Biological age as estimated by baseline circulating metabolites is associated with incident diabetes and mortality.

OBJECTIVES: It is unclear how metabolomic assessment of biological aging performs in non-White populations and whether such an approach can predict future mortality. We aimed to evaluate the application of serum metabolomics combined with machine learning methodologies to predict incident diabetes and mortality in a Thai population. DESIGN, SETTING AND PARTICIPANTS: We analyzed serum samples and mortality data over 11 years from among 454 participants with no previous history of diabetes and with a fasting plasma glucose ≥85th percentile (5.4 mmol/L) but <7 mmol/L. MEASUREMENTS: Untargeted serum metabolomics were assessed using liquid chromatography/mass spectrometry. A deep artificial neural network was used to predict biological age based on serum metabolite profiles and chronological age. RESULTS: The mean age of participants was 40.5 ± 6.4 years, and 70.8% were men. We found a significant positive correlation between metabolomic age and chronological age (r = 0.71, P < 0.001). After 5 years, 61 of 404 participants with available glycated hemoglobin status (15.1%) progressed to diabetes. Chronological age was associated with incident diabetes but was not significant (P = 0.08), after adjusting for BMI and sex. Metabolomic age was significantly related to incident diabetes after controlling for BMI and sex (P < 0.05). Over the 11-year follow-up, 10 participants died owing to non-accidental causes. When metabolomic age and chronological age were included together in the model, metabolomic age (but not chronological age) was associated with mortality, independent of age, sex, and BMI. Among all identifiable metabolites, beta-D-mannosylphosphodecaprenyl and phosphatidylserines were the five leading metabolites associated with mortality. CONCLUSION: We concluded that serum metabolomic profile was associated with incident diabetes as well as mortality over our 11-year study period, which may render it potentially useful in assessing biological aging in humans.

Longitudinal study of vitamin D status among Thai individuals in a sun-abundant country.

Background: Vitamin D deficiency is a major public health problem worldwide, even in countries with abundant sunshine. Understanding the risk factors for vitamin D deficiency is important to inform public health recommendations. We conducted a longitudinal analysis of vitamin D status in Thai individuals to assess changes in vitamin D status over time and identify potential determinants. Study design: This study is a long term prospective cohort study. Methods: Of the 1239 participants who were employees of the Electricity Generating Authority of Thailand, serum 25-hydroxyvitamin D (25(OH)D) levels were measured by liquid chromatography/tandem mass spectrometry from samples collected in 2009 and 2019. Results: There was a significant 14.8% increase in serum total 25(OH)D (P < 0.001) from 2009 to 2019, which resulted from significant increases in both 25(OH)D3 and 25(OH)D2. The epimeric form of 25(OH)D2 also increased significantly, while there was no increase in the epimeric form of 25(OH)D3. A univariate analysis showed significant associations between increased total 25(OH)D and increasing age, male sex, and lower body mass index. After controlling for baseline vitamin D status, multivariate regression analyses found that the direction of association and significance from univariate analyses persisted for total 25(OH)D and 25(OH)D3. However, a univariate association found between female sex and an increase in 25(OH)D2 was not significant in multivariate regression analysis. Conclusions: A long-term trend of improved vitamin D status was found among Thai adult individuals over a 10-year period; however, improvements were less noticeable in women.

Update on vitamin D status in sunshine-abundant Thailand, 2019-2020.

OBJECTIVE: The prevalence of vitamin D deficiency worldwide remains unknown. In the Thai 4th National Health Examination Survey (2008-2009) cohort, ∼45% and 7% of the adult population had serum 25-hydroxyvitamin-D [25(OH)D] levels below the threshold of 75 and 50 nmol/L, respectively. Vitamin D has been a hot topic in the scientific community. The aim of this study was to uncover the current situation regarding vitamin D status in Thailand. METHODS: Participants were 4098 adults ages 10 to 96 y, randomly selected from the Thai 6th National Health Examination Survey (2019-2020) cohort. Serum 25(OH)D levels were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean ± SE and adjusted odds ratio (95% CI). RESULTS: Mean vitamin D status based on serum 25(OH)D was 88.2 nmol/L and differed by age, sex, residency, and religion. The prevalence of serum 25(OH)D <75 and <50 nmol/L were 31% and 4%, respectively. The prevalence of vitamin D deficiency was lower in individuals who lived in the northeastern part of Thailand or were male. The risk for vitamin D deficiency was lower than that in 2009. In multiple linear regression analysis, female sex, younger age, urbanization, a higher body mass index, Muslim religion, and living in Bangkok or the central region of Thailand were independently associated with lower serum 25(OH)D levels. CONCLUSIONS: The vitamin D status in the Thai population has improved over the past 10 y. This improvement may reflect an increased awareness related to adequate vitamin D status.

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.

Vitamin D epimers are associated with circulating haemoglobin levels independently of C-reactive protein.

Vitamin D deficiency has been shown to be associated with anaemia. Circulating 25(OH)D consists of both epimeric and nonepimeric forms. However, the relative roles of epimeric and nonepimeric vitamin D in regulating anaemia and haemoglobin levels remain unknown. Therefore, in this study, we examined the effect of vitamin D, including its epimers, on haemoglobin levels, independently of its effect on circulating high-sensitivity C-reactive protein (hsCRP). This was a cross-sectional study of 1655 subjects from a long-term follow-up cohort at the Electricity Generating Authority of Thailand. Venous blood sample were collected for determination of vitamin D [25(OH)D2, 25(OH)D3, 3'-epi-25(OH)D2, and 3'-epi-25(OH)D3], haemoglobin, and hsCRP levels. Data are presented as mean ± standard deviation. Age, sex, and body mass index (BMI) were significantly associated with circulating haemoglobin levels, while no association was found between total serum 25(OH)D and haemoglobin levels. However, when total 25(OH)D was separated into 3'-epimeric and non-3'-epimeric forms, 3'-epi-25(OH)D was significantly associated with haemoglobin levels, independently of age, sex, and BMI (P < 0.01). No association was found between non-3'-epi-25(OH)D and haemoglobin. When hsCRP was added to the model, the effect 3'-epi-25(OH)D on haemoglobin levels remained significant (P < 0.01). In conclusion, vitamin D epimers are associated with circulating haemoglobin levels, which supports the role of vitamin D in red blood cell and iron physiology.

A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men.

OBJECTIVE: Bone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men. METHODS: This cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men. RESULTS: The mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS. CONCLUSION: In older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.

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.

Postoperative Copeptin as a Biomarker for Development of Diabetes Insipidus Following Hypothalamic-Pituitary Surgery.

OBJECTIVE: Copeptin is a surrogate marker of arginine vasopressin release with better stability and simplicity of measurement. Postoperative copeptin levels may guide clinicians in stratifying patients who need close monitoring of fluid balance. The objective is to determine whether copeptin is a predictive marker of postoperative diabetes insipidus (DI). METHODS: This is a prospective diagnostic study. Patients who underwent neurosurgical intervention of the sellar-suprasellar regions were recruited. Serum copeptin levels were measured before and after surgery, within 24 hours. Logistic regression analysis and diagnostic performance measures were calculated to determine the relationship between postoperative copeptin levels and DI. RESULTS: Of 82 patients, 26 (31.7%) developed postoperative DI, with 7 patients (8.5%) having permanent DI. The samples for copeptin measurement were taken at 13 ± 2.1 hours postoperatively. From the receiver operating characteristic analysis, low postoperative copeptin levels (<2.5 pmol/L) demonstrated an acceptable ability to predict DI (area under the curve, 0.72; 95% CI, 0.60-0.84). Discriminative power was stronger in the permanent DI group (area under the curve, 0.82; 95% CI, 0.64-1.00). Postoperative copeptin levels <2.5 pmol/L were associated with DI (specificity > 91%). However, postoperative copeptin levels >20 pmol/L were rarely associated with DI, with a negative predictive value of 100%. CONCLUSIONS: In patients undergoing sellar-suprasellar interventions, low postoperative copeptin levels within the first postoperative day predict postoperative DI, whereas high levels exclude it. Copeptin measurement should be applied in the clinical practice of postoperative care in patients following hypothalamic-pituitary surgery. This study may expand the potential use of copeptin, including in the Asian population.

Sleep variability, 6-sulfatoxymelatonin, and diabetic retinopathy.

PURPOSE: Recent evidence suggests that diabetic retinopathy (DR) is associated with abnormal melatonin regulation, possibly related to dysfunction of the melanopsin-expressing intrinsically photosensitive retinal ganglion cells. This study explored melatonin regulation in type 2 diabetes (T2D) patients with DR and its relation to sleep and circadian functioning. METHODS: Thirty-five participants (10 non-diabetic controls, 10 T2D without DR, and 15 T2D with DR) were recruited. Overnight urine 6-sulfatoxymelatonin (aMT6s) and objective sleep and wrist activity (7-day actigraphy) were obtained. RESULTS: After adjusting for covariates, having T2D with DR was significantly associated with lower urinary aMT6s (ß = - 1.369, p = 0.004) compared with controls, while having T2D without DR was not (p = 0.418). T2D patients with DR reported poorer sleep quality (p = 0.014) and had greater variability of sleep duration (p = 0.017) than others, while no differences were found in sleep duration, efficiency, and rest-activity rhythm. After adjusting for covariates, lower nocturnal aMT6s was significantly associated with greater sleep variability. CONCLUSION: T2D patients with DR exhibited low overnight production of aMT6s which likely contributed to sleep irregularities possibly due to weak circadian signaling. Whether or not melatonin supplementation could improve health in T2D patients with DR remains to be explored.

Global 11 Beta-Hydroxysteroid Dehydrogenase Activity Assessed by the Circulating Cortisol to Cortisone Ratio is Associated with Features of Metabolic Syndrome.

Background: 11 Beta-hydroxysteroid dehydrogenases (11HSDs) are enzymes involved in the interconversion of cortisol and cortisone. There are two isoenzymes of 11HSD, 11HSD1 and 11HSD2. A causative role of 11HSD, particularly 11HSD1, in metabolic syndrome is well established in experimental animals. However, its role in human metabolic syndrome is less clear. We examined the influence of global 11HSD activity on metabolic syndrome in the general population, using the circulating cortisol:cortisone ratio as an index of global 11HSD activity. Methods: A subsample of 269 sera randomly selected from the Thai National Health Examination Survey IV samples was analyzed for serum cortisol and cortisone levels by liquid chromatography-tandem mass spectrometry. Results: There was no association between serum cortisol and age. However, circulating cortisone was negatively correlated with age (r = -0.12, P < 0.001), and the serum cortisol:cortisone ratio was positively associated with age (r = 0.03, P < 0.001). No association was found between serum cortisol:cortisone ratio and body mass index (BMI) or serum lipids. Multivariate analyses showed that the serum cortisol:cortisone ratio was associated with high blood pressure (P < 0.05) independent of age, BMI, and sex. In subjects without hypertension, the serum cortisol to cortisone ratio was associated with mean systolic blood pressure after controlling for age, BMI, and sex. The cortisol:cortisone ratio was not significantly different between subjects with and without diabetes. After excluding the 16 subjects with diabetes, it was found that the serum cortisol:cortisone ratio was positively associated with fasting plasma glucose independent of age, BMI, and sex (P < 0.01). Conclusions: The global index of 11HSD activity, assessed by the circulating cortisol:cortisone ratio, was related to high blood pressure and fasting plasma glucose and may serve as a proxy to global 11HSD activity.

Independent and Opposite Associations Between Branched-Chain Amino Acids and Lysophosphatidylcholines With Incident Diabetes in Thais.

Branched-chain amino acids (BCAAs) and lysophosphatidylcholines (LPCs) have been reported to be associated with diabetes. The purpose of the present study was to investigate the relative contributions of BCAAs and LPCs to the progression of prediabetes to diabetes using a targeted metabolomic approach. This study was part of a health survey of employees of the Electricity Generating Authority of Thailand (n = 79; nine females and 70 males). A targeted metabolomics analysis was performed using an AbsoluteIDQ® p180 kit, flow injection analysis, and liquid chromatography-tandem mass spectrometry. The highest variable importance in projection (VIP) scores for the progression to diabetes of the amino acids and phospholipids were associated with isoleucine and LPC acyl C28:1, respectively. Using logistic regression analysis, we found that high baseline isoleucine concentration was associated with a higher incidence of diabetes, while high LPC acyl 28:1 was associated with a lower incidence. Isoleucine and LPC acyl 28:1 were independently associated with incident diabetes in a model that also included conventional risk factors for diabetes (baseline fasting plasma glucose (FPG), age, sex, and body mass index (BMI)). In addition, isoleucine and LPC acyl 28:1 were independently associated with serum HbA1c 5 years later in a robust regression model that also included baseline FPG, age, sex, and BMI. Isoleucine, LPC acyl 28:1, age, and FPG were significantly associated with HbA1c at this time. In conclusion, these results provide evidence that isoleucine and LPC acyl C28:1 have respective positive and negative independent associations with incident diabetes.

The differences in the relationship between obstructive sleep apnea severity and trabecular bone score in men and women with type 2 diabetes.

AIMS: Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) may adversely affect bone. Gender is a well-established factor influencing bone health. We investigated the impact of OSA on bone mineral density (BMD) and trabecular bone score (TBS) in T2DM. METHODS: Eighty-one T2DM patients [33 men and 48 women] participated. OSA was diagnosed using an overnight monitor, with its severity assessed by an apnea hypopnia index (pAHI). The measurements of hypoxia, including the percentage of total sleep time in which oxygen saturation remains below 90% (pT90), the oxygen desaturation index (pODI) and minimum O2 (min O2), were reported. Lumbar spine (L1-4) and femoral neck (FN) BMD were measured using dual-energy X-ray absorptiometry (DXA). TBS was computed from DXA images. RESULTS: Sixty-five patients (80.2%) had OSA. pAHI, pT90, pODI and min O2 were not correlated to L1-4 BMD, FN BMD or TBS in all participants by multiple regression analyses adjusting for age, gender and BMI. However, an interaction between gender and pAHI, and gender and pODI were significantly associated with TBS (b = 0.003, p = 0.034 and b = 0.004, p = 0.046, respectively). We therefore reassessed an association between pAHI or pODI and TBS separately between men and women. After adjusting for age and BMI, more severe OSA (higher pAHI) and higher pODI significantly associated with lower TBS (b = -0.002, p = 0.034 and b = -0.003, p = 0.021, respectively) in men. On the other hand, higher pAHI non-significantly associated with better trabecular microarchitecture as indicated by higher TBS (b = 0.002, p = 0.059) in women. When considered only postmenopausal (n = 33), higher pAHI and higher pODI were significantly associated with higher TBS (b = 0.004, p = 0.003 and b = 0.004, p = 0.008, respectively). CONCLUSIONS: In T2DM patients, there is a complex interrelationship among OSA severity, gender and TBS. More severe OSA predicted lower TBS in men, but predicted higher TBS in postmenopausal women.

Thyroid function is associated with body mass index and fasting plasma glucose in Thai euthyroid population.

AIMS: Several population-based studies found the associations between body mass index and thyroid function within the normal range. Furthermore, these thyroid functions are related with insulin resistance and plasma glucose levels. This study aimed to investigate the associations between thyroid functions and metabolic parameters in Thai euthyroid population. METHODS: Participants from the Thai National Thai Health Examination Survey were randomly measured for TSH, FT4, anti-thyroperoxidase, and anti-thyroglobulin. Euthyroidism was defined by TSH 0.27-4.20 mIU/L and FT4 0.93-1.71 ng/dL. RESULTS: A total of 2242 euthyroid participants were included. Fifty-one percent were female. Mean age, fasting plasma glucose, and body mass index were 55 ±â€¯21 years, 93 ±â€¯29 mg/dL, and 23.4 ±â€¯4.6 kg/m2, respectively. Multivariate regression analysis after age and sex adjustment showed a negative association of serum FT4 with body mass index (ß = -0.070, p = 0.001) and the relationship was still significant after subjects with positive anti-thyroperoxidase were excluded (ß = -0.068, p = 0.003). In contrast, serum TSH was positively associated with body mass index (ß = 0.052, p = 0.012). Moreover, serum FT4 was positively associated with fasting plasma glucose levels (ß = 0.097, p < 0.001). CONCLUSIONS: Small variations of serum TSH and FT4 within the reference range may contribute to the differences in metabolic indexes such as body mass index and fasting plasma glucose.

Seroprevalence of anti--Pythium insidiosum antibodies in the Thai population.

Pythiosis is a life-threatening disease of humans and other animals in tropical and subtropical countries. The causative agent is Pythium insidiosum. Diagnosis of pythiosis can be missed due to the lack of awareness in the medical community. Treatment of the disease is difficult and challenging. Most pythiosis patients end up losing an infected organ (i.e., eye or leg), and many die from uncontrolled infection. In 2006, the largest series of human cases of pythiosis (∼100) was reported from Thailand, highlighting the nationwide distribution of this high morbidity and mortality disease. The global distribution of P. insidiosum is demonstrated by its detection in several regions around the world. Epidemiological studies of exposure to the pathogen in the general population are lacking. Here we used a combination of two established diagnostic tools (i.e., ELISA and Western blot) to explore the seroprevalence of anti-P. insidiosum antibodies in 2641 individuals, aged ≥ 15 years, sampled from Thailand. Four individuals were identified with anti-P. insidiosum antibodies in their sera, thus providing a statistically-estimated prevalence of ∼7 in 10000 or ∼32000 in the entire Thai population. The detection of the anti-P. insidiosum antibodies in healthy people with no history of pythiosis suggests that subclinical infections can occur. Taking into account the seroprevalence of anti-P. insidiosum antibodies, the global distribution of the organism, the nationwide distribution of patients, and the high morbidity and mortality of the disease, awareness of pythiosis should be raised as a public health concern in Thailand and other countries.

Lack of associations between thyroid function and obstructive sleep apnea severity in adults with prediabetes and diabetes mellitus.

PURPOSE: Hypothyroidism is associated with a high frequency of obstructive sleep apnea (OSA). However, the prevalence of OSA in hypothyroid patients is not different from the general population in many reports. The importance of thyroid function screening in sleep-disordered breathing is still controversial. This study aimed to explore the association between thyroid dysfunction and OSA in the adults with prediabetes or diabetes mellitus type 2, who have very high prevalence of OSA. METHODS: OSA was assessed using an in-home monitoring device, WatchPAT200. OSA severity was measured using apnea-hypopnea index (AHI), oxygen desaturation index (ODI), minimum oxygen saturation (minO2), and time spent under oxygen saturation < 90% (T90). Patients with pre-existing thyroid dysfunction were excluded. RESULTS: Participants included 70 men and 118 women with mean age 52.8 ± 10.9 years and body mass index 28.2 ± 4.9 kg/m2. One hundred forty participants (75%) had OSA, with a median AHI of 10.1 (interquartile range 4.8, 18.3). The percentage of positive thyroid autoantibody (thyroperoxidase and thyroglobulin antibody) was similar among the subjects with and without OSA. There was no correlation between the levels of thyroid function (TSH, FT3, FT4, TSH/FT3, and TSH/FT4 ratio) and the severity indices of OSA (AHI, ODI, minO2, and T90). CONCLUSIONS: These data do not support universal screening for thyroid dysfunction in OSA patients with diabetes or prediabetes.

More evening preference is positively associated with systemic inflammation in prediabetes and type 2 diabetes patients.

Currently it is not known whether morningness-eveningness preference in non-night shift working population is associated with systemic inflammation. This study investigated the relationship between morningness-eveningness and systemic inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP) in 163 non-night shift working patients with abnormal glucose tolerance (86 type 2 diabetes and 77 prediabetes). Morningness-eveningness was assessed by Composite Scale of Morningness, and participants were screened for Obstructive sleep apnea (OSA). Sleep duration, efficiency, and variability were obtained using actigraphy, and depressive symptoms and dietary patterns were also captured. Participants' mean age was 54.7 ± 10.4 years and median hs-CRP was 1.39 (interquartile range 0.82, 3.33) mg/L. More evening preference was significantly associated with higher natural log transformed (ln) hs-CRP (B = -0.051, p = 0.001). Diabetes status, glycemic control, OSA severity, sleep duration, caloric consumption and timing were not related to hs-CRP. After adjusting for age, sex, body mass index, depressive symptoms, sleep efficiency, sleep variability, percentage of daily caloric intake from protein, and statin use, more evening preference was independently associated with higher ln hs-CRP (B = -0.032, p = 0.014). In summary, in non-night shift working patients with abnormal glucose tolerance, more evening preference was independently associated with higher systemic inflammation. This finding underscore the importance of circadian regulation on cardiovascular health.

Vitamin D insufficiency predicts mortality among older men, but not women: A nationwide retrospective cohort from Thailand.

AIM: Previous studies on the association between low vitamin D level and increased mortality mainly came from high-income countries. The primary objective of the present study was to examine the effect of sex on the association between 25-hydroxyvitamin D2 and D3 and mortality among community-dwelling older people in Thailand. METHODS: A cohort of individuals aged ≥60 years from the Thai 4th National Health Examination Survey carried out in 2008 were followed and linked to a vital registry in 2015. Data regarding comorbid diseases, physical activity and serum vitamin D were obtained at the baseline assessment. Factors associated with all-cause mortality were determined using Cox proportional hazards models. RESULTS: A total of 1268 participants with a median age of 74.0 years (interquartile range 67.0-81.0) were included. The prevalence of vitamin D insufficiency was 24.5% and 43.9% in men and women, respectively. Vitamin D insufficiency was significantly associated with all-cause mortality only among men (adjusted HR 1.77, 95% CI 1.25-2.51), but not women. Analysis of 25-hydroxyvitamin D3 divided into tertiles also showed an association with an adjusted HR of 1.83 (95% CI 1.23-2.72) for the lowest tertile in men. Diabetes was an effect modifier for low serum vitamin D and male sex, with HR 3.34 (95% CI 1.76-6.33, P < 0.001) in diabetic men with vitamin D insufficiency. CONCLUSIONS: Low serum vitamin D is an independent risk factor for increased mortality in community-dwelling Thai older men. Further randomized controlled study to investigate the benefit of vitamin D3 supplementation in older persons, particularly men, is warranted. Geriatr Gerontol Int 2018; 18: 1585-1590.

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 Association between Daytime Napping Characteristics and Bone Mineral Density in Elderly Thai Women without Osteoporosis.

Low bone mass is more prevalent with increasing age. Studies have found associations between sleep duration, sleep quality and obstructive sleep apnea and bone mineral density (BMD). However, less is known about the relationship between daytime napping and BMD. We aimed to investigate the association between daytime napping and BMD in elderly Thai women. Demographic data, lifestyle information and sleep characteristics were obtained by interviewing 387 elderly women. Weight and height were measured. Serum 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay. BMD was measured by dual-energy X-ray absorptiometry (DXA). Higher BMI and having type 2 diabetes (T2DM) were correlated with higher lumbar spine 2-4 (L2-4) BMD, while younger age, higher BMI and higher serum 25(OH)D level were correlated with higher femoral neck (FN) and total hip (TH) BMD. After adjusting for age, age at menopause, BMI, 25(OH)D level and T2DM, a higher frequency of weekly daytime napping was associated with lower FN and TH BMD but not at L2-4 BMD. Additionally, longer daytime napping duration was negatively associated with BMD at TH. In summary higher frequency and longer duration of daytime napping are associated with lower femoral BMD in elderly women. Mechanisms underlying these associations should be further explored.