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Zebrafish are an ideal model organism to study lipid metabolism and to elucidate the molecular underpinnings of human lipid-associated disorders. Unlike murine models, to which various standardized high lipid diets such as a high-cholesterol diet (HCD) are available, there has yet to be a uniformly adopted zebrafish HCD protocol. In this study, we have developed an improved HCD protocol and thoroughly tested its impact on zebrafish lipid deposition and lipoprotein regulation in a dose- and time-dependent manner. The diet stability, reproducibility, and fish palatability were also validated. Fish fed HCD developed hypercholesterolemia as indicated by significantly elevated ApoB-containing lipoproteins (ApoB-LPs) and increased plasma levels of cholesterol and cholesterol esters. Feeding of the HCD to larvae for 8 days produced hepatic steatosis that became more stable and sever after 1 day of fasting and was associated with an opaque liver phenotype (dark under transmitted light). Unlike larvae, adult fish fed HCD for 14 days followed by a 3-day fast did not develop a stable fatty liver phenotype, though the fish had higher ApoB-LP levels in plasma and an upregulated lipogenesis gene fasn in adipose tissue. In conclusion, our HCD zebrafish protocol represents an effective and reliable approach for studying the temporal characteristics of the physiological and biochemical responses to high levels of dietary cholesterol and provides insights into the mechanisms that may underlie fatty liver disease., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Long-term fasting (LF) is increasingly emerging as a non-pharmacological approach to modulate risk factors associated with the development of atherosclerotic cardiovascular diseases (ASCVD). However, protection from ASCVD is more tied to the functionality of high-density lipoprotein (HDL) than its plasma levels. Our prospective interventional study focuses on the functional properties of lipoproteins in modulating cholesterol homeostasis on peripheral cells and examines how LF may influence this and lipoprotein subclass composition. For that purpose, we investigated its impact on HDL-cholesterol efflux capacity (CEC), and on serum cholesterol loading capacity (CLC)., Methods: Forty healthy subjects (50 % females) underwent medically supervised 9-day fasting (250 kcal/day) in a specialised facility. Thirty-two subjects had a follow-up examination after one month of food reintroduction., Results: LF was well tolerated and increased self-reported energy levels. Fasting reduced triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C). Very-low-density lipoprotein cholesterol (VLDL-C) and LDL3-C showed sustained reductions at follow-up. Only HDL-C, specifically HDL2-C levels, increased at follow-up. Total HDL-CEC decreased during LF and increased above baseline at follow-up. Fasting decreased ATP binding cassette (ABC)A1-mediated HDL-CEC whereas ABCG1-mediated HDL-CEC remained unaffected. Aqueous diffusion increased at follow up. LF decreased serum CLC and then returned to baseline levels., Conclusions: LF not only maintains lipoprotein functionality but also contributes to a favorable shift in the atherogenic risk profile, which persists even after food reintroduction. This further emphasizes the importance of considering HDL functionality alongside traditional lipid measurements to understand the potential for non-pharmacological interventions like LF to promote cardiovascular prevention and health., Trial Registration Number: NCT05031598., Competing Interests: Declaration of competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FG, AH, RM and FWT are employees of the Buchinger Wilhelmi Development and Holding GmbH, Überlingen. The other authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: Studies on the influence of fasting plasma glucose (FPG) on the development of carotid plaque (CP) and intima media thickness (CIMT) mainly focused on single FPG measures. We investigated whether changes in FPG (ΔFPG) are associated with incident CP and CIMT change (ΔCIMT) over time., Methods: Analyses were based on information from 1896 participants from the VIPVIZA trial (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention), with baseline and 3-year follow-up data on FPG, ultrasonographic CP (none or ≥1 lesion/s) and CIMT assessments. We studied the association between baseline FPG (prior to intervention) or 3-year ΔFPG (mmol/L) and incident CP (logistic regression) or ΔCIMT (linear regression). Analyses were adjusted for multiple potential confounders., Results: 1896 and 873 individuals, respectively, were included in the analysis on incident CP and ΔCIMT. Participants were 60 years old at baseline and 61% and 54% were females, in the CP and CIMT analyses, respectively. Every mmol/L increase in FPG was associated with an increased odds of incident CP (odds ratio: 1.42, 95% confidence interval [CI]: 1.17, 1.73), but there was no association with ΔCIMT (mean difference: 0.002 mm, 95% CI: -0.003, 0.008) after 3 years. Baseline FPG was not associated with incident CP nor ΔCIMT progression., Conclusions: In middle-aged individuals with low to moderate risk for cardiovascular diseases, 3-year ΔFPG was positively associated with the risk of incident CP, but not with ΔCIMT. Single measures of FPG may not be sufficient in estimating cardiovascular risk among individuals with low to moderate risk., 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 © 2023. Published by Elsevier B.V.)

Background and Aims: Subclinical atherosclerosis (SA) diagnosis is key to primary prevention of atherosclerotic cardiovascular disease (ASCVD). SA is common among diabetics. Ankle brachial index (ABI) and coronary artery calcium (CAC) are markers of SA. This study examined whether adding ABI and CAC to diabetic individuals improved ASCVD risk prediction beyond established risk factors., Methods: MESA is an observational cohort of 6814 participants without clinical cardiovascular disease. All participants with diabetes and impaired fasting glucose were included in the analysis. The association between CAC, ABI, and incident ASCVD, and all-cause mortality was examined using Cox proportional hazard regression. The risk prediction models including ABI and/or CAC in addition to standard risk factors alone were compared., Results: Of the 1719 participants, 55% were male and average age was 64 (±9.6) years old. Participants with diabetes or impaired fasting glucose with higher CAC and lower ABI had higher ASCVD and all-cause mortality. ABI and CAC enhanced ASCVD discrimination over standard risk factors, with C-index (95% CI) of 0.689 (0.66, 0.718) for risk factors alone, 0.696 (0.668, 0.724) for ABI, 0.719 (0.691, 0.747) for CAC, and 0.721 (0.693, 0.749) for CAC + ABI. Similarly, for all-cause mortality, both CAC and ABI improved risk discrimination in addition to standard risk factors alone., Conclusions: In a large population-based study of individuals with diabetes or impaired fasting glucose, the addition of ABI and CAC to conventional risk factors improved 10-year ASCVD risk prediction. ABI and CAC are non-invasive and cost-effective tests; therefore, these markers should be included into ASCVD risk stratification for primary prevention in the diabetic and impaired fasting glucose population., 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., (Published by Elsevier B.V.)

Studies have shown that fasting during Ramadan has different effects on circulating levels of several biochemical markers. This study aims to conduct a comprehensive evaluation of studies related to the effect of fasting in the holy month of Ramadan on lipid profile, uric acid, and HbA1c in CKD patients. Studies were systematically searched and collected from three databases (PubMed, Scopus, and Web of Science). After screening, the quality and risk of bias assessment of the selected articles were evaluated. Study heterogeneity was assessed using the Cochrane test and I² statistic. In case of any heterogeneity random effects model with the inverse-variance method was applied. All analyses were performed using STATA software version 16. Four observational studies were included in this study. The results of this meta-analysis were that cholesterol (Weighted mean differences (WMD):0.21 with 95% CI:-0.09-0.51 (P-value=:0.18)), LDL (WMD:0.06 with 95% CI -0.24-0.36 (P-value:0.69)), triglyceride (WMD:0.05 with 95% CI:-0.25-0.35 (P-value:0.73)) had not-significant increase. Uric acid (WMD: -0.11 with 95% CI: -0.42-0.21 (P-value:0.51)) and HbA1c (WMD: -0.22 with 95% CI: -0.79-0.36 (P-value: 0.46)) show a non-significant decrease. The results of the analyses did not report significant changes in the lipid profile, uric acid, and HbA1c in CKD patients after Ramadan fasting., Competing Interests: Declaration of Competing Interest The authors have not disclosed any competing interests., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Fasting before coronary procedures is currently recommended to reduce complications despite the lack of scientific evidence., Objectives: The TONIC (Comparison Between Fasting and No Fasting Before Interventional Coronary Intervention on the Occurrence of Adverse Events) noninferiority trial investigated the safety and comfort of a nonfasting strategy (ad libitum food and drinks) vs traditional fasting (>6 hours for solid food and liquids) before coronary procedures., Methods: In this monocentric, prospective, single-blind randomized controlled trial, 739 patients undergoing coronary procedures were included and randomized to a fasting or a nonfasting strategy. Emergency procedures were excluded. The primary endpoint was a composite of vasovagal reaction, hypoglycemia (defined by blood sugar ≤0.7 g/L), and isolated nausea and/or vomiting. Noninferiority margin was 4%. Secondary endpoints were contrast-induced nephropathy and patients' satisfaction., Results: Among the 739 procedures (697 elective and 42 semiurgent), 517 angiographies, and 222 angioplasties (including complex and high-risk procedures) were performed. The primary endpoint occurred in 30 of 365 nonfasting patients (8.2%) vs 37 of 374 fasting patients (9.9%), demonstrating noninferiority (absolute between-group difference, -1.7%; 1-sided 95% CI upper limit: 1.8%). No food-related adverse event occurred, and contrast-related acute kidney injuries were similar between groups. Overall, procedure satisfaction and perceived pain were similar in both groups, but nonfasting patients reported less hunger and thirst (P < 0.01). In case of redo coronary procedures, most patients (79%) would choose a nonfasting strategy., Conclusions: The TONIC randomized trial demonstrates the noninferiority of a nonfasting strategy to the usual fasting strategy for coronary procedures regarding safety, while improving patients' comfort., Competing Interests: Funding Support and Author Disclosures The study’s sponsor was Assistance Publique–Hôpitaux de Paris (Délégation à la Recherche Clinique et à l'Innovation). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiovascular diseases (CVD) are the leading cause of death worldwide. Fasting is common in many religions and is associated with health benefits. This systematic review to compares the impact of different religious fasting practices, on risk of cardiometabolic diseases., Data Synthesis: The search covered five databases following PRISMA guidelines to identify papers published in English from inception to March 2023 (updated January 2024). Inclusion criteria were healthy adults in observational studies, who engaged in religious fasting practices, studies were included where data on matched non-fasting individuals was available. Outcomes were systolic and diastolic blood pressure, body mass index (BMI), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and fasting plasma glucose levels. A meta-analysis was conducted, and the review was registered (CRD42022352197). Fourteen studies were met the inclusion criteria with ten studies data being suitable for meta-analysis, reporting on 755 adults participating in fasting practices and 661 non-fasting controls. Religious fasting was associated with a reduction in BMI (-0.40 kg/m 2 , 95% CI [-0.70, -0.10], p < 0.01). Observance of Ramadan fasting was associated with decreased systolic blood pressure (-3.83  mmHg, 95% CI [-7.44, -0.23], p = 0.04). The observance of Orthodox Christian fasting was associated with a reduction in TC (-0.52 mmoL/l, 95%CI [-0.64, -0.39], p < 0.01). No difference was found for the other outcomes., Conclusion: This review found religious fasting practices which were associated with a reduction in some biomarkers of cardiometabolic diseases risk. Further research on other fasting practices is needed due to limited data., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Consumption of processed red meat has been associated with increased risk of developing type 2 diabetes (T2D), but challenges in dietary assessment call for objective intake biomarkers., Objectives: This study aimed to investigate metabolite biomarkers of meat intake and their associations with T2D risk., Methods: Fasting plasma samples were collected from a case-control study nested within Västerbotten Intervention Program (VIP) (214 females and 189 males) who developed T2D after a median follow-up of 7 years. Panels of biomarker candidates reflecting the consumption of total, processed, and unprocessed red meat and poultry were selected from the untargeted metabolomics data collected on the controls. Observed associations were then replicated in Swedish Mammography clinical subcohort in Uppsala (SMCC) (n = 4457 females). Replicated metabolites were assessed for potential association with T2D risk using multivariable conditional logistic regression in the discovery and Cox regression in the replication cohorts., Results: In total, 15 metabolites were associated with ≥1 meat group in both cohorts. Acylcarnitines 8:1, 8:2, 10:3, reflecting higher processed meat intake [r > 0.22, false discovery rate (FDR) < 0.001 for VIP and r > 0.05; FDR < 0.001 for SMCC) were consistently associated with higher T2D risk in both data sets. Conversely, lysophosphatidylcholine 17:1 and phosphatidylcholine (PC) 15:0/18:2 were associated with lower processed meat intake (r < -0.12; FDR < 0.023, for VIP and r < -0.05; FDR < 0.001, for SMCC) and with lower T2D risk in both data sets, except for PC 15:0/18:2, which was significant only in the VIP cohort. All associations were attenuated after adjustment for BMI (kg/m 2 )., Conclusions: Consistent associations of biomarker candidates involved in lipid metabolism between higher processed red meat intake with higher T2D risk and between those reflecting lower intake with the lower risk may suggest a relationship between processed meat intake and higher T2D risk. However, attenuated associations after adjusting for BMI indicates that such a relationship may at least partly be mediated or confounded by BMI., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people., Methods: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively., Results: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (β = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; β = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (β = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women., Conclusions: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between particulate matter and fasting blood glucose (FBG) has shown conflicting results. Genome-wide association studies have shown that KCNQ1 rs2237892 polymorphism is associated with the risk of diabetes. Whether KCNQ1 rs2237892 polymorphism might modify the association between particulate matter and FBG is still uncertain., Methods: Data collected from a family-based cohort study in Northern China, were used to perform the analysis. A generalized additive Gaussian model was used to examine the short-term effects of air pollutants on FBG. We further conducted interaction analyses by including a cross-product term of air pollutants by rs2237892 within KCNQ1 gene., Results: A total of 4418 participants were included in the study. In the single pollutant model, the FBG level increased 0.0031 mmol/L with per 10 μg/m 3 elevation in fine particular matter (PM 2.5 ) for lag 0 day. After additional adjustments for nitrogen dioxide (NO 2 ) and sulfur dioxide (SO 2 ), similar results were observed for lag 0-2 days. As for particulate matter with particle size below 10 μm (PM 10 ), the significant association between the daily average concentration of the pollutant and FBG level was observed for lag 0-3 days. Additionally, rs2237892 in KCNQ1 gene modified the association between PM and FBG level. The higher risk of FBG levels associated with elevations in PM 10 and PM 2.5 were more evident as the number of risk allele C increased. Individuals with a CC genotype had the highest risk of elevation in FBG levels., Conclusion: Short-term exposures to PM 2.5 and PM 10 were associated with higher FBG levels. Additionally, rs2237892 in KCNQ1 gene might modify the association between the air pollutants and FBG levels., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Aims: Despite advancements in preventive medicine and pharmacotherapy, diabetes remains an overwhelming health problem. Evidence from randomized controlled trials (RCTs) suggests that probiotics may offer beneficial effects on glycemic control. Our objective was to perform a systematic review and meta-analysis of RCTs to quantify the effect of probiotic administration on glycemic homeostasis in type 2 diabetes., Methods: Medline, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for relevant trials published until October 12, 2021. RCTs that lasted ≥3 weeks and assessed the effects of probiotics on the markers of glycemic homeostasis in type 2 diabetes were included. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q statistic and quantified using the I 2 statistic. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence., Results: A total of 33 eligible trial comparisons (n = 1927) were included in this meta-analysis. Our results revealed that compared with placebo, a median probiotic dose of ∼10 9  cfu/day significantly reduced the glycated hemoglobin (HbA 1c ) levels (MD: -0.19% [95% CI: -0.32, -0.07]; P = 0.003), fasting blood glucose levels (MD: -1.00 mmol/L [95% CI: -1.45, -0.56]; P < 0.0001), fasting insulin levels (MD: -5.73 pmol/L [95% CI: -12.17, 0.72]; P = 0.08), and HOMA-insulin resistance (IR) (MD: -1.00 [95% CI: -1.32, -0.68]; P < 0.00001). The certainty of evidence was graded low for HbA 1c and fasting glucose, moderate for fasting insulin, and high for HOMA-IR. Probiotic supplements do not induce clinically significant reductions in HbA 1c levels, but lead to marginally clinically significant reductions in fasting glucose and fasting insulin levels in patients with type 2 diabetes. Compared with single-strain and low-dose probiotics, multi-strain and high-dose probiotics have a greater beneficial effect on glycemic homeostasis. In addition, probiotic treatment may be more effective in patients with a high baseline body mass index and age., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Anorexia nervosa (AN) is a metabo-psychiatric disorder where alterations of cytokines, neuropeptides, neurotransmitters, and the interactions between these factors can play an important role. Thus, the primary goal of the presented study was a cross-sectional analysis of immune-related proteins in patients with AN. Moreover, the correlations between these molecules and selected neuropeptides were studied. Twenty-five adolescent inpatients girls in the acute stage of a restrictive type of AN were enrolled in the study within the first year of the disease. Additionally, thirty similar in age and height controls (CG) were also assessed. The levels of 24 immune-related proteins, including cytokines, chemokines, and proteases, were measured. Moreover, selected adipocytokines, gastrointestinal hormones, and centrally produced neuropeptides levels were determined. Finally, the correlations between these molecules were analyzed. The fasting levels of CXCL1, CXCL9, FGF2, GrB, IL1, IL6, IL8, MMP8, MMP9, CTSS were statistically lower in AN than in the CG. The concentrations of many immune-related proteins remain unchanged despite their metabolic and mental condition. Moreover, significant correlations were found between leptin and CXCL1, CXCL9, GrB, IL1, IL6, and MMP8. Leptin receptors were correlated with GrB, while resistin was associated with MMP9. Our findings suggest that the initial stage of restrictive AN among adolescents within the first year of the disease is not connected with a pro-inflammatory state. Some immune-related protein changes may be associated with altered neuropeptides, primarily leptin, its receptors, and resistin. Future research should clarify which changes are primary and secondary to weight loss and whether these changes normalize with increasing weight. This would aid in understanding the complex etiopathogenesis of AN and in the search for new methods of treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background & Aims: Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers., Methods: During 18-24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g. whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers., Results: The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (β = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (β = -0.06; 95% CI: -0.09, -0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, β = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (β = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (β = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol., Conclusions: Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials. The study was registered at clinicaltrials.gov with NCT00992641., Competing Interests: Conflict of interest The authors declare they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Gestational diabetes mellitus (GDM) is one of the most common complication of pregnancy that has significant impacts on both mother and her offspring health. The present study aimed to examine the effect of carbohydrate counting, carbohydrate counting combined with DASH, and control dietary interventions on glycemic control, and maternal and neonatal outcomes., Methods: A total of 75 pregnant women with GDM at 24th - 30th week of gestation were enrolled and randomized to follow one of the three diets: control or carbohydrate counting, or carbohydrate counting combined with Dietary Approach to Stop Hypertension (DASH). Only 70 of them completed the study until delivery. Fasting blood samples were taken at baseline and the end of the study to measure fasting blood glucose (FBG), fasting insulin, glycated hemoglobin (HbA1c), and fructosamine. Homeostatic model assessment-insulin resistance (HOMA-IR) score was calculated using HOMA2 calculator program. The participants recorded at least four blood glucose readings per day. Maternal and neonatal outcomes were collected from medical records. Dietary intake was assessed by three-day food records at the baseline and the end of the study., Results: Adherence to the three dietary interventions, resulted in decreased FBG levels significantly among all the participants (P < 0.05). Consumption of the carbohydrate counting combined with the DASH diet showed significant reduction in serum insulin levels and HOMA-IR score compared to carbohydrate counting group and control group. Means of fructosamine and HbA1c did not differ significantly among the three intervention diet groups. Overall mean of 1-h postprandial glucose (1 h PG) level was significantly lower in the carbohydrate counting combined with DASH group compared with that in the carbohydrate counting group and the control group (P < 0.001). The number of women who were required to commence insulin therapy after dietary intervention was significantly lower in carbohydrate counting group and carbohydrate counting combined with DASH group (P = 0.026). There were no significant differences in other maternal and neonatal outcomes among the three dietary intervention groups., Conclusions: The carbohydrate counting and the carbohydrate counting combined with DASH dietary interventions resulted in beneficial effects on FBG and 1 h PG compared with the control diet. The three dietary interventions produced similar maternal and neonatal outcomes in women with GDM., Trial Registration: This trial was registered on ClinicalTrials.gov under the identification code: NCT03244579. https://clinicaltrials.gov/ct2/show/NCT03244579., Competing Interests: Conflict of interest The authors declare that they have no competing interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Numerous studies demonstrate acute anti-inflammatory properties of individual spices, but none have examined the effect of longer-term consumption of a spice blend incorporated in a meal., Objectives: We investigated the effect of longer-term spice consumption on inflammatory cytokines and monocyte subsets [classical (CM), intermediate (IM), nonclassical (NCM)] in adults at risk of cardiometabolic disease., Methods: A 3-period, randomized, crossover, controlled feeding trial was conducted. Participants (n = 71 recruited; n = 63 completed) randomly consumed diets differing in terms of the quantity of spices: 0.547 g (low-dose spice diet; LSD), 3.285 g (medium-dose spice diet; MSD), or 6.571 g (high-dose spice diet; HSD) · d-1 · 2100 kcal-1, for 4 wk with a ≥2-wk washout between diets. At baseline and after each diet period, proinflammatory cytokines (IL-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and TNF-α) in plasma and LPS-stimulated peripheral blood mononuclear cell culture supernatants, and the phenotype and function of monocyte subsets, were measured in fasted participants. Postprandial proinflammatory cytokines also were quantified at baseline by consumption of a low-spice-dose test meal, and after each diet period by consumption of a test meal containing a spice dose corresponding to daily spice consumption during the preceding 4-wk diet period., Results: Fasting plasma IL-6 was reduced (mean ± SEM: -118.26 ± 50.63 fg/mL; P < 0.05) after MSD compared with baseline. Postprandial plasma IL-1β, IL-8, and TNF-α were lower (mean ± SEM : -9.47 ± 2.70 fg/mL, -0.20 ± 0.05 pg/mL, and -33.28 ± 12.35 fg/mL, respectively) after MSD compared with LSD (main diet effect; P < 0.05). CM adherence was reduced (mean ± SEM: -0.86 ± 0.34; P = 0.034) after HSD compared with LSD. IM migration was reduced after MSD and HSD compared with LSD (mean ± SEM: -0.39 ± 0.09 and -0.56 ± 0.14, respectively; P < 0.05)., Conclusions: Four weeks of MSD consumption reduced fasting plasma IL-6 and postprandial plasma IL-1β, IL-8, and TNF-α as well as altering monocyte function.This trial was registered at clinicaltrials.gov as NCT03064932., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Dicarbonyls are highly reactive compounds and major precursors of advanced glycation end products (AGEs). Both dicarbonyls and AGEs are associated with development of age-related diseases. Dicarbonyls are formed endogenously but also during food processing. To what extent dicarbonyls from the diet contribute to circulating dicarbonyls and AGEs in tissues is unknown., Objectives: To examine cross-sectional associations of dietary dicarbonyl intake with plasma dicarbonyl concentrations and skin AGEs., Methods: In 2566 individuals of the population-based Maastricht Study (age: 60 ± 8 y, 50% males, 26% with type 2 diabetes), we estimated habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by combining FFQs with our dietary dicarbonyl database of MGO, GO, and 3-DG concentrations in > 200 commonly consumed food products. Fasting plasma concentrations of MGO, GO, and 3-DG were measured by ultra-performance liquid chromatography-tandem mass spectrometry. Skin AGEs were measured as skin autofluorescence (SAF), using the AGE Reader. Associations of dietary dicarbonyl intake with their respective plasma concentrations and SAF (all standardized) were examined using linear regression models, adjusted for age, sex, potential confounders related to cardiometabolic risk factors, and lifestyle., Results: Median intake of MGO, GO, and 3-DG was 3.6, 3.5, and 17 mg/d, respectively. Coffee was the main dietary source of MGO, whereas this was bread for GO and 3-DG. In the fully adjusted models, dietary MGO was associated with plasma MGO (β: 0.08; 95% CI: 0.02, 0.13) and SAF (β: 0.12; 95% CI: 0.07, 0.17). Dietary GO was associated with plasma GO (β: 0.10; 95% CI: 0.04, 0.16) but not with SAF. 3-DG was not significantly associated with either plasma 3-DG or SAF., Conclusions: Higher habitual intake of dietary MGO and GO, but not 3-DG, was associated with higher corresponding plasma concentrations. Higher intake of MGO was also associated with higher SAF. These results suggest dietary absorption of MGO and GO. Biological implications of dietary absorption of MGO and GO need to be determined. The study has been approved by the institutional medical ethical committee (NL31329.068.10) and the Minister of Health, Welfare and Sports of the Netherlands (Permit 131088-105234-PG)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

LPL is a key player in plasma triglyceride metabolism. Consequently, LPL is regulated by several proteins during synthesis, folding, secretion, and transport to its site of action at the luminal side of capillaries, as well as during the catalytic reaction. Some proteins are well known, whereas others have been identified but are still not fully understood. We set out to study the effects of the natural variations in the plasma levels of all known LPL regulators on the activity of purified LPL added to samples of fasted plasma taken from 117 individuals. The enzymatic activity was measured at 25°C using isothermal titration calorimetry. This method allows quantification of the ability of an added fixed amount of exogenous LPL to hydrolyze triglyceride-rich lipoproteins in plasma samples by measuring the heat produced. Our results indicate that, under the conditions used, the normal variation in the endogenous levels of apolipoprotein C1, C2, and C3 or the levels of angiopoietin-like proteins 3, 4, and 8 in the fasted plasma samples had no significant effect on the recorded activity of the added LPL. Instead, the key determinant for the LPL activity was a lipid signature strongly correlated to the average size of the VLDL particles. The signature involved not only several lipoprotein and plasma lipid parameters but also apolipoprotein A5 levels. While the measurements cannot fully represent the action of LPL when attached to the capillary wall, our study provides knowledge on the interindividual variation of LPL lipolysis rates in human plasma., Competing Interests: Conflict of interest G. O. is a board member and shareholder in Lipigon Pharmaceuticals AB. All other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The healthy eating index-2015 (HEI-2015) reflects diet quality in reference to the 2015-2020 Dietary Guidelines for Americans (DGA). Little is known regarding its application in individuals with chronic spinal cord injury (SCI)., Objective: To explore the relationship between diet quality as assessed by the HEI-2015 and cardiovascular risk factors among individuals with chronic SCI., Design: This is a cross-sectional analysis of baseline data collected from August 2017 through November 2019 for an interventional study that evaluates the effects of a high-protein/low-carbohydrate diet on cardiovascular risk factors in individuals with chronic SCI at the University of Alabama at Birmingham., Participants/setting: Twenty-four free-living adults with SCI (mean age, 45 ± 12 y; 8F/16M, level of injury: nine cervical, 15 thoracic; mean duration of injury: 20 ± 13 y) were included., Main Outcome Measures: Participants underwent a 2-hour oral glucose tolerance test (OGTT) and a dual-energy x-ray absorptiometry scan. Dietary intake was assessed by three, 24-hour multiple-pass dietary recalls to calculate the HEI-2015 using the simple HEI scoring algorithm method., Data Analysis: Multiple linear regression analyses were performed to predict indices of lipid metabolism and glucose homeostasis and C-reactive protein (CRP) from the HEI-2015. Principal component analysis was used to reduce the number of covariates (level of injury, sex, and body fat percentage)., Results: On average, participants' diets were of low quality (HEI-2015, 47.2 ± 10.8). The regression models for fasting glucose (FG), cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and CRP had moderate to large effect sizes (adjusted R 2 ≥ 13%), suggesting good explanatory abilities of the predictors. Small or limited effect sizes were observed for glucose tolerance, fasting insulin, triglycerides, and Matsuda index (adjusted R 2 < 13%). The HEI-2015 accounted for a moderate amount of variation in FG (partial omega-squared, ω P 2  = 13%). Each 10-point HEI-2015 score increase was associated with a 3.3-mg/dL decrease in FG concentrations. The HEI-2015 accounted for a limited amount of variation in other indices (ω P 2 < 5%)., Conclusions: Among participants with SCI, higher conformance to the 2015-2020 DGA was 1) moderately associated with better FG homeostasis; and 2) trivially associated with other cardiovascular risk factors. Because of the small sample size, these conclusions cannot be extrapolated beyond the study sample. Future larger studies are warranted to better understand the relationship between diet quality and cardiovascular disease risks in this population., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the effects of blood glucose control and the kidneys' functions, depending on fasting, in the streptozotocin-induced diabetes model in rats via TNF-α, NLRP-3, TGF-β1 and VCAM-1 mRNA expression in the present study. 32 Wistar albino rats were allocated randomly into four main groups; H (Healthy, n = 6), HF (Healthy fasting, n = 6), D (Diabetes, n = 10), DF (Diabetes and fasting, n = 10). Blood glucose and HbA1c levels significantly increased in the D group compared to the healthy ones (p < 0.05). However, the fasting period significantly improved blood glucose and HbA1c levels 14 days after STZ induced diabetes in rats compared to the D group. Similar findings we obtained for serum (BUN-creatinine) and urine samples (creatinine and urea levels). STZ induced high glucose levels significantly up-regulated TNF-α, NLRP-3, TGF-β1 and VCAM-1 mRNA expression and fasting significantly decreased these parameters when compared to diabetic rats. Histopathological staining also demonstrated the protective effects of fasting on diabetic kidney tissue. In conclusion, intermittent fasting regulated blood glucose level as well as decreasing harmful effects of diabetes on kidney tissue. The fasting period significantly decreased the hyperglycemia-related inflammatory cytokine damage on kidneys and also reduced apoptosis in favor of living organisms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: To evaluate the association between fasting blood glucose (FBG) and salt sensitivity of blood pressure (SSBP)., Methods and Results: This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. Subjects were classified into salt sensitive (SS) and salt resistant groups according to blood pressure (BP) changes during the modified Sullivan's acute oral saline load and diuresis shrinkage test. Multivariate logistic and linear regression were used to evaluate associations between FBG with SS or BP changes. A total of 2051 participants were included in the analyses with 581 (28.33%) for SS. Multiple analysis showed that for every interquartile range increase in FBG, the OR (95%CI) for SS was 1.140 (1.069, 1.215), β (95%CI) for mean arterial pressure change (ΔMAP 1 ), systolic and diastolic BP changes during saline load were 0.421 (0.221, 0.622), 0.589 (0.263, 0.914) and 0.340 (0.149, 0.531), respectively. Compared to the lowest FBG quartile (Q 1 ), the OR (95%CI) for SS in Q 3 and Q 4 were 1.342 (1.014, 1.776) and 1.577 (1.194, 2.084), respectively. Compared to subjects with normal FBG, the β (95%CI) for ΔMAP 1 was 0.973 (0.055, 1.891) in subjects with impaired FBG, and was 1.449 (0.602, 2.296) in patients with diabetes mellitus. Stratified analyses showed significant and stronger associations between FBG with SSBP in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers., Conclusion: Our findings suggest FBG is an independent, dose-dependent associated factor for SSBP, and prevention of SS focusing on controlling FBG elevation in the early stage is important., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 The Italian Diabetes Society, 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.)

Aims: This study aimed to evaluate the effects of Ramadan diurnal intermittent fasting (RDIF; 29-30 days) on cardiometabolic risk factors (CMRF) in healthy adults, and examine the effect of various cofactors on the outcomes using sub-group meta-regression., Data Synthesis: We conducted a systematic review and meta-analysis to measure the effect sizes of changes in CMRF in healthy adult Muslims observing RDIF. Ten scientific databases (EBSCOhost, CINAHL, Cochrane, EMBASE, PubMed/MEDLINE, Scopus, Google Scholar, ProQuest Medical, ScienceDirect, and Web of Science) were searched from the date of inception (1950) to the end of November 2020. The CMRF searched and analyzed were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), diastolic blood pressure (DBP), and heart rate (HR). We identified 91 studies (4431 adults aged 18-85 years) conducted between 1982 and 2020 in 23 countries distributed over four continents. RDIF-induced effect sizes for CMRF were: TC (no. of studies K = 77, number of subjects N = 3705, Hedge's g = -0.092, 95% confidence interval (CI): -0.168, 0.016); TG (K = 74, N = 3591, Hedge's g = -0.127, 95% CI: -0.203, 0.051); HDL-C (K = 68, N = 3528, Hedge's g = 0.138, 95% CI: 0.051, 0.224); LDL-C (K = 65, N = 3354, Hedge's g = -0.115, 95% CI: -0.197, -0.034); VLDL-C (K = 13, N = 648, Hedge's g = -0.252, 95% CI: -0.431, 0.073), DBP (K = 32, N = 1716, Hedge's g = -0.255, 95% CI: -0.363, 0.147), and HR (K = 12, N = 674, Hedge's g = -0.082, 95% CI: -0.300, 0.136). Meta-regression revealed that the age of fasting people was a significant moderator of changes in both HDL-C (P = 0.02) and VLDL-C (P = 0.01). Male sex was the only significant moderator of changes in LDL-C (P = 0.055). Fasting time duration was the only significant moderator of HDL-C (P = 0.001) at the end of Ramadan., Conclusions: RDIF positively impacts CMRF, which may confer short-term transient protection against cardiovascular disease among healthy people., (Copyright © 2021 The Italian Diabetes Society, 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.)

Background & Aims: Melatonin appears as a supplement capable of helping with diabetes. However, there is no evidence from meta-analyses that showed significant results in insulin resistance and glycated hemoglobin. This study aimed to review the literature on randomized clinical trials that evaluated melatonin supplementation effects, compared to placebo, on diabetes parameters in humans., Methods: We conducted a systematic review and meta-analysis in the following databases: Pubmed, LILACS, Scielo, Scopus, Web of Science, Cochrane, and Embase. We included randomized clinical trials investigating melatonin supplementation's effects, compared to placebo, on fasting blood glucose, insulin resistance, and glycated hemoglobin. Non-randomized clinical trials, observation studies, and animal models were excluded. The Cochrane scale assessed the quality of the studies. We conducted a meta-analysis on fasting blood glucose, insulin resistance, and glycated hemoglobin., Results: Sixteen studies were included, of which 56% showed benefits from supplementation with melatonin in diabetes parameters compared with placebo. Our meta-analysis showed significant results for fasting blood glucose [mean difference: -4.65; 95% CI: -8.06, -1.23; p = < 0.01; I 2  = 58%], glycated hemoglobin [mean difference: -0.38; 95% CI: -0.67, -0.10; p = 0.30; I 2  = 18%], and insulin resistance [mean difference: -0.58; 95% CI: -1.00, -0.15; p = 0.17; I 2  = 35%]., Conclusions: Our results showed that melatonin supplementation was useful for reducing diabetes parameters when compared to placebo., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Individuals with fasting triglycerides (TG) <150 mg/dL can experience a deleterious postprandial TG response ≥220 mg/dL to a high-fat meal (HFM). The purpose of this study was to identify individuals based on fasting TG that would benefit most from additional postprandial screening., Methods: We conducted a secondary analysis of 7 studies from our laboratories featuring 156 disease-free participants (64 M, 92 F; age 18-70 years; BMI 18.5-30 kg/m 2 ). Participants observed a 10-12 h overnight fast, after which they consumed an HFM (10-13 kcal/kg body mass; 61-64% kcal from fat). Two methods were used to identify lower and upper fasting TG cut points. Method 1 identified the lower limit as the TG concentration at which ≥90% of individuals presented peak postprandial TG (PPTG) <220 mg/dL and the upper limit as the concentration which ≥90% of individuals presented PPTG ≥220 mg/dL. Method 2 utilized receiver operating characteristic (ROC) curves and identified the lower limit as the fasting TG concentration where sensitivity was ≈95% and the upper limit as the concentration at which specificity was ≈95%., Results: In Method 1, 90% of individuals with fasting TG >130 mg/dL (>1.50 mmol/L) exhibited PPTG ≥220 mg/dL (≥2.50 mmol/L), while 100% of individuals with fasting TG <66 mg/dL (0.75 mmol/L) had PPTG that did not exceed 220 mg/dL (2.50 mmol/L). In Method 2, when sensitivity was ≈95%, the corresponding fasting TG concentration was 70 mg/dL (0.79 mmol/L). When specificity was ≈95%, the corresponding fasting TG concentration was 114 mg/dL (1.29 mmol/L). Based on methods 1 and 2, there was a moderate positive association (r = 0.37, p < 0.004) between fasting and PPTG for individuals with fasting TG between 70 and 130 mg/dL (0.79-1.50 mmol/L), in which 24% exhibited PPTG ≥220 mg/dL (≥2.50 mmol/L) while 76% did not., Conclusions: Postprandial TG testing is likely most useful for individuals with fasting TG concentrations between 70 and 130 mg/dL (0.79-1.50 mmol/L). Outside of this range, postprandial TG responses are largely predictable. Establishing a specific patient group for which postprandial TG testing is most useful may lead to earlier risk detection in these individuals., Competing Interests: Conflict of interest Nathaniel D. M. Jenkins currently serves on the AHA Research Committee, as well as two AHA Research-related subcommittees. Nathaniel D. M. Jenkins is also currently supported by an AHA research grant (18AIREA33960528), as well as an NIH Clinical Research Loan Repayment Award. Within the last year, Nathaniel D. M. Jenkins has received compensation as a book reviewer, as well as a chapter author, for Human Kinetics. All other authors have nothing to disclose., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Hyperuricemia is an independent risk factor for the metabolic syndrome and cardiovascular disease. We hypothesized that asymptomatic carriers for hereditary fructose intolerance (OMIM 22960) would have increased uric acid and altered component of the metabolic syndrome when exposed to fructose overfeeding., Methods: Six heterozygotes for HFI (hHFI) and 6 controls (Ctrl) were studied in a randomized, controlled, crossover trial. Participants ingested two identical test meals containing 0.7 g kg -1 glucose and 0.7 g kg -1 fructose according to a cross-over design, once after a 7-day on a low fructose diet (LoFruD, <10 g/d) and on another occasion after 7 days on a high fructose diet (HiFruD, 1.4 g kg -1  day -1 fructose + 0.1 g kg -1  day -1 glucose). Uric acid, glucose, and insulin concentrations were monitored in fasting conditions and over 2 h postprandial, and insulin resistance indexes were calculated., Results: HiFruD increased fasting uric acid (p < 0.05) and reduced fasting insulin sensitivity estimated by the homeostasis model assessment (HOMA) for insulin resistance (p < 0.05), in both groups. Postprandial glucose concentrations were not different between hHFI and Ctrl. However HiFruD increased postprandial plasma uric acid, insulin and hepatic insulin resistance index (HIRI) in hHFI only (all p < 0.05)., Conclusions: Seven days of HiFruD increased fasting uric acid and slightly reduced fasting HOMA index in both groups. In contrast, HiFruD increased postprandial uric acid, insulin concentration and HIRI in hHFI only, suggesting that heterozygosity for pathogenic Aldolase B variants may confer an increased susceptibility to the effects of dietary fructose on uric acid and hepatic insulin sensitivity. This trial was registered at the U.S. Clinical Trials Registry as NCT03545581., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy., Methods: A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75 g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n = 59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n = 94); combined group (FPG&1h/2h-PG group; n = 42). Non-GDM pregnancies were included (n = 485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis., Results: Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p < 0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR] = 2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR = 2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR = 2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR = 2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference)., Conclusions: Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM., Competing Interests: Conflicts of interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Fasting changes mitochondrial function, and mTOR acts as a major regulator of mitochondrial energy production ensuring the survival under reduced supply of nutrition. This study assessed the role of protein arginine methyltransferase 1 (PRMT1), which regulates mitochondrial function, in the context of fasting., Methods: The effect of fasting on mTOR signaling and mTOR-regulated mitochondrial mass was assessed in LO2 cells (in vitro) and C57BL/6J mice (in vivo). Biochemical parameters of fasting were determined in blood samples of mice. PRMT1 expression was investigated by transfecting LO2 cells with an expression vector. Gene expression was determined by real-time quantitative PCR, protein interaction by chromatin immunoprecipitation, protein expression by Western blotting and immunofluorescence microscopy, and the mitochondrial mass by MitoTracker staining., Results: After 48 h of fasting, mTOR and PRMT1 expression, as well as mitochondrial mass, were significantly reduced in LO2 cells, and in liver tissue sections. Fasting downregulated the expression of miR-21 and upregulated the expression of its target phosphatase and tensin homolog (PTEN), which was responsible for reduced mTOR expression. Inhibition of mTOR reduced phosphorylation of STAT1, and thereby PRMT1 expression in LO2 cells. Low PRMT1 down-regulated the expression of peroxisome proliferator-activated receptor (PPAR)-γ and thereby decreased mitochondrial mass. Supplementation of insulin contracted the effect of fasting on all mentioned parameters., Conclusions: Fasting downregulates miR-21 and increases its target PTEN, thereby inhibiting mTOR signaling, p-STAT1, PRMT1, and mitochondrial mass. These findings highlight the role of mTOR and PRMT1 in the regulation of cellular energy availability., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background & Aims: Fasting and energy-restricted diets have been evaluated in several studies as a means of improving cardiometabolic biomarkers related to body fat loss. However, further investigation is required to understand potential alterations of leptin and adiponectin concentrations. Thus, we performed a systematic review and meta-analysis to derive a more precise estimate of the influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans, as well as to detect potential sources of heterogeneity in the available literature., Methods: A comprehensive systematic search was performed in Web of Science, PubMed/MEDLINE, Cochrane, SCOPUS and Embase from inception until June 2019. All clinical trials investigating the effects of fasting and energy-restricted diets on leptin and adiponectin in adults were included., Results: Twelve studies containing 17 arms and a total of 495 individuals (intervention = 249, control = 246) reported changes in serum leptin concentrations, and 10 studies containing 12 arms with a total of 438 individuals (intervention = 222, control = 216) reported changes in serum adiponectin concentrations. The combined effect sizes suggested a significant effect of fasting and energy-restricted diets on leptin concentrations (WMD: -3.690 ng/ml, 95% CI: -5.190, -2.190, p ≤ 0.001; I 2  = 84.9%). However, no significant effect of fasting and energy-restricted diets on adiponectin concentrations was found (WMD: -159.520 ng/ml, 95% CI: -689.491, 370.451, p = 0.555; I 2  = 74.2%). Stratified analyses showed that energy-restricted regimens significantly increased adiponectin (WMD: 554.129 ng/ml, 95% CI: 150.295, 957.964; I 2  = 0.0%). In addition, subsequent subgroup analyses revealed that energy restriction, to ≤50% normal required daily energy intake, resulted in significantly reduced concentrations of leptin (WMD: -4.199 ng/ml, 95% CI: -7.279, -1.118; I 2  = 83.9%) and significantly increased concentrations of adiponectin (WMD: 524.04 ng/ml, 95% CI: 115.618, 932.469: I 2  = 0.0%)., Conclusion: Fasting and energy-restricted diets elicit significant reductions in serum leptin concentrations. Increases in adiponectin may also be observed when energy intake is ≤50% of normal requirements, although limited data preclude definitive conclusions on this point., Competing Interests: Conflict of interest GMT serves as a consultant for a phone app that aids users in tracking adherence to intermittent fasting regimens. This consulting consists of providing research-based information about intermittent fasting. The remaining authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Preoperative oral carbohydrates are strongly recommended for routine use before various elective procedures. The regimen mainly includes preoperative oral single-dose carbohydrate (2-3 h before surgery) and preoperative oral double-dose carbohydrates (10 h before surgery and 2-3 h before surgery). The choice between the two options is still controversial., Methods: A total of 139 patients with gastric cancer who underwent radical gastrectomy were recruited from a hospital in Sichuan Province, China. The patients were randomly assigned to a single-dose group (n = 70) or a double-dose group (n = 69). Insulin resistance indicators, subjective comfort indicators, inflammatory mediators, immunological indicators, postoperative recovery indexes, and complications were compared between the two groups., Results: There were no differences in insulin resistance indicators (fasting plasma glucose, fasting insulin, and homeostasis model assessment indexes), inflammatory mediators (C-reactive protein, interleukin-6, and tumor necrosis factor-α), immunological indicators (CD3+, CD4+, CD8+, and CD4+/CD8+) between the single-dose group and double-dose group (all P > 0.05) at preoperative day 1, preoperative 3 h, and postoperative day 1. There were no differences in subjective comfort indicators (thirst, hunger, anxiety, nausea, fatigue, and weakness) between the two groups (all P > 0.05) at preoperative day 1, preoperative 3 h, preoperative 1 h, and postoperative day 1. The postoperative recovery indexes and complications (exhaust time, liquid intake time, postoperative hospital stay, complication incidence, unplanned readmission rate, and unplanned reoperation rate 30 days after operation) did not significantly differ between the two groups (all P > 0.05). The number of preoperative nighttime urinations in the double-dose group was higher than that in the single-dose group (88.3% VS 48.5%, P < 0.001), and the number of hours of preoperative sleep in the double-dose group was lower than that in the single-dose group (4.56 ± 0.68 VS 5.71 ± 0.57, P < 0.001)., Conclusion: Oral carbohydrates administered the night before surgery did not enhance the effects of oral carbohydrates administered 2-3 h before surgery on insulin resistance, subjective comfort, inflammation, and immunity and might affect the patients' night rest. In making a decision between oral carbohydrate regimes, evening carbohydrates could be omitted., Trial Registration: ChiCTR, ChiCTR1900020608. Registered January 10, 2019, http://www.chictr.org.cn: ChiCTR1900020608., Competing Interests: Conflict of interest The authors confirm that there are no conflicts of interest to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: The relationships between uric acid (UA) and prediabetes is poorly explored in youth. We investigated the association between UA, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), insulin resistance (IR) and low insulin sensitivity (IS) in youth with overweight/obesity (OW/OB)., Methods and Results: A cross-sectional study was performed in 2248 youths with OW/OB (age 5-17 years). The sample was stratified in sex-specific quintiles (Q1 to Q5) of UA and the associations with fasting (FG), 2-h post-load glucose (2H-PG), IR and low IS were investigated. IR and low IS were estimated by assessment model of insulin resistance (HOMA-IR) and whole-body IS index (WBISI), respectively. IFG was defined as FG ≥ 100 < 126 mg/dL, IGT as 2H-PG ≥140 < 200 mg/dL, IR as HOMA-IR ≥75th percentile and low IS as WBISI ≤25th percentile by sex. Age, body mass index z-score, 2H-PG, HOMA-IR and WBISI, increased across sex-quintiles of UA while FG did not. The prevalence of IFG and IR were significantly increased in Q5 vs Q1 (reference quartile, P < 0.025). The prevalence of IGT increased from Q3 to Q5 vs Q1 (P < 0.025-0.0001) and that of low IS from Q2 to Q5 vs Q1 (P < 0.005-0.0001)., Conclusions: In youth with OW/OB, rates of IGT and low IS increased progressively across quintiles of UA. On the contrary, IFG and IR were associated only with the highest quintile of UA. Our data suggest that UA is a biomarker of impaired glucose metabolism prevalently in post-challenge condition rather than in fasting state., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 The Italian Diabetes Society, 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.)

Background: This study aimed to investigate the relationship between lipopolysaccharide (LPS) and zonulin levels and also to show the effect of acute hyperglycemic stress induced by oral glucose tolerance testing (OGTT) on zonulin levels in pre-diabetic patients., Methods: Four groups were constituted according to the criteria of the American Diabetes Association (ADA), based on OGTT results: control group (n:40); prediabetic group (n:56), divided into two subgroups: impaired fasting glucose group (IFG) (n:36), and impaired glucose tolerance (IGT) + IFG group (n:20) and type-2 diabetes mellitus (T2DM) group (n:45)., Results: Zonulin and LPS did not significantly differ between the prediabetes and control groups, but were significantly higher in the T2DM group compared to both the prediabetic and the control group (P<0.001). After OGTT, zonulin and LPS were significantly higher in the prediabetes group compared to the control group (P<0.01 and P<0.05, respectively), and significantly lower in the IFG and IFG+IGT groups compared to the T2DM group (P<0.001, P<0.001 and P<0.001, P<0.001, respectively). A positive correlation was detected between fasting zonulin and 2-hour zonulin (r=0.727, P<0.001) and between fasting LPS (r=0.555, P<0.001) and 2-hour LPS (r=0.567, P<0.001) in the prediabetic group. Increased zonulin and LPS levels and the positive correlation between these levels during the prediabetic period although non significant suggests onset of intestinal permeability., Conclusions: During acute hyperglycemia in prediabetic patients, up-regulation of zonulin and LPS may affect intestinal function. The intestines may play a key role in up-regulation of glucose and the pathogenesis of diabetes., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background & Aims: Postprandial metabolic abnormalities are considered important and independent risk factors for cardiovascular diseases. However, the effects of the Mediterranean diet on postprandial metabolism and the mechanism underpinning the effects on clinical variables have not been exhaustively explored. Therefore, the aims of the present study were to evaluate the acute and medium-term effects (8 weeks) on postprandial glucose and lipid metabolism of a diet resembling a typical Mediterranean diet (Med-D) compared to a western-type diet (Control-D), and the mechanisms underlying those effects., Methods: Twenty-nine overweight/obese individuals of both genders, aged 20-60 years, were enrolled and randomly assigned to two isoenergetic dietary interventions: 1) a Med-D (n = 16), and 2) a Control-D (n = 13). Adherence to the dietary interventions was assessed by a 7-day food record. A meal test resembling the assigned diet was performed at baseline and after 8 weeks of intervention. Blood samples at fasting and over 4-h after the meal were collected to assess metabolic parameters and short chain fatty acid (SCFA) levels. Fecal samples were also collected to evaluate the microbiota composition., Results: Glucose and insulin responses were significantly reduced at baseline after the Med test meal compared to the Control meal (p < 0.05) and this effect was strengthened after 8 weeks of intervention with the Mediterranean diet (p < 0.05); together with an improvement in OGIS. At the end of the intervention, postprandial plasma butyric acid incremental area under the curve (IAUC) was significantly increased in the Med-D group (p = 0.019) and correlated inversely with plasma insulin IAUC and directly with oral glucose insulin sensitivity (OGIS) (r: -0.411, p = 0.046 and r: 0.397, p = 0.050 respectively). These metabolic changes were accompanied by significant changes in gut microbiota, such as an increase in the relative abundance of Intestinimonas butyriciproducens and Akkermansia muciniphila (p < 0.05) in the Med-D compared to Control-D group., Conclusions: Our study provides strong evidence that a diet resembling the traditional Med-D improves postprandial glucose metabolism and insulin sensitivity. Furthermore, the study highlights a possible involvement of gut microbiota metabolites - such as butyric acid, and of dietary fiber as a precursor - in improving glucose metabolism and insulin sensitivity., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Type-1 diabetes mellitus (T1DM) is associated with metabolic changes leading to alterations in glucose and lipid handling. While T1DM-associated effects on many major plasma lipids have been characterised, such effects on plasma free fatty acids (FFA) have not been fully examined. Using gas chromatography-mass spectrometry, we measured the plasma concentrations of FFA species in individuals with T1DM (n = 44) and age/sex-matched healthy controls (n = 44). Relationships between FFA species and various parameters were evaluated. Plasma concentrations of myristate (14:0), palmitoleate (16:1), palmitate (16:0), linoleate (18:2), oleate (18:1c9), cis-vaccenate (18:1c11), eicosapentaenoate (20:5), arachidonate (20:4) and docosahexanoate (22:6) were reduced in the T1DM group (p < 0.0001 for all, except p = 0.0020 for eicosapentaenoate and p = 0.0068 for arachidonate); α-linolenate (18:3) and dihomo-γ-linolenate (20:3) concentrations were unchanged. The saturated/unsaturated FFA ratio, n-3/n-6 ratio, de novo lipogenesis index (palmitate (main lipogenesis product)/linoleate (only found in diet)) and elongase index (oleate/palmitoleate) were increased in the T1DM group (p = 0.0166, p = 0.0089, p < 0.0001 and p = 0.0008 respectively). The stearoyl-CoA desaturase 1 (SCD1) index 1 (palmitoleate/palmitate) and index 2 (oleate/stearate) were reduced in T1DM (p < 0.0001 for both). The delta-(5)-desaturase (D5D) index (arachidonate/dihomo-γ-linolenate) was unchanged. Age and sex had no effect on plasma FFA concentrations in T1DM, while SCD1 index 1 was positively correlated (p = 0.098) and elongase index negatively correlated with age (p = 0.0363). HbA1c was negatively correlated with all plasma FFA concentrations measured except α-linolenate and dihomo-γ-linolenate. Correlations were observed between plasma FFA concentrations and cholesterol and HDL concentrations, but not LDL concentration or diabetes duration. Collectively, these results aid our understanding of T1DM and its effects on lipid metabolism., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Backgrounds & Aims: Intestinal microbiota may be causally involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aimed to study the effect of short-term overfeeding on human gut microbiota in relation to baseline and overfeeding-induced liver steatosis. We also asked whether the baseline microbiota composition is associated to the overfeeding-induced increase in liver fat., Methods: In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000 kcal/day of diets rich in either saturated fat, unsaturated fat, or simple sugars for 3 weeks. Fasting blood samples and 1 H-MR spectroscopy were used for extensive clinical phenotyping as previously reported (PMID: 29844096). Fecal samples were collected for the analysis of the gut microbiota using 16S rRNA amplicon sequencing, imputed metagenomics and qPCR. Microbiota results were correlated with dietary intakes and clinical measurements before and during overfeeding., Results: The overall community structure of the microbiota remained highly stable and personalized during overfeeding based on between-sample Bray-Curtis dissimilarity, but the relative abundances of individual taxa were altered in a diet-specific manner: overfeeding saturated fat increased Proteobacteria, while unsaturated fat increased butyrate producers. Sugar overfeeding increased Lactococcus and Escherichia coli. Imputed functions of the gut microbiota were not affected by overfeeding. Several taxa affected by overfeeding significantly correlated with the changes in host metabolic markers. The baseline levels of proteobacterial family Desulfovibrionaceae, and especially genus Bilophila, were significantly associated to overfeeding-induced liver fat increase independently of the diet arm. In general, limited overlap was observed between the overfeeding-induced microbiota changes and the liver fat-associated microbiota features at baseline., Conclusions: Our work indicates that the human gut microbiota is resilient to short-term overfeeding on community level, but specific taxa are altered on diet composition-dependent manner. Generalizable microbiota signatures directly associated with liver steatosis could not be identified. Instead, the carriage of Bilophila was identified as a potential novel risk factor for diet-induced liver steatosis in humans. Clinical trial registry number: NCT02133144 listed on NIH website: ClinicalTrials.gov., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Konjac glucomannan (KGM) is a hypoglycemic polysaccharide with a wide range of molecular weights. But study on hypoglycemic effects of KGMs relate to molecular weight is limited. In this study, KGMs with high and medium molecular weights, and the degraded KGMs were analyzed with physicochemical properties, hypoglycemic effects and mechanisms. Results showed that as the molecular weight KGMs decreased, the viscosity decreased, molecular flexibility increased, while chemical groups, crystal structures and main chains showed little change. KGMs with medium molecular weights (KGM-M1, KGM-M2) showed better effects on increasing body weight, decreasing levels of fasting blood glucose, insulin resistance, total cholesterol and low density lipoprotein cholesterol, and enhancing integrity of pancreas and colon, than KGMs with high or low molecular weights (KGM-H, KGM-L) in type 2 diabetic rats. Mechanism analysis suggested that KGM-M1 and KGM-M2 had higher antioxidant and anti-inflammatory activities on elevating superoxide dismutase, decreasing malondialdehyde and tumor necrosis factor-α levels. Moreover, KGM-M1 and KGM-M2 increased gut microbiota diversity, Bacteroidetes/Firmicutes ratio and Muribaculaceae, decreased Romboutsia and Klebsiella, and improved 6 diabetic related metabolites. Combined, KGM-M1 and KGM-M2 showed higher hypoglycemic effects, due to regulatory activities of antioxidant, anti-inflammatory, intestinal microbiota, and relieved metabolic disorders., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: There were COVID-19 patients with SARS-COV-2 nucleic acid long-term positive. This article aims to understand the relevant factors that affect SARS-COV-2 clearance time., Methods: The clinical data of 115 COVID-19 patients with SARS-COV-2 nucleic acid positive time exceeding 14 days were collected retrospectively, and the relationship between clinical characteristics, chest CT scans, blood cells, biochemical indicators, and the time of viral nucleic acid turning negative were analyzed., Results: The time from symptom onsets to nucleic acid turning negative was (32.5 ± 8.7) days in this group of patients. The time of nucleic acid turning negative: no fever group was longer than fever group, diabetes group was longer than no comorbidity group, elevated levels of ALT (alanine aminotransferase), or GLU (fasting blood glucose) group, decreased levels of ALB (albumin) group or HDLC (high-density lipoprotein cholesterol) group was longer than it's normal group separately (P < 0.05). Cox multivariate regression analysis showed that ALT [odds ratio (OR): 2.164 (95% CI: 1.276-3.670), P = 0.004], GLU [OR: 2.064 (95% CI: 1.195-3.566), P = 0.009] and HDLC [OR: 0.527 (95% CI: 0.307-0.907), P = 0.021] were independent factors which affected the time of nucleic acid turning negative., Conclusions: ALT, GLU and HDLC were independent factors that influenced the time of nucleic acid turning negative. Although diabetes or hyperglycemia is a known risk factor, HDLC is the first to be identified, clinicians should be aware of dyslipidemia in covid-19 patients., (Copyright © 2020. Published by Elsevier Ltd.)

In type 2 diabetes, liver insulin resistance and excess hepatic glucose production results in elevated fasting glucose. A bedtime snack has been recommended to improve fasting glucose, yet there is little evidence supporting this recommendation. Moreover, the optimal composition of a bedtime snack is unknown., Purpose: To determine whether a low-carbohydrate protein-rich bedtime snack (Egg) could reduce fasting plasma glucose levels in people with type 2 diabetes when compared to a high-carbohydrate protein-rich bedtime snack (Yogurt) or a No Bedtime Snack condition. Secondary outcomes included glucose control assessed by continuous glucose monitoring (CGM) and fasting insulin sensitivity markers., Methods: Using a randomized crossover design, participants with type 2 diabetes (N = 15) completed three separate isocaloric conditions: i) Egg, ii) Yogurt, and iii) No Bedtime Snack, each lasting three days. CGM was collected throughout and duplicate fasting blood samples were obtained on the morning of day 4 in each condition., Results: Fasting plasma glucose (P = 0.04, d = 0.68), insulin (P = 0.04, d = 0.45), and nocturnal glucose (P = 0.02, d = 0.94) were significantly lower, and quantitative insulin sensitivity check index (QUICKI; P = 0.003) was improved, in the Egg compared to the Yogurt bedtime snack. There were no significant differences between either bedtime snack and No Bedtime Snack., Conclusion: In the short-term, a low-carbohydrate bedtime snack (Egg) lowered fasting glucose and improved markers of insulin sensitivity when compared to a high-carbohydrate protein-matched bedtime snack (Yogurt). However, consuming a low- or high-carbohydrate bedtime snack did not appear to lower fasting glucose compared to consuming an isocaloric diet with no bedtime snack. CLINICAL TRIAL REGISTRY: clinicaltrials.gov (NCT03207269)., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: The relationship among distribution of pathological values at the Oral Glucose Tolerance Test (OGTT), metabolic risk factors and pregnancy outcomes in women with Gestational Diabetes (GDM), has not been clearly identified. We retrospectively compared metabolic and therapeutic parameters, maternal-fetal outcomes and post-partum OGTTs, with respect to the number and distribution of altered values of diagnostic OGTT in pregnancy. Secondly, we assessed whether insulin therapy predictive factors were identifiable., Methods and Results: This analysis included 602 pregnant women with GDM, followed in Diabetes and Pregnancy Unit of Perugia Hospital from diagnosis to childbirth. All women were diagnosed diabetic upon 75g OGTT, according IADPSG criteria. Women were divided into 3 groups, respect to distribution of diagnostic blood glucose (BG) values at OGTT: Group 1: only fasting BG (OGTT0h); Group 2: 1 and/or 2h (OGTT1-2h); Group 3: both fasting and 1 h and/or 2h (OGTT0+1-2h) BG. Pregnant women with fasting hyperglycemia at OGTT (Groups 1 and 3) had similar metabolic characteristics (weight, prevalence of obesity, gestational weight gain, HbA1c), a greater need for insulin therapy, and a higher risk of impaired glucose tolerance persistence after childbirth, as compared to Group 2. No significant differences were observed in terms of maternal and neonatal outcomes (p > 0.05), except for a greater prevalence of caesarean sections in Group 3., Conclusion: The metabolic characteristics of GDM women are mirrored by OGTT values at diagnosis, but are not associated with adverse pregnancy outcomes. Intensive management and a tailored treatment of GDM improve maternal-neonatal outcomes, regardless of diagnostic values distribution and pre-gestational metabolic characteristics., (Copyright © 2020 The Italian Diabetes Society, 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.)

Objective: Galectin-3 binding protein (Gal-3BP) is one of the major fucosylated glycoprotein family members and has recently been implicated in non-alcoholic fatty liver disease, hyperlipaemia and coronary artery disease. Here, we analysed the serum concentrations of Gal-3BP in menopausal women to evaluate the association of circulating Gal-3BP and insulin resistance in females after menopause., Materials and Methods: We evaluated serum levels of Gal-3BP in sixty-two non-diabetic women with menopausal status for at least one year. The clinical features, biochemical profiles and homeostasis model assessment of insulin resistance (HOMA-IR) indices were obtained routinely., Results: Gal-3BP levels increased in women with higher HOMA-IR indices and were positively correlated with HOMA-IR indices. The Gal-3BP level was also an independent risk factor for a high HOMA-IR index and showed the most influence on the HOMA-IR index compared to fasting plasma glucose, triglyceride, age and body mass index. The cut-off value of the serum Gal-3BP level was 2234.32 ng/ml, with areas under the ROC curve (AUCs) of 0.68 (HOMA-IR index 1.5), 0.81 (HOMA-IR index 2.0) and 0.93 (HOMA-IR index 2.5)., Conclusion: Serum levels of Gal-3BP are associated with impaired insulin sensitivity in non-diabetic menopausal women., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Aims: Seventy percent of Africans living with diabetes are undiagnosed. Identifying who should be referred for testing is critical. Therefore we evaluated the ability of the Atherosclerosis Risk in Communities (ARIC) diabetes prediction equation with A1C added (ARIC + A1C) to identify diabetes in 451 African-born blacks living in America (66% male; age 38 ± 10y (mean ± SD); BMI 27.5 ± 4.4 kg/m 2 )., Methods: All participants denied a history of diabetes. OGTTs were performed. Diabetes diagnosis required 2-h glucose ≥200 mg/dL. The five non-invasive (Age, parent history of diabetes, waist circumference, height, systolic blood pressure) and four invasive variables (Fasting glucose (FPG), A1C, triglycerides (TG), HDL) were obtained. Four models were tested: Model-1: Full ARIC + A1C equation; Model-2: All five non-invasive variables with one invasive variable excluded at a time; Model-3: All five non-invasive variables with one invasive variable included at a time; Model-4: Each invasive variable singly. Area under the receiver operator characteristic curve (AROC) predicted diabetes. Youden Index identified optimal cut-points., Results: Diabetes occurred in 7% (30/451). Model-1, the full ARIC + A1C equation, AROC = 0.83. Model-2: With FPG excluded, AROC = 0.77 (P = 0.038), but when A1C, HDL or TG were excluded AROC remained unchanged. Model-3 with all non-invasive variables and FPG alone, AROC=0.87; but with A1C, TG or HDL included AROC declined to ≤0.76. Model-4: FPG as a single predictor, AROC = 0.87. A1C, TG, or HDL as single predictors all had AROC ≤ 0.74. Optimal cut-point for FPG was 100 mg/dL., Conclusions: To detect diabetes, FPG performed as well as the nine-variable updated ARIC + A1C equation., (Published by Elsevier Ltd.)

Background: Hyperlipidemia is one of the major risk factors for cerebrovascular disease and it is common practice to obtain fasting lipid profile prior to starting lipid lowering therapy (LLT). Recent AHA Guidelines published in 2018 allow for a non-fasting value to be used., Objective: To determine if obtaining fasting lipid levels in addition to random lipid levels prompts changes in hyperlipidemia management of acute stroke patients., Methods: 206 patients met the study criteria which included a diagnosis of acute ischemic stroke or transient ischemic attack on admission and availability of both random and fasting LDL levels collected within 72 h of each other. Patients were divided into three groups based on random LDL at admission: Group A: LDL < 70, Group B: LDL 70-99, and Group C: LDL ≥ 100 mg/dL. The dataset was analyzed to conform to the 2018 AHA/ACC guidelines using an LDL cutoff of 70 mg/dL., Results: In 206 patients, statin management would change based on the fasting LDL level in 12 patients, 11 of whom were in Group B. Our data suggests that lipid management is more likely to change if the initial random LDL falls between 70-99 mg/dL as compared to a value outside of this range (P < 0.001). We present a decision algorithm to guide lipid management in acute stroke patients., Conclusions: Foregoing a fasting lipid panel to guide LLT in patients with ischemic stroke is appropriate in most cases but for select patients with random LDL levels between 70 and 99, fasting lipid profile should be obtained prior to deciding upon LLT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: To investigate the association of VitD with GDM, and examine the potential modifying effect of prepregnancy BMI in Chinese pregnant women., Methods: 3318 pregnant women underwent oral glucose tolerance test (OGTT) were selected from Zhoushan Pregnant Women Cohort. Plasma VitD levels were measured in the first (T1) and/or second trimester (T2). Multiple linear and logistic regression models were used for evaluating the association of VitD with GDM., Results: Prepregnancy BMI was positively associated with all three time-point glucose of OGTT. 25(OH)D level in T1 (β = -0.003) and T2 (β = -0.004), and its change from T1 to T2 (β = -0.004) were significantly and inversely associated with fasting blood glucose (FBG) of OGTT, but not 1-h and 2-h postload blood glucose of OGTT, respectively. The negative associations of VitD and FBG were stronger among overweight/obese women. VitD deficiency (25(OH)D < 20 ng/ml) in T2 was associated with an increased risk of GDM with increased FBG, GDM subtype 1 (OR: 2.10) and subtype 3 (OR: 2.19). Moreover, prepregnancy BMI modified this effect on GDM subtype 1 (BMI < 24: OR = 1.42; BMI ≥ 24: OR = 9.61, P for interaction = 0.002). Lower VitD increment from T1 to T2 was associated with a higher risk for GDM among overweight/obese women. Additionally, GDM prevalence fluctuated with the season, i.e. lower in summer/fall and higher in winter/spring., Conclusions: Maternal VitD deficiency was associated with a higher risk of GDM subtype with increased FBG, and the risk is much greater among overweight/obesity women. The lower the VitD increment during pregnancy, the greater the risk of GDM, especially in overweight/obesity women. Furthermore, seasonal variation of GDM may be exhibited as a critical confounder in the association of VitD and GDM., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied. Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared. Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested. Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05). RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides. The chemical composition of six legume polysaccharides were determined. Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition. Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide., Competing Interests: Declaration of competing interest We declare that we have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Triglyceride (TG) is a tri-ester composed of a glycerol and 3 fatty acids. Degradation of TG in adipose tissue is increased in the fasting state but inhibited in the postprandial state. Although insulin suppresses adipose TG degradation, patients with insulin resistance have high concentrations of insulin and free glycerol (FG) in the fasting state., Objective: We examined whether the fasting FG concentration reflects visceral obesity and insulin sensitivity in middle-aged Japanese men., Methods: We measured the fasting serum FG concentration in 72 males aged 30 to 50 years using a simple enzymatic method. The subjects were divided into tertiles according to their homeostasis model assessment of insulin resistance (HOMA-IR). Besides routine glucose- and lipid-related parameters, we determined insulin sensitivity as the rate of glucose disappearance in a 2-step hyperinsulinemic-euglycemic clamp and the abdominal visceral fat area (VFA) by magnetic resonance imaging., Results: The highest HOMA-IR tertile group had a higher fasting FG concentration than the middle- and lowest-tertile groups (0.077 ± 0.024 vs 0.063 ± 0.017 and 0.061 ± 0.016 mmol/L, P < .05 and P < .01). The FG concentration was positively correlated with VFA (rs = 0.36; P < .01) and the HOMA-IR score (rs = 0.26, P < .05) but negatively correlated with insulin sensitivity (rs = -0.26, P < .05). Multivariate regression analysis revealed that the FG concentration is independently associated with VFA and insulin sensitivity., Conclusion: The fasting FG concentration reflects VFA and insulin sensitivity in middle-aged Japanese men. The fasting FG concentration may be a potential surrogate marker of visceral obesity and insulin resistance in outpatients., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Several factors affect the quality of life and personal well-being of transplant recipients, including Ramadan fasting for Muslims. This study aimed to assess the effect of Ramadan fasting on the renal and liver functions of liver transplantation recipients and to propose a protocol for adapting an Immunosuppression regimen and follow-up schedule for patients wishing to fast after liver transplantation., Patients and Methods: This prospective study was conducted on 45 recipients who wished to fast Ramadan from 17th May to 14th June 2018, at Ain Shams Center for Organ Transplantation, Cairo, Egypt., Results: The mean age of the patients was 55.5 ± 7.2 (37-68) years, and 84.4% were males; the mean time from liver transplantation was 51.6 ± 28 months (14-117). Thirty-seven patients (82.2%) completed Ramadan fasting, three patients (6.6%) had interrupted fasting, and five patients (11.1%) had to stop fasting because of an unacceptable rise in renal function. There was a statistically significant difference between the pre- and post-fasting states in terms of the serum creatinine level (p = 0.004).However, the serum creatinine did not exceed the upper normal value in the patients who completed fasting., Conclusion: Our data seem promising for Ramadan fasting with an adapted immunosuppression protocol and regular follow-up for recipients wishing to fast. Further multicentre studies on a larger number of patients are warranted., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Hypoglycemia is defined by a low blood glucose level associated to clinical symptoms. Hypoglycemia may be related to treatment of diabetes, but also to drugs, alcohol, critical illness, cortisol insufficiency including hypopituitarism, insulinoma, bariatric or gastric surgery, pancreas transplantation or glucagon deficiency, or may be surreptitious. Some hypoglycemic episodes remain unexplained, and genetic, paraneoplastic and immune causes should be considered. Genetic causes may be related to endogenous hyperinsulinism and to inborn errors of metabolism (IEM). Endogenous hyperinsulinism is related to monogenic congenital hyperinsulinism, and especially to mutations of the glucokinase-activating gene or of insulin receptors, both characterised by postprandial hypoglycemia with major hyperinsulinism. In adulthood, IEM-related hypoglycemia can persist in a previously diagnosed childhood disease or may be a presenting sign. It is suggested by systemic involvement (rhabdomyolysis after fasting or exercising, heart disease, hepatomegaly), sometimes associated to a family history of hypoglycemia. The timing of hypoglycemic episodes with respect to the last meal also helps to orientate diagnosis. Fasting hypoglycemia may be related to type 0, I or III glycogen synthesis disorder, fatty acid oxidation or gluconeogenesis disorder. Postprandial hypoglycemia may be related to inherited fructose intolerance. Exercise-induced hyperinsulinism is mainly related to activating mutation of the SLC16A1 gene. Besides exceptional ectopic insulin secretion, paraneoplastic causes involve NICTH (Non-Islet-Cell Tumour Hypoglycemia), caused by Big-IGF2 secretion by a large tumour, with low blood levels of insulin, C-peptide and IGF1. Autoimmune causes involve antibodies against insulin (HIRATA syndrome), especially in case of Graves' disease, or against the insulin receptor. Medical history, timing, and insulin level orientate the diagnosis., (Copyright © 2020. Published by Elsevier Masson SAS.)

This article focuses on the establishment of an accurate and sensitive quantitation method for the analysis of furan fatty acids. In particular, the sensitivity of GC/MS and UPLC/ESI/MS/MS was compared for the identification and quantification of furan fatty acids. Different methylation methods were tested with respect to GC/MS analysis. Special attention needs to be paid to the methylation of furan fatty acids, as acidic catalysts might lead to the degradation of the furan ring. GC/MS analysis in full-scan mode demonstrated that the limit of quantitation was 10 μM. UPLC/ESI/MS/MS in multiple reaction monitoring mode displayed a higher detection sensitivity than GC/MS. Moreover, the identification of furan fatty acids with charge-reversal derivatization was tested in the positive mode with two widely used pyridinium salts. Significant oxidation was unexpectedly observed using N -(4-aminomethylphenyl) pyridinium as a derivatization agent. The formed 3-acyl-oxymethyl-1-methylpyridinium iodide derivatized by 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide improved the sensitivity more than 2,000-fold compared with nonderivatization in the negative mode by UPLC/ESI/MS/MS. This charge-reversal derivatization enabled the targeted quantitation of furan fatty acids in human plasma. Thus, it is anticipated that this protocol could greatly contribute to the clarification of pathological mechanisms related to furan fatty acids and their metabolites., (Copyright © 2020 Xu et al.)

Aims: The triglycerides-glucose (TyG) index, the product of fasting plasma glucose (FPG) and triglycerides (TG) is a novel index. Many previous studies have reported that the TyG index might be a strong predictor of incident type 2 diabetes. We determined whether the TyG index could be a useful predictor for diabetes diagnosis and compared it to the FPG and TG as predictors of type 2 diabetes., Methods: A total of 617 subjects without baseline diabetes were examined and followed up for a median period of 9.2 years. We performed a mixed effect cox regression analysis to evaluate the risk of developing diabetes across the quartiles of the TyG index, calculated as ln[triglyceride (mg/dl)×FPG (mg/dl)/2], and plotted a receiver operating characteristic (ROC) curve to assess discrimination among TyG, FPG and TG., Results: During 4,871.56 person-years of follow-up, there were 163 incident cases of diabetes. The risk of diabetes increased across the quartiles of the TyG index. Those in the highest quartile of TyG had a higher risk of developing diabetes (adjusted HR 3.38 95% CI 2.38-4.8, ptrend<0.001) than those in the lowest quartile. The area under the curve (AUC) of the ROC plots were 0.79 (95% CI 0.74-0.83) for FPG, 0.64 (95% CI 0.60-0.69) for TyG and 0.59 (95% CI 0.54-0.64) for TG., Conclusion: The TyG index was significantly associated with risk of incident diabetes and could be a valuable biomarker of developing diabetes. However, FPG appeared to be a more robust predictor of diabetes., (Copyright © 2019 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: The previous study served impaired fasting glucose (IFG), a pre-diabetic state which was much greater than that of diabetic patients, have reached no consensus on its cut-off value. In this study, we aimed to explore the cut-off value of IFG via the associations of blood lipids with fasting plasma glucose (FPG)., Design: A cross-sectional study in Jilin province, China, 2012., Sample: 13,093 participants aged 18-79 years in Jilin province were involved in the study. The Lamba-Mu-Sigma (LMS) method and generalized additive model (GAM) were used to explore the associations of different levels of FPG and blood lipids., Results: The distributions of FPG, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c) were significantly different by gender (p<0.01). In general, both LMS and GAM results showed that the TG and HDL-c curves had a steeper tendency when the FPG was greater than 6.0mmol/L., Conclusion: FPG was positively associated with TG while negatively associated with HDL-c, and the associations were stronger in females. The cut-off value of IFG was suggested to be 6.0mmol/L., (Copyright © 2019 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: Caspase-1 is implicated in several important inflammatory diseases and controls adipocyte differentiation and insulin sensitivity. Interleukin-10 (IL-10) is an anti-inflammatory cytokine and plays an important role in chronic inflammatory conditions. This study was planned to determine if there is any relationship between Caspase-1 and IL-10 levels in women with PCOS., Materials and Methods: Forty-two women with PCOS and thirty-seven healthy controls were evaluated in this controlled clinical study. Caspase-1 and IL-10 levels, serum lipid sub-fractions, fasting glucose, fasting insulin and other hormones (gonadotropins, androgens), malondialdehyde (MDA) and glutathione (GSH) levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance., Results: Free androgen index (FAI), HOMA-IR, MDA and Caspase-1 levels were significantly higher in subjects with PCOS. However, the women with PCOS had considerably lower GSH concentration levels than healthy subjects. Serum IL-10 levels were higher in study subjects than in controls, though it was statistically insignificant. Caspase-1 was positively associated with IL-10., Conclusion: These outcomes propose that Caspase-1 may have a role in triggering the processes leading to chronic low-grade inflammation in women with PCOS, independent of insulin resistance, androgen excess and oxidative stress. Nevertheless, the precise role of Caspase-1 in the pathogenesis of the disease remains to be elucidated., Competing Interests: Declaration of Competing Interest Authors declare that there is no funding for the study., (Copyright © 2020. Published by Elsevier B.V.)