of this clinically compatible delivery approach in vivo.

The Association between Maternal Dietary Protein Intake and Risk of Gestational Diabetes Mellitus.

BACKGROUND: The amount and type of dietary protein affect glucose metabolism. However, the association between dietary protein intake and gestational diabetes mellitus (GDM) risk is vague. We examined this association. Methods: We included 152 GDM and 168 non-GDM participants (total 320), age 18-45 years from Arash Women's Hospital, Tehran, Iran. Protein intake was ascertained from 168-item Food Frequency Questionnaire at 24-40 weeks' gestation. GDM was defined as fasting blood sugar >95 mg/dL and/or oral glucose tolerance test >155 mg/dL. Dietary data were assessed using N4 software and statistical analysis was performed using SPSS 21. We tested the association between the amount of protein consumed from red and processed meat, poultry, dairy, egg, seafood, and vegetable plus sociodemographic and lifestyle covariates and GDM risk using multivariate logistic regression analysis. RESULTS: There was a significant association between the physical activity (P < 0.035), socioeconomic status (P < 0.013), body mass index, age, and each trimester's weight (P < 0.001), and risk of GDM. No significant association was observed between the intake of protein from major protein sources and risk of GDM. The only significant association was observed for egg consumption which was lower in GDM participants (P = 0.004), yet this association turned nonsignificant after adjustment for confounders, except for the fourth quartile (odds ratio: 0.43, 95% confidence interval: 0.208, 0.893). CONCLUSIONS: According to our findings, dietary intake of total and major protein sources could not affect the GDM risk. Differences between Iranian and Western population and the reverse causality might be the main reasons for this nonsignificant association.

E4orf1: A protein for enhancing glucose uptake despite impaired proximal insulin signaling.

BACKGROUND: Type 2 diabetes is often linked with impaired proximal insulin signaling. Hence, a therapeutic agent that enhances cellular glucose uptake without requiring proximal insulin signaling would be desirable for improving glycemic control. The E4orf1 peptide (E4) derived from human adenovirus 36 (Ad36) promotes cellular glucose uptake in vitro and in vivo, independent of insulin. E4 bypasses a part of insulin signaling to upregulate cellular glucose uptake. We tested the hypothesis that E4 requires the distal but not proximal insulin signaling to enhance cellular glucose disposal. METHODS: 3T3-L1 preadipocytes inducibly expressing E4 or a null vector (NV) were treated with inhibitor of insulin receptor (S961), inhibitor of insulin like growth factor-1receptor (IGF-1R) (Picropodophyllin, PPP), PPP+S961, or phosphatidyl inositol-3 kinase (PI3K) inhibitor (Wortmannin, WM). We used PPP and S961 to block the proximal insulin signaling, or WM to block the distal insulin signaling. Cells were exposed to 0 or 100nM insulin. RESULTS: As expected, when the proximal or distal insulin signaling was blocked in NV cells, insulin could not enhance pAKT protein abundance, Glut4 translocation, or glucose uptake. Whereas, E4 cells significantly increased pAKT abundance, Glut4 translocation and glucose uptake independent of the presence of insulin or proximal insulin signaling. Enhanced glucose disposal in E4 cells was completely abrogated when the distal insulin signaling was blocked. CONCLUSIONS: E4 bypasses the proximal insulin signaling but uses the distal insulin signaling to activate pAkt and in turn Glut4 translocation to improve cellular glucose uptake. E4 offers a promising template to improve glycemic control when the proximal insulin signaling is impaired.