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The aim of the present work was to investigate the influence of fasting and refeeding on body condition, gut physiology and microbiota in reared O. mykiss. Ninety-six fish were randomly allotted among three groups subjected to different feeding plan: C (control, fed for 5 weeks); R (restricted ration over 3 weeks followed by 2 weeks feeding); F (fasted over 3 weeks followed by 2 weeks feeding) in a well’s fresh water flow-through rearing plan. Sampling occurred at 0, 1, 2, 4, 7, 14 days during the refeeding period. At day 0 and throughout the feeding period until day 14, the weight of the fish was significantly affected by the feeding restriction. Feed deprivation reduced significantly the viscerosomatic and hepatosomatic indexes. Brush border membrane enzymes’ specific activity was modulated by feeding regimes until day 7, to level in all experimental groups at day 14. At the end of the restricted/fasted period, the microbiota of the C group was made up of 70% of Actinobacteria, 24% of Proteobacteria, 4.2% of Firmicutes and

During Ramadan, Muslims fast from dawn to dusk for the duration of the month. The current literature focuses on adults who fast, with little attention to pediatric practices. An anonymous, digital survey was conducted using Qualtrics software and distributed to residents, fellows, or attendings in Michigan in 2019. Overall, 278 participants were included in the analysis, with 87% (242/278) identifying as pediatric trained physicians. In all, 82% (228/278) of physicians identified as non-Muslim and 76% (211/278) had never partaken in the Muslim fast. About 52% (141/273) of participants had at least a moderate amount of exposure to Muslim pediatric patients in their clinical practice. Most physicians (66%; 175/265) reported they never asked their pediatric patients or their families about fasting. About 61% (167/273) of participants rated their understanding of fasting as minimal to none. Another 52% (142/273) of participants reported feeling somewhat or extremely uncomfortable discussing fasting recommendations with their pediatric patients and their families. Our study is the first of its kind in assessing current knowledge and practice regarding pediatric Muslim fasting among physicians in the United States. In addition, it highlights a gap in physicians' understanding and comfort in providing anticipatory guidance for their Muslim patients.

It is unclear how effective intermittent fasting is for losing weight and body fat, and the effects may depend on the timing of the eating window. This randomized trial compared time-restricted eating (TRE) with eating over a period of 12 or more hours while matching weight-loss counseling across groups.To determine whether practicing TRE by eating early in the day (eTRE) is more effective for weight loss, fat loss, and cardiometabolic health than eating over a period of 12 or more hours.The study was a 14-week, parallel-arm, randomized clinical trial conducted between August 2018 and April 2020. Participants were adults aged 25 to 75 years with obesity and who received weight-loss treatment through the Weight Loss Medicine Clinic at the University of Alabama at Birmingham Hospital.All participants received weight-loss treatment (energy restriction [ER]) and were randomized to eTRE plus ER (8-hour eating window from 7:00 to 15:00) or control eating (CON) plus ER (≥12-hour window).The co-primary outcomes were weight loss and fat loss. Secondary outcomes included blood pressure, heart rate, glucose levels, insulin levels, and plasma lipid levels.Ninety participants were enrolled (mean [SD] body mass index, 39.6 [6.7]; age, 43 [11] years; 72 [80%] female). The eTRE+ER group adhered 6.0 (0.8) days per week. The eTRE+ER intervention was more effective for losing weight (-2.3 kg; 95% CI, -3.7 to -0.9 kg; P = .002) but did not affect body fat (-1.4 kg; 95% CI, -2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (-4.2%; 95% CI, -14.9 to 6.5%; P = .43). The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d. The eTRE+ER intervention also improved diastolic blood pressure (-4 mm Hg; 95% CI, -8 to 0 mm Hg; P = .04) and mood disturbances, including fatigue-inertia, vigor-activity, and depression-dejection. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups. In a secondary analysis of 59 completers, eTRE+ER was also more effective for losing body fat and trunk fat than CON+ER.In this randomized clinical trial, eTRE was more effective for losing weight and improving diastolic blood pressure and mood than eating over a window of 12 or more hours at 14 weeks.ClinicalTrials.gov Identifier: NCT03459703.

Twelve years following gastric bypass surgery, a cachectic 69-year-old woman presented with both fasting and postprandial hypoglycaemia. Postprandial symptoms were relieved by dietary modification and acarbose, as is common in such cases. During a supervised fast, symptomatic hypoglycaemia occurred. Concurrent laboratory testing showed suppression of plasma insulin, c-peptide, proinsulin and insulin-like growth factor II. However, beta-hydroxybutyrate was also low, surprising given insulin deficiency. Elevated plasma free fatty acid (FFA) concentrations suggested that lipolysis was not impaired, making cachexia/malnutrition a less likely cause of hypoglycaemia. The apparent diagnosis was failure to counter-regulate—subsequent plasma carnitine measurements showed carnitine deficiency which presumably prevented FFA transport across mitochondrial membranes for ketogenesis. Repletion with high-dose oral carnitine supplements effected resolution of fasting hypoglycaemia.

The incidence of Type 2 Diabetes Mellitus (DM) in Malaysia is increasing, with 59% in Malays followed by the other races. Fasting in Ramadhan for those with DM is challenging and needs close monitoring with sufficient and comprehensive medical advice. Diabetic complications during fasting is mainly seen in patients with improper disease control or inadequate information. This novel diabetes in Ramadhan patient education program aims to facilitate knowledge attainment and improve dissemination of information to mitigate the risk of complications in Ramadhan and to pave the way to fasting safely. This program provided comprehensive education on fasting in Ramadhan for people with DM in an engaging manner. The program was organised into three main parts: (1) patient self-educating activity; (2) specialized medical advice; and (3) lifestyle guide. This program was conducted at the UiTM Medical clinic facilities by the Endocrine team consisting mainly of physicians and diabetic educators. This program was facilitated by a specially designed educational guide, detailing important information on the risk categories for fasting in Ramadhan, timing of blood sugar monitoring, when to break the fast in the event of complication with management steps, medication adjustment, dietary advice and tips on keeping active during the fasting month. This innovative program has been tailored for use in the local population, and provides an essential service that is hugely beneficial, but currently lacking in this country. With this comprehensive and engaging platform, important information on managing diabetes in Ramadhan can be accessible to a wider population, leading to better patient care, and hence a has huge potential for sustainability.&nbsp

Diets high in saturated fat (HFD) disrupt dopamine neurotransmission, whereas fasting alters tonic and phasic dopamine release to drive motivation and food consumption. However, functional compartments in the nucleus accumbens (NAc) influencing these effects are not well characterized, and sex comparisons have not been made. This study sought to determine whether consumption of a HFD, sex, or being fed versus fasted altered baseline dopamine release and reuptake throughout NAc subregions. Male and female C57BL/6 mice were fed a control diet or nutrient matched HFD for six weeks. Ex-vivo fast-scan cyclic voltammetry revealed females had significantly slower dopamine reuptake in the NAc core than males when fed ad lib control diet. Fasting enhanced dopamine release and reuptake in the NAc core but not the medioventral shell. Further, being fasted versus fed significantly increased dopamine release throughout the NAc core in control males but specifically promoted release and reuptake in only the ventrolateral core of HF-fed males, effects which were lacking in females. Finally, fasting promoted dopamine release and reuptake in the rostral NAc core of controls and more caudally in HFD groups. These data support that dopamine neurotransmission is heterogeneous in NAc subregions and suggest the ventrolateral core is responsive to energy state. Furthermore, a rostrocaudal gradient in the NAc core might control valence responses to fasting that could promote overeating after chronic HFD consumption.

In human studies, new model systems are needed for improved mechanistic investigation of developmental predisposition for metabolic disease but also to serve as benchmarks in early life prevention or intervention efforts. In this regard, human infant umbilical cord-derived mesenchymal stem cells (MSCs) are an emerging tool. However, long-term clinical relevance to in vivo markers of metabolic disease is unknown.In a cohort of 124 mother/child dyads, this study tested the hypothesis that triglyceride content (TG) of infant MSCs undergoing adipogenesis in vitro (MSC-TG) is associated with in vivo adiposity (percent fat mass) from birth to early childhood and with fasting glucose and insulin in early childhood.MSC-TG was positively associated with in vivo child adiposity at birth, age 4 to 6 months, and age 4 to 6 years. MSC-TG was associated with fasting glucose, but not insulin, at 4 to 6 years. Importantly, MSC-TG explained an additional 13% variance in child adiposity at 4 to 6 years, after accounting for other established birth predictors (weight and percent fat mass at birth) and other established covariates related to child adiposity (e.g., breastfeeding exposure, physical activity).This work demonstrates the strength of the MSC model for predicting offspring metabolic phenotype into childhood, even when considering the important contribution of other early life risk factors.

Serum lipids, glucose and uric acid are well-known risk factors for metabolic syndrome and cardiovascular diseases; however, how serum uric acid levels are associated with fasting glucose and lipid levels remains to be evaluated.A cross-sectional study was performed in 104,328 males and 74,916 females. Quantile regression analyses were adopted to optimally fit the associations between levels of uric acid, lipids and glucose. Fasting high-density lipoprotein cholesterol (HDL-C) levels were negatively associated with serum uric acid levels; the associations remained stable in males but strengthened in females with increasing uric acid concentrations. Non-HDL-C and triglyceride (TG) levels were positively associated with serum uric acid levels; the associations also strengthened across deciles of uric acid levels from low to high. Fasting glucose levels were positively associated with uric acid levels in both sexes except in males in the 1st and 2nd deciles of uric acid concentrations; the association coefficients for females were higher than coefficients in males in each decile of uric acid levels. All associations had distinguishable patterns by sex except non-HDL-C, which was associated with uric acid levels with relatively similar trends between sexes. Adjustment for known confounding factors only slightly altered the above associations.Fasting serum uric acid levels are associated with fasting levels of HDL-C, non-HDL-C, TG and glucose; the associations strengthened with the deciles of uric acid increase and displayed non-negligible sex differences.

The safety and efficacy of intravenous edaravone, a neuroprotectant used for the treatment of amyotrophic lateral sclerosis (ALS), have been shown in clinical trials. An oral suspension of edaravone has been developed, but the food effect on its pharmacokinetic profile has not been evaluated. This study aimed to assess the food effect on the pharmacokinetic profile of edaravone after oral administration and to investigate dosing regimens and administration instructions with different meal intake and timing.Data from 3 Phase I clinical studies were used to evaluate the effect of food on the pharmacokinetic profiles of a single dose of edaravone oral suspension. In all 3 studies, participants received a single dose of edaravone with various meal conditions. Healthy Japanese adult male participants (Studies 1, 2, and 3) or female participants (Study 3) aged 20 to 45 years at the time of informed consent were included.In Study 1, 6 participants were enrolled and 5 completed the study. Nine and 16 participants were treated in Studies 2 and 3, respectively, and all completed the study. The COral administration of edaravone with a meal decreased the plasma concentration of edaravone. Oral administration of edaravone 8 hours after a high-fat meal, 4 hours after a low-fat meal, 2 hours after a light meal, and 1 hour before a high-fat meal showed no effect of food on the PK profile of unchanged edaravone compared with that observed under a fasted condition.gov identifiers: NCT04481750, NCT04481789, and NCT05342597.

Background: We investigated whether fasting glucose (FG) variability could predict the risk of dementia.Methods: This cohort study analyzed data from Koreans with diabetes after at least three health examinations by the Korean National Health Insurance Corporation between 2005 and 2010, which included at least one examination between 2009 and 2010. A total of 769,554 individuals were included, excluding those aged

This study described and compared glycaemic changes with the use of the following Continuous Glucose Monitoring (CGM) metrics: time in range, time in hyperglycaemia and time in hypoglycaemia from retrospective CGM data among children and adolescents with Type 1 Diabetes Mellitus (T1DM), before and during Ramadan to better understand the impact of fasting during this season.This study was conducted in 2 tertiary centres: Hospital Putrajaya (HPJ) and Hospital Universiti Sains Malaysia (HUSM) from February to May 2020. Muslim T1DM patients between ages 8 to18 who intended to fast during Ramadan were given Ramadan-focused education. CGM iPro2Of the 32 patients, only 24 (12 female) were analysed. Mean age was 13.6 ± 3.1 years old, mean HbAlc was 9.6 ± 1.9% and mean duration of illness was 5.4 ± 3.4 years. Majority (91.7%) were on multiple dose injections (MDI) while only 8.3% were on continuous subcutaneous insulin infusion (CSII). All fasted in Ramadan without acute complications. Retrospective CGM analysis revealed similar results in time in range (TIR), time in hyperglycaemia and time in hypoglycaemia before and during Ramadan, indicating no increased hypoglycaemic or hyperglycaemic events related to fasting. Glycaemic variability before Ramadan as measured by the LBGI, HBGI and MAG, were similar to values during Ramadan.Ramadan fasting among T1DM children and adolescents, by itself, is not associated with short-term glycaemic deterioration. T1DM youths can fast safely in Ramadan with the provision of focused education and regular SMBG.

Cloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.The purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.A single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUCA total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the CThe T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.

An orodispersible tablet (ODT) formulation of morphine sulfate has been developed to provide a novel alternative for patients with severe pain requiring opioids. This formulation has been developed in a range of doses (1-30 mg), enabling relief from severe pain to be achieved and maintained with the lowest possible morphine dose for each patient. The ODT formulation is particularly suitable for patients with swallowing difficulties.The aim of this study was to compare the pharmacokinetics and bioequivalence of the ODTs with reference formulations of morphine sulfate.Three randomized, single-dose, laboratory-blinded, phase I, crossover studies were conducted in adult healthy volunteers under fasting conditions. The pharmacokinetics of a 30 mg morphine sulfate ODT were compared with those of equivalent doses of currently marketed oral immediate-release formulations: tablets (SevredolA total of 104 subjects were included across the three studies. The pharmacokinetics of the ODTs were assessed in 100 subjects and were found to be similar to those of the reference formulations. The time to maximum plasma concentration (TThe ODTs were safe, well tolerated, and showed similar pharmacokinetics to those of the reference formulations. The development of a range of doses of morphine sulfate ODTs may provide a new alternative for the oral administration of immediate-release morphine for pain management in pediatric, geriatric and adult populations with swallowing problems.

Fasting blood glucose (FBG) variability may make an impact on adverse events in patients with diabetes mellitus. However, the association between long-term changes in FBG and cancer remains unclear. We aimed to investigate this association in a large-scale longitudinal study.Data were collected from 46 761 patients with type 2 diabetes mellitus aged 20-80 years who participated in the Diabetes Standardized Management Program in Shanghai, China. We adopted four indicators, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average real variability (ARV) to describe FBG variability. Adjusted multivariable Cox regression analyses and restricted cubic splines were used to investigate the association between long-term FBG variability and cancer risk. We also determined the interactive effect of FBG variability with hypertension and FBG-mean with hypertension on cancer risk, respectively.In this study, we confirmed 2218 cancer cases (51.1% male) over a median follow-up of 2.86 years. In the multivariable-adjusted models, participants in the highest quartile of FBG variability had an increased risk of cancer compared with those in the lowest quartile. The nonlinear association was found when using FBG-VIM, FBG-ARV, and FBG-SD in restricted cubic spline plots. There was a significant interaction effect of FBG variability with hypertension on cancer, whereas the effect of FBG-mean with hypertension did not attain significance.Our retrospective cohort study demonstrated a positive association between the long-term changes in FBG and cancer risk in patients with type 2 diabetes mellitus. FBG variability may independently predict cancer incidence.背景: 空腹血糖(FBG)变异性可能对糖尿病患者的不良事件产生影响。然而，空腹血糖的长期变化与癌症之间的联系仍不清楚。本研究旨在一项大规模纵向研究中调查和量化这种关联。 方法: 对参加中国上海市糖尿病标准化管理项目的46,761例年龄在20到80岁的2型糖尿病患者进行调查。我们采用标准差(SD)、变异系数(CV)、独立于均值的变异(VIM)和平均实际变异(ARV)4个指标来描述FBG的变异性。调整后的多变量COX回归分析和限制三次样条法被用来调查长期空腹血糖(FBG)变异性与癌症风险之间的关系。我们还分别确定了空腹血糖变异性与高血压和空腹血糖均值与高血压之间的交互作用对癌症风险的影响。 结果: 在这项研究中，我们确认了2218例癌症病例(51.1%为男性)，平均随访时间为2.86年。在多变量校正模型中，FBG变异性最高四分位的参与者比那些最低四分位数的参与者患癌症的风险更高。在限制三次样条图中使用FBG-VIM、FBG-ARV和FBG-SD时，发现了非线性关联。FBG变异性与高血压之间存在显著的交互作用，而FBG均值与高血压之间的交互作用不显著。 结论: 我们的回顾性队列研究显示，FBG的长期变化与2型糖尿病患者的癌症风险呈正相关。FBG变异性可独立预测癌症发病率。.

Nonalcoholic steatohepatitis (NASH) is associated with several cardiovascular risk factors, including atherogenic dyslipidemia. Recently, fasting prior to lipid profile evaluation has been thought to be unnecessary for most individuals. We investigated the impact of fasting for up to 9 h on the serum and hepatic lipid profiles in Sprague-Dawley (SD) rats of dietary-induced NASH model in comparison to SD rats fed a normal diet. In both groups, fasting affected the serum and hepatic triglyceride (TG), serum free fatty acid (FFA) and leptin levels, histopathologically assessed hepatocyte ballooning, and hepatic mRNA expression levels of several genes related to lipid metabolism. In contrast, the serum adiponectin and aminotransferase levels, serum and hepatic total cholesterol contents, and liver histopathological findings of hepatic steatosis, lobular inflammation and fibrosis were not influenced by fasting. A significant fasting time-dependent reduction was seen in the serum TG level only in the normal SD rats group. Regarding the hepatic TG level, a significant fasting time-dependent increase was seen only in the NASH model rat group. A significant fasting time-dependent reduction was also seen in the serum FFA level only in the NASH model rat group. Our present results indicate that excessive fasting can be avoided before blood or hepatic tissue sampling for the evaluation of several parameters in non-NASH and/or NASH model rats. Further investigations are needed in humans to determine whether excessive fasting before blood or hepatic tissue sampling can be avoided in both healthy individuals and NASH patients.

Time-restricted eating (TRE) is a dietary intervention that limits food consumption to a specific time window each day. The effect of TRE on body weight and physiological functions has been extensively studied in rodent models, which have shown considerable therapeutic effects of TRE and important interactions among time of eating, circadian biology, and metabolic homeostasis. In contrast, it is difficult to make firm conclusions regarding the effect of TRE in people because of the heterogeneity in results, TRE regimens, and study populations. In this review, we 1) provide a background of the history of meal consumption in people and the normal physiology of eating and fasting; 2) discuss the interaction between circadian molecular metabolism and TRE; 3) integrate the results of preclinical and clinical studies that evaluated the effects of TRE on body weight and physiological functions; 4) summarize other time-related dietary interventions that have been studied in people; and 4) identify current gaps in knowledge and provide a framework for future research directions.

Background: Smoking is a serious public health challenge across the world. Fasting in Ramadan requires people to stay away from smoking as well as activities such as eating, drinking, and sexual intercourse. We examined the effect of fasting on cigarette smoking and nicotine addiction during the Ramadan. Methodology: This study was designed as a descriptive cross-sectional survey. A questionnaire was prepared to determine sociodemographic data and smoking habits of a sample population. The questionnaire was delivered through face-to-face interviews at several family medicine clinics in Turkey, with smokers who fast in Ramadan. Results: There were 354 persons, of which 278 were male (78.5%), 76 were female (21.5%), and the mean age was 32.92 ± 11.84 years. A significant decrease in cigarette consumption during the Ramadan was reported by 285 (80.5%) smokers (p < .001). The number of smokers who had difficulty resisting the urge to smoke was less in Ramadan than non-Ramadan periods (p < .001). Religious sentiments were reported as the most important reason for coping with nicotine abstinence (53.7%). Significantly in 14.7% of the cases, participants stopped smoking during the whole period of Ramadan. Conclusions: Religious beliefs and willpower were found to be effective in helping people reduce or temporary stop smoking. Fasting may play a significant role in changing smoking behavior. Smoking cessation along with counseling supported by the state, health authorities, and clergy can be useful in the fight against smoking in Ramadan.

The primary objective of this study was to assess the pharmacokinetic profiles of acetylsalicylic acid (ASA) and salicylic acid (SA) after administration of two different formulations of aspirin under fasting and fed conditions.The study was a randomized, open-label, parallel-group, 2-arm crossover study conducted at a single center. Healthy subjects were randomized to receive 300 mg of aspirin in either a 15-mL oral solution (pre-packaged vial containing powder and solvent that are combined at the time of administration) or a single solid tablet to be chewed and swallowed with 150 mL of water. Treatment visits were separated by a 10-day wash-out period.At 3 minutes, ASA concentrations for the oral solution fed state and fasting state arms exceeded those for the chewed tablet (fed 299 vs. 139 ng/mL; fasting 356 vs. 204 ng/mL). Compared to the chewed tablet, the mean plasma ASA concentration was 74% greater with the oral solution under fasting conditions, and 115% greater under fed conditions. Similarly, at 3 minutes, the mean SA plasma concentration with the oral solution under fed and fasting conditions exceeded those for the chewed tablet (fed 310 vs. 160 ng/mL; fasting 330 vs. 185 ng/mL). Under fasting conditions, the mean plasma ASA AUCThis phase 1 study showed that use of an aspirin oral solution provided more rapid exposure to higher plasma concentration levels of ASA and SA than chewing a solid tablet.

Tree nuts have glucoregulatory effects and influence gut microbiota composition. The effect of peanuts on the microbiota has not been investigated.The aim was to examine the effect of 28 g/d of peanuts for 6-wks, compared to an isocaloric lower-fat higher-carbohydrate (LFHC) snack, on gut microbiota composition. A secondary aim was to identify functional and active compositional differences in a subset of participants using metatranscriptomics.In a randomized, crossover trial, 50 adults (48% female; 42 ± 15 y; BMI 28.3 ± 5.6 kg/mNo between-condition differences in α- or β- diversity were observed. Following peanut intake, Ruminococcaceae were significantly more abundant [Linear discriminant analysis score (LDA) = 2.8; P = 0.027)] compared to LFHC. Metatranscriptomics showed increased expression of the K03518 (aerobic carbon-monoxide dehydrogenase small subunit) gene following peanut intake (LDA = 2.0; P = 0.004) and Roseburia intestinalis L1-82 was identified as a contributor to the increased expression.An increased abundance of Ruminococcaceae was observed following consumption of 28 g/d of peanuts in adults with elevated fasting glucose after 6-wks. Metatranscriptomics revealed increased expression of the K03518 gene. These results suggest peanut intake enriches a known butyrate producer and the increased expression of a gene implicated in butyrate production adds further support for peanut-induced gut microbiome modulation. NCT: 03654651.

Background. Worldwide, higher-than-optimal fasting plasma glucose (FPG) is among the leading modifiable risk factors associated with all- cause mortality and disability-adjusted life years (DALYs) due to the direct sequelae of diabetes and the increased risk for cardiovascular and chronic kidney disease. Objectives. To report deaths and DALYs of health outcomes attributable to high FPG by age and sex for South Africa (SA) for 2000, 2006 and 2012. Methods. Comparative risk assessment methodology was used to estimate the burden attributable to high FPG. A meta-regression analysis was performed using data from national and small-area studies to estimate the population distribution of FPG and diabetes prevalence. Attributable fractions were calculated for selected health outcomes and applied to local burden estimates from the second South African National Burden of Disease Study (SANBD2). Age-standardised rates were calculated using World Health Organization world standard population weights. Results. We estimated a 5% increase in mean FPG from 5.31 (95% confidence interval (CI) 5.18 - 5.43) mmol/L to 5.57 (95% CI 5.41 - 5.72) mmol/L and a 75% increase in diabetes prevalence from 7.3% (95% CI 6.7 - 8.3) to 12.8% (95% CI 11.9 - 14.0) between 2000 and 2012. The age-standardised attributable death rate increased from 153.7 (95% CI 126.9 - 192.7) per 100 000 population in 2000 to 203.5 (95% CI 172.2 - 240.8) per 100 000 population in 2012, i.e. a 32.4% increase. During the same period, age-standardised attributable DALY rates increased by 43.8%, from 3 000 (95% CI 2 564 - 3 602) per 100 000 population in 2000 to 4 312 (95% CI 3 798 - 4 916) per 100 000 population in 2012. In each year, females had similar attributable death rates to males but higher DALY rates. A notable exception was tuberculosis, with an age-standardised attributable death rate in males double that in females in 2000 (14.3 v. 7.0 per 100 000 population) and 2.2 times higher in 2012 (18.4 v. 8.5 per 100 000 population). Similarly, attributable DALY rates were higher in males, 1.7 times higher in 2000 (323 v. 186 per 100 000 population) and 1.6 times higher in 2012 (502 v. 321 per 100 000 population). Between 2000 and 2012, the age-standardised death rate for chronic kidney disease increased by 98.3% (from 11.7 to 23.1 per 100 000 population) and the DALY rate increased by 116.9% (from 266 to 578 per 100 000 population). Conclusion. High FPG is emerging as a public health crisis, with an attributable burden doubling between 2000 and 2012. The consequences are costly in terms of quality of life, ability to earn an income, and the economic and emotional burden on individuals and their families. Urgent action is needed to curb the increase and reduce the burden associated with this risk factor. National data on FPG distribution are scant, and efforts are warranted to ensure adequate monitoring of the effectiveness of the interventions.

Anadolu’nun İslamlaşması ve Türkleşmesinde ile Yesevî öğretisinin yayılmasında büyük etkileri olan Yunus Emre’nin dini düşünce sisteminin incelenmesi ve araştırılması kuşkusuz büyük önem arz etmektedir. Onun dini, tasavvufi, ahlaki, sosyal, kültürel, siyasi, tarihi, ilmi ve edebi kişiliğiyle ilgili bugüne kadar yüzlerce makale, onlarca kitap kaleme alınmıştır. Ne var ki namaz, abdest, oruç, hac vb. içsel manaları ihmal edilen, salt zahiri düzeyde kalan şekilsel şeriat formlarının değer ve derecesine, hakikat makamı, namaz, abdest, oruç ve hac anlayışına dair şimdiye kadar araştırdığımız kadarıyla, bir çalışma henüz yapılmamıştır. Zahir-batın, şeriat-tarikat ve şeriat-hakikat düalizmi, erdemli ideal insan -insan-ı kâmil- olma yolunda bunların kıymet ve konumuna ilişkin yaklaşımlar, sufi öğretinin temel konuları arasında daima yer almıştır. Hatta dinin biçimsel -zahir- yapısını ön plana çıkaran fakih, müderris ve mollalarla tam tersine onun özünü, ruhunu, ahlaki hedeflerini -batınını- önceleyen sufiler arasında bu durum, zaman zaman bir çatışmanın da konusu olagelmiştir. O bakımdan, bu çalışmada, Yunus Emre’de şeriat ve hakikat makamına özgü namaz, abdest, oruç ve hac anlayışları irdelenmiş; şeriat makamı formlarının hafife alınıp alınmadığı ile yadsınıp yadsınmadığına ilişkin sorulara cevap aranmıştır. Araştırmamıza, Yunus Emre’nin farklı nüsha ve baskılarından oluşan Risâletu’n-Nushiye’si ve Dîvân’ıyla, diğer bazı araştırmalar kaynaklık etmiştir. Literatür taraması yönteminin kullanıldığı bu araştırmada şeriat makamı ritüellerinin Tanrı’ya yakınlaşma, ona vuslatta bir araç, giriş ve eşik mesabesinde olduğu; dolayısıyla, asıl -ideal- namaz, abdest ve orucun ten ile taat, teni yumak ve yıkamakla değil; gönülde Tanrı’yı daima anış naz ve niyazla, gönlü pak etmekle; asıl haccın ise O’nu ırakta -yabanda- yani Mekke’de değil; gönülde ve kendinde aramakla gerçekleşeceği sonucuna varılmıştır., Undoubtedly, it is important to examine and study the religious thought system of Yunus Emre, who had significant impacts on the Islamization and Turkification of Anatolia and the spread of the Yesevī school. Hundreds of articles and books have been written about his religious, mystical, moral, social, cultural, political, historical, scientific, and literary personality. However, no study has yet been conducted on the value and degree of sharīʿa forms, such as prayer, ablution, fasting, and pilgrimage, which their inner meanings is neglected, remain at the purely apparent level, and on his understating of the mode of ḥaqīqah, prayers, ablution, fasting, pilgrimage, etc. as far as we have seen in the literature review. Explicit-implicit, sharīʿa-tariqa, and sharīʿa-ḥaqīqah dualism and approaches to the value and position on the way to being a virtuous ideal human being (i.e., the perfect human) have always been among the basic subjects of the sūfī school. This has from time to time been the subject of a conflict between the jurists, professors, and mullahs, who emphasized the formal -explicit - structure of the religion, and the sūfīs, who prioritized its essence, spirit, and moral goals -esoteric-. In this regard, the understandings of Yunus Emre regarding prayers, ablution, fasting, and pilgrimage specific to the sharīʿa and the authority of ḥaqīqah were examined, and answers were sought to the questions about whether the forms -rituals- of sharīʿa authority were taken lightly or not in the present study. The sources of the present study were Yunus Emre’s Risālah al-Nushiyya, which consists of different copies and editions, and his Dīwān, as well as some other studies. In the present study, in which the literature review method was used, it was found that the rituals of the sharīʿa were a means, entrance, and threshold for moving closer and reaching God. Therefore, the real -ideal- prayers, ablution, and fasting were not actually achieved by washing the skin but by always remembering God in the heart, by clearing the heart, and the real pilgrimage was not in the far -wilderness- namely, in Mecca, but would be achieved by looking for God in the heart and oneself.

This study evaluated the safety, pharmacokinetic parameters, and bioequivalence (BE) of pomalidomide (POM) capsules (specification: 4 mg) acquired from 2 sponsors (test [T] and reference [R]), under fasting and fed conditions. A single-center, randomized, open-label, 2-cycle, self-crossover, single-dose clinical trial was conducted. Subjects were divided into fasting (n = 28) and fed (n = 28) groups and assigned randomized treatment sequences (T-R or R-T). Blood samples for pharmacokinetic evaluation were collected within 48 hours of administration, and safety was assessed throughout. Exposure to POM was similar following single-oral-dose administrations of T or R between the fasting and fed states. T and R exhibited BE, as demonstrated by statistical analysis; the 90%CIs of the geometric mean ratios of maximum plasma concentration, area under the plasma concentration-time curve (AUC)from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the acceptable BE range (80%-125%). Administering POM capsules with high-fat meals resulted in a 2.5-hour delay in time to maximum concentration and an ≈20.4% reduction in maximum plasma concentration. However, AUCs were comparable after dose administrations with and without food. The fast and fed groups revealed that POM capsules were tolerated in healthy Chinese male subjects, and so were orally bioavailable in healthy subjects under fasting and fed states.

Studies that investigated the relationship between fasting blood glucose (FBG) and intracerebral hemorrhage (ICH) outcomes were insufficient.We aimed to investigate the association between FBG level and in-hospital clinical outcomes in patients with primary ICH.A total of 34,507 patients were enrolled in the final study. Compared with the reference group, the ≥6.1 and7 mmol/L group showed nonsignificant higher in-hospital mortality (adjusted odds ratio [OR] 1.20, 95% confidence interval [CI] 0.69-2.11, p = 0.52), and a significant higher proportion of intracranial hematoma evacuation (adjusted OR 1.56, 95% CI 1.26-1.92, p 0.001). The ≥7 mmol/L group showed both significant higher in-hospital mortality (adjusted OR 2.08, 95% CI 1.42-3.04, p = 0.52) and a significant higher proportion of intracranial hematoma evacuation (adjusted OR 2.09, 95% CI 1.78-2.47, p 0.001).Higher FBG level was correlated with both higher mortality and proportion of evacuation of intracranial hematoma.

Age associated neurodegenerative changes are acknowledged to play a causative role in a majority of neurological diseases that accompany aging in organisms. To alleviate the deteriorative effects of aging in the brain, we investigated the effects oftwo types of intermittent fasting (IF) methods: alternate day fasting (ADF) and time- restricted feeding (TRF) in young (3 months) and old (24 months) in male Wistar rats comparing the results with age matched controls. The evaluation of biomarkers of oxidative stress showed significant decline in the old (ADF and TRF) groups in addition to up regulation in antioxidant levels. It was observed that ADF and TRF methods helped reduce ROS accumulation in the mitochondria and increased the activity of the electron transport chain complexes especially C-I and III. Gene expression analysis of autophagy genes like beclin and LC3B showed upregulated expression in ADF and TRF group. Sirtuin1 expression too significantly increased during fasting in both young and old groups showing fasting induced protection from aging. Histological analysis of sections of cerebral cortex and CA1 area provide evidence that fasting protected neurons against degeneration with age. Our results prompt us to conclude that the efficacy of these fasting methods ADF and TRF are reliable anti- aging strategies with respect to dietary restriction interventions. Moreover, both these methods compete closely in conferring protection from oxidative stress and inducing neuroprotective changes in brain of aged rats when compared to their young counterparts.

Average pre-operative fasting times for clear liquids are many times longer than those specified in national and international guidelines. We sought to decrease fasting times by applying a quality management tool aimed at continuous improvement. Through the application of iterative 'plan-do-study-act' cycles, tools to reduce pre-operative liquid fasting times were developed and applied, the effects measured, analysed and interpreted and the conclusions used to inform the next plan-do-study-act cycle. The first step was the introduction of unrestricted drinking until the patient was called to the operating theatre, with training of anaesthetic staff, adaption of local standard procedures and verbal information for patients. This did not result in short liquid fasting times, median (IQR [range]) 12.0 (9.5-14.0 [0.8-23.5]) h. In the second cycle, fasting cards were introduced as a subliminal written training tool for staff, patients and their relatives. This enabled short liquid fasting times to be achieved for outpatients (2.6 (0.8-5.1 [0.3-16]) h) and pre-admission patients (3.4 (1.8-9.4 [0.2-17.2]) h), but not for inpatients (6.5 (2.0-11.7 [0.2-16.2]) h). The third cycle included lectures for ward staff, putting up information posters throughout the hospital, revision of all written materials and provision of screencasts on the homepage for staff and patients. This decreased median liquid fasting time to 2.1 (1.2-3.8 [0.4-18.8]; p lt; 0.0001) h, with inpatients having the shortest fasting time of 1.4 (1.1-3.8 [0.4-18.8]) h. Repeated quality improvement cycles, adapted to local context, can support sustained reductions in pre-operative liquid fasting times.

Endothelial dysfunction is a predictive risk factor for the development of atherosclerosis and is assessed by flow-mediated dilation (FMD). Although it is known that NO-dependent endothelial dysfunction occurs after consuming a high-fat meal, the magnitude of the effect and the factors that affect the response are unquantified.We conducted a systematic review and meta-analysis exploring the quantitative effects of a single high-fat meal on endothelial function and determined the factors that modify the FMD response.Six databases were systematically searched for original research published up to January 2022. Eligible studies measured fasting and postprandial FMD following consumption of a high-fat meal. Meta-regression was used to analyze the effect of moderator variables.There were 131 studies included, of which 90 were suitable for quantitative meta-analysis. A high-fat meal challenge transiently caused endothelial dysfunction, decreasing postprandial FMD at 2 hours [-1.02 percentage points (pp); 95% CI: -1.34 to -0.70 pp; P 0.01; I2 = 93.3%], 3 hours [-1.04 pp; 95% CI: -1.48 to -0.59 pp; P 0.001; I2 = 84.5%], and 4 hours [-1.19 pp; 95% CI: -1.53 to -0.84 pp; P 0.01; I2 = 94.6%]. Younger, healthy-weight participants exhibited a greater postprandial reduction in the FMD percentage change than older, heavier, at-risk groups after a high-fat meal ( P 0.05). The percentage of fat in the meals was inversely associated with the magnitude of postprandial changes in FMD at 3 hours (P 0.01).A single, high-fat meal adversely impacts endothelial function, with the magnitude of the impact on postprandial FMD moderated by the fasting FMD, participant age, BMI, and fat content of the meal. Recommendations are made to standardize the design of future postprandial FMD studies and optimize interpretation of results, as high-fat meals are commonly used in clinical studies as a challenge to assess endothelial function and therapeutics. This trial was registered at PROSPERO as CRD42020187244.

The mammalian liver must cope with various metabolic and physiological changes that normally recur every day and result primarily from rest-activity and fasting-feeding cycles. In this article, I present evidence supporting a temporal compartmentalization of rhythmic hepatic metabolic processes into four main clusters: regulation of energy homeostasis, maintenance of information integrity, immune response, and genetic information flow. I further review literatures and discuss how both the circadian and the newly discovered 12-h ultradian clock work together to regulate these four temporally separated processes in mouse liver, which, interestingly, is largely uncoupled from the liver zonation regulation.

Fibroblast growth factor 21 (FGF21) is a metabolic hormone that is synthesized and secreted by cellular and metabolic stresses. Serum FGF21 levels are associated with clinical parameters in patients with various diseases, including metabolic disorders. Animal models that allow FGF21 levels to be monitored in vivo are important for research and clinical applications of FGF21. Here, a novel Fgf21-reporter mouse strain (Fgf21

Linezolid, an oxazolidinone antibacterial agent with several formulations, has been widely used for over 20 years. This study aimed to compare the bioequivalence, pharmacokinetics, and safety of test and reference linezolid tablets after a single oral dose under fasting/fed conditions. In this open-label, randomized, two-period, crossover, bioequivalence study, 48 healthy volunteers were enrolled equally to fasting or fed groups to receive one 600-mg test or reference linezolid tablet in each period. Pharmacokinetic parameters were calculated using noncompartmental methods. Adverse events (AEs) were recorded to assess safety. The geometric mean terminal half-lives of test and reference formulations were 3.8 and 3.6 hours, respectively, under both fasting and fed conditions. The median time to reach the maximum observed concentration was 1.0 hour (both formulations) in the fasting group, and 2.0 hours (test formulation) and 2.5 hours (reference formulation) in the fed group. No substantial differences were observed in the area under plasma concentration-time curve (AUC) from time 0 to the last sampling time (AUC

Eldecalcitol is an active vitamin D

Ramadan interferes with circadian rhythms mainly by disturbing the routine patterns of feeding and smoking. The objective of this study was to investigate the circadian pattern of ST elevation acute myocardial infarction (STEMI) during the month of Ramadan. We studied consecutive STEMI patients 1 month before and after Ramadan (non-Ramadan group-NRG) and during Ramadan (Ramadan group-RG). The RG group was also divided into two groups, based on whether they chose to fast: fasting (FG) and non-fasting group (NFG). The time of STEMI onset was compared. A total of 742 consecutive STEMI patients were classified into 4 groups by 6 h intervals according to time-of-day at symptom onset. No consistent circadian variation in the onset of STEMI was observed both between the RG ( P = .938) and NRG ( P = .766) or between the FG ( P = .232) and NFG ( P = .523). When analyzed for subgroups of the study sample, neither smoking nor diabetes showed circadian rhythm. There was a trend towards a delay from symptom onset to hospital presentation, particularly at evening hours in the RG compared with the control group. In conclusion, there was no significant difference in STEMI onset time, but the time from symptom onset to hospital admission was significantly delayed during Ramadan.

Aims: To assess the independent and joint impact of visit-to-visit fasting blood glucose variability (VVV-FBG) and mean fasting glucose level (M-FBG) on all-cause mortality.Materials and methods: This prospective cohort study included 48,843 Chinese with type 2 diabetes. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) to evaluate the association of VVV-FBG and M-FBG with all-cause mortality. The potential nonlinear associations were examined by restricted cubic splines, and additive interaction was evaluated by the relative excess risk due to interaction (RERI). Cox generalized additive models (CGAM) and bivariate response surface models were further used to assess the joint effects of VVV-FBG and M-FBG.Results: A total of 4087 deaths was observed during a median follow-up of 6.99 years. Compared with patients with values at the 5th percentile of ARV and M-FBG, we observed a 23% and 38% increased risk of premature deaths among those with values at the 95th percentile of ARV (HR: 1.23, 95% CI 1.10,1.37) and M-FBG (HR: 1.38, 95% CI 1.26,1.51), respectively. The interaction between glycemic variability (ARV) and M-FBG was significant on both the additive scale [RERI: 0.80 (0.29, 1.32)] and multiplicative scale [HR: 1.90 (1.10, 3.28)]. Subjects with high VVV-FBG and high M-FBG conferred the highest risk of all-cause mortality (HR: 1.89, 95% CI: 1.64,2.17), compared to low VVV-FBG and low M-FBG. The CGAM revealed significant synergistic effects between glycemic variability and M-FBG (P < 0.05). Moreover, bivariate surface plot revealed that the risk of death increased more rapidly in type 2 diabetes patients at the lower M-FBG level combined with lower glycemic variability level.Conclusions: The coexistence of great glycemic variability and high level of glucose might exacerbate the independent risk of premature mortality in type 2 diabetes patients, highlighting the importance of achieving normal and stable glucose levels simultaneously in the management of glucose. This article is protected by copyright. All rights reserved.

25-hydroxyvitamin D (25(OH)D) affects glucose metabolism by increasing insulin secretion and insulin receptor expression. However, whether 25(OH)D deficiency will increase the risk of gestational diabetes mellitus (GDM) has not been clearly reported. The purpose of this study is to assess the relationship between vitamin D levels in the second trimester of pregnancy and the risk of GDM.According to the inclusion and exclusion criteria, 247 pregnant women came to the fourth hospital of Shijiazhuang (The affiliated obstetrics and gynecology hospital of Hebei Medical University) for obstetrics were investigated during the period of January 1, 2019 to December 31, 2020. The levels of 25(OH)D in the second trimester (16-20 weeks) and oral 75 g glucose tolerance test (OGTT) at 24-28 weeks of pregnancy were reviewed. The sociodemographic data were collected from questionnaire. Multivariate logistic regression was used to analyze the relationship between vitamin D levels and GDM.The incidence of GDM in the observation group (25(OH)D ≤ 26 ng/ml) was higher than that in the control group (25(OH)D 26 ng/ml) (p = 0.039). Compared with control group, the observation group had significantly higher level of fasting plasma glucose (FPG) (4.7 [4.5-5.0] mmol/L vs. 4.6 [4.4-4.8] mmol/L, p = 0.012). In the whole study, the level of 25(OH)D was negatively correlated with FPG (r = - 0.164，p = 0.010). After adjusting for age, pre-pregnancy BMI, parity and adverse pregnancy history, compared with the observation group (25 (OH) D ≤ 26 ng/ml), the risk of developing GDM decreased by 50.9% in control group (25(OH)D 26 ng/ml) (odds ratio [OR] = 0.491, 95% confidence interval [CI] = 0.243-0.989, p = 0.047).Adequate vitamin D levels during the second trimester of pregnancy may reduce the risk of GDM.

Emerging evidence suggests that fasting could play a key role in cancer treatment by fostering conditions that limit cancer cells' adaptability, survival, and growth. Fasting could increase the effectiveness of cancer treatments and limit adverse events. Yet, we lack an integrated mechanistic model for how these two complicated systems interact, limiting our ability to understand, prevent, and treat cancer using fasting. Here, we review recent findings at the interface of oncology and fasting metabolism, with an emphasis on human clinical studies of intermittent fasting. We recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer-free survival, treatment efficacy and reduce side effects in cancer patients.

Worldwide obesity has risen to record levels generating a major risk factor for metabolic syndrome, diabetes, hypertension, and cardiovascular disease as well as cancer and neurodegenerative diseases. Here we discuss the impact of obesity on lifespan and cardiometabolic disease in mice and humans and how different types of fasting can help prevent and treat them. We argue that specific types of fasting regimens which are associated with low burden, high long-term compliance and safety, can reduce obesity and other disease risk factors, lower morbidity and extend healthspan.

Intestinal drug solubility is a key parameter controlling oral absorption but varies both intra and inter individuals and between the fasted and fed states, with food intake known to alter the bioavailability of many compounds. Intestinal solubility can be measured in vitro either using sampled fed human intestinal fluid (FeHIF) or simulated fed intestinal fluid (SIF) but neither approach is optimal. FeHIF is difficult to obtain and variable, whilst for fed SIF multiple recipes are available with no consensus on the ideal version. A recent study characterised FeHIF aspirates using a multidimensional approach and calculated nine simulated media recipes that covered over ninety percent of FeHIF compositional variability. In this study the equilibrium solubility of thirteen drugs have been measured using the nine simulated media recipes and compared to multiple previous design of experiment (DoE) studies, which have examined the impact of fed SIF media components on solubility. The measured nine media solubility data set is only statistically equivalent to the large scale 92 media DoE in 4 out of 13 drug comparisons, but has improved equivalence against small scale DoEs (9 or 10 media) with 6 out of 9 or 10 out of 12 (9 and 10 media respectively) equivalent. Selective removal of non-biorelevant compositions from the 92 media DoE improves statistical equivalence to 9 out of 13 comparisons. The results indicate that solubility equivalence is linked to media component concentrations and compositions, the nine media system is measuring a similar solubility space to previous systems, with a narrower solubility range than the 92 point DoE but equivalent to smaller DoE systems. Phenytoin and tadalafil display a narrow solubility range, a behaviour consistent with previous studies in fed and fasted states and only revealed through the multiple media approach. Custom DoE analysis of the nine media results to determine the most statistically significant component influencing solubility does not detect significant components. Indicating that the approach has a low statistical resolution and is not appropriate if determination of media component significance is required. This study demonstrates that it is possible to assess the fed intestinal equilibrium solubility envelope using the nine media recipes obtained from a multi-dimensional analysis of fed HIF. The derivation of the nine media compositions coupled with the results in this study indicate that the solubility results are more likely to reflect the fed intestinal solubility envelope than previous DoE studies and highlight that the system is worthy of further investigation.

Elderly patients have higher risks for complications during Ramadan fasting. Educating patients is essential for fasting safely.To evaluate the impact of pre-Ramadan education in reducing risk of hypoglycemia and achieving glycemic control in elderly.A prospective study carried out in outpatients clinics of Internal Medicine department in Assiut university hospital. It included 316 type 2 diabetic patients who intended to fast. They were grouped into 2 groups; 65 years and ≥ 65 years patients. The patients received pre-Ramadan individual education sessions. A semi-structured questionnaire was used to collect the data to stratify the risk of fasting. The study was carried out in 3 phases. Assessment of hypoglycemia and biochemical parameters after the education was the primary outcome.Fasting blood glucose decreased during and after Ramadan in elderly significantly (p = 0.0001). The patients who achieved fasting blood glucose less than 8 mmol/L increased from 29.3% to 46.6% after Ramadan in elderly patients. HbA1c decreased significantly after Ramadan (p = 0.001). The main cause of breaking fast was hypoglycemia in both groups; 9% vs.7.7% in patients 65 and ≥ 65 years respectively. The waist circumference showed significant decrease in patient with 65 years old or more (p = 0.05). Total cholesterol and LDL increased with no statistical significance in patients ≥ 65 years (p = 0.512, 0.470). Both groups showed improvement of HDL cholesterol during and after Ramadan (P = 0.0001).Pre-fasting education had positive impact on decreasing the risk of symptomatic hypoglycemia in elderly diabetic patients.

While glucose tolerance is widely known to deteriorate with age, there are individuals whose borderline elevated glucose does not presage development of diabetes, but there are people who do develop overt diabetes. In addition, elevated glucose may also presage other morbidities, particularly for those who show progressive deterioration in glucose control over time. This concept of the glucose trajectory has taken on recent significance with sophisticated mathematical modeling that can identify several different arcs, primarily based on longitudinal changes in fasting plasma glucose. Other trajectories, calculated on changes in glycated hemoglobin, or integrated responses to oral glucose tolerance tests, are less well characterized. The author has reviewed the literature in an attempt to clarify these different themes of age-related deterioration in glucose control, highlight conflicting definitions of glucose trajectory, and potentially identify avenues of further investigation. Genetic contributions to the risk of development of type 2 diabetes, artificial intelligence and mathematical models of diabetes risk, and the discrepancy between fasting glucose and postprandial measures, including glycated hemoglobin, in risk prediction are also considered.

We aimed to develop a risk prediction model for gestational diabetes mellitus (GDM) based on the common maternal demographics and routine clinical variables in Chinese population.Individual information was collected from December 2018 to October 2019 by a pretested questionnaire on demographics, medical and family history, and lifestyle factors. Multivariable logistic regression was performed to establish a predictive model for GDM by variables in pre- and early pregnancy. The consistency and discriminative validity of the model were evaluated by Hosmer-Lemeshow goodness-of-fit testing and ROC curve analysis. Internal validation was appraised by fivefold cross-validation. Clinical utility was assessed by decision curve analysis.Total 3263 pregnant women were included with 17.2% prevalence of GDM. The model equation was: LogitP = -11.432 + 0.065 × maternal age (years) + 0.061 × pre-pregnancy BMI (kg/mThe predictive model of GDM exhibited well acceptable predictive ability, discriminative performance, and clinical utilities. The project was registered in clinicaltrial.gov.com with identifier of NCT03922087.

The concomitant investigation of apoptosis (a regulated cell death) and autophagy (a conserved cell survival mechanism) in immune cells is rare. More detailed knowledge of these two types of self-consumption in circulating lymphocytes and monocytes would be important, since conditions such as fasting and acute exercise could promote health by a coordinated/linked modulation of autophagy and apoptosis in these mononuclear cells. In this study we performed flow cytometry to quantify numbers of apoptotic and autophagic mononuclear cells, lymphocytes and monocytes in fasting, standardized fed, and exercise conditions, using Annexin V, LC3B, and p62, respectively. We show that within total mononuclear cells lymphocytes are less apoptotic and autophagic than monocytes during fasting (p

Nuclear receptor Pregnane X Receptor (PXR; NR1I2) has transcriptional regulation functions for energy homeostasis in the liver. Mouse PXR has a conserved phosphorylation motif at serine 347 (serine 350 in humans) within the ligand-binding domain. PXR phosphorylated at this motif is expressed in mouse livers in response to fasting. Mice with a PXR∗Ser347Ala knockin mutation (PXR KI) were generated to block phosphorylation, and utilized to investigate the role of Ser347 phosphorylation in vivo. PXR KI mice had decreased body weight at 8-weeks of age and had much greater weight loss after fasting compared with PXR WT mice. The cDNA microarray analysis of hepatic mRNAs showed that cell death or apoptotic signaling was induced in fasting PXR KI mice. Moreover, increasing hepatic lipids, triglycerides and the development of hypertriglyceridemia were observed in fasting PXR KI mice. These findings are indicative that blocking phosphorylation prevents mice from maintaining hepatic energy homeostasis. Thus, phosphorylated PXR may be an essential factor to prevent the liver from developing damage caused by fasting.

Context Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4). Objective To determine whether GLP-1r signaling contributes to insulin secretion in the absence of enteral stimulation and increased plasma levels, and whether this is affected by DPP4. Methods Single-site study conducted at an academic medical center of 20 nondiabetic subjects and 13 subjects with type 2 diabetes. This was a crossover study in which subjects received either a DPP4 inhibitor (DPP4i; sitagliptin) or placebo on 2 separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60-minute infusions of the GLP-1r blocker exendin[9-39] (Ex-9) and saline. The main outcome measures were arginine-stimulated secretion of C-Peptide (C-PArg) and insulin (InsArg). Results Plasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both α- and β-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by ~14% (P Conclusion GLP-1r activation contributes to β-cell secretion in diabetic and nondiabetic people during α-cell activation, but in the absence of increased circulating GLP-1. These results are compatible with regulation of β-cells by paracrine signals from α-cells. This process may be affected by DPP4 inhibition.

Previous studies involving diabetics have shown different associations between fasting plasma glucose (FPG) and bone mineral density (BMD). The different effects of FPG on BMD are due to varying effects of antidiabetic drugs, glycemic control and diabetic complications in the diabetic patients. It is necessary to identify the association in subjects without diabetes.A total of 2367 females over 65 were included in this cross-sectional study. Subjects were grouped by FPG quartile. BMD and the prevalence of osteoporosis were compared among different FPG quartiles. Multiple logistic regression was used to analyze the independent contribution of FPG to osteoporosis.Subjects in lower FPG quartile had lower BMD (P 0.05). Subjects with osteoporosis had a lower FPG than the subjects of osteopenia, and both were lower than subjects with normal bone mass (P 0.001 for all). Compared with the lowest FPG quartile, subjects in the 3rd and the 4th quartiles have a lower risk of osteoporosis in the lumbar spine (OR 0.77, 95% CI 0.59-0.98; OR 0.76, 95% CI 0.56-0.99, respectively), the total hip (OR 0.72, 95% CI 0.56-0.96; OR 0.75, 95% CI 0.53-0.99, respectively), and the femoral neck (OR 0.73, 95% CI 0.50-0.97; OR 0.71, 95% CI 0.54-0.92, respectively) after adjustment for age, BMI, education, physical activity and menopausal age.FPG was positively associated with BMD in non-diabetic elderly females. Low FPG may increase the risk of osteoporosis in the non-diabetic elderly females in China.

Objective: antimuscarinic treatment in fasted mice and rats causes clonic convulsion soon after food intake. This study was designed to evaluate the electrophysiological markers of these convulsions and fasting in electrocorticograms in rats. Methods: Male Wistar albino rats were stereotaxically implanted with 10 cortical electrodes, and baseline electroencephalogram recordings were taken for 10 minutes. After weighing, rats were deprived of food for 52 hours. At the 24th and 52nd hours of deprivation, continuous electroencephalogram recordings were repeated. After the deprivation period, animals were treated with saline or scopolamine (3 mg/kg). Twenty minutes after injections, animals were given food pellets. After eating food, electroencephalogram recordings were taken for 60 minutes and all animals were observed simultaneously to determine the incidence and onset of convulsions. Results: these results show that food deprivation for 52 hours decreased the amplitude of the gamma band when compared to basal (P, NA

Simultaneous evaluation of sex-specific effect of body mass index (BMI) and hyperglycemia on the risk of gastric cancer has been rarely reported. Here, we investigated the sex-specific effect of BMI and hyperglycemia on gastric cancer.Persons who underwent National gastric cancer screening from 2006 to 2007 and had no gastric cancer at baseline, were enrolled and followed up to 2015. The risk of gastric cancer by BMI and glucose was measured using risk ratios (RRs) and 95% confidence intervals (CI). Adjusted Cox analysis was performed to evaluate the risk of death.Gastric cancers developed in 29,775 of 5.17 million. In the adjusted analysis, low BMI (18.5 kg/mGastric cancer risk and all-cause mortality by BMI was L-shape with sex-specific cut-off value. The effect of fasting glucose on gastric cancer risk was different by sex.

Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

This study aimed to investigate the serum irisin levels and diet quality of newly-diagnosed type 2 diabetes mellitus (T2DM) patients in comparison with healthy controls and to identify the correlations between serum irisin levels with diet quality, anthropometric measurements and biochemical parameters.This case-control study was conducted with 38 newly-diagnosed T2DM patients and 38 healthy control individuals. Diet quality was calculated from the semi-quantitative food frequency questionnaire by using the Healthy Eating Index (HEI) 2015. The anthropometric measurements were taken and body composition was analyzed with bioelectric impedance analysis (BIA) method. Biochemical parameters and serum irisin levels were analyzed in blood samples which were obtained after overnight fasting.Irisin levels were higher in the T2DM group compared to the healthy control group (2.57 ± 0.44 ng/mL and 2.15 ± 0.44 ng/mL, respectively; p 0.001). The optimal cut-off value for irisin to predict T2DM was 2.195 ng/mL (specificity = 71.1%, sensitivity = 78.9%). In both groups, irisin levels were not associated with overall HEI 2015; however, they were positively associated with total and whole fruit scores in the T2DM group (p 0.05). After adjustment according to age, sex and BMI, in the T2DM group HDL cholesterol positively affected by irisin levels, while in the control group triglyceride positively affected irisin levels (p 0.05).High levels of irisin in newly diagnosed T2DM patients compared to healthy individuals indicate that irisin may have a role in the monitoring and treatment of T2DM. Though irisin levels were not associated with total diet quality, they were associated with fruit consumption.