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Despite a growing body of research indicating a link between fasting glucose levels and mortality, the relationship between fasting glucose and all-cause and cancer mortality remains inconsistent. In this study, we used Cox regression and restricted cubic spline models to analyze the association and dose-response relationship between fasting plasma glucose levels and all-cause and cancer mortality in a retrospective cohort based on data from the 2015 health check-ups of residents in Quzhou City. After a mean follow-up of 5.31 years for 148,755 study participants, 10,345 deaths occurred, with an all-cause mortality density of 131.09/10,000 person-years, of which 2,845 were cancer deaths, with a cancer mortality density of 36.05/10,000 person-years. There was a "J" shaped dose-response relationship between fasting plasma glucose levels and all-cause and cancer mortality. Relative to normal fasting glucose (NFG), the risk of all-cause mortality (HRs and 95% CIs) in the impaired fasting glucose (IFG) and diabetes mellitus (DM) groups was 1.11 (1.06, 1.16) and 1.43 (1.35, 1.52), respectively, and the risk of cancer mortality in the DM group was 1.22 (1.09, 1.37). In this cohort study, we found that fasting plasma glucose levels were significantly associated with the risk of all-cause and cancer mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aim: Although benefits of flaxseed and fasting mimicking diet (FMD), each alone, have been shown in the management of metabolic dysfunction-associated steatotic liver disease (MASLD), the benefit of combining the two is not clear. This study aimed to investigate the effect of the combination of FMD and flaxseed supplementation on surrogate measures of MASLD., Methods: The present study was conducted as a randomized, parallel, open-label controlled clinical trial on a hundred patients with MASLD for 12 weeks. Eligible participants were assigned to four groups including control group (lifestyle modification recommendations); flaxseed group (30 g/day of flaxseed powder consumption); FMD group (16 h of fasting per day), and combination of FMD with flaxseed. Changes in anthropometric parameters, serum levels of lipids, glycemic measures, High-sensitivity C-reactive protein (hs-CRP), and liver enzymes, and hepatic steatosis and fibrosis by transient elastography were assessed., Results: Serum triglycerides, total cholesterol, fasting blood glucose and insulin, hs-CRP and liver enzymes decreased in all intervention groups. Hepatic steatosis score decreased in the intervention groups, but not significantly in comparison to the control group. Hepatic fibrosis score decreased significantly in the intervention groups compared to control., Conclusion: Our data indicate that the combination of FMD with flaxseed consumption is not superior to either of the interventions alone in the management of MASLD., Competing Interests: Competing interests The authors declare no competing interests. Ethical approval The study protocol was approved by the ethics committee of the National Nutrition and Food Technology Research Institute (Ethics committee reference number IR.SBMU.NNFTRI.1402.001) and all participants signed a written informed consent form. This study complies with the Declaration of Helsinki and was performed according to ethics committee approval., (© 2024. The Author(s).)

Background: The majority of Chinese Americans is foreign-born, and it is well-documented that immigration to the United States (US) leads to increased risk for chronic diseases including type 2 diabetes. Increased disease risk has been attributed to changes in lifestyle behaviors following immigration, but few studies have considered the psychosocial impact of immigration upon biomarkers of disease risk., Purpose: To examine associations of psychological stress and social isolation with markers of type 2 diabetes risk over time among US Chinese immigrants., Methods: In this longitudinal study of 614 Chinese immigrants, participants completed assessments of perceived stress, acculturative stress, negative life events, and social isolation annually at three time points. Fasting blood samples were obtained at each time point to measure blood glucose, glycated hemoglobin, and insulin resistance. Mean duration between baseline and follow-up assessments was approximately 2 years., Results: Increases in migration-related stress, perceived stress and social isolation were associated with significant increases in fasting glucose at follow-up independent of age, body mass index, length of US residence, and other potential covariates. Moreover, increases in glucose varied depending on perceived stress levels at baseline, such that those with higher baseline stress had a steeper increase in glucose over time., Conclusions: Psychological stress and social isolation are associated with increases in fasting glucose in a sample of US Chinese immigrants. Findings suggest that the unique experiences of immigration may be involved in the risk of developing type 2 diabetes, a condition that is prevalent among US Chinese despite relatively low rates of obesity., (© Society of Behavioral Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cardiovascular diseases (CVD) are among the most prevalent and preventable chronic diseases in the 21st century The global burden of disease: 2004 update. The Report in Sections. A person's risk of developing CVD can be reduced by adopting healthy lifestyles, spiritual and religious practices The American Heart Association Life's Simple 7 in African Americans of the Jackson Heart Study. Fasting as a spiritual practice is not exempted from these benefits. Most world's religions recommend a period of fasting. The obligatory Ramadan fasting in Islam may provide an interesting opportunity to reduce food intake and increase physical activity. The main objective of this study is to investigate the effect of Ramadan fasting on cardiovascular risk factors on healthy adult Muslims., Method: The study was pre/post-test single arm intervention conducted at the staff clinic of Family Medicine department, AKTH, and Northwest, Nigeria. Kano. The study recruited healthy adults 18yrs and above not on any medications that can affect metabolic profiles consecutively from two weeks before Ramadan fasting of 2018 and the last week of Ramadan of the same year. The questionnaire included information on sociodemographic, clinical parameters and Lifestyle pattern., Result: Thirty healthy volunteers were included in this study, 25 males (83.3%) and 5 females (16.7%). The mean age was 38.23 ± 6.35(SD). Twenty-five participants were married (83.3%) with 4 singles (13.3%) and 1 divorcee (3.3%). During Ramadan fasting, weight reduced (67.90 ± 11.61 versus 66.53 ± 12.13 4th week of Ramadan p-value < 0.002) Body Mass Index (22.89 ± 3.63 versus 4th week of Ramadan 22.38 ± 3.64 p-value < 0.002) and systolic blood pressure (120.33 ± 19.91versus 4th week of Ramadan 115.33 ± 14.32 p-value 0.003) reduced significantly compared to baseline. The waist circumference, pulse rate, fasting blood sugar and cholesterol were reduced but were not statistically significant., Conclusion: The result from this study suggested that Ramadan fasting may be a useful means of reducing burden of cardiovascular diseases, as the improved cardiovascular risk factors associated with fasting may translate into a significant health benefit., Competing Interests: Declarations Ethical approval Ethical approval was obtained from AKTH Research and Ethics Committee. Reference (NHREC/21/08/2008/AKTH/EC/2224). All participants signed informed consent for the study. Consent for publication Not applicable. Clinical trial number Not applicable since no drugs were introduced. The intervention was religious practice fasting during Ramadan. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: With the ageing of people living with HIV/AIDS (PLWHA), the prevalence of chronic comorbidities, especially hyperglycaemia, is increasing among elderly PLWHA. Antiretroviral therapy (ART) is associated with fasting plasma glucose (FPG) levels. This study aimed to investigate both short-term and long-term FPG characteristics and trends across different ART regimens in elderly Chinese PLWHA., Methods: This retrospective cohort study, based on hospital treatment information, classified ART regimens as this retrospective cohort study used hospital treatment data. ART regimens are classified into three categories: non-nucleoside reverse transcriptase inhibitors (NNRTIs) based, protease inhibitors (PIs) based and integrase strand transfer inhibitor (INSTIs) based. Propensity score matching was applied to control for confounding factors. Follow-up FPG characteristics were then described, and a generalised linear mixed model was employed to estimate FPG trends under different regimens within 1-year and 5-year periods following ART initiation., Results: Participants had an average age of 58.28 years, with 75.02% male. FPG increased following ART initiation, with the most significant rise within 1 year of ART, followed by stabilisation. The FPG increase within 1 year was slower in the PIs-based group compared with the NNRTIs-based group ( β =-0.08, 95% CI -0.15 to -0.01), while there was a higher prevalence of diabetes within 5 years of ART (31.55% vs 22.33%, standardised difference=0.357). The FPG increase within 1 year of ART did not differ between NNRTIs-based and INSTIs-based groups ( β =-0.01, 95% CI -0.20, 0.18)., Conclusion: Our study highlights that elderly Chinese PLWHA experience an increase in FPG levels, particularly during the first year of ART, with variations observed across different ART regimens. The higher long-term prevalence of diabetes in the PIs-based regimen group emphasises the need for tailored glucose management strategies. Routine glucose monitoring and proactive management are crucial for preventing and controlling diabetes in this population, particularly given the long-term metabolic risks associated with ART., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults., Materials and Methods: This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up until December 31, 2019. The explanatory variable was the level of plasma glucose, including PPG with a fasting time of 0-3.9 h (PPG 0-3.9h ) and 4-7.9 h (PPG 4-7.9h ), plasma glucose with a fasting time ≥8 h (PG fasting ), and plasma glucose at 2 h after oral glucose tolerance test (PG 2hOGTT ). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazard models., Results: A 1-natural-log-unit increase in PPG 4-7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50-7.00]. However, PPG 0-3.9h , PG fasting , PG 2hOGTT , haemoglobin A 1c , and insulin were not significantly associated with cancer mortality. The positive association of PPG 4-7.9h with cancer mortality remained in those without a prior diagnosis of cancer., Conclusions: High PPG 4-7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG 4-7.9h may reduce cancer mortality., (© 2024 John Wiley & Sons Ltd.)

Introduction: There has been a surge in interest in identifying the factors that impact cognitive impairment (CI) in patients with multiple sclerosis (MS). The purpose of our study was to examine the correlation between fasting blood sugar (FBS), fasting insulin level, as well as insulin sensitivity and cognitive function in patients with MS., Material and Methods: A total of 85 patients with MS enrolled in this cross-sectional study. Insulin sensitivity (IS) was determined using the quantitative insulin sensitivity check index (Quicki) formula. Cognitive function was evaluated using the Persian version of the Brief International Cognitive Assessment for MS (BICAMS). Spearman correlation test was employed to examine the correlation between cognition and FBS, insulin and IS., Results: The mean ± SD age of the participants was 39.4 ± 10.2 years, and 62 (72.9%) were female. The participants had a FBS level of 87.05 ± 11.73 mg/dL, insulin level of 10.14 ± 7.57 μU/mL and a Quicki index of 0.36 ± 0.05. A higher score on the BVMT-R and BVMT-R-Delayed subtests showed a significant negative correlation with FBS (r: -0.32; p: 0.003 and r: -0.31; p: 0.004, respectively). Conversely, a significant negative correlation (r: -0.24; p: 0.031) was observed between higher fasting insulin levels and the CVLT&#95;II score. IS showed a positive correlation with the CVLT-II (r: 0.24; p: 0.027) and BVMT&#95;R (r: 0.21; p: 0.054) subtests., Conclusion: Our data indicate that elevated fasting glucose, developed fasting insulin levels and reduced insulin sensitivity may serve as potential predictors for CI in patients with MS., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Aims: The International Diabetes Federation (IDF) has recently recommended determination of 1-hour plasma glucose (1-hPG) during an oral glucose tolerance test (OGTT) to diagnose intermediate hyperglycemia (IH) and type 2 diabetes (T2DM). Herein, we investigated the cardiometabolic characteristics of individuals with IH and T2DM according to IDF criteria., Methods: We studied 3086 individuals stratified on the basis of fasting, 1-hPG and 2-hPG in four groups: 1) normal glucose tolerance (NGT), 2) isolated impaired fasting glucose (iIFG,), 3) IH (fasting glucose < 126 mg/dL, 1-hPG 155-208 mg/dL, and/or 2-hPG 140-199 mg/dL, and 4) newly diagnosed T2DM (fasting glucose, 1-hPG and/or 2-hPG≥126 mg/dL, 209 mg/dL and 200 mg/dL, respectively)., Results: Individuals with IH and T2DM exhibited higher adiposity, blood pressure, uric acid, a worse lipid and inflammatory profile and a progressive reduction in Matsuda index of insulin sensitivity, insulinogenic index, and disposition index as compared to the NGT group. Moreover, individuals with IH and T2DM exhibited lower Matsuda, insulinogenic, and disposition indexes as compared to the iIFG group., Conclusions: 1-h PG-based criteria for diagnosis of IH and diabetes identify individuals having an unfavorable cardiometabolic risk profile with a progressive reduction in insulin sensitivity associated with impaired β cell function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the positive rate of late-onset gestational diabetes mellitus (GDM) by additional fasting blood glucose (FBG) screening at 32-34 gestational weeks (GW) and analyse the perinatal outcomes of late-onset GDM after standard treatment., Design: An Prospective cohort study., Setting: Single centre in China., Population: 1130 singleton pregnancies with negative GDM screening in their first and second trimester., Methods: Additional FBG testing was performed at 32-34 GW. Pregnancies with FBG ≥5.1 mmol/L were diagnosed as GDM and received standardized treatment. Perinatal outcomes were collected and compared., Main Outcome Measures: Diagnosis of late-onset GDM, obstetric and neonatal outcomes., Results: 6.3% (71/1130) of participants had FBG values ≥5.1 mmol/L and were diagnosed with late-onset GDM. Sixty-five (91.5%) were treated by dietary therapy and 6 (8.5%) by insulin therapy. The perinatal outcomes of full-term delivery were compared. The incidence of macrosomia (22.7% vs. 5.1%, adjusted odds ratio (aOR) 5.51, 95% confidence interval (CI) 1.83-16.61, p = 0.002) and NICU transferring (18.3% vs. 10.1%, aOR 1.94, 95% CI 1.01-3.74, p = 0.046) was significantly higher in late-onset GDM group than that in FBG <5.1 mmol/L group. Elevated FBG was associated with overweight or obesity during pregnancy (54.9% vs. 34.9%, OR 2.27, 95% CI 1.40-3.68, p = 0.001)., Conclusions: 6.3% of singleton pregnancies with normal GDM screening results in the first and second trimester were found to have late-onset GDM by additional FBG screening at 32-34 GW, and their risk of macrosomia during a full-term pregnancy remains significantly higher after standard treatment., (© 2024 John Wiley & Sons Ltd.)

Purpose: Diabetes mellitus (DM) is a global health concern linked to various complications, including cardiovascular disease (CVD). However, long-term follow-up studies on the risk of DM and CVD using different blood glucose assessment methods in the general Korean population are lacking. This study aimed to assess the predictive abilities of fasting plasma glucose (FPG), 2-h oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) for new-onset DM and high CVD risk in a middle-aged and older Korean population., Methods: This study used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort. Blood sugar measures (FPG, OGTT, and HbA1c) were examined. The primary endpoint was the development of new-onset DM, and CVD risk was evaluated using the Framingham risk score. The predictive abilities for new-onset DM based on glycemic values were evaluated using Harrell's Concordance index and 95% confidence intervals., Results: Among the 10,030 participants, data of 6813 participants without DM at baseline were analyzed. The study revealed that OGTT outperformed FPG and HbA1c in predicting new-onset DM. The combination of FPG and HbA1c did not significantly enhance predictions for DM compared with OGTT alone. OGTT also outperformed FPG and HbA1c in predicting high CVD risk, and this difference remained significant even after adjusting for additional confounders., Conclusion: OGTT has superior predictive capabilities in identifying new-onset DM and high CVD risk in the Korean population. This suggests that relying solely on individual blood sugar measures may be insufficient for assessing DM and CVD risks., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions globally, particularly affecting individuals with type 2 diabetes mellitus (T2DM)., Objective: Our study aims to elucidate the diagnostic value of fasting C-peptide in combination with insulin resistance for assessing hepatic fibrosis in patients with T2DM and comorbid NAFLD., Design: This was a retrospective study., Setting: The study was conducted at the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine., Participants: The research involved 76 type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, diagnosed at our hospital from April 2020 to October 2022. Patients were categorized into the non-progressive hepatic fibrosis group (n = 64) and progressive hepatic fibrosis group (n = 12) based on fibrosis-4 value., Interventions: General data, systolic/diastolic blood pressure, fasting plasma glucose, fasting C-peptide, fasting insulin, glycosylated hemoglobin, uric acid, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were collected. Insulin resistance was calculated using a designated formula., Primary Outcomes Measures: The predictive impact of fasting C-peptide in combination with insulin resistance was evaluated through receiver operating characteristic curves., Results: The age, body mass index, fasting C-peptide, fasting insulin, aspartate transaminase, and insulin resistance showed a significant increase in the progressive hepatic fibrosis group compared to the non-progressive group (P = .006, P = .014, P < .001, P < .001, P = .004, and P = .021). The combination's sensitivity demonstrated an elevation compared to fasting C-peptide or insulin resistance alone (P = .005)., Conclusions: Fasting C-peptide in combination with insulin resistance proves to have a substantial predictive impact on hepatic fibrosis in type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, holding valuable clinical diagnostic potential.

Objective: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100-125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first-trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first- trimester fasting plasma glucose levels, as compared with gestational diabetes, a well-established risk factor for diabetes, in up to 5-year follow-up postpartum., Methods: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post-delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic-area under the curve (ROC-AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status., Results: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut-off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity., Conclusions: Increased first-trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first-trimester fasting plasma glucose has a more pronounced impact on progression to diabetes., (© 2024 International Federation of Gynecology and Obstetrics.)

Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreases, blood, guts, and nervous systems of mice, but their effect on kidney disease is unknown. In addition, a FMD has not been tested in rats. Here, we show that cycles of a newly developed low-salt FMD (LS-FMD) restored normal proteinuria and nephron structure and function in rats with puromycin-induced nephrosis compared with that in animals with renal damage that did not receive the dietary intervention. LS-FMD induced modulation of a nephrogenic gene program, resembling renal developmental processes in multiple kidney structures. LS-FMD also activated podocyte-lineage reprogramming pathways and promoted a quiescent state in mature podocytes in the rat kidney damage model. In a pilot clinical study in patients with chronic kidney disease, FMD cycles of 5 days each month for 3 months promoted renoprotection, including reduction of proteinuria and improved endothelial function, compared with that in patients who did not receive the FMD cycles. These results show that FMD cycles, which promote the reprogramming of multiple renal cell types and lead to glomerular damage reversal in rats, should be tested further for the treatment of progressive kidney diseases.

To date, no studies have been conducted to assess the impact of fasting stress hyperglycemia ratio (SHR) on all-cause mortality. Therefore, the objective of our study is to investigate the association between SHR and all-cause mortality in a population of American adults. The study population was derived from NHANES data spanning from 2005 to 2018. The exposure variable SHR was derived from fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c%), and the specific calculation formula was as follows: (FBG (mmol/L))/(1.59 × HbA1c (%) - 2.59). The outcome variable was all-cause mortality. A total of 18,457 participants were enrolled in this prospective cohort study. Following a median follow-up period of 90 months, all-cause mortality was observed in 10.32% of the subjects. Cox proportional hazards regression model indicates that there is no significant difference between SHR and all-cause mortality in the fully adjusted model, whether analyzed as a continuous or categorical variable (P for trend > 0.05). Through the 2-piecewise Cox proportional hazards regression model, we have determined that the inflection point of SHR in relation to all-cause mortality is 0.88. It has also been observed that when the value of SHR is on the left side of the inflection point (SHR ≤ 0.88), there is a significant 77% (HR: 0.23; 95% CI: 0.10-0.50) reduction in all-cause mortality for each additional unit increase in SHR. Conversely, when the value of SHR exceeds 0.88, there is a substantial 2.40-fold (HR: 2.40; 95% CI: 1.61-3.58) increase in the risk of all-cause mortality (P for log likelihood ratio test < .001). The subgroup analysis results demonstrate that sex has the potential to modify the association between SHR and all-cause mortality within the population exhibiting SHR ≤ 0.88. The relationship between SHR and all-cause mortality follows a U-shaped pattern, where in the lowest risk of death for the average American adult is observed at an SHR value of 0.88. Furthermore, in men with SHR ≤ 0.88, there is a significant inverse relationship between the increase in SHR and the risk of all-cause mortality., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

There is a need to investigate the effect of lifestyle modifications on cardiometabolic health-related issues that occur during menopause. The aim of this study was to compare the effect of resistance and endurance circuit training program alone (exercise group, n = 34) with the effect of time-restricted eating (16:8) combined with a training program (combination group, n = 28) on cardiometabolic health in 62 menopausal women (aged 51.3 ± 4.69 years). Testing was conducted before and after a 12-week period and included an assessment of body composition, glycemic control, lipid panel, blood pressure, and anthropometric measurements. Decreases in body mass index and systolic blood pressure were significantly greater in the combination group than in the exercise group (F(1,60) = 4.482, p = 0.038, η 2  = 0.07; F(1,57) = 5.215, p = 0.026, η 2  = 0.08, respectively, indicating moderate effects). There were significant decreases in fat mass (p = 0.001, r = 0.654), glucose level (p = 0.017, r = 0.459), insulin level (p = 0.013, r = 0.467), homeostatic model assessment for insulin resistance (p = 0.009, r = 0.499), waist circumference (p = 0.002, r = 0.596), and waist-to-height ratio (p = 0.003, r = 0.588) (indicating moderate effect) in the combination group, while there were no significant changes in the exercise group. There were no changes in lipid panel indicators in either group. This is the first study to investigate the effect of time-restricted eating combined with exercise in menopausal women. The results of the study provide evidence that the combination of time-restricted eating and exercise leads to a greater body mass index reduction than exercise alone in menopausal women.Trial registration: ClinicalTrials.gov, NCT06138015 registered 18 November 2023-Retrospectively registered, https://clinicaltrials.gov/study/NCT06138015 ., (© 2024. The Author(s).)

Background/objectives: Traditional glycemic monitoring in type 2 diabetes is limited, whereas continuous glucose monitoring (CGM) offers better insights into glucose fluctuations. This study aimed to determine the correlations and relative contributions of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels to hyperglycemia., Methods: We utilized CGM and recorded carbohydrate intake data from lifestyle diaries of 59 patients enrolled in the Diabetes and Lifestyle Cohort Twente (DIALECT-2). Correlations between FPG and the glucose management indicator (GMI), FPG and Time Above Range (TAR), PPG and GMI, and PPG and TAR were conducted. Daily and mealtime relative contributions of PPG and FPG to glycated hemoglobin (HbA 1c ) and GMI were determined, considering two ranges: on target (<7.0%, 53 mmol/mol) and not on target (≥7.0%, 53 mmol/mol). Correlations between mealtime PPG and carbohydrate consumption were examined., Results: FPG and PPG correlated with GMI (r = 0.82 and 0.41, respectively, p < 0.05). The relative contribution of PPG in patients with HbA 1c , GMI, and TAR values not on target was lower than in patients with HbA 1c , GMI, and TAR values on target. When analyzing different mealtimes, patients with target GMI values had a higher PPG (73 ± 21%) than FPG after breakfast (27 ± 21%, p < 0.001). Individuals with elevated GMI levels had lower PPG after lunch (30 ± 20%), dinner (36 ± 23%), and snacks (34 ± 23%) than FPG. PPG after breakfast positively correlated (r = 0.41, p < 0.01) with breakfast carbohydrate intake., Conclusions: Both PPG and FPG contribute to hyperglycemia, with PPG playing a larger role in patients with better glycemic control, especially after breakfast. Targeting PPG may be crucial for optimizing glucose management.

Objective: Fasting insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) index are relatively simple and reliable noninvasive markers of insulin resistance (IR). Given the relevance of correctly diagnosing IR, we emphasize the importance of establishing reliable reference intervals (RIs) for these markers. This study aimed to determine the RIs of fasting insulin and HOMA-IR index in adults living in Rio de Janeiro and, secondarily, to verify potential RI differences between sexes., Subjects and Methods: Serum insulin levels of 146,497 individuals (ages 20-60 years) who underwent blood sampling in the state of Rio de Janeiro were obtained retrospectively through access to an extensive laboratory database. Insulin was measured using the electrochemiluminescence immunoassay method. After applying exclusion criteria, 21,684 individuals (18,576 [86%] women) were included. The RIs were estimated using a computational mining approach that integrates a selection of R packages., Results: The 95% RIs in women and men and in the overall population were, respectively, 2.54-13.30 μU/mL (15.3-80.12 pmol/L), 2.43-11.89 μU/mL (14.6-71.7 pmol/L), and 2.52-13.14 μU/mL (15.2-79.2 pmol/L) for fasting insulin levels and 0.39-2.86, 0.38-2.81, and 0.39-2.86 for HOMA-IR values. Despite significant differences in insulin levels and HOMA-IR index between men and women, the use of sex-specific RIs was not justified., Conclusion: The RIs of fasting insulin levels and HOMA-IR values found in the overall population can be applied to both sexes. Thus, for our population, we suggest the RIs of 2.52-13.14 μU/mL (15.1-78.8 pmol/L) for fasting insulin and 0.39-2.86 for the HOMA-IR index., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Background: Fasting-induced headaches (FIHs) have been shown to occur on the first day of Ramadan and clearly decline thereafter. Despite the wealth of knowledge about different types of headaches (e.g., migraine-, cluster-, and tension-type headaches), research on the mechanism underlying FIHs, as well as their treatment, remains scarce. Our study aimed to investigate any association between FIHs during the first day of Ramadan and potential headache-related biomarkers, including fasting blood glucose (FBG), C-reactive protein (CRP), magnesium, vitamin B9, vitamin B12, homocysteine, and calcitonin gene related peptide (CGRP), and to assess whether a prophylactic use of paracetamol may influence these biomarkers., Methods: As part of a randomized, open-label clinical trial that evaluated the effect of paracetamol as a prophylactic therapy for FIH, blood samples from stratified subjects in the prophylaxis and control groups were withdrawn while fasting after the 1st dose of paracetamol (in the prophylaxis group) and prior to reporting headache occurrence., Results: Plasma and serum were separated for 61 subjects; 31 and 30 subjects from the prophylaxis and control groups, respectively. Overall, no significant differences were found in the levels of FBG, CRP, magnesium, vitamin B9, and vitamin B12 in headache-suffering subjects compared to those without headache despite the use of paracetamol for prophylaxis. Homocysteine, however, was significantly reduced in all subjects who experienced FIH compared to those without headache (median 6.9 [1.6] vs. 7.7 [2.7] umol/L; p = 0.041). On the contrary, when the CGRP was measured using immunoassay, it was found to be significantly elevated in all headache-suffering subjects compared to those without headache (median 126.1 [17.7] vs. 105.8 [19.6] pg/mL; p ≤ 0.0001). This difference was maintained upon comparing the headache to non-headache subjects in both the prophylaxis (median 121.5 [15.4] vs. 105.8 [9.4] pg/mL; p < 0.01) and control groups (median 128.5 [28.3] vs. 105.8 [23.8] pg/mL; p < 0.01). Additionally, an elevated CGRP level was found to increase the odds of having a FIH [OR = 1.32; 95%CI 1.06-1.22]., Conclusions: Our findings revealed the role of CGRP in FIHs for the first time and suggest further investigation in signaling pathways downstream CGRP receptors. Furthermore, the modulation CGRP or CGRP receptors could have a clinical application in the prevention of FIHs., Trial Registration: This study was registered with the Saudi Food and Drug Authority in the Saudi Clinical Trials Registry (SCTR; No. 22122102)., (© 2024. The Author(s).)

Objective: Although abnormal lipid metabolism is one of the major risk factors for diabetes, the correlation between lipids and glucose is rarely discussed in the general population. The differences in lipid-glucose correlations across gender and ethnicity have been even more rarely studied. We examined the association between fasting blood glucose (FBG) and lipids, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB), using 6,093 participants aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES)., Methods: Analyses were performed using multiple logistic regression and generalised additive models., Results: When other confounders were considered, we found that fasting glucose was positively correlated with triglycerides and negatively correlated with HDL-C, whereas total cholesterol, LDL-C cholesterol, and fasting glucose were related to each other in a U-curve fashion, with inflection points of 5.17 mmol/L and 2.3 mmol/L, respectively.This relationship persisted in subgroups of different sexes and races. A positive correlation was found between fasting glucose and ApoB, but subgroup analyses revealed that this relationship was not correlated across gender and race., Conclusion: In the general population, fasting blood glucose levels were positively correlated with TG, negatively correlated with HDL-C, and U-shaped with total cholesterol and LDL-C. The likelihood of developing diabetes was 40% higher when LDL-C was greater than 2.3 mmol/L than in patients with LDL-C less than 2.3 mmol/L., (© 2024. The Author(s).)

Depressive disorder is a significant public health problem worldwide, which adversely affects children and adolescents' health. Impaired fasting blood glucose (IFG) is more common in depressive disorder, which becomes a clinical problem that needs to be focused on. The study purposed to determine the prevalence and related factors of IFG in Chinese children and adolescents with depressive disorder and the relationship between triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) ratio and IFG. This research encompassed 756 individuals aged 8 to 18 with major depressive disorders, all diagnosed under DSM-5 criteria at the Third People's Hospital of Fuyang from January 2020 to December 2021. We detected fasting blood glucose (FBG) and lipid levels and assessed the suicidal behaviors and depressive symptoms severity of each participant. The sociodemographic and included study variables were collected and analyzed. Our study employed multiple logistic regression to discern independent factors affecting IFG in conjunction with depressive disorders among children and adolescents. The prevalence of IFG was 6.5% (49/756). IFG was positively correlated with FBG, BMI, TG, TG/HDL-C, and was negatively correlated with gender and the type of antidepressant drug taken. Binary logistic analysis showed that male (OR = 2.57, 95% CI: 1.43-4.63, P = 0.002) and higher levels of TG (OR = 1.63, 95% CI: 1.11-2.38, P = 0.013) were independently associated with IFG in children and adolescents with depressive disorder. The incidence of IFG in children and adolescents with depressive disorder was high and was positively related to the TG/HDL-C ratio. The evaluation and management of IFG in pediatric depression should extend beyond pharmacological interventions. Comprehensive strategies in both assessment and management of IFG are essential to address this condition effectively in young patients facing depressive disorders., (© 2024. The Author(s).)

Purpose: We aimed to investigate the association between maternal fasting plasma glucose (FPG) trajectories during pregnancy and children's refractive errors at 6 years of age., Design: Based on the Ma'anshan Birth Cohort (MABC) in China, a total of 1987 mother-child pairs were included in this study., Methods: Using the group-based trajectory model, trajectory fitting was performed on FPG levels during the first, second, and third trimesters of pregnancy. Children's vision was measured at 6 years of age using the standard logarithmic visual acuity E-chart and cycloplegic refraction examination. Logistic regression models and multi-informant generalized estimating equations were used to analyze the association between maternal blood glucose level and 6-year-old children's visual acuity., Results: Children born of mothers with high level FPG trajectory had a higher risk of developing refractive error (odds ratio [OR] = 1.46 [95% CI: 1.08, 1.97]), hypermetropia (OR = 1.64 [95% CI: 1.09, 2.46]), and astigmatism (OR = 1.60 [95% CI: 1.06, 2.41]) at age 6 compared to those with low level trajectory. Maternal blood glucose level in the first (β = -.012 [95% CI: -.024, -.001]) and the second (β = -.016 [95% CI: -.025, -.006]) trimesters was associated with 6-year-old children's distance vision value., Conclusion: High level of FPG trajectories during pregnancy has been observed to be associated with 6-year-old children's refractive error, hypermetropia, and astigmatism. The first and the second trimesters may be critical periods for the effects of maternal blood glucose on children's vision. The long-term effect of maternal glucose metabolism on children's visual development deserves further study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Insulin sensitivity (IS) is an important factor in type 2 diabetes (T2D) and can be estimated by many different indices., Objective: We aimed to compare the genetic components underlying IS indices obtained from fasting and oral glucose-stimulated plasma glucose and serum insulin levels., Methods: We computed 21 IS indices, classified as fasting, OGTT0,120, and OGTT0,30,120 indices, using fasting and oral glucose tolerance test (OGTT) data in 2 cohorts. We used data from a family cohort (n = 313) to estimate the heritability and the genetic and phenotypic correlations of IS indices. The population cohort, Inter99 (n = 5343), was used to test for associations between IS indices and 426 genetic variants known to be associated with T2D., Results: Heritability estimates of IS indices ranged between 19% and 38%. Fasting and OGTT0,30,120 indices had high genetic (ρG) and phenotypic (ρP) pairwise correlations (ρG and ρP: 0.88 to 1) The OGTT0,120 indices displayed a wide range of pairwise correlations (ρG: 0.17-1.00 and ρP: 0.13-0.97). We identified statistically significant associations between IS indices and established T2D-associated variants. The PPARG rs11709077 variant was associated only with fasting indices and PIK3R rs4976033 only with OGTT0,30,120 indices. The variants in FAM63A/MINDY1, GCK, C2CD4A/B, and FTO loci were associated only with OGTT0,120 indices., Conclusion: Even though the IS indices mostly share a common genetic background, notable differences emerged between OGTT0,120 indices. The fasting and OGTT-based indices have distinct associations with T2D risk variants. This work provides a basis for future large-scale genetic investigations into the differences between IS indices., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Obesity is associated with alterations in circulating IGF1, IGF1-binding proteins (IGFBPs), insulin, inflammatory markers, and hormones implicated in cardiovascular disease, diabetes, cancer, and aging. However, the effects of 4 and 6 h time-restricted eating (TRE) on circulating IGF1 and IGFBPs is uncertain., Objective: This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined., Design: An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out., Participants/setting: This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups., Intervention: Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations., Main Outcome Measures: IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis., Statistical Analysis: Repeated measures ANOVA and mediation analysis were conducted., Results: Body weight significantly decreased with TRE (-3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the "higher weight loss" subgroup. Changes in insulin and HOMA-IR were related to TRE adherence., Conclusions: Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Elaborating and understanding disparities in the burden of cardiovascular disease attributable to high fasting plasma glucose is important to improve diabetes prevention and promote cardiovascular health. In this study, we pool data on 791,373 people aged 25 years and older from three population-based surveys, and estimate the burden of cardiovascular disease attributable to high fasting plasma glucose between 2010 and 2018 in China by age, sex, region and socio-demographic index. In 2018, an estimated total of 498.61 thousand (95% uncertainty interval 463.93 to 534.12) cardiovascular disease-related deaths are attributable to high fasting plasma glucose in China. High fasting plasma glucose accounts for 1076.09 years of life lost per 100,000 people (95% uncertainty interval 1026.88-1129.04) due to cardiovascular disease in 2018, with substantial variation across provinces. In 2018, the higher age-standardised cardiovascular disease mortality rate attributable to high fasting plasma glucose is observed in the high-middle socio-demographic index region and the middle socio-demographic index region. Nationally, compared to 2010, exposure to high fasting plasma glucose and population aging in 2018 are the primary drivers of increased fasting plasma glucose-related deaths due to cardiovascular disease. Findings of this study emphasize the importance of developing population-specific tailored measures in China and other regions with similar condition., (© 2024. The Author(s).)

Background: The use of non-invasive risk scores to detect undiagnosed type 2 diabetes (T2D) ensures the restriction of invasive and costly blood tests to those most likely to be diagnosed with the disease. This study assessed and compared the performance of the African Diabetes Risk Score (ADRS) with three other diabetes risk prediction models for identifying screen-detected diabetes based on fasting plasma glucose (FPG) or glycated haemoglobin (HBA1c)., Methods: Age, sex, waist circumference, body mass index, blood pressure, history of diabetes and physical activity levels from the SA-NW-PURE study were used to externally validate the ADRS and other established risk prediction models. Discrimination was assessed and compared using C-statistics and nonparametric methods. Calibration was assessed using calibration plots, before and after recalibration., Results: Nine hundred and thirty-seven participants were included; 14% had prevalent undiagnosed T2D according to FPG and 26% according to HbA1c. Discrimination was acceptable and was mostly similar between models for both diagnostic measures. The C-statistics for diagnosis by FPG ranged from 0.69 for the Simplified FINDRISC model to 0.77 for the ADRS model and 0.77 for the Simplified FINDRISC model to 0.79 for the ADRS model for diagnosis by HbA1c. Calibration ranged from acceptable to good, though over- and underestimation were present. All models improved significantly following recalibration., Conclusions: The models performed comparably, with the ADRS offering a non-invasive way to identify up to 79% of cases. Based on its ease of use and performance, the ADRS is recommended for screening for T2D in certain Black population groups in South Africa. HbA1c as a means of diagnosis also showed comparable performance with FPG. Therefore, further validation studies can potentially use HbA1c as the standard to compare to., (© 2024. The Author(s).)

Background: Abnormalities in biochemical parameters and changes in eating habits are considered complications of obesity. Oleoylethanolamide (OEA), an endocannabinoid-like compound, has been shown to have protective effects on many metabolic disorders. Given this evidence, the present study aimed to assess the effects of OEA on lipid profile parameters, fasting blood sugar (FBS), and dietary habits in healthy obese people., Methods: In this randomized, double-blind, placebo-controlled clinical trial, which was carried out in 2016 in Tabriz, Iran, 60 obese people were enrolled in the study based on inclusion criteria. The intervention group consumed 125 mg of OEA capsules, and the placebo group received the same amount of starch twice for 8 weeks. Blood samples (5 mL) were taken at baseline and the end of the study in a fasting state. Serum concentrations of FBS, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) were measured by enzymatic methods using commercial kits. The low-density lipoprotein cholesterol (LDL-C) concentration was obtained using the Friede-Wald formula. To assess dietary habits, a food frequency questionnaire (147 items) was used at baseline and the end of the study. A value less than < 0.05 was considered to indicate statistical significance., Results: The TG concentration decreased significantly in the intervention group (mean (SD): 166.29 (70.01) mg/dL to 142.22 (48.05) mg/dL, p = 0.047). Changes in the placebo group were not significant (p > 0.05). After adjusting for baseline values and demographic characteristics, the difference in TG between groups remained significant (p = 0.044). Changes in other biochemical parameters were not significant. There was no significant difference between or within groups in terms of food groups., Conclusion: OEA, as a complementary agent, plays a protective role in TG regulation. However, future studies with longer durations are needed to explore the impact of OEA on regulating dietary habits and to identify the mechanisms related to metabolic abnormalities in obese people., Trial Registration: The study was registered in the Iranian Registry of Clinical Trials (IRCT) center as IRCT201607132017N30 with URL. www.IRCT.IR in date 03/10/2016., (© 2024. The Author(s).)

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

Sedentary behavior has significant deleterious effects on human health. Sedentary behaviors associated with cardiovascular and metabolic disorders by decreasing lipoprotein lipase activities, impaired lipid and carbohydrate metabolism. This cross sectional study was done to see the association between fasting serum glucose and serum total cholesterol in sedentary male. This study was conducted in the Department of Physiology, Mymensingh Medical College, Bangladesh from Octy 2021 to June 2022. A total number of 100 subjects were included in this study. Among them, fifty (50) sedentary males were taken as study group (Group II) and fifty (50) active males were taken as control group (Group I). Age of both control and study group ranged from 25-60 years. Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test & Pearson's correlation coefficient test. Both of these biochemical parameters showed statistically significant difference in study group. The mean±SD of fasting serum glucose of control group (Group I) and study group (Group II) were 4.45±0.51 mmol/L and 5.91±0.60 mmol/L; and the mean±SD of serum total cholesterol level of control group (Group I) and study group (Group II) were 176.14±27.16 mg/dl and 252.58±18.97 mg/dl respectively. Fasting serum glucose and serum total cholesterol shows positive correlation in study group in comparison to control group. From this finding it can be concluded that there was significant correlation of fasting serum glucose and serum total cholesterol in sedentary males.

Type-2 diabetes mellitus is a global pandemic with immense social, health and financial consequences. The pathophysiology of type-2 diabetes is significantly influenced by overweight and obesity. Type-2 diabetes often goes hand-in-hand with high blood pressure. One way to check type-2 diabetes is by measuring fasting blood glucose. This cross-sectional analytical study looked at how blood pressure, body mass index (BMI) and fasting serum glucose relate to each other in women with type-2 diabetes in the Mymensingh locality. The research took place at the Physiology Department of Mymensingh Medical College, Bangladesh from Octy 2023 to June 2024. We included 200 participants: 100 apparently healthy women of 30-65 years without diabetes as the control group and 100 women with diabetes of same age group as the study group. The data was analyzed using SPSS software. Weight and height were measured anthropometrically in kilograms and meters, respectively. Blood pressure was checked with an aneroid sphygmomanometer for both systolic and diastolic values. To see if there were significant differences between groups, we used the unpaired Students 't' test and shared results as mean±SD. For relationships among fasting serum glucose, blood pressure and BMI, we used Pearson's correlation coefficient test. The average BMI for those in the control group was 24.19±1.22 kg/m². In contrast, the study group's average BMI was higher at 28.04±1.66 kg/m². The study group also had a greater average systolic blood pressure of 130.65±6.06 mm Hg compared to 115.30±5.07 mm Hg for controls. For diastolic blood pressure, values were also higher in the study group: 85.65±5.71 mm Hg compared to the control's 75.65±5.25 mm Hg. Fasting serum glucose levels showed a positive correlation with both BMI and blood pressure. We recommended from this study that routine evaluation of these parameters is important for preventing complications associated with type-2 diabetes mellitus.

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.)

Purpose: This retrospective cohort study aims to investigate whether high-normal fasting blood glucose (FBG) affects assisted reproductive technology (ART) outcomes undergoing single blastocyst frozen-thawed embryo transfer (FET) cycles in women with normal body mass index (BMI)., Methods: 944 women with normal BMI and FBG levels undergoing single blastocyst FET cycles were enrolled. Based on the median of FBG (4.97 mmol/L, 1 mmol/L = 18 mg/dL), the subjects were categorized into the low-normal group (3.90 ≤ FBG ≤ 4.97 mmol/L, n = 472) and the high-normal group (4.97 < FBG < 6.10 mmol/L, n = 472). Multivariable logistic regression and receiver operating characteristic (ROC) were used to analyze the relationship between high-normal FBG and ART outcomes., Primary Outcome: live birth rate (LBR)., Results: LBR was significantly lower in the high-normal group than in the low-normal group (36.8% vs. 45.1%, p = 0.010), and the miscarriage rate was considerably higher than that in the low-normal group (23.9% vs. 16.5%, p = 0.041). High-normal FBG of female was an independent predictor of live birth (adjusted OR:0.747, 95% CI: 0.541-0.963, p = 0.027) and miscarriage (adjusted OR:1.610, 95% CI: 1.018-2.547, p = 0.042). ROC analyses showed that the cut-off values of FBG (endpoints: live birth and miscarriage) were 5.07 mmol/L, and 5.01 mmol/L, respectively., Conclusions: In women with normal BMI, high-normal FBG is an independent risk factor for lower LBR and higher miscarriage rate in single blastocyst FET cycles. Attention to preconception FBG monitoring in this particular population may allow early intervention to improve ART outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims/hypothesis: Fatty acid-binding protein 4 (FABP4) has been reported to act as a hepatic insulin resistance factor. We previously reported that fasting FABP4 was correlated with insulin resistance measurements derived from the glucose clamp, and another study reported that postprandial FABP4 levels were decreased in healthy volunteers but were not reported (or known) in participants with type 2 diabetes. We have limited knowledge about the direct effect of FABP4 on muscle cells. We investigated the postprandial FABP4 levels in participants with type 2 diabetes, and the basic mechanism of muscle insulin resistance and FABP4., Methods: We performed a meal tolerance test and hyperinsulinaemic-euglycaemic clamp in 22 participants with type 2 diabetes and 26 participants without diabetes. We measured fasting and postprandial serum FABP4. We cultured mouse C2C12 muscle cells, and investigated the effect of FABP4 on glucose uptake. We analysed insulin signalling by western blot and insulin binding assay., Results: The postprandial FABP4 level in participants with type 2 diabetes was higher than that in participants without diabetes. Participants without diabetes had lower postprandial FABP4 than fasting except for one participant, whereas one-third of participants with type 2 diabetes had higher postprandial FABP4 than fasting. Postprandial FABP4 was correlated with the muscle insulin resistance M/I value from a glucose clamp in participants without diabetes (r=-0.42, p<0.05). The increase in FABP4 after a meal correlated with the muscle insulin resistance M/I value (r=-0.44, p<0.05) and the difference between fasting and postprandial glucagon in participants with type 2 diabetes (r=0.36, p<0.05). FABP4 alone appears to increase glucose uptake, and the combination of FABP4 and insulin decreases glucose uptake when compared with insulin alone. FABP4 inhibits insulin signalling of muscle cells through decreases in phosphorylation of insulin receptor substrate 1 and Akt. The physiological concentration of FABP4 did not inhibit insulin binding to muscle cells., Conclusions/interpretation: These results suggested that the postprandial FABP4 level is associated with insulin resistance, and FABP4 may suppress insulin signals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To determine how age affects insulin resistance during the menstrual cycle and insulin resistance-associated indices: the Triglyceride-glucose and Triglyceride-glucose-BMI indexes., Methods: This prospective observational study used fasting plasma glucose, fasting insulin, triglycerides, body mass index (BMI), and days since the start of the menstrual period collected from the NHANES dataset (1999-2006). Insulin resistance was determined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The participants were categorized as young (16-34 years) or older (>35 years). Rhythmicity during the menstrual cycle was analyzed using the Cosinor and Cosinor2 packages for R., Main Outcome Measures: Cosine fit curves for insulin resistance during the menstrual cycle and age-associated effects on rhythmicity., Results: Using 1256 participants, rhythmicity was observed for fasting insulin and HOMA-IR (p < 0.05) but not for fasting plasma glucose, the Triglyceride-glucose index, or the Triglyceride-glucose-BMI index. Significant amplitudes for fasting insulin and HOMA-IR were observed when age was considered. Acrophases for fasting insulin and HOMA-IR were significant only for the younger group, and the differences between these groups were significant, suggesting that the changes in scores for insulin resistance for the younger and older groups occur at different times of their menstrual cycle., Conclusions: Insulin resistance does fluctuate during the menstrual cycle, and it is at a maximum at different times for younger and older women. Since these results are unadjusted, this study is preliminary and further investigation is required., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at <24 weeks of gestation with hypertensive disorders of pregnancy (HDP) and compare the strengths of the associations of HDP with FPG and HbA1c levels. Totally, 1,178 participants were included in this prospective cohort study. HDP, FPG, HbA1c, and potential confounding factors were included in multiple logistic regression models. The number of HDP cases was 136 (11.5%). When FPG and HbA1c were included in the model separately, quartile 4 (Q4) of FPG (87-125 mg/dL) and HbA1c (5.2-6.3% [33-45 mmol/mol]) levels had higher odds of HDP than quartile 1. The odds ratios (ORs) were 1.334 (95% confidence interval [CI]: 1.002-1.775) for Q4 of FPG and 1.405 (95% CI: 1.051-1.878) for Q4 of HbA1c. When the participants were divided into two categories based on the cut-off value with the maximum Youden Index of FPG or HbA1c, the ORs for high FPG (≥84 mg/dL) or high HbA1c (≥5.2% [33 mmol/mol]) were 1.223 (95% CI: 1.000-1.496) and 1.392 (95% CI: 1.122-1.728), respectively. When both FPG and HbA1c were included in the model simultaneously, the statistical significance of Q4 of FPG disappeared, whereas that of HbA1c remained. In two-category models, the same results were obtained. High FPG and HbA1c levels at <24 weeks of gestation were risk factors for HDP in pregnant Japanese women. In addition, high HbA1c levels were more strongly associated with HDP than high FPG levels.

Background: Beta-thalassemia major (β-TM) patients are more likely to experience blood glucose intolerance and to date; the blood markers that could evaluate this are debatable. So, this study aimed to assess the roles of glycated hemoglobin A1c (HbA1c) and fructosamine in evaluating glucose intolerance in children with β-TM and figuring out role of insulin resistance in these patients., Methods: One hundred children diagnosed with β-TM and 100 age and sex-matched controls were enrolled. Fasting plasma glucose (FPG), 2-h post-prandial blood glucose (2-h PG), HbA1c, fructosamine, fasting insulin level (FINS), insulin resistance index (HOMA-IR), and insulin sensitivity index (HOMA-IS) were evaluated., Results: FPG and 2-h PG revealed glucose intolerance in 51 patients (51%), 19 of them had diabetes mellitus. HbA1c, fructosamine, FINS, and HOMA-IR showed a high statistically significant increase in patients compared to controls, (P < 0.001). Results revealed fructosamine was more specific in detecting prediabetes state and more sensitive in identifying diabetes mellitus in our patients when compared to HbA1c., Conclusions: Despite controversies on HbA1c in children with β-TM, it is still valuable in glucose intolerance detection. Fructosamine showed more sensitivity and specificity. Furthermore, insulin resistance was prevalent in children with β-TM highlighting the necessity of regular glycemic state evaluation., Impact: Glucose intolerance is a common complication in beta thalassemia patients. Conflicting data was reported about the role of HbA1c and fructosamine in evaluating glucose intolerance in thalassemic patients. Fructosamine does not yet have a threshold that may be used to distinguish between patients who have diabetes mellitus and those who do not. Fructosamine was more specific in detecting blood glucose intolerance compared to HbA1c and was more sensitive for diagnosing diabetes mellitus. Insulin resistance was common in patients with beta-thalassemia and often present before the onset of overt diabetes., (© 2024. The Author(s).)

Treatment with glucagon-like peptide 1 receptor agonists reduces liver steatosis and cardiometabolic risk (CMR). Few data are available on lipid metabolism, and no information is available on the postprandial lipidomic profile. Thus, we investigated how exenatide treatment changes lipid metabolism and composition during fasting and after a mixed-meal tolerance test (MMTT) in adults with severe obesity without diabetes. Thirty individuals (26 females and 4 males, 30-60 years old, BMI >40 kg/m2, HbA1c 5.76%) were assigned (1:1) to diet with exenatide 10 μg twice daily treatment (n = 15) or without treatment as control (n = 15) for 3 months. Fasting and postprandial lipidomic profile (by liquid chromatography quadrupole time-of-flight mass spectrometry) and fatty acid metabolism (following a 6-h MMTT/tracer study) and composition (by gas chromatography-mass spectrometry) were evaluated before and after treatment. Both groups had slight weight loss (-5.5% vs. -1.9%, exenatide vs. control; P = 0.052). During fasting, exenatide, compared with control, reduced some ceramides (CERs) and lysophosphatidylcholines (LPCs) previously associated with CMR, while relatively increasing unsaturated phospholipid species (phosphatidylcholine [PC], LPC) with protective effects on CMR, although concentrations of total lipid species were unchanged. During MMTT, both groups showed suppressed lipolysis equal to baseline, but exenatide significantly lowered free fatty acid clearance and postprandial triacyclglycerol (TAG) concentrations, particularly saturated TAGs with 44-54 carbons. Exenatide also reduced some postprandial CERs, PCs, and LPCs previously linked to CMR. These changes in lipidomic profile remained statistically significant after adjusting for weight loss. Exenatide improved fasting and postprandial lipidomic profiles associated with CMR mainly by reducing saturated postprandial TAGs and CERs independently of weight loss and diabetes., (© 2024 by the American Diabetes Association.)

Background and Aims: Intermittent fasting is a nutritional strategy that focuses on when to eat, rather than what to eat. Although the effectiveness of intermittent fasting practices in many metabolic diseases is known, its effect on microbiota and its underlying mechanism has not yet been clarified. This study aimed to investigate the effect of Ramadan fasting, one of the intermittent fasting practices, on gut microbiota and fatty acid binding protein 4 (FABP4)., Methods: The study involved 10 male volunteers, 6 of whom were overweight and 4 were obese. They fasted for an average of 14-15 hours daily from dawn to sunset during the 29-day Ramadan month between 23 March - 20 April 2023 and met the inclusion criteria. The participants' nutritional and physical activity status before and during Ramadan, as well as their anthropometric measurements before and after Ramadan, intestinal microbiota, transaminases, gamma-glutamyl transferase, C reactive protein, total cholesterol (C), high-density lipoprotein (HDL) C, low-density lipoprotein C, triglycerides (TG), and FABP4 levels, were evaluated within the scope of the study., Results: The study found a statistically significant increase in both alpha and beta diversity in the intestinal microbiota following Ramadan fasting (p<0.05). The F/B ratio, Firmicutes phylum, Clostridia class, Clostridiales order, and Ruminococcaceae family exhibited statistically significant decreases, while the Bacteroidetes and Proteobacteria phyla, Bacteroidia, Alphaproteobacteria, and Erysipelotrichi classes, Bacteroidales, Erysipelotrichales, and Actinomycetales orders, Erysipelotrichaceae family and Prevotella genus, demonstrated statistically significant increases (p<0.05). Participants who achieved an average weight loss of 2.3±0.99 kg at the end of Ramadan showed a significant increase in HDL-C and a significant decrease in TG levels (p<0.05). Although FABP4 levels decreased after fasting, this difference was not statistically significant (p>0.05)., Conclusion: Ramadan fasting induces weight loss, modifies gut microbiota, and improves blood lipid profile and FABP4 levels, suggesting the need for more extensive studies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) brings heavy clinical and economic burdens to patients worldwide. High fasting plasma glucose (HFPG) was proven to be an important modifiable risk factor. However, the global burden distribution of HFPG-attributable MASLD has not been fully studied. This study aimed to describe the epidemiological distribution and trends of the burden of HFPG-attributable MASLD worldwide. The data source was the 2021 Global Burden of Disease Study. Descriptive statistics were mainly conducted using disability-adjusted life years (DALYs) and deaths of HFPG-attributable MASLD from 1990 to 2021, as well as their age-standardized rates (ASRs) and population-attributable fractions. Subgroup analyses were conducted by region, age group, and sex. We found that 213.48 thousand DALYs and 10.02 thousand deaths in MASLD were attributable to HFPG worldwide in 2021, with an increase of 2.96 and 3.32 times compared with 1990, respectively. Over the past 32 years, age-standardized DALY rates (ASDRs) have fluctuated upward, reaching 2.45 per 100,000 people in 2021, with an increase of 81.21%. The ASDRs continued to rise in low, low-middle, and high social demographic index (SDI) regions, fluctuated upward at high levels in middle SDI regions, and were relatively low in high-middle SDI regions. People aged 50-69 accounted for the largest proportion of DALYs, while people over 70 had the largest increase of 3.73 times. Men had higher ASDRs, and the sex difference has been gradually expanding over the past 32 years, peaking at the age of 45-49. In conclusion, the burden of HFPG-attributable MASLD has continued to increase globally, with differences in geographical area, age, and sex distribution. HFPG, as a modifiable risk factor, should be given more importance. The implementation of targeted health intervention strategies is recommended for each country based on trends in the burden of HFPG-attributable MASLD., (© 2024. The Author(s).)

Objective: The aim of this study was to develop and validate a machine learning-based model to predict the development of impaired fasting glucose (IFG) in middle-aged and older elderly people over a 5-year period using data from a cohort study., Methods: This study was a retrospective cohort study. The study population was 1855 participants who underwent consecutive physical examinations at the First Affiliated Hospital of Soochow University between 2018 and 2022.The dataset included medical history, physical examination, and biochemical index test results. The cohort was randomly divided into a training dataset and a validation dataset in a ratio of 8:2. The machine learning algorithms used in this study include Extreme Gradient Boosting (XGBoost), Support Vector Machines (SVM), Naive Bayes, Decision Trees (DT), and traditional Logistic Regression (LR). Feature selection, parameter optimization, and model construction were performed in the training set, while the validation set was used to evaluate the predictive performance of the models. The performance of these models is evaluated by an area under the receiver operating characteristic (ROC) curves (AUC), calibration curves and decision curve analysis (DCA). To interpret the best-performing model, the Shapley Additive exPlanation (SHAP) Plots was used in this study., Results: The training/validation dataset consists of 1,855 individuals from the First Affiliated Hospital of Soochow University, yielded significant variables following selection by the Boruta algorithm and logistic multivariate regression analysis. These significant variables included systolic blood pressure (SBP), fatty liver, waist circumference (WC) and serum creatinine (Scr). The XGBoost model outperformed the other models, demonstrating an AUC of 0.7391 in the validation set., Conclusions: The XGBoost model was composed of SBP, fatty liver, WC and Scr may assist doctors with the early identification of IFG in middle-aged and elderly people., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cui, Pu, Li, Zheng, Lin, Liu, Xue, Zhu and He.)

Aims: This study was aimed at assessing the association of oral glucose tolerance test (OGTT) glucose threshold levels and the requirement of insulin therapy in twin pregnancies with gestational diabetes mellitus (GDM). Methods: In this post hoc analysis of a cohort study spanning 18 years, 446 patients with twin pregnancy and GDM (246 managed with lifestyle modification and 200 requiring pharmacotherapy) were included. We collected and evaluated maternal characteristics, as well as fasting, 1-h, and 2-h glucose concentrations from a standardized 75-g OGTT. The assessment methods included logistic regression analysis, positive and negative predictive values, area under the curve (AUC), and random forest analysis. Results: The fasting ( p < 0.01, OR: 1.03 [95% CI 1.01-1.05]) and 1-h ( p < 0.01; OR: 1.01 [95% CI 1.00-1.02]) glucose levels during the OGTT were significantly associated with the subsequent need for insulin therapy, with thresholds of 95 mg/dL for fasting glucose and 184 mg/dL for the 1-h OGTT. Additionally, indications for insulin therapy were marked by thresholds of 108 mg/dL at G0, 215 mg/dL at G60, and 86 mg/dL at G120. Conclusion: Identifying threshold values for insulin therapy and risk stratification in twin pregnancy are crucial for optimal patient management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Anja Catic et al.)

Objective: The long-term glucose monitoring is essential to the risk assessment of diabetic retinopathy (DR), the aim of this study was to investigate the predictive ability of visit-to-visit fasting blood glucose (FBG) indices on the risk of DR., Methods: This was a community-based, cohort study conducted from 2013 to 2021. DR was diagnosed by digital fundus photography. The FPG indices included FBG, var. Associations of each FBG indices and DR were estimated using multinomial logistic regression models adjusting for confounders, and discrimination was determined by area under the curve (AUC). Predictive utility of different models was compared by changes in AUC, integrated discrimination improvement (IDI), and net reclassification index (NRI)., Results: This study analyzed 5054 participants, the mean age was 46.26 ± 11.44 years, and 2620 (51.84%) were women. After adjustment for confounders, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for FBG, SD, CV, VIM, ARV, M-FBG, and cumulative FBG load were 1.62 (1.52-1.73), 2.74 (2.38-3.16), 1.78 (1.62-1.95), 1.11 (0.95-1.29), 1.72 (1.56-1.91), 2.15 (1.96-2.36), and 2.57 (2.31-2.85), respectively. The AUC of the model with separate cumulative FBG load and classical risk factors was 0.9135 (95%CI 0.8890-0.9380), and no substantive improvement in discrimination was achieved with the addition of other FBG indices once cumulative FBG load was in the model., Conclusions: Cumulative FBG load is adequate for capturing the glucose-related DR risk, and the predictive utility of cumulative FBG load is not significantly improved by adding or replacing other FBG indices in the assessment of DR risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ju, Guo, Ai, Yang, Zhu, Shi, Li, Yu, Xiao, Su, Yan, Li, Lian, Wang, Ding, Wang, Lu, Cui and Li.)

Background: Remnant cholesterol (RC), a potent atherogenic lipid, has been shown to be strongly correlated with insulin resistance and the pathogenesis of diabetes mellitus. However, the relationship between RC and normoglycemia reversal in individuals with impaired fasting glucose (IFG) is crucial and remains unclear. This investigation, which aimed to clarify this association, is important for understanding and potentially improving the management of diabetes., Method: This study, which included 15,019 IFG participants from 11 Chinese cities between 2010 and 2016, was conducted with a rigorous research process. Cox regression analysis revealed intriguing findings regarding the relationship between RC and normoglycemia reversal in individuals with IFG. Potential nonlinear associations were further explored via smooth curve-fitting techniques and 4-knot restricted cubic spline functions, ensuring a comprehensive analysis. To examine the validity of the results, an array of subgroup and sensitivity analyses were conducted, further bolstering the robustness of the findings., Results: By the end of the 2.89-year median follow-up period, 6,483 of the 15,019 IFG participants (43.17%) had reverted to normoglycemia. The findings, which reveal that increased RC levels are inversely associated with the likelihood of normoglycemia reversal, are novel and significant. According to the fully adjusted Cox proportional hazards model analysis, an increase of one standard deviation in RC was associated with a 20% decrease in the likelihood of normoglycemia reversal among IFG participants (HR: 0.80, 95% CI: 0.77-0.82). A nonlinear association between RC and normoglycemia reversal was observed, with an inflection point at 41.37 mg/dL. This suggests that the growth rate of the likelihood of reversion decreased and stabilized after the inflection point was reached. Moreover, significant interactions were observed between the age groups, providing a more nuanced understanding of this complex relationship., Conclusion: Among Chinese adults with IFG, RC exhibited a negative nonlinear relationship with the probability of normoglycemia reversal. When RC levels reached or exceeded 41.38 mg/dL, the probability of achieving normoglycemia progressively diminished and subsequently stabilized. Maintaining RC levels below 41.38 mg/dL can significantly improve the probability of normoglycemia reversal among individuals with IFG, especially those aged 60 years or older., (© 2024. The Author(s).)

Context: Glucagon plays a role in the development of type 2 diabetes, yet its role in prediabetes (preDM) remains uncertain., Objective: To evaluate glucagon levels in the fasting state and its response to glucose inhibition in preDM through meta-analysis., Methods: A systematic search across Pubmed, Embase, Web of Science, and Cochrane Library identified studies assessing glucagon levels during 75 g oral glucose tolerance test (OGTT) in both preDM and normal glucose tolerance (NGT) cohorts. Data on glucagon, glucose, and insulin were pooled using a random-effect model., Results: Although glucagon levels decreased in both preDM and NGT groups upon glucose challenge, glucagon levels at 0 hours, 0.5 hours, 1 hour, and 1.5 hours in preDM were significantly higher compared to NGT, despite higher glucose levels at all time points and higher insulin levels at 0 hours, 1 hour, 1.5 hours, and 2 hours during OGTT. Subgroup analysis revealed that in studies using the radioimmunoassay method, glucagon levels in preDM were higher at 0.5 hours and 1 hour than NGT, while in studies using the ELISA method, glucagon levels were similar to those of the NGT group despite higher glucose in preDM compared to NGT. Fasting glucagon level was inadequately suppressed in both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Responsiveness to glucose inhibition was preserved in IFG, while glucagon level in IGT group at 0.5 hours after glucose intake was not suppressed and was higher than NGT., Conclusion: Glucagon was not adequately suppressed during OGTT in preDM. Glucagon dysregulation is a contributing mechanism underlying both IFG and IGT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Gestational diabetes mellitus (GDM) adversely affects offspring glucose homeostasis and risk of developing obesity. Here, we examined the association between glycemia in pregnant women with overweight or obesity without GDM and offspring metabolic health. Maternal fasting glucose concentrations and glucose 2-h after an oral glucose tolerance test (OGTT) were measured in 208 women with a pre-pregnancy body mass index (BMI) of 28-45 kg/m 2 without GDM. Offspring outcomes were collected at birth, 3, and 5 years of age. Linear mixed models with time as fixed factor and subject ID as random effects were used for analysis. No associations were found between maternal fasting or 2-h glucose concentrations with offspring glucose and insulin concentrations from birth to 5 years of age. However, maternal fasting glucose in GW 28 and 36, and 2-h OGTT glucose in GW 28 were positively associated with C-peptide concentration at birth. Maternal fasting glucose concentrations in GW 28 and 36 were positively associated with weight-for-length, and maternal fasting glucose in GW 36 was associated with BMI z-score at birth. In summary, blood glucose in pregnant women with overweight or obesity is positively associated with offspring C-peptide concentration, weight-for-length, and BMI z-score at birth, even in the absence of GDM., (© 2024. The Author(s).)

Background: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population., Methods: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence., Results: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and - 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles., Conclusions: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs., (© 2024. The Author(s).)

Background: Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM., Methods: Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants' glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA., Results: Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance., Conclusions: A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality., Trial Registration: The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070., (© 2024. The Author(s).)

Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p < 0.001). In the Cox survival analysis, a higher fasting glucose (hazard ratio 1.053, p = 0.007) was associated with worse mortality for INOCA without DM (N = 501). On the contrary, a higher eGFR (hazard ratio 0.967, p = 0.012) was protective of better survival for non-diabetic INOCA (N = 501). In conclusion, for non-diabetic INOCA, higher fasting glucose was associated with worse mortality and higher eGFR was protective for better survival., (© 2024. The Author(s).)

Chronic pain represents a significant unmet medical need, affecting one-fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non-opioid, non-NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated the safety and pharmacokinetic profile of EC5026 in two phase I trials, a single-ascending dose (SAD) study and a fed-fasted study. The SAD study evaluated EC5026 doses ranging from 0.5 to 24 mg in healthy volunteers. EC5026 was well tolerated. No treatment-emergent adverse events were considered related to EC5026. No apparent treatment- or dose-related trends in laboratory results, vital signs, physical examinations, or electrocardiograms were observed. A linear, near-dose-proportional increase in exposure was observed with progressive doses in the SAD study; plasma exposure was below or near the lower limit of quantification after 0.5-2 mg doses. Mean half-lives ranged from 41.8 to 59.1 h. for doses of 8-24 mg, supporting a once-daily dosing regimen. In the fed-fasted study using 8 mg EC5026 tablets, higher peak concentrations (66%) and total exposures (53%) were observed under the fed condition. Plasma concentrations declined in a monoexponential manner with mean half-lives of 59.5 h. in the fed state and 66.9 h. in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity., (© 2024 EicOsis Human Health, Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Glycemic control is crucial in peritoneal dialysis (PD) patients with diabetes. Although fasting blood glucose (FBG) is the most commonly used index to measure blood glucose levels, there is currently no evidence supporting the association between FBG level and mortality risk in PD patients., Methods: A total of 3548 diabetic PD patients between 2002 and 2018 were enrolled from the National Health Insurance Service database of Korea. We investigated the association between FBG levels and the risk of all-cause and cause-specific mortality., Results: Patients with FBG levels 80-99 mg/dL exhibited the highest survival rates, whereas those with FBG levels ≥180 mg/dL had the lowest survival rates. Compared with FBG levels 80-99 mg/dL, the adjusted hazard ratios and 95% confidence interval for all-cause mortality significantly increased as follows: 1.02 (0.87-1.21), 1.41 (1.17-1.70), 1.44 (1.18-2.75), and 2.05 (1.73-2.42) for patients with FBG 100-124 mg/dL, FBG 125-149 mg/dL, FBG 150-179 mg/dL, and FBG ≥180 mg/dL, respectively. The risk for all-cause mortality also showed an increasing pattern in patients with FBG levels <80 mg/L. The risk of cardiovascular death significantly increased as FBG levels exceeded 125 mg/dL. However, the risk of infection-related and malignancy-related deaths did not show a significant increase with increasing FBG levels., Conclusion: There was an increase in the risk of all-cause mortality as FBG levels exceeded 125 mg/dL in PD patients with diabetes, and the risk of cardiovascular death showed a strong correlation with FBG levels compared with other causes of death., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)