Metabolomic profile associated with obstructive sleep apnoea severity in obese pregnant women with gestational diabetes mellitus: A pilot study.

Obstructive sleep apnoea (OSA) is prevalent in obese women with gestational diabetes mellitus (GDM). The present pilot study explored associations between OSA severity and metabolites in women with GDM. A total of 81 obese women with diet-controlled GDM had OSA assessment (median gestational age [GA] 29 weeks). The metabolic profile was assayed from fasting serum samples via liquid chromatography-mass spectrometry (LC-MS) using an untargeted approach. Metabolites were extracted and subjected to an Agilent 1,290 UPLC coupled to an Agilent 6,545 quadrupole time-of-flight (Q-TOF) MS. Data were acquired using electrospray ionisation in positive and negative ion modes. The raw LC-MS data were processed using the OpenMS toolkit to detect and quantify features, and these features were annotated using the Human Metabolite Database. The feature data were compared with OSA status, apnea-hypopnea index (AHI), body mass index (BMI) and GA using "limma" in R. Correlation analyses of the continuous covariates were performed using Kendall's Tau test. The p values were adjusted for multiple testing using the Benjamini-Hochberg false discovery rate correction. A total of 42 women (51.8%) had OSA, with a median AHI of 9.1 events/hr. There were no significant differences in metabolomics profiles between those with and without OSA. However, differential analyses modelling in GA and BMI found 12 features that significantly associated with the AHI. These features could be annotated to oestradiols, lysophospholipids, and fatty acids, with higher levels related to higher AHI. Metabolites including oestradiols and phospholipids may be involved in pathogenesis of OSA in pregnant women with GDM. A targeted approach may help elucidate our understanding of their role in OSA in this population.

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.

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.

Eveningness Is Associated With Greater Depressive Symptoms in Type 2 Diabetes Patients: A Study in Two Different Ethnic Cohorts.

BACKGROUND: Eveningness is associated with greater depressive symptoms in the general population. Depression and type 2 diabetes (T2D) commonly coexist. We aimed to explore the association between morningness-eveningness and depressive symptoms in T2D patients in the United States and in Thailand. PARTICIPANTS: T2D patients (n = 182) from an endocrinology clinic in Chicago, Illinois, and six hospitals in Thailand (n = 251) were enrolled. METHODS: Diabetes history was collected. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression scale (CES-D). The Chicago cohort completed the Morningness-Eveningness Questionnaire (MEQ) and the Thai cohort completed the Composite Scale of Morningness (CSM). Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). RESULTS: The mean (SD) CES-D score was 13.7 (9.1) in Chicago and 11.9 (6.4) in Thailand. In Chicago participants, after adjusting for age, sex, ethnicity, hemoglobin A1c, insulin use, and PSQI score, greater eveningness (lower MEQ scores) was associated with higher CESD scores (B = -0.117, p = 0.048). In Thai participants, after adjusting for age, sex, and PSQI score, eveningness (lower CSM score) was associated with higher CES-D score (B = -0.147, p = 0.016). In both cohorts, however, eveningness was not independently associated with the likelihood of being in the at-risk range for clinical depression (CES-D ≥ 16). CONCLUSIONS: Eveningness is independently associated with greater depressive symptoms in T2D in two different ethnic cohorts. The results support the association between individual differences in circadian rhythms and psychological functioning in T2D.

The relationship between sleep and glucagon-like peptide 1 in patients with abnormal glucose tolerance.

Glucagon-like peptide 1 plays a role in glucose regulation. Sleep disturbances (obstructive sleep apnea, insufficient or poor sleep quality) have been shown to adversely affect glucose metabolism. This study aimed to explore the relationship between sleep and glucagon-like peptide 1 regulation in patients with abnormal glucose tolerance. Seventy-one adults with haemoglobin A1c levels between 5.7% and < 6.5% and no history of diabetes participated. Habitual sleep duration and efficiency were obtained from 7-day actigraphy recordings. Obstructive sleep apnea was assessed using an overnight home monitor. Glucagon-like peptide 1 levels were measured during a 75-g glucose tolerance. The area under the curve of glucagon-like peptide 1 was calculated. The mean age (SD) was 55.1 (8.3) years and median (interquartile range) haemoglobin A1c was 5.97% (5.86, 6.23). There was no relationship between sleep duration or efficiency and fasting or area under the curve glucagon-like peptide 1. Glucagon-like peptide 1 levels did not differ among those sleeping ≤ 5.75, > 5.75-< 6.5 or ≥ 6.5 h per night. Increasing apnea-hypopnea index, an indicator of obstructive sleep apnea severity, correlated with lower area under the curve glucagon-like peptide 1 (B -0.242, P = 0.045), but not with fasting glucagon-like peptide 1 (B -0.213, P = 0.079). After adjusting for sex, haemoglobin A1c and body mass index, increasing apnea-hypopnea index was negatively associated with having area under the curve glucagon-like peptide 1 in the highest quartile (odds ratio 0.581, P = 0.028, 95% CI 0.359, 0.942). This study demonstrated that increasing obstructive sleep apnea severity was associated with lower glucagon-like peptide 1 response to glucose challenge. This could possibly be an additional mechanism by which obstructive sleep apnea affects glucose metabolism. Whether raising glucagon-like peptide 1 levels in patients with abnormal glucose tolerance with more severe obstructive sleep apnea will be beneficial should be explored.

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.

Higher sleep variability is associated with poorer glycaemic control in patients with type 1 diabetes.

Sleep disturbances have been linked to insulin resistance and poor glycaemic control in patients with type 2 diabetes. However, the data are limited in type 1 diabetes. Recently, varying day-to-day sleep schedules, i.e. sleep variability, have been associated with adverse metabolic profile in healthy individuals. This study explored whether sleep variability affects glycaemic control and insulin requirement in type 1 diabetes. Forty-one adult patients with type 1 diabetes wore an actigraphy for 5 nights. Standard deviation of sleep duration, efficiency and mid-sleep time were sleep variability parameters. Sleep apnoea risk and self-reported sleep quality were assessed by the Berlin questionnaire and Pittsburgh Sleep Quality Index. Haemoglobin A1c, diabetes complications and insulin regimen were obtained from medical records. After adjusting for neuropathic symptoms, sleep apnoea risk and poor self-reported sleep quality, higher sleep variability was significantly associated with poorer glycaemic control (standard deviation of sleep duration, B = 0.100, P = 0.004; and standard deviation of mid-sleep time, B = 0.068, P = 0.04). In addition, standard deviations of sleep duration and mid-sleep time were highly correlated, suggesting that participants changed their sleep duration along with sleep timing. After adjusting for covariates, the standard deviation of sleep duration (P = 0.009) and standard deviation of mid-sleep time (P = 0.012) were associated with higher insulin requirement. In summary, higher sleep variability, which likely reflects sleep deprivation alternating with sleep compensation along with shifts in their circadian timing, was associated with poorer glycaemic control and higher insulin requirement in patients with type 1 diabetes. Increased sleep regularity may improve metabolic control in type 1 diabetes.

Shorter sleep duration is associated with poorer glycemic control in type 2 diabetes patients with untreated sleep-disordered breathing.

PURPOSE: The purpose of this study is to explore the impact of sleep duration on glycemic control in type 2 diabetes patients with untreated sleep-disordered breathing (SDB). METHODS: Ninety type 2 diabetes patients participated in the study. SDB was diagnosed using an overnight in-home monitoring device (WatchPAT200). Sleep duration was recorded by wrist actigraphy for 7 days. Medical records were reviewed for hemoglobin A1c (HbA1c) values. RESULTS: Seventy-one patients (78.8 %) were diagnosed with SDB [apnea-hypopnea index (AHI) ≥ 5]. In patients with SDB, there was no significant relationship between AHI and glycemic control. In addition, oxygen desaturation index, minimum oxygen saturation, and time spent below oxygen saturation of 90 % were not significantly correlated with glycemic control. Sleep duration, however, was inversely correlated with HbA1c (r = -0.264, p 0.026). Multiple regression analysis adjusting for age, sex, body mass index, insulin use, diabetes duration, and AHI revealed that sleep duration was significantly associated with HbA1c (p = 0.005). Each hour reduction in sleep duration was associated with a 4.8 % increase in HbA1c of its original value (95 % CI 1.5-8.0). CONCLUSION: In type 2 diabetes patients with untreated SDB, shorter sleep duration was independently associated with poorer glycemic control. Sleep duration optimization may lead to improved glycemic control in this population.

The Effect of Vitamin D Supplementation on Metabolic Phenotypes in Thais with Prediabetes.

OBJECTIVE: To investigate the effects of vitamin D supplement for three months on anthropometric and glucose homeostatic measures in Thai adults with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). MATERIAL AND METHOD: Forty-seven IFG and/or IGT subjects enrolled in the study. Subjects were randomized into three groups, control (n = 18), vitamin D2 (20,000 IU weekly, n = 19) or vitamin D3 (15,000 IU weekly, n = 10). Anthropometric variables were obtained at baseline and at 3-month. Oral glucose tolerance test was performed at baseline and at 3-month. Total serum 25(OH)D, 25(OH)D3, and 25(OH)D2 were measured by LC-MS/MS. Insulin resistance (HOMA-IR) and insulin secretion index (HOMA%B) were calculated by the homeostasis model assessment. RESULTS: The total 25(OH)D levels significantly increased from baseline in both the vitamin D2 and the vitamin D3 groups, while there was no change in the control group. D3 supplementation raised 25(OH)D3 significantly (+13.7 ± 4.9 ng/mL, p < 0.01) while D2 increased 25(OH)D2 levels (+25.9?4.2 ng/mL, p<0.001) but with a decrease in 25(OH)D3 (-13.1?3.1 ng/mL, p<0. 001). Subjects were classified into two groups, i.e., control (n = 18) and D2 or D3 supplementations (n = 29). After three months, waist circumference (WC) significantly decreased in subjects of vitamin D supplementation group. Body weight (BW p = 0.05), systolic blood pressure (SBP, p = 0.05), body mass index (BM, p = 0.06), and HOMA-IR (p = 0.09) also tended to decrease. Subjects with an increase of total 25(OH)D levels > 10 ng/mL (23 of 29 subjects) had significant decrease in HOMA-IR and increase in disposition index. Using robust regression analysis, we found the use of D3 was associated with a larger decrease in WC (coefficient = -3.5, p < 0.001) independent of the change in total 25(OH)D and baseline BMI. No difference between D2 and D3 was observed for other metabolic measures. CONCLUSION: Weekly supplementations of vitamin D2 (20,000 IU) or vitamin D3 (15,000 IU) improve metabolic phenotypes in subjects with prediabetes. D3 supplement may decrease waist circumference more than D2 supplement.

Lean mass inversely predicts plasma glucose levels after oral glucose load independent of insulin secretion or insulin sensitivity in glucose intolerance subjects.

Muscle mass inversely relates to 2 hours glucose levels after oral glucose load in non-diabetic subjects. A study in glucose intolerance subjects has never been performed. We conducted this study to determine the relationship between muscle mass and glucose level after oral glucose load in glucose intolerance subjects. Sixty Thai subjects, 44 drug-naïve, newly diagnosed type 2 diabetes mellitus and 16 impaired glucose tolerance were studied. The 180 min 75 g oral glucose tolerance test was performed. Total body fat and lean mass were measured by dual-energy x-ray absorptiometry. Insulin sensitivity was determined by insulin sensitivity index using model of Matsuda & DeFronzo. The 1st-phase and total insulin secretion were determined from glucose tolerance data. Pearson correlation and linear regression were used for the analysis. Lean mass was inversely correlated with area-under-curves of glucose 0-180 min (r =-0.320; p=0.013). The relationship was significant after adjustment with age and body-mass-index (r =-0.350; p=0.007). Area-under-curves of glucose 0-180 min was correlated with height (r =-0.282; p=0.029), fasting glucose (r =0.742; p<0.0001), log area-under-curves of insulin 0-180 min (r =-0.258; p=0.047) and log 1st-phase insulin secretion (r =-0.518; p<0.0001). By multivariate analysis, fasting glucose (standardized ß=4.54; p<0.001), log 1st-phase insulin secretion (standardized ß=-43.09; p=0.005) and lean mass (standardized ß=-0.003; p=0.011) were the significant parameters predicting area-under-curves of glucose 0-180 min. In conclusion, lean mass inversely predicted glucose levels after oral glucose load independent of insulin secretion and insulin sensitivity in glucose intolerance subjects.

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

BACKGROUND: It 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. METHODS: Thirty-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. RESULTS: Vitamin 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. CONCLUSION: Genetic variation in DBP (rs4588 SNP) influences responsiveness to vitamin D3 but not vitamin D2.

Thai traditional massage increases biochemical markers of bone formation in postmenopausal women: a randomized crossover trial.

BACKGROUND: The effect of massage therapy on bone metabolism in adults has only scarcely been explored. In a randomized crossover trial, we investigated the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover. METHODS: Forty-eight postmenopausal women participated in the study. All volunteers were randomized to a 2-hour session of Thai traditional massage twice a week for 4 weeks and a 4-week control period after a 2-week washout, or vice versa. Twenty-one subjects were allocated to receiving Thai traditional massage first, followed by the control period, while 27 were initially allocated to the control period. RESULTS: Serum P1NP increased significantly after Thai traditional massage (P <0.01), while there was no change in serum osteocalcin or CTX. During the control period, there was no significant change in P1NP, osteocalcin or CTX compared to baseline. When age and height were taken into account, P1NP in postmenopausal women whose ages were in the middle and higher tertiles and whose heights were in the lower and middle tertiles (n = 22) had a 14.8 ± 3.3% increase in P1NP after massage (P <0.001), while no change in P1NP was found in the rest of the women (n = 26). CONCLUSIONS: Thai traditional massage results in an increase in bone formation as assessed by serum P1NP, particularly in postmenopausal women who are older and have a smaller body build. Future studies with larger samples and additional design features are warranted. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01627028.

The association between rest-activity parameters and hemoglobin A1c in patients with prediabetes.

Circadian abnormalities can adversely affect glucose metabolism. This study determined whether behavioral circadian parameters, as assessed by rest-activity rhythm, were predictors of glycemic control in patients with prediabetes. Seventy-nine patients with prediabetes participated. Nonparametric rest-activity rhythm parameters, sleep duration and efficiency were obtained from 7-d actigraphy recordings. Sleep-disordered breathing severity was assessed using a home sleep apnea test. Hemoglobin A1c (HbA1c) was obtained to evaluate glycemic control. The results revealed that shorter sleep duration, lower relative amplitude and higher L5 (average activity of the least active 5-h period) were associated with higher HbA1c, while other sleep variables were not related to HbA1c. Multiple stepwise regression analysis adjusting for age, sex, body mass index and sleep duration revealed that lower relative amplitude, but not L5, was independently associated with higher HbA1c (B = -0.027, p = 0.031). In summary, among patients with prediabetes, an abnormal circadian rhythm was associated with higher HbA1c, implying a greater risk of developing diabetes. These results support the role of circadian rhythmicity in glucose control among those with prediabetes.

The glucose-lowering effect of low-dose diacerein and its responsiveness metabolic markers in uncontrolled diabetes.

OBJECTIVE: Diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, decreases macrophage infiltration in adipose tissue and thus increases insulin sensitivity and signalling. We conducted this study to determine the efficacy of low-dose diacerein in improving glycaemic control in type 2 diabetes mellitus (T2DM) patients with inadequate glycaemic control and to identify the metabolic determinants for such improvement. We randomised 25 T2DM patients with poor glycaemic control, despite being treated with at least three glucose-lowering agents, to receive diacerein 50 mg once-daily (n = 18) or placebo (n = 17) for 12 weeks. Changes in glycated haemoglobin (HbA1c) were evaluated at the 4th and 12th weeks. Metabolic profiling was performed using liquid chromatography electrospray ionisation quadrupole time-of-flight mass spectrometry. RESULTS: HbA1c levels were significantly reduced from baseline in the diacerein group at 12 weeks (- 0.6%, p < 0.05), whereas fasting plasma glucose (FPG) levels were not significantly decreased (- 18.9 mg/dl, p = 0.06). Partial least squares-discriminant analysis demonstrated an association between the serum abundance of threo-isocitric acid (ICA) and HbA1c response in the diacerein group. After adjusting for serum high-sensitivity C-reactive protein, ICA was still significantly related to the change in HbA1c. Retrospective trial registration Current Controlled Trials TCTR20200820004, 20 August 2020.

Implementation of diabetes care and educational program via telemedicine in patients with COVID-19 in home isolation in Thailand: A real-worldexperience.

BACKGROUND: The coronavirus disease (COVID-19) outbreak in Bangkok led to a shortage of hospital capacity, and a home isolation system was set up. We described the process of diabetes self-management education and support (DSMES) and glycemic management via telemedicine, along with outcomes in home-isolated patients with COVID-19 infection. METHODS: A retrospective chart review of glucose values, insulin and corticosteroids use, and outcomes was performed. RESULTS: A volunteer group of 21 endocrinologists and 21 diabetes educators/nurses formed the consultation team. Patients with diabetes or at high-risk of diabetes and receiving corticosteroids were referred by primary volunteer physicians. Glucometers and related supplies, and insulin were donated, and delivered via same-day delivery services. A chat group of an individual patient/their caregiver, diabetes educator, endocrinologist, and primary physician was formed (majority via LINE® platform) to assess the patient's clinical status and need. Real-time virtual DSMES sessions were performed and treatments were adjusted via smartphone application or telephone. There were 119 patients (1,398 service days), mean (SD) age 62.0 (13.6) years, 85.7% had a history of type 2 diabetes, and 84.0% received corticosteroids. Insulin was used in 88 patients; 69 of whom were insulin-naïve. During the first 10 days, there were 2,454 glucose values. The mean glucose level on day 1 was 280.6 (122.3) mg/dL, and declined to 167.7 (43.4) mg/dL on day 10. Hypoglycemia occurred in 1.4% of the values. A majority of patients (79.5%) recovered at home. CONCLUSION: Diabetes care and DSMES delivered via telemedicine to patients on home isolation during COVID-19 pandemic was safe and effective.

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.

Effects of an intensive lifestyle intervention and the role of sleep in people living with HIV and prediabetes: a pilot and feasibility study.

OBJECTIVES: Prediabetes is prevalent in people living with HIV (PLWH). Insufficient and irregular sleep are linked to abnormal glucose metabolism. This study aimed to investigate the differences in sleep characteristics between PLWH with and without prediabetes, determine the acceptability/feasibility and effects of a pilot six-month intensive lifestyle intervention (ILI) program on glucose metabolism in those with prediabetes, and determine how sleep modulates these effects. RESULTS: Thirty-nine PLWH (20 normoglycemia and 19 prediabetes) participated. There were no differences in sleep characteristics between individuals with normoglycemia and prediabetes. Next, thirteen individuals with prediabetes completed a six-month ILI program. The ILI program resulted in significant body weight reduction at 6 months (63.5 ± 13.9 to 61.9 ± 14.0 kg, p = 0.012), which was maintained at 12 months (p < 0.001). Waist circumferences were significantly decreased at 12 months (85.4 ± 11.7 to 82.9 ± 12.7 cm, p = 0.014). An increase in sleep variability was significantly associated with an increase in 2-h plasma glucose, independent of changes in BMI (b = 0.603), and physical activity (b = 0.774). This pilot study suggested that ILI in PLWH with prediabetes is feasible and effective in improving metabolic control, with its effects possibly modulated by sleep variability. These findings should be confirmed in a larger study to reduce diabetes risk in this population. Trail registration: ClinicalTrial.gov, NCT03545217 (date of registration: May 22, 2018).

Discrepant influence of vitamin D status on parathyroid hormone and bone mass after two years of calcium supplementation.

OBJECTIVE: To investigate the influence of vitamin D status on parathyroid hormone and bone mass after a 2-year supplementation of calcium alone. PATIENTS AND METHODS: Randomized, double-blind, placebo-controlled clinical trial, in healthy postmenopausal women without osteoporosis: three hundred and thirty-six subjects aged 60-97 years were studied and randomized to receive elemental calcium 500 mg/day (n = 175) or placebo (n = 161) for 2 years. MEASUREMENTS: Changes in parathyroid hormone (PTH) and bone mineral density (BMD) from baseline and vitamin D status. Values are presented as means +/- SD. RESULTS: After 2 years, subjects with calcium supplementation had significant decrease in plasma PTH level (4.4 +/- 1.7 vs 4.7 +/- 1.9 pmol/l, P < 0.01), improved lumbar BMD (1.031 +/- 0.12 vs 1.004 +/- 0.12 g/cm(2), P < 0.001) and total hip BMD (0.890 +/- 0.10 vs 0.883 +/- 0.10 g/cm(2), P < 0.001) without change in femoral neck BMD. In the placebo group, PTH level significantly increased (4.8 +/- 1.6 vs 4.5 +/- 1.5 pmol/l, P < 0.001), lumbar BMD slightly increased (1.027 +/- 0.14 vs 1.018 +/- 0.14 g/cm(2), P < 0.001), total hip and femoral neck BMD decreased (0.876 +/- 0.11 vs 0.887 +/- 0.11 g/cm(2), P < 0.001 and 0.783 +/- 0.10 vs 0.798 +/- 0.10 g/cm(2), P < 0.001, respectively). When subjects were classified according to baseline 25-hydroxyvitamin D [25(OH)D] levels into those with 25(OH)D in the lower tertile (lowVitD) and those in the middle and upper tertiles combined (normVitD). The degree of PTH suppression after calcium supplementation was significantly higher in the normVitD compared to the lowVitD groups (-5.6 +/- 26.7%vs 1.3 +/- 27.2%, P < 0.05). No effect of vitamin D status on the change in lumbar BMD after calcium supplementation was demonstrated. Despite the higher suppression of PTH, there was a slight decrease in femoral neck BMD after calcium supplementation in the normVitD group while femoral neck BMD was more or less maintained in the lowVitD group (-0.6 +/- 3.2%vs 0.5 +/- 2.9%, P < 0.05). CONCLUSION: Calcium supplementation appears to affect femoral bone mass less in Thai postmenopausal women with adequate vitamin D status, despite higher suppression of PTH.

Acute changes in biochemical markers of bone resorption and formation after Thai traditional massage.

BACKGROUND: Mechanical loadings by active exercise or passive low amplitude vibration have been demonstrated to enhance bone mass or delay bone loss. Traditional Thai massage can be anabolic to bone due to the application of physical loading on the body in a rhythmic fashion. OBJECTIVE: To explore the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover immediately after the massage. MATERIAL AND METHOD: Subjects consisted of 30 healthy females aged 20-40 years. Each subject received Thai traditional massage for 2 hours by a single masseuse. Bone mineral density (BMD) at baseline was measured by dual-energy X-ray absorptiometry (DEXA). C-terminal telopeptide of type 1 collagen (CTx-I) and total procollagen type 1 amino-terminal propeptide (P1NP) were determined by electrochemiluminescence immunoassay. RESULTS: There was a 4.8% increase in serum P1NP concentrations after massage (median 43.4 ng/ml vs. 41.3 ng/ml, p < 0.05). Serum CTx-I also decreased after massage (median 2-hour vs. baseline 0.29 ng/ml vs. 0.31 ng/ml, p < 0.05). There was a nearly significant negative correlation between the percentage change in serum P1NP and BMD at the total femur (r = -0.37, p = 0.056) whereas the statistically significant correlation disappeared between percentage change in bone turnover and the other sites of BMD. CONCLUSION: Thai traditional massage induces acute changes in bone formation and resorption markers. Study on the more prolonged effects of Thai traditional massage is warranted to explore its implication in the enhancement of bone health.

Glycemic effect of post-meal walking compared to one prandial insulin injection in type 2 diabetic patients treated with basal insulin: A randomized controlled cross-over study.

Studies demonstrate that post-meal walking decreases postprandial hyperglycemia in type 2 diabetic patients but it has never been tested with the active treatment comparator. The objective of this study was to determine the effect of post-meal walking on glycemic control compared with one prandial insulin in type 2 diabetic patients who failed basal insulin. A randomized controlled cross-over study of post-meal walking or one prandial insulin was done in type 2 diabetic patients who were being treated with basal insulin between May 2017 and March 2018. In post-meal walking group, patients walked after meal for 15-20 minutes one meal a day every day for 6 weeks. In prandial insulin (basal plus) group, one prandial insulin was injected before breakfast or main meal with rapid-acting insulin. The primary outcome was a difference in HbA1c reduction in post-meal walking compared with basal plus groups. Fourteen patients completed the study. By intention-to-treat analysis, HbA1c was reduced by -0.05(range:-1.08 to 0.74) and -0.19(range:-0.8 to 0.56) % in post-meal walking and basal plus groups respectively. By per-protocol analysis, post-meal walking and basal plus groups decreased HbA1c by 0.13(range:-0.74 to 1.08) and 0.2(range:-0.56 to 0.8) %, respectively. There was were no significant differences in HbA1c reduction from baseline in each group and between groups in both intention-to-treat and per-protocol analysis. Fructosamine levels were decreased by 17.5(-59 to 43) and 10(-15 to 40) µmol/L, respectively at 3 and 6 weeks in post-meal walking group whereas the respective changes in basal plus group were 12.5(-17 to 64) and 17.5(-28 to 38) µmol/L and there were no significant differences in fructosamine reduction from baseline in each group and between groups. In conclusion, although post-meal walking might be as effective as one prandial insulin to improve glycemic control in type 2 diabetic patients who failed basal insulin but the magnitude of reduction was small. A longer-term study with a larger sample size or with a different walking protocol is required.