Hataikarn Nimitphong

Vitamin D status and sun exposure in southeast Asia

Vitamin D deficiency is more common in South Asia and Southeast Asia than is appreciated. Most studies defined 25-hydroxyvitamin D levels [25(OH)D] levels of less than 50 nmol/L (20 ng/mL) as vitamin D deficiency. With this cut-off level, the prevalence of vitamin D deficiency was about 70% or higher in South Asia and varied from 6–70% in Southeast Asia. The determinants for the variation of vitamin D status are skin pigmentation, aging, the sun protection behaviors such as application of a sunscreen, religious, lifestyle and nutritional differences. Advanced age is a known risk factor for vitamin D deficiency. Interestingly, elderly in countries such as Korea and Thailand, had higher 25(OH)D levels when compared with young people. This widespread vitamin D deficiency problem especially in the young generation is an urgent health issue that needs to be remedied.

Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D3 or D2supplementation

BackgroundIt is not known whether genetic variation in the vitamin D binding protein (DBP) influences 25-hydroxyvitamin D levels [25(OH)D] after vitamin D supplementation. We aimed to investigate the changes of total 25(OH)D, 25(OH)D3 and 25(OH)D2 in a Thai cohort, according to type of vitamin D supplement (vitamin D3 or D2) and DBP genotype, after receiving vitamin D3 or D2 for 3 months.MethodsThirty-nine healthy subjects completed the study. All subjects received 400 IU of either vitamin D3 or D2, plus a calcium supplement, every day for 3 months. Total serum 25(OH)D, 25(OH)D3 and 25(OH)D2 were measured by LC-MS/MS. Individual genotyping of rs4588 in the DBP gene was performed using real-time PCR.ResultsVitamin D3 supplementation of 400 IU/d increased 25(OH)D3 significantly (+16.2 ± 4.2 nmol/L, p <0.001). Vitamin D2 (400 IU/d) caused increased 25(OH)D2 levels (+22.0 ± 2.11 nmol/L, p <0.001), together with a decrease of 25(OH)D3 (−14.2 ± 2.0 nmol/L, p <0.001). At 3 month, subjects in vitamin D3 group tended to have higher total 25(OH)D levels than those in vitamin D2 (67.8 ± 3.9 vs. 61.0 ± 3.0 nmol/L; p = 0.08). Subjects were then classified into two subgroups: homozygous for the DBP rs4588 C allele (CC), and the rest (CA or AA). With D3 supplementation, subjects with CA or AA alleles had significantly less increase in 25(OH)D3 and total 25(OH)D when compared with those with the CC allele. However, no difference was found when the supplement was vitamin D2.ConclusionGenetic variation in DBP (rs4588 SNP) influences responsiveness to vitamin D3 but not vitamin D2.

Circulating Sclerostin and Irisin Are Related and Interact with Gender to Influence Adiposity in Adults with Prediabetes

Objectives. Sclerostin, an osteocyte-specific protein, has been found to be related to adiposity and glucose metabolism. Irisin, a myokine, can affect browning of white fat and influence glucose and energy homeostasis. Taken together, this suggests a probable network among fat, bone, and muscle that may influence health outcomes. The aims of this study were to investigate the relationship of circulating sclerostin and irisin and their association with adiposity (assessed by body mass index (BMI)). Materials/Methods. A cross-sectional study included 98 adults with impaired fasting glucose and/or impaired glucose tolerance. 75 gm OGTT was performed in all subjects. Fasting plasma samples were obtained for glycated hemoglobin, calcium, creatinine, serum sclerostin and irisin. Results. Circulating irisin and sclerostin were highly correlated (r = −0.4; P < 0.001). After controlling for age, gender, and BMI, irisin was significantly related to sclerostin (P < 0.001). Multivariate linear regression analysis demonstrated that circulating sclerostin (β = −0.45; P < 0.05) and irisin (β = −0.46; P < 0.05) were negatively associated with BMI, independent of age in males. In females, no relationship of sclerostin or irisin to BMI was found. Conclusions. Circulating irisin and sclerostin are highly related. Interventions targeting irisin could affect sclerostin and vice versa.

Relationships among sleep timing, sleep duration and glycemic control in Type 2 diabetes in Thailand.

There is evidence that the sleep and circadian systems play a role in glucose metabolism. In addition to physiological factors, sleep is also affected by behavioral, environmental, cultural and social factors. In this study, we examined whether morning or evening preference, sleep timing and sleep duration are associated with glycemic control in patients with type 2 diabetes residing in Thailand. Two hundred and ten type 2 diabetes patients who were not shift workers completed an interview and questionnaires to collect information on diabetes history, habitual sleep duration and sleep timing. Chronotype, an individual’s tendency for being a “morning” or “evening” person, was assessed using the Composite Score of Morningness (CSM), which reflects an individual’s subjective preference for activities in the morning or evening, as well as mid-sleep time on weekend nights (MSF), which reflects their actual sleep behavior. Most recent hemoglobin A1c (HbA1c) values were retrieved from medical records. Evening preference (as indicated by lower CSM), later bedtime on weekends, and shorter sleep duration correlated with higher HbA1c (r = −0.18, p = 0.01; r = 0.17, p = 0.01 and r = −0.17, p = 0.01, respectively), while there was no association between MSF or wake up time and glycemic control. In addition, later bedtime on weekends significantly correlated with shorter sleep duration (r = −0.34, p < 0.001). Hierarchical regression analyses adjusting for age, sex, body mass index, insulin use and diabetes duration revealed that later bedtime on weekends was significantly associated with poorer glycemic control (B = 0.018, p = 0.02), while CSM was not. Mediation analysis revealed that this association was fully mediated by sleep duration. In summary, later bedtime on weekends was associated with shorter sleep duration and poorer glycemic control in patients with type 2 diabetes. It is likely that patients with later weekend bedtimes curtail their sleep by waking up earlier. Exploring the potential reasons for this phenomenon (e.g. cultural influences, metropolitan lifestyle, environmental factors, family and social obligations) specific to a Thai population may help identify behavioral modifications (i.e. earlier bedtime and/or sleep duration extension) that could possibly lead to improved glycemic control in this population.

Hepatic fat content is a determinant of postprandial triglyceride levels in type 2 diabetes mellitus patients with normal fasting triglyceride.

Postprandial hypertriglyceridemia is common in type 2 diabetes mellitus (T2D). Significant numbers of T2D patients who have normal fasting triglyceride (TG) have postprandial hypertriglyceridemia. The role of regional adipose tissue and adiponectin on postprandial TG responses in this group of T2D patients is unclear. This study aimed to examine the contribution of regional adipose tissue and adiponectin to the variation of postprandial TG responses in T2D patients who have normal fasting TG levels. Thirty-one Thai T2D patients who had fasting TG<1.7 mmol/L were studied. All were treated with diet control or sulphonylurea and/or metformin. None was treated with lipid-lowering agents. Mixed-meal test was performed after overnight fast. Plasma glucose, insulin, and TG were measured before and 1, 2, 3, and 4 hours after the test. Adiponectin was measured in fasting state. Visceral as well as superficial and deep subcutaneous abdominal adipose tissues were determined by magnetic resonance imaging, and hepatic fat content (HFC) was determined by magnetic resonance spectroscopy. Univariate and multivariate regression analyses of postprandial TG and regional adipose tissue and metabolic parameters were performed. The TG levels before and 1, 2, 3, and 4 hours after the mixed meal were 1.32+/-0.40 (SD), 1.40+/-0.41, 1.59+/-0.40, 1.77+/-0.57, and 1.80+/-0.66 mmol/L, respectively (P<.0001). The area under the curve (AUC) of postprandial TG was positively and significantly correlated with fasting TG (r=0.84, P<.0001) and log.HFC (r=0.456, P=.033) and was inclined to be correlated with log.deep subcutaneous adipose tissue (r=0.38, P=.05) and sex (r=0.326, P=.073). The AUC of postprandial TG was not correlated with age, body mass index, waist circumference, log.superficial subcutaneous adipose tissue, log.visceral adipose tissue, hemoglobin A1c, fasting glucose, AUC.glucose, log.fasting insulin, log.AUC.insulin, log.homeostasis model assessment%B, log.homeostasis model assessment of insulin resistance, and adiponectin. Only fasting TG (beta=.815, P<.0001) and log.HFC (beta=.249, P=.035) predicted AUC of postprandial TG in regression model (adjusted R2=0.84, P<.0001). In conclusion, in T2D patients with normal fasting TG, the increase of postprandial TG levels is directly determined by fasting TG level and the amount of hepatic fat.

Vitamin D Binding Protein Gene Polymorphism as a Risk Factor for Vitamin D Deficiency in Thais

OBJECTIVE Vitamin D deficiency is related to increased risks for a number of diseases. To date, at least 3 candidate genes, vitamin D binding protein (VDBP) gene (GC), 25-hydroxylase (CYP2R1), and 7-dehydrocholesterol reductase/NAD synthetase 1 (DHCR7/NADSYN1), have been associated with serum 25-hydroxyvitamin D (25[OH]D) levels, but their influences on the prevalence of vitamin D deficiency in relation to other known risk factors have not been clearly defined. METHODS The study assessed 4,476 individuals aged 14 to 93 years from the Thailand 4th National Health Examination Survey (2008-2009) and the Electricity Generating Authority of Thailand (EGAT) (2008) cohorts. The GC rs2282679 polymorphism on chromosome 4q12-q13 was genotyped by real-time polymerase chain reaction (PCR). Serum 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Vitamin D deficiency was defined as a 25(OH)D concentration <20 ng/mL. RESULTS Data were expressed as mean ± SD. There were 2,747 (61.4%) males and 1,729 (38.6%) females in the study, with an average body mass index (BMI) of 23.7 ± 4.2 kg/m2 and a mean total 25(OH)D of 28.9 ± 9.0 ng/mL. Serum 25(OH)D levels decreased progressively with the presence of the C allele. Using multiple logistic regression analysis, vitamin D deficiency was significantly associated with the GC rs2282679 genotype (odds ratio [OR] per C allele 1.80, 95% confidence interval CI 1.57-2.01), independent of established risk factors for vitamin D deficiency including age, sex, and BMI. CONCLUSION A specific GC gene polymorphism is associated with lower 25(OH)D levels independent of age, sex, and adiposity in Thai subjects.

Relationship of vitamin D status and bone mass according to vitamin D-binding protein genotypes

BackgroundVitamin D-binding protein (DBP) may alter the biological activity of total 25-hydroxyvitamin D [25(OH)D]; this could influence on the effects of vitamin D in relation to bone mineral density (BMD) and fractures. Emerging data suggest that fetuin-A may be involved in bone metabolism. We aimed to investigate the influence of DBP gene polymorphism on the relationship of vitamin D status and fetuin-A levels to BMD and bone markers.MethodsThis cross-sectional study was part of a health survey of employees of the Electricity Generating Authority of Thailand (1,734 healthy subjects, 72% male). Fasting blood samples were assayed for 25(OH)D, fetuin-A, N-terminal propeptides of type 1 procollagen (P1NP), C-terminal cross-linking telopeptides of type I collagen (CTx-I), and DBP rs2282679 genotypes. L1–L4 lumbar spine and femoral BMD were measured using dual-energy X-ray absorptiometry.ResultsThe DBP rs2282679 genotype distribution conformed to the Hardy–Weinberg equilibrium. There were no correlations between 25(OH)D levels and BMD and bone markers. But a trend of positive correlation was observed for the DBP genotypes with total hip BMD, and for the interaction between 25(OH)D and DBP genotypes with BMD at all femoral sites. We further analyzed data according to DBP genotypes. Only in subjects with the AA (common) genotype, 25(OH)D levels were positively related to BMD and bone markers, while fetuin-A was negatively related to total hip BMD, independently of age, gender and BMI.ConclusionsThe interaction between vitamin D status, as measured by circulating 25(OH)D and DBP rs2282679 genotypes, modified the association between 25(OH)D and BMD and bone markers. Differences in DBP genotypes additionally influenced the correlation of fetuin-A levels with femoral BMD.

Associations between nocturnal urinary 6-sulfatoxymelatonin, obstructive sleep apnea severity and glycemic control in type 2 diabetes.

ABSTRACT Reduced nocturnal secretion of melatonin, a pineal hormone under circadian control, and obstructive sleep apnea have been both identified as risk factors for the development of type 2 diabetes mellitus. Whether they interact to impact glycemic control in patients with existing type 2 diabetes is not known. Therefore, this study explores the relationships between obstructive sleep apnea, melatonin and glycemic control in type 2 diabetes. As diabetic retinopathy may affect melatonin secretion, we also explore the relationship between retinopathy, melatonin and glycemic control. Fifty-six non-shift workers with type 2 diabetes, who were not using beta-blockers, participated. Most recent hemoglobin A1c (HbA1c) levels and the results of ophthalmologic examinations were obtained from medical records. Obstructive sleep apnea was diagnosed using an ambulatory device. Sleep duration and fragmentation were recorded by 7-day wrist actigraphy. The urinary 6-sulfatoxymelatonin/creatinine ratio, an indicator of nocturnal melatonin secretion, was measured in an overnight urine sample. Mediation analyses were applied to explore whether low nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio could be a causal link between increasing obstructive sleep apnea severity [as measured by an Apnea Hypopnea Index (AHI)] and poorer glycemic control, and between the presence of retinopathy and glycemic control. AHI and HbA1c were log-scale (ln) transformed. Obstructive sleep apnea was found in 76.8%, and 25.5% had diabetic retinopathy. The median (interquartile range) of urinary 6-sulfatoxymelatonin/creatinine ratio was 12.3 (6.0, 20.1) ng/mg. Higher lnHbA1c significantly correlated with lower 6-sulfatoxymelatonin/creatinine ratio (p = 0.04) but was not directly associated with OSA severity. More severe obstructive sleep apnea (lnAHI, p = 0.01), longer diabetes duration (p = 0.02), retinopathy (p = 0.01) and insulin use (p = 0.03) correlated with lower urinary 6-sulfatoxymelatonin/creatinine ratio, while habitual sleep duration and fragmentation did not. A mediation analysis revealed that lnAHI negatively correlated with urinary 6-sulfatoxymelatonin/creatinine ratio (coefficient = −2.413, p = 0.03), and urinary 6-sulfatoxymelatonin/creatinine negatively associated with lnHbA1c (coefficient = −0.005, p = 0.02), after adjusting for covariates. Mediation analysis indicated that the effect of lnAHI on lnHbA1c was indirectly mediated by urinary 6-sulfatoxymelatonin/creatinine ratio (B = 0.013, 95% CI: 0.0006, 0.0505). In addition, having retinopathy was significantly associated with reduced nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio, and an increase in HbA1c by 1.013% of its original value (B = −0.013, 95% CI: −0.038, −0.005). In conclusion, the presence and severity of obstructive sleep apnea as well as the presence of diabetic retinopathy were associated with lower nocturnal melatonin secretion, with an indirect adverse effect on glycemic control. Intervention studies are needed to determine whether melatonin supplementation may be beneficial in type 2 diabetes patients with obstructive sleep apnea.

Prevalence of dyslipidemia and goal attainment after initiating lipid-modifying therapy: a Thai multicenter study.

Previous studies focused on attaining low-density lipoprotein cholesterol (LDL-C) goals after lipid-modifying therapy (LMT), but data on achieving normal levels of triglyceride and high-density lipoprotein cholesterol (HDL-C) are limited. We reviewed medical records of patients initiated on LMT. High risk was defined as patients with coronary heart disease, diabetes, or 10-year Framingham risk >20%. Among 806 patients enrolled, 429 were at high risk. Prior to initiation of LMT, 66%, 35%, and 44% overall and 69%, 35%, and 45% in the high-risk group had elevated LDL-C, elevated triglyceride, and low HDL-C, respectively. After 12 months of LMT, 21%, 32%, and 39% overall and 26%, 25%, and 43% in the high-risk group still had elevated LDL-C, elevated triglyceride, and low HDL-C, respectively. Approximately 1 of 5 patients continued to experience elevated LDL-C coupled with elevated triglyceride and/or low HDL-C. In conclusion, a substantial proportion of patients initiated on LMT continued to have lipid abnormalities.

Night-shift work is associated with poorer glycaemic control in patients with type 2 diabetes

The circadian system plays a role in regulating metabolism. Night‐shift work, a form of circadian misalignment, is associated with increased type 2 diabetes risk. This study aimed to determine if night‐shift workers with type 2 diabetes experience poorer glycaemic control than non‐shift workers. Patients with type 2 diabetes (104 unemployed, 85 day workers and 60 night‐shift workers) participated. Sleep duration, sleep quality, morningness–eveningness preference, depressive symptoms and dietary intake were assessed using standardized questionnaires. Haemoglobin A1c levels were measured. Night‐shift workers had significantly higher haemoglobin A1c levels compared with others, while there were no differences between day workers and unemployed participants (median 7.86% versus 7.24% versus 7.09%, respectively). Additionally, night‐shift workers were younger, had a higher body mass index, and consumed more daily calories than others. Among night‐shift workers, there were no significant differences in haemoglobin A1c levels between those performing rotating versus non‐rotating shifts (P = 0.856), or those with clockwise versus counterclockwise shift rotation (P = 0.833). After adjusting for age, body mass index, insulin use, sleep duration, morningness–eveningness preference and percentage of daily intake from carbohydrates, night‐shift work, compared with day work, was associated with significantly higher haemoglobin A1c (B = 0.059, P = 0.044), while there were no differences between unemployed participants and day workers (B = 0.016, P = 0.572). In summary, night‐shift work is associated with poorer glycaemic control in patients with type 2 diabetes.