Tremella fuciformis beverage improves glycated hemoglobin A1c and waist circumference in overweight/obese prediabetic subjects: a randomized controlled trial.

BACKGROUND: Prediabetes is increasing worldwide. Previous studies have demonstrated the potential of ß-glucan derived from oat or barley to lower blood glucose, body weight, and plasma lipid levels. These findings offer a potentially attractive strategy for reducing the risk of diabetes in prediabetic individuals. However, the effects of ß-glucan from Tremella fuciformis on glucose metabolism and anthropometric measurements in humans have yet to be studied. We hypothesized that ß-glucan from Tremella fuciformis may improve metabolic parameters in subjects with prediabetes. This study aimed to investigate the effects of a once-daily beverage containing Tremella fuciformis (snow mushroom) on anthropometric measurements, metabolic biomarkers, and insulin sensitivity in overweight/obese subjects with prediabetes. METHODS: In this double-blind RCT, 56 participants were randomly assigned to receive either a Tremella fuciformis beverage or placebo daily for 12 weeks. All parameters were assessed at baseline and after the intervention. RESULTS: After 12 weeks, participants in the intervention group exhibited significant improvements in glycated hemoglobin A1c (HbA1C; 6.03 ± 0.26% at baseline vs. 5.96 ± 0.25% at 12 weeks, p = 0.047, Cohen's d = 0.39) and waist circumference (95.2 ± 12.51 cm at baseline vs. 93.46 ± 11.48 cm at 12 weeks, p = 0.022, Cohen's d = 0.45). There were no adverse events reported. CONCLUSION: This exploratory study demonstrated that Tremella fuciformis beverage consumption may improve HbA1C and waist circumference in overweight/obese prediabetic individuals. Further research, including larger-scale RCTs and mechanistic studies, is needed to confirm these findings and optimize the therapeutic potential of Tremella fuciformis derivatives in managing prediabetes and preventing type 2 diabetes. TRIAL REGISTRATION: Registered in Thai Clinical Trials Registry (14/07/2021, TCTR20210714004).

Saliva and wastewater surveillance for SARS-CoV-2 during school reopening amid COVID-19 pandemic in Thailand.

Objectives: School closure during the coronavirus disease 2019 (COVID-19) pandemic resulted in a negative impact on children. Serial testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proposed as a measure for safety school reopening. We aimed to study the usefulness of SARS-CoV-2 surveillance by saliva testing and performing wastewater surveillance for SARS-CoV-2 in a day school in a resource-limited setting. Methods: We conducted a cluster randomized study to investigate the potential use of saliva antigen testing compared to saliva pooling for nucleic acid detection in a primary school in Thailand from December 2021 to March 2022. Wastewater surveillance in the school was also performed. Results: A total of 484 participants attended the study. SARS-CoV-2 was detected in two participants from the tests provided by the study (one in the pool nucleic acid test arm, and another in the quantitative antigen test arm). Additional ten participants reported positive results on an additional rapid antigen test (RAT) performed by nasal swab when they had symptoms or household contact. There was no difference among arms in viral detection by intention-to-treat and per protocol analysis (p = 0.304 and 0.894, respectively). We also investigated the feasibility of wastewater surveillance to detect the virus in this setting. However, wastewater surveillance could not detect the virus. Conclusions: In a low COVID-19 prevalence, serial saliva testing and wastewater surveillance for SARS-CoV-2 rarely detected the virus in a day school setting. Performing RAT on nasal swabs when students, teachers or staff have symptoms or household contact might be more reasonable.

Association between ApoA1 Gene, Plasma Lipid Profile, hsCRP Level, and Risk of Arterial Stiffness in Thai Elderly.

Introduction: Apolipoprotein A1 (ApoA1) gene polymorphism is linked to high-density lipoprotein cholesterol (HDL-C) levels. Variations in this gene, along with dyslipidemia and inflammation, may increase the risk of vascular stiffness. This study aimed to investigate the link between ApoA1 rs670 genetic variations, various biochemical parameters, and the risk of arterial stiffness in older people. Methods: This population-based cross-sectional study included 355 participants (≥60 years) who completed a demographic and lifestyle information questionnaire. Clinical and anthropometric examination, biochemical analysis, and ApoA1 rs670 genotyping by real-time PCR were performed. The cardio-ankle vascular index (CAVI) was used to assess arterial stiffness. Results: Age, BMI, waist circumference, SBP, LDL-C, and high-sensitivity C-reactive protein (hs-CRP) were associated with high CAVI (≥9) among older people. The mean CAVI (8.19 ± 2.78) for the ApoA1 rs670 AA genotype was lower than that of the GG genotypes (8.94 ± 1.00, p < 0.05). These results are supported by HDL-C (OR = 0.47, 95% CI: 0.24-0.93; p=0.030) and high hs-CRP (OR = 0.30, 95% CI: 0.16-0.57; p=0.006) levels together with adjusted ORs of both variables. Conclusion: ApoA1 rs670 genetic variations involved in the synthesis, transport, and processing of HDLs, hypertension, and inflammation are linked to arterial stiffness. Further studies are required to clarify these mechanisms.

The Detection of SARS-CoV2 Antigen in Wastewater Using an Automated Chemiluminescence Enzyme Immunoassay.

The SARS-CoV-2 virus, which is driving the current COVID-19 epidemic, has been detected in wastewater and is being utilized as a surveillance tool to establish an early warning system to aid in the management and prevention of future pandemics. qPCR is the method usually used to detect SARS-CoV-2 in wastewater. There has been no study using an immunoassay that is less laboratory-intensive than qPCR with a shorter turnaround time. Therefore, we aimed to evaluate the performance of an automated chemiluminescence enzyme immunoassay (CLEIA) for SARS-CoV-2 antigen in wastewater. The CLEIA assay achieved 100% sensitivity and 66.7% specificity in a field-captured wastewater sample compared to the gold standard RT-qPCR. Our early findings suggest that the SARS-CoV-2 antigen can be identified in wastewater samples using an automated CLEIA, reducing the turnaround time and improving the performance of SARS-CoV-2 wastewater monitoring during the pandemic.

Targeted metabolomics suggests a probable role of the FTO gene in the kynurenine pathway in prediabetes.

Background: Genome-wide association studies have identified the alpha-ketoglutarate dependent dioxygenase gene (FTO) as the first susceptibility gene of obesity. In the present study, we utilized targeted metabolomics in an attempt to further elucidate mechanisms underlying the action of the FTO gene. Methods: This study was part of a health survey of employees of the Electricity Generating Authority of Thailand (n = 79, 10 female and 69 male). Targeted metabolomics was performed by liquid chromatography-mass spectrometry using Biocrates AbsoluteIDQ-p180 kit. Genotyping of FTO rs9939609 was performed by real-time PCR (TaqMan™ MGB probes). Results: Using OPLS-DA variable importance in projection (VIP), tryptophan was found to be among the metabolites with the 10 highest VIP scores. Pearson's correlation analysis showed that kynurenine and tryptophan were positively correlated only in subjects with the rs9939609 A allele (n = 32, r = 0.56, p < 0.001) and the correlation coefficients were significantly higher in subjects having the A allele than in those without the A allele (p < 0.05). Moreover, the kynurenine/tryptophan ratio was significantly associated with the presence of the A allele, independently of body mass index and sex. Conclusions: The FTO gene is likely to influences the conversion of tryptophan to kynurenine.

A Simple Method to Detect SARS-CoV-2 in Wastewater at Low Virus Concentration.

Background: Since its initial appearance in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Wastewater surveillance has been demonstrated as capable of identifying infection clusters early. The purpose of this study was to investigate a quick and simple method to detect SARS-CoV-2 in wastewater in Thailand during the early stages of the second outbreak wave when the prevalence of the disease and the virus concentration in wastewater were low. Methods: Wastewater samples were collected from a hospital caring for patients with COVID-19 and from 35 markets, two of which were associated with recently reported COVID-19 cases. Then, samples were concentrated by membrane filtering prior to SARS-CoV-2 detection by RT-qPCR. Results: SARS-CoV-2 RNA was detected in the wastewater samples from the hospital; the Ct values for the N, ORF1ab, and S genes progressively increased as the number of patients admitted to the treatment floor decreased. Notably, the ORF1ab and S genes were still detectable in wastewater even when only one patient with COVID-19 remained at the hospital. SARS-CoV-2 RNA was detected in the wastewater samples from fresh market where COVID-19 cases were reported. Conclusions: Our findings suggest that wastewater surveillance for SARS-CoV-2 is sensitive and can detect the virus even in places with a high ambient temperature and relatively low prevalence of COVID-19.

Beta cell function, incretin hormones, and incretin effect in obese children and adolescents with prediabetes.

BACKGROUND: Defects of incretin hormones and incretin effect may be underlying mechanisms of abnormal glucose metabolism in youth. OBJECTIVE: To assess incretin hormone dynamics during an oral glucose tolerance test (OGTT) and incretin effect in obese children with prediabetes in comparison with those with normal glucose tolerance (NGT). METHODS: Overweight and obese children were enrolled and classified according to OGTT results as NGT and prediabetes. Insulin sensitivity, insulin secretion, incretin hormone concentrations during OGTT; and incretin effect derived from OGTT and intravenous glucose tolerance test were determined and compared between NGT and prediabetes groups. RESULTS: Sixty-three patients (43 NGT and 20 prediabetes) were enrolled. Their median (interquartile range) age was 12.5 (11.1, 13.8) years. Peak glucagon-like peptide-1 (GLP-1) was demonstrated at 30 min during OGTT and was higher in the prediabetes group (49.2 [35.6, 63.6] versus 36.5 [27.6, 44.2] pmol/L, p = 0.009). However, incremental areas under the curves (iAUCs) of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were not different between the two groups. There was no difference in incretin effect between NGT and prediabetes (NGT: 66.5% [60.2%, 77.5%] vs. prediabetes: 70.0% [61.5%, 75.0%], p = 0.645). Incretin effect had positive correlations with iAUCs of both GLP-1 and GIP (GLP-1: r = 0.40, p = 0.004 and GIP: r = 0.37, p = 0.009). CONCLUSIONS: Comparing between obese children with prediabetes and NGT, there were no differences in overall incretin hormone changes during OGTT and incretin effect. Incretin effect was positively correlated with iAUCs of GLP-1 and GIP.

Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer's Disease.

OBJECTIVES: This study compares glycoproteomes in Thai Alzheimer's disease (AD) patients with those of cognitively normal individuals. METHODS: Study participants included outpatients with clinically diagnosed AD (N = 136) and healthy controls without cognitive impairment (N = 183). Blood samples were collected from all participants for biochemical analysis and for Apolipoprotein E (APOE) genotyping by real-time TaqMan PCR assays. Comparative serum glycoproteomic profiling by liquid chromatography-tandem mass spectrometry was then performed to identify differentially abundant proteins with functional relevance. RESULTS: Statistical differences in age, educational level, and APOE ɛ3/ɛ4 and ɛ4/ɛ4 haplotype frequencies were found between the AD and control groups. The frequency of the APOE ɛ4 allele was significantly higher in the AD group than in the control group. In total, 871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups, respectively. There were 49 and 297 upregulated and downregulated glycoproteins, respectively, in AD samples compared with the controls. Unique AD glycoproteins were associated with numerous pathways, including Alzheimer's disease-presenilin pathway (16.6%), inflammation pathway mediated by chemokine and cytokine signaling (9.2%), Wnt signaling pathway (8.2%), and apoptosis signaling pathway (6.7%). CONCLUSION: Functions and pathways associated with protein-protein interactions were identified in AD. Significant changes in these proteins can indicate the molecular mechanisms involved in the pathogenesis of AD, and they have the potential to serve as AD biomarkers. Such findings could allow us to better understand AD pathology.

Role of MT1A Polymorphism and Environmental Mercury Exposure on the Montreal Cognitive Assessment (MoCA).

PURPOSE: Many age-related structural and functional changes in the brain have important consequences. Long-term exposure to mercury and the impact of functional polymorphisms of metal-regulating proteins such as metallothioneins (MTs) can result in neurological-neurobehavioral effects in elderly individuals. Therefore, the aims of this study are to examine the associations between biomarkers of mercury exposure and cognitive impairment and to investigate the effect of the rs8052394 single nucleotide polymorphism (SNP) of the potential modifier gene MT1A on different domains of the Montreal Cognitive Assessment (MoCA). MATERIALS AND METHODS: We studied 436 participants aged ≥55 years from the Electricity Generating Authority of Thailand study. They underwent a physical examination, an extensive cognitive assessment with the MoCA (cutoff <26 points), and a biochemical analysis related to diabetes and dyslipidemia. The blood mercury level was determined by inductively coupled plasma mass spectrometry. Genotyping of the MT1A rs8052394 SNP was performed by the restriction fragmentation length polymorphism method. RESULTS: The mean age of the study population was 58.8±3.01 years, and most had ≥12 years of education (75.7%). The primary study finding was that the prevalence of mild cognitive impairment (MCI) in older Thai adults was 39.7%. The frequency distributions of the G allele of the rs8052394 SNP of the MT1A gene were significantly associated with the total and sub-domain MoCA scores. The prevalence of MCI was significantly associated with increased age, hypertriglyceridemia, hyperhomocysteinemia, the third tertile of blood mercury concentration, and the rs8052394 variant genotype of MT1A (P values for all odds ratios <0.05). CONCLUSION: These findings suggested that neurocognitive effects associate with mercury exposure and genetic susceptibility in toxicokinetics. Public health strategies can be used to implement as a comprehensive action plan to educate vulnerable populations on how to reduce mercury exposure. Concurrently, impact of such genetic predisposition requires replication for identifying and protecting susceptible individuals from mercury toxicity.

Vitamin D supplementation is associated with serum uric acid concentration in patients with prediabetes and hyperuricemia.

AIMS: Vitamin D deficiency is associated with a number of noncommunicable conditions. We conducted a randomised controlled trial to determine the effect of vitamin D supplementation on serum uric acid concentration in patients with prediabetes, in whom hyperuricaemia is common. METHODS: Seventy-one volunteers (35-80 years), with impaired fasting glucose and/or impaired glucose tolerance were randomised to three groups, vitamin D3, vitamin D2 and control, and followed for 12 months. RESULTS: After 12 weeks, vitamin D supplementation was associated with a reduction in serum uric acid concentration in participants with baseline uric acid concentration > 6 mg/dL, but no significant change was observed in controls. We then assessed the dose-response relationship between vitamin D supplementation and the change in serum uric acid concentration and found that the change in serum total 25-hydroxyvitamin D did not correlate with the change in serum uric acid that occurred during vitamin D supplementation. The factors associated with larger reductions in serum uric acid were a higher baseline serum uric acid and a larger increase in serum 1,25-dihydroxyvitamin D. CONCLUSIONS: Vitamin D supplementation lowers serum uric acid in prediabetic patients with hyperuricaemia, and supplementation might be considered to help alleviate hyperuricaemia in these patients.

The Involvement of Selenium in Type 2 Diabetes Development Related to Obesity and Low Grade Inflammation.

BACKGROUND: Effects of the micronutrient selenium have been proposed in obesity and type 2 diabetes mellitus (T2DM) that involve impairments in glucose metabolic pathways and the insulin signaling cascade, mediated through oxidative stress and inflammation. However, the evidence collected to date through animal and epidemiologic studies has been inconclusive. Therefore, in the present study, we aimed to evaluate the relationships of selenium status and inflammation with T2DM and obesity. METHODS: Participants in the re-survey of the Electricity Generating Authority of Thailand (EGAT)2 study conducted in 2013 (N=655, age 45-60 years) were allocated to three groups based on their body mass index (World Health Organization Asia-Pacific Classification), and their serum selenium and high-sensitivity C-reactive protein (hs-CRP) concentrations and other clinical parameters were compared. RESULTS: Significant differences in serum selenium and hs-CRP among the groups were associated with differences in fasting blood glucose and glycated hemoglobin, as well as differences in the prevalence of prediabetes or T2DM. The adjusted odds ratios (ORs) (95% confidence intervals) for prediabetes or diabetes were 1.991 (1.318-3.009) and 3.786 (2.087-6.896) for the lowest and highest tertiles of serum selenium concentration in the entire sample and obese participants, respectively. Furthermore, the rising extent of hs-CRP increased the significantly associated with prediabetes or diabetes (adjusted ORs; 2.268 for the entire sample, 4.043 for the overweight and 1.910 for the obesity). CONCLUSION: Selenium status may be linked to both obesity and T2DM through its effects on signaling pathways. Further nutrigenomic studies are required to clarify the relationship between selenium and metabolic diseases.

Serum Kisspeptin and Its Relation to Metabolic Parameters and Glucose Metabolism in Prepubertal and Pubertal Obese Children.

OBJECTIVE: Kisspeptin, a puberty control neuropeptide, has been discovered to have an additional role in metabolism and glucose homeostasis regulation. This study aimed to determine the association of serum kisspeptin with metabolic parameters and glucose metabolism in obese children. Design, Patients and Measurements. A cross-sectional study of 270 obese children was conducted. All children underwent an oral glucose tolerance test and had serum kisspeptin, glycated hemoglobin (HbA1c), and lipid profile measurements. Body fat mass was assessed by bioelectrical impedance analysis. Serum kisspeptin levels of both prepubertal and pubertal children with two HbA1c ranges, <5.7% (normal range) and 5.7-6.4% (prediabetes range), were analyzed and correlated with metabolic parameters and glucose metabolism status. RESULTS: The median (IQR) serum kisspeptin level of only pubertal (not prepubertal) children with prediabetes HbA1c was higher than those with normal HbA1c (53.2 (33.9, 69.8) and 37.8 (29.6, 67.5) pg/mL; p = 0.015, respectively). There were no differences in serum kisspeptin levels among children with different glucose metabolism status. During pubertal progression, serum kisspeptin reached the highest level at Tanner stage II only in obese boys. Additionally, there was a positive correlation between serum kisspeptin and HbA1c after adjusting for puberty (ß = 12.87; p = 0.001). No correlations between serum kisspeptin and insulin sensitivity indices, insulin secretion indices, lipid profile, blood glucose, as well as percentage of body fat were demonstrated. CONCLUSIONS: Serum kisspeptin levels in pubertal obese children with prediabetes HbA1c were greater than those with normal HbA1c. Serum kisspeptin was positively associated with HbA1c, but not with glucose metabolism status.

No changes in gut microbiota after two-week sleep extension in chronically sleep-deprived individuals.

BACKGROUND: Gut microbiota has been linked to obesity and glucose metabolism. Insufficient sleep is also known to be associated with insulin resistance, and sleep extension was reported to improve glucose metabolism in short sleepers. This study aimed to explore whether sleep extension was associated with changes in gut microbiota and whether there was a relationship with glucose parameters. METHODS: We performed a secondary analysis of eight short-seeping but otherwise healthy subjects who participated in a cross over study of two-week home sleep extension and two weeks of habitual sleep. After each sleep condition, stool samples were collected and glucose parameters were obtained. Stool DNA extraction was performed and 16S rRNA was sequenced by MiSeq™. The resulting sequence data were processed to infer relative abundances of taxa present and then analyzed to detect any differences in the abundances of the taxa or overall diversity of the microbiome. RESULTS: Mean (SD) sleep duration during habitual sleep and sleep extension was 5.58 (0.53) and 6.60 (0.43) hours/night, respectively. Using the Bray-Curtis index, there was no significant dissimilarity of the genus-level microbial community between the two sleeping conditions (ADONIS, R2 = 0.017, p = 0.988 and ANOSIM, R = -0.131, p = 0.991). Within-sample microbial diversity (ie, the Shannon index) also did not find significant differences (p = 0.861). There was no significant relationship between per-individual dissimilarity and objective and subjective sleep variables, or glycemic parameters. Only higher sleep efficiency was related to higher abundance of the phyla Tenericutes. CONCLUSION: Two-week sleep extension in short sleepers was not associated with changes in gut microbiota.

Effects of Two-Week Sleep Extension on Glucose Metabolism in Chronically Sleep-Deprived Individuals.

STUDY OBJECTIVES: Sleep deprivation is known to be associated with insulin resistance and diabetes risk. This study investigated whether 2-week sleep extension in chronically sleep-deprived individuals would improve glucose metabolism. METHODS: A crossover study was conducted in volunteers without diabetes who reported sleeping ≤ 6 h/night. They were randomized to maintain their habitual sleep or extend sleep time for 2 weeks, then crossed over after a washout period. Sleep was monitored by actigraphy. Oral glucose tolerance tests (75 g) with insulin levels was performed at the end of each period. Mixed-effect linear regression analysis, adjusting for sequence and period effects, was applied. RESULTS: A total of 21 participants (19 females) with mean (standard deviation) age of 33.1 (6.1) years completed the protocol. Mean sleep duration during habitual sleep was 318.7 (44.3) minutes and the participants extended their sleep by 36.0 (45.2) minutes during sleep extension. The average washout period was 21 (11) days. There were no significant effects of sleep extension on any metabolic parameters. The per-protocol analysis included eight participants who could sleep more than 6 hours during sleep extension (mean sleep duration 396 [25] minutes, extended by 60.1 [28.5] minutes). Among these individuals, sleep extension improved Homeostatic Model Assessment of Insulin Resistance (adjusted mean difference -0.50 [95% confidence interval [CI] -0.89, -0.11, P = .013]), early insulin secretion (insulinogenic index; mean difference 0.39 [95% CI 0.15, 0.63, P = .001]), and ß-cell function (disposition index, mean difference 1.07 [95% CI 0.17, 1.97, P = .02]). CONCLUSIONS: Sleep extension in chronically sleep-deprived individuals improved glucose metabolism in only those who could objectively extend their sleep to more than 6 h/night. Our findings suggest that a critical amount of sleep is needed to benefit metabolic outcomes.

Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Emerging evidence shows that non-nutritive sweeteners might induce glucose intolerance. This study aims to determine the effects of chronic exposure to sucralose on glycemic response, insulin secretion and sensitivity, and glucagon-like peptide-1 (GLP-1) release in healthy subjects. METHODS: Healthy volunteers who did not use non-nutritive sweeteners and were normoglycemia after oral glucose tolerance test (OGTT) were recruited. Subjects underwent a 75-g OGTT on two separate occasions, preceded by blindly consuming pills containing either 200 mg sucralose or placebo for 4 wk in a randomized crossover trial. Plasma glucose, insulin, and active GLP-1 levels were obtained after ingesting 75-g glucose. On the following day, intravenous glucose tolerance test (IVGTT) was performed to evaluate the acute insulin response (AIR). RESULTS: Fifteen participants (11 females, age 31.9 ± 10 y, body mass index 23.1 ± 3 kg/m2) participated in the study. AIR was lower after exposure to sucralose than placebo (58.9 ± 48.61 versus 69.94 ± 73.81 µU/mL, P < 0.001). Whole-body insulin sensitivity (estimated using the Matsuda index) was lower in sucralose than placebo (4.69 ± 1.67 versus 5.31 ± 2.56, P < 0.005). AUC of active GLP-1 was significantly higher in the sucralose than placebo (23.16 ± 18.86 versus 18.5 ± 22.22 pmol/L ⋅ 120 min, P < 0.001). CONCLUSIONS: The continuous exposure to sucralose reduced AIR, decreased insulin sensitivity, and enhanced GLP-1 release in healthy subjects. However, the clinical significance of these results needs to be investigated in longer follow-up studies.

The genetic determinants of circulating C3-epimers of 25-hydroxyvitamin D.

BACKGROUND: The complexity of vitamin D metabolites especially the contribution of C3-epimers of 25-hydroxyvitamin D (C3-epimers) in human sera remains unclear. We hypothesized that genetic polymorphisms in the vitamin D-related gene pathway contribute to variation in C3-epimer levels. Therefore, we investigated candidate single nucleotide polymorphisms (SNPs) concerning C3-epimer levels. METHODS: The candidate SNPs, including DHCR7/NADSYN1 (rs12785878), CYP2R1 (rs2060793) and GC (rs2282679), were genotyped in 1727 members of the third project of the Electricity Generating Authority of Thailand 3/1 cohort investigation. Each SNP was tested under three genetic effects (dominant, recessive and additive models) concerning the levels of total serum 25(OH)D [the sum of 25(OH)D2+3 and 3-epi-25(OH)D2+3], non-C3-epimers [25(OH)D2+3] and C3-epimers [3-epi-25(OH)D2+3], using linear regression analysis. RESULTS: Among the participants, the median (range) levels of non-C3-epimers and C3-epimers were 22.7 (6.4-49.2) ng/mL and 1.3 (0.01-14.2) ng/mL, respectively. In regression analysis, we found the genetic variation of two SNPs, the DHCR7/NADSYN1 (rs12785878; G > T) and GC (rs2282679; T > G) under additive genetic models, explained the variation of C3-epimer levels about 1.5% (p = 1.66 × 10-7) and 1.1% (p = 1.10 × 10-5), respectively. Interestingly, participants carrying the minor T-allele of rs12785878 exhibited a trend to increase C3-epimer levels, while those carrying the minor G-allele of rs2282679 exhibited a trend to decrease levels of both non-C3-epimers and C3-epimers. In addition, CYP2R1 (rs2060793; G > A) was clearly associated only with non-C3-epimer levels (p = 2.46 × 10-8). In multivariate analyses, sex, age and BMI were predictors for variation in C3-epimer concentration; sex and age for variation in non-C3-epimers. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate genetic models concerning the variation in C3-epimer levels. Our results emphasize that genetic determinants and the potential factors of C3-epimers differ from non-C3-epimers. This study contributes fundamental knowledge of the endogenous vitamin D pathway.

The Association of Gut Microbiota with Nonalcoholic Steatohepatitis in Thais.

OBJECTIVES: Nonalcoholic steatohepatitis (NASH) can progress to advanced fibrosis; the link between intestinal bacterial overgrowth and NASH has been proposed. Gut microbiota may promote inflammation and provoke disease progression. We evaluated gut microbiota pattern in NASH and its influencing factors. METHODS: A case-controlled study with sixteen NASH and eight control subjects was done. We performed DNA extraction from stool samples and bacterial 16S rRNA sequencing using MiSeq™. The sequences were clustered into operational taxonomic units using Quantitative Insights Into Microbial Ecology software. We calculated relative abundances, determined alpha diversity, obtained beta diversity by principal coordinate analysis, and conducted the partial least-squares regression model. RESULTS: The relative abundance of Bacteroidetes tended to be higher in NASH group. The Bacteroidetes/Firmicutes (B/F) ratio was significantly elevated in NASH patients. The pattern of gut microbiota in NASH was clearly separated from that of control subjects. Factors influencing the separation of NASH from control subjects were age, diabetes, body mass index, Bacteroidetes phylum, metformin, Actinobacteria, Verrucomicrobia, Thermotogae, and Caldithrix and Bacteroidetes/Firmicutes ratio. CONCLUSIONS: Bacteroidetes phylum (Bacteroides and Prevotella genus) is abundant in NASH subjects, who exhibited an elevated B/F ratio. NASH patients showed a specific pattern of gut microbiota independent of diabetes or metformin use.

Continuous Positive Airway Pressure Therapy in Gestational Diabetes With Obstructive Sleep Apnea: A Randomized Controlled Trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with gestational diabetes mellitus (GDM). This study assessed the effects of continuous positive airway pressure (CPAP) in obese pregnant females with GDM and OSA. METHODS: A randomized controlled trial was conducted (April 2014 - June 2016). Obese females at 24 to 34 weeks gestation and with diet-controlled GDM were screened for OSA. Those with OSA were randomly assigned to receive 2 weeks nightly CPAP or be part of a waitlist control group. After 2 weeks, all patients were offered CPAP. The primary outcome was glucose metabolism, obtained from an oral meal tolerance test (MTT) at baseline and 2 weeks. Pregnancy outcomes were collected. RESULTS: Eighteen patients were randomized to CPAP and 18 to control groups. There were no significant changes between groups in fasting glucose, glucose response to MTT, and insulin sensitivity or secretion after 2 weeks. Those adherent to CPAP had significantly improved insulin secretion (P = .016) compared to the control group. When a counterfactual instrumental variable approach was applied to deal with nonadherence, the CPAP group had significantly improved insulin secretion (P = .002) and insulin sensitivity (P = .015). Lower rates of preterm delivery (P = .002), unplanned cesarean section (P = .005), and neonatal intensive care unit admissions (P < .001) were observed among those who used CPAP longer than 2 weeks. CONCLUSIONS: Two weeks of CPAP in females with GDM and OSA did not result in improved glucose levels, but insulin secretion improved in those adherent to CPAP. Continued CPAP use was possibly associated with improved pregnancy outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea and Gestational Diabetes: Incidence and Effects of Continuous Positive Airway Pressure Treatment on Glucose Metabolism; Identifier: NCT02108197; URL: https://clinicaltrials.gov/ct2/show/NCT02108197.

Lower nocturnal urinary 6-sulfatoxymelatonin is associated with more severe insulin resistance in patients with prediabetes.

OBJECTIVE: Melatonin, a neurohormone secreted by the pineal gland, controls circadian rhythmicity, modulates sleep and plays a role in glucose metabolism. Low secretion of nocturnal urinary 6-sulfatoxymelatonin (aMT6S) was associated with incident diabetes. Sleep disturbances have also been shown to be risk factors for diabetes. In this study, we explored the relationship between nocturnal urinary aMT6s and markers of glucose metabolism in prediabetes patients, considering sleep related factors. METHODS: Sixty two non-shift working patients with prediabetes [hemoglobin A1c (HbA1c) 5.7-6.49%] who were not on beta-blockers participated. Sleep duration and efficiency was recorded using 7-day actigraphy. Obstructive sleep apnea was evaluated using an overnight in-home monitoring device. Nocturnal urinary aMT6s/creatinine ratio was measured from an overnight urine sample. Oral glucose tolerance test (OGTT, 75-grams glucose) was performed, with measurements of insulin and glucose levels. RESULTS: Mean (SD) age was 55.3 (8.2) years and mean HbA1c level was 6.01 (0.2)%. Mean (SD) sleep duration 6.0 (0.9) h, sleep efficiency was 83.4 (6.6)% and a median (interquartile rage) apnea hypopnea index was 10.3 (3.6, 16.4). Median nocturnal urinary aMT6s was 17.4 (9.4, 28.2) ng/mg creatinine. Higher nocturnal urinary aMT6s significantly correlated with lower fasting insulin (p = 0.004), lower insulin response to OGTT (p = 0.027), and lower fasting and whole body insulin resistance as indicated by lower HOMA-IR and higher Matsuda insulin sensitivity index (p = 0.006 and p = 0.011, respectively), but it was not correlated with fasting glucose, glucose response to OGTT, or HbA1c. Sleep duration inversely correlated with HbA1c but no other correlations were found between other sleep variables and markers of glucose metabolism or nocturnal urinary aMT6s. After adjusting for body mass index, higher nocturnal urinary aMT6s significantly correlated with lower HOMA-IR (p = 0.025) and fasting insulin levels (p = 0.014). CONCLUSION: Nocturnal urinary aMT6s inversely correlated with fasting insulin resistance and insulin levels in patients with prediabetes. These results support the role of melatonin in glucose metabolism.