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).

Summary of the Thai Osteoporosis Foundation (TOPF) Clinical Practice Guideline on the diagnosis and management of osteoporosis 2021.

Objectives: The Thai Osteoporosis Foundation (TOPF) is an academic organization that consists of a multidisciplinary group of healthcare professionals managing osteoporosis. The first clinical practice guideline for diagnosing and managing osteoporosis in Thailand was published by the TOPF in 2010, then updated in 2016 and 2021. This paper presents important updates of the guideline for the diagnosis and management of osteoporosis in Thailand. Methods: A panel of experts in the field of osteoporosis was recruited by the TOPF to review and update the TOPF position statement from 2016. Evidence was searched using the MEDLINE database through PubMed. Primary writers submitted their first drafts, which were reviewed, discussed, and integrated into the final document. Recommendations are based on reviews of the clinical evidence and experts' opinions. The recommendations are classified using the Grading of Recommendations, Assessment, Development, and Evaluation classification system. Results: The updated guideline comprises 90 recommendations divided into 12 main topics. This paper summarizes the recommendations focused on 4 main topics: the diagnosis and evaluation of osteoporosis, fracture risk assessment and indications for bone mineral density measurement, fracture risk categorization, management according to fracture risk, and pharmacological management of osteoporosis. Conclusions: This updated clinical practice guideline is a practical tool to assist healthcare professionals in diagnosing, evaluating, and managing osteoporosis in Thailand.

Effects of second-line antihyperglycemic drugs on the risk of chronic kidney disease: applying a target trial approach to a hospital-based cohort of Thai patients with type 2 diabetes.

BACKGROUND: The reno-protective effect of second-line treatments in type 2 diabetes has been assessed by clinical trials but generalizability to routine clinical practice is still uncertain. We aimed to assess the effectiveness of these treatments, when added to metformin, on the risk of chronic kidney disease (CKD). METHODS: A real-world, hospital-based, type 2 diabetes cohort was retrospectively assembled at Ramathibodi Hospital from 2010 to 2019. Patients who received sulfonylureas (SU), thiazolidinediones (TZD), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose cotransporter-2 inhibitors (SGLT2i), as second-line antihyperglycemic treatment were included. Treatment effect models with inverse probability weighting and regression adjustment were used to estimate CKD risk according to treatment. RESULTS: CKD was identified in 4,132 of the 24,777 patients with type 2 diabetes (16.7%). The CKD incidence (95% CI) was 4.1% (2.2%, 6.9%), 13.5% (12.5%, 14.6%), 14.8% (13.5%, 16.1%), and 18.0% (17.4%, 18.5%) for patients receiving SGLT2i, DPP4i, TZD, and SU treatment, respectively. The average treatment effects (i.e., the difference in CKD risk) for SGLT2i, DPP4i, and TZD compared to SU were - 0.142 (- 0.167, - 0.116), - 0.046 (- 0.059, - 0.034), and - 0.004 (- 0.023, 0.014), respectively, indicating a significant reduction in CKD risk of 14.2% and 4.6% in the SGLT2i and DPP4i groups, respectively, compared to the SU group. Furthermore, SGLT2i significantly reduced CKD risk by 13.7% (10.6%, 16.8%) and 9.5% (6.8%, 12.2%) when compared to TZD and DPP4i, respectively. CONCLUSIONS: Our study identified 14.2%, 13.7%, and 9.5% reduced CKD risk in Thai patients with type 2 diabetes who were treated with SGLT2i compared to those treated with SU, TZD, and DPP4i, respectively, in real-world clinical data. Previous evidence of a reno-protective effect of SGLT2i reported in other populations is consistent with our observations in this Southeast Asian cohort.

Association between gut microbiota and prediabetes in people living with HIV.

The prevalence of prediabetes is rapidly increasing in general population and in people living with HIV (PLWH). Gut microbiota play an important role in human health, and dysbiosis is associated with metabolic disorders and HIV infection. Here, we aimed to evaluate the association between gut microbiota and prediabetes in PLWH. A cross-sectional study enrolled 40 PLWH who were receiving antiretroviral therapy and had an undetectable plasma viral load. Twenty participants had prediabetes, and 20 were normoglycemic. Fecal samples were collected from all participants. The gut microbiome profiles were analyzed using 16S rRNA sequencing. Alpha-diversity was significantly lower in PLWH with prediabetes than in those with normoglycemia (p<0.05). A significant difference in beta-diversity was observed between PLWH with prediabetes and PLWH with normoglycemia (p<0.05). Relative abundances of two genera in Firmicutes (Streptococcus and Anaerostignum) were significantly higher in the prediabetes group. In contrast, relative abundances of 13 genera (e.g., Akkermansia spp., Christensenellaceae R7 group) were significantly higher in the normoglycemic group. In conclusion, the diversity of gut microbiota composition decreased in PLWH with prediabetes. The abundances of 15 bacterial taxa in the genus level differed between PLWH with prediabetes and those with normoglycemia. Further studies on the effect of these taxa on glucose metabolism are warranted.

Vitamin D and Visceral Obesity in Humans: What Should Clinicians Know?

The extraskeletal effect of vitamin D on adipose tissue biology and modulation in human obesity is of great interest and has been extensively investigated. Current evidence from preclinical and clinical studies in human adipose tissue suggests that the anti-inflammatory effects of vitamin D are evident and consistent, whereas the effects of vitamin D on adipocyte differentiation, adipogenesis, and energy metabolism and the effects of vitamin D supplementation on adipokine levels are inconclusive. Interventional studies related to medical and surgical weight loss in humans have shown small or no improvement in vitamin D status. Additionally, the benefit of vitamin D supplementation for the reduction in visceral adipose tissue has only been demonstrated in a few studies. Overall, the findings on the relationship between vitamin D and visceral adipose tissue in humans are still inconclusive. Further studies are required to confirm the beneficial effects of vitamin D on ameliorating adipose tissue dysfunction.

Metformin for Preventing Progression From Prediabetes to Diabetes Mellitus in People Living With Human Immunodeficiency Virus.

Background Diabetes mellitus (DM) and human immunodeficiency virus (HIV) itself increase the risk for cardiovascular diseases in people living with HIV (PLHIV). Prediabetes, a condition preceding DM, is common in PLHIV receiving antiretroviral therapy (ART). Both metformin and lifestyle interventions have been established to reduce the risk of progression from prediabetes to DM in the general population. This study aimed to evaluate the efficacy of metformin for preventing DM in prediabetic PLHIV. Methods An open-label randomized controlled clinical trial was conducted in HIV-positive persons with prediabetes. The participants were randomized into two groups: the metformin group (received metformin) and the control group (did not receive metformin). All participants were counseled regarding diet control and lifestyle modification and followed for 12 months. The primary endpoint was the development of DM. Fasting plasma glucose (FPG), two-hour plasma glucose (2-h PG) after 75 g oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), and computer-based homeostatic model assessment index of beta-cell function (HOMA%B) and insulin resistance (HOMA-IR) were analyzed. Results Seventy-four participants were enrolled, 37 in each group. The mean age was 49.6 years, and 68.9% were males. At baseline, the mean CD4 cell count was 570 cells/mm3, and the mean body mass index (BMI) was 24.6 kg/m2. Baseline characteristics including age, sex, BMI, waist/hip ratio, duration of ART, ART regimen, CD4 cell count, and HIV RNA were similar between the two groups. The mean FPG, 2-h PG, HbA1c, HOMA%B, and HOMA-IR at baseline were also similar between the two groups. At 12 months, one participant in the metformin group and three in the control group developed DM (risk reduction: 5.41%; 95% confidence interval (CI): -6.92%-18.78%). When we compared changes in parameters between the two groups, there were trends toward more changes in HbA1c ([Formula: see text]HbA1c) at both six months (metformin group versus control group: -0.17% ± 0.20% versus 0.02% ± 0.58%; p = 0.074) and 12 months (metformin group versus control group: -0.05% ± 0.23% versus 0.06% ± 0.27%; p = 0.065). When we considered changes in all parameters in each group, the metformin group had significant reductions in body weight (BW) and BMI at both six and 12 months, and significant reductions in HbA1c and HOMA-IR at six months. No participant had adverse effects that led to the discontinuation of metformin. No cardiovascular event was observed during the study period. Conclusions Metformin tends to improve HbA1c and insulin resistance and may prevent progression from prediabetes to DM in HIV-positive persons with prediabetes. A further large study with a longer study period is needed to evaluate the long-term benefit of metformin.

The effect of Cissus quadrangularis L. on delaying bone loss in postmenopausal women with osteopenia: A randomized placebo-controlled trial.

BACKGROUND: Osteopenia refers to bone density that is not normal but also not as low as that noted in osteoporosis. Osteopenia leads to osteoporosis and increases the risk of fractures. Current research is focused on agents that will prevent or slow the progression of bone loss. On the basis of published evidence, Cissus quadrangularis (CQ) might potentially provide a novel natural treatment for osteopenia. PURPOSE: To determine the effect of 24 weeks of consecutive treatment with CQ on delaying bone loss and safety in postmenopausal women (PMW) with osteopenia. METHODS: This study is a randomized, placebo-controlled trial. Here, 134 enrolled PMW with osteopenia (> 40 years and having no period for 1-10 years) received CQ at 1.2 (CQ1.2) or 1.6 g/day (CQ1.6) or placebo. The %change in bone mineral density (BMD) at the lumbar spine (L1-L4), femoral neck, and total hip served as the primary outcome. The %change in bone turnover markers (BTMs), including C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), was the secondary outcome. These outcomes were compared between the CQ vs. placebo group at weeks 12 and 24. The least significant change (LSC) was used to monitor clinical changes. The adverse events (AE) were monitored. RESULTS: A total of 108 participants completed this study. The %BMD changes in the CQ-treated groups did not differ at any site after 24 weeks compared to the placebo. Statistically significant differences were detected in CQ1.6 at the lumbar spine (0.011 ± 0.025 g/cm2, p = 0.008) and CQ1.2 at the femoral neck (-0.015 ± 0.036 g/cm2, p = 0.024) compared to baseline, but these changes did not exceed the LSC. Reduced bone remodeling activity was detected in both CQ-treated groups. Compared to the placebo, the %P1NP change was significantly reduced in CQ1.6 (-2.46 ± 26.05%; p < 0.01) at week 12 and in CQ1.2 (-3.36 ± 29.47%; p < 0.01) and CQ1.6 (-9.95 ± 22.22%; p < 0.01) at week 24. These results correlated with the within-group comparison, which showed a continuously significant increase in both BTMs in the placebo group. However, a stable CTX and a significant reduction in P1NP (p < 0.05) were detected in both CQ-treated groups. This reduction exceeded the LSC of P1NP. The incidence of adverse events did not differ among the three groups. CONCLUSION: This is the first clinical report that showed a promising effect on delaying bone loss of orally administration of CQ for 24 weeks, as indicated by a slower bone remodeling process via a reduction in BTMs. However, no change in BMD was observed.

Prevalence and predictors of asymptomatic vertebral fracture in patients with end-stage renal disease.

Objective: This study aimed to investigate the prevalence and predictors of asymptomatic vertebral fracture in patients with end-stage renal disease undergoing hemodialysis. Methods: This cross-sectional study included 80 patients with end-stage renal disease undergoing hemodialysis. Medical history, Fracture Risk Assessment Tool and anteroposterior and lateral radiographs of the thoracolumbar and lumbosacral spine were obtained. Vertebral fractures were identified using the Genant semiquantitative assessment. Results: Radiography demonstrated asymptomatic vertebral fracture in 22 patients (27.5%). FRAX® results for major osteoporotic fracture (area under the curve, 0.64) and hip fracture (area under the curve, 0.62) were able to discriminate patients with prevalent asymptomatic vertebral fracture. A multivariate analysis demonstrated that a 1-year average corrected calcium (odds ratio, 0.38), steroid use (odds ratio, 8.99), and a serum albumin concentration <25 g/dL (odds ratio, 28.82) significantly predicted prevalent asymptomatic vertebral fracture (clinical model; area under the curve, 0.82). Combining the 1-year average corrected calcium and serum albumin concentration <25 g/dL with FRAX® results for major osteoporotic fracture (area under the curve, 0.78) and FRAX® results for hip (area under the curve, 0.75) produced a significantly greater area under the curve value to predict fracture when compared with FRAX® result for major osteoporotic fracture and FRAX® result for hip (P = 0.022). Conclusion: Asymptomatic vertebral fracture is prevalent. FRAX® results for major osteoporotic fracture and hip provided lower ability in predicting asymptomatic vertebral facture when compared to the clinical model. Combining a 1-year average corrected calcium and serum albumin concentration <25 g/dL with FRAX® result for major osteoporotic fracture or hip improved the model's performance and provided comparable area under the curve to the clinical model.

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.

Pioglitazone for the Treatment of Metabolic-Associated Fatty Liver Disease in People Living With HIV and Prediabetes.

Background Metabolic-associated fatty liver disease (MAFLD) is increasingly common among people living with the human immunodeficiency virus (PLHIV) and can progress to cirrhosis and cirrhotic-related complications. Pioglitazone is known to improve insulin sensitivity that results in decreasing serum fatty acids and resolution of non-alcoholic steatohepatitis. This study was aimed to evaluate the efficacy of pioglitazone for the treatment of MAFLD in PLHIV and prediabetes. Methods A randomized controlled trial was conducted in HIV-positive individuals with prediabetes who had evidence of a fatty liver by abdominal ultrasonography or controlled attenuation parameter (CAP) ≥ 238 decibels per meter (dB/m) through using transient elastography. Participants were randomized to take pioglitazone, 30 mg/day, (pioglitazone group) or placebo (control group) and were followed up and assessed for 48 weeks. Results  A total of 98 participants were enrolled, 49 in each group. The mean age was 50.8 years and 66.3% were males. All participants had received antiretroviral therapy with undetectable HIV ribonucleic acid (RNA) and the mean CD4 cell count was 463.2 cells/mm3. The mean baseline CAP and liver stiffness were 285.7 dB/m and 5.4 kilopascals (kPa), respectively. At 24 weeks, the mean change of the CAP level was -25.7 dB/m in the pioglitazone group and -5.6 dB/m in the control group (p = 0.040); the mean change of liver stiffness was 0.014 kPa in the pioglitazone group and 0.403 kPa in the control group (p = 0.199). At 48 weeks, the mean change of the CAP level was -23.5 dB/m in the pioglitazone group and 10.2 dB/m in the control group (p < 0.001); the mean change of liver stiffness was -0.184 kPa in the pioglitazone group and 0.554 kPa in the control group (p = 0.016). The mean changes of fasting plasma glucose (FPG) at 24 and 48 weeks were -14.9 and -17.5 mg/dL in the pioglitazone group, respectively, and -3.6 and 4.5 mg/dL in the control group, respectively (p < 0.05). The mean change of the body mass index, lipid profiles, and liver enzymes were not different between the two groups at both time points (p > 0.05). No serious adverse effects were observed in either group. Conclusions  Pioglitazone significantly reduces CAP, liver stiffness, and FPG in PLHIV with prediabetes and MAFLD. Further studies with long-term follow-up duration are warranted to determine the role of pioglitazone for clinical use 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.

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).

Vitamin D Inhibits Adipokine Production and Inflammatory Signaling Through the Vitamin D Receptor in Human Adipocytes.

OBJECTIVE: The purpose of this study was to investigate the effects of vitamin D on adipokine expression and inflammation in human adipose tissues and adipocytes and evaluate the molecular mechanisms involved. METHODS: Omental and abdominal subcutaneous human adipose tissues were treated with 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), and adipokine levels were measured. Vitamin D effects were measured with or without dexamethasone because glucocorticoids are known to affect vitamin D actions. Using RNA interference, we examined whether the vitamin D receptor (VDR) mediated vitamin D actions on adipokine expression and inflammatory signaling pathways in human adipocytes. RESULTS: mRNA levels and secretion of leptin and IL-6 were suppressed by 1,25(OH)2 D3 in omental adipose tissues. Cotreatment with dexamethasone did not affect these inhibitory actions but partially blocked CYP24A1 induction. Similar results were observed in the subcutaneous depot. In addition, 1,25(OH)2 D3 suppressed leptin and IL-6 expression as well as nuclear factor-κB and extracellular signal-regulated kinase-1/2 phosphorylation in human adipocytes. Adipokine expression also was decreased by 25-hydroxyvitamin D3 (25(OH)D3 ), but not vitamin D3 . Knockdown of VDR increased the inflammatory signaling activity in the control condition and blocked the inhibitory effects of 1,25(OH)2 D3 on adipokine and inflammatory signaling pathways. CONCLUSION: Vitamin D acts through VDR to inhibit inflammatory pathways and adipokine expression in human adipocytes. Increasing vitamin D status may ameliorate obesity-associated metabolic complications by decreasing adipose tissue inflammation.

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.

Vitamin D regulation of adipogenesis and adipose tissue functions.

Vitamin D insufficiency is associated with obesity and its related metabolic diseases. Adipose tissues store and metabolize vitamin D and expression levels of vitamin D metabolizing enzymes are known to be altered in obesity. Sequestration of vitamin D in large amount of adipose tissues and low vitamin D metabolism may contribute to the vitamin D inadequacy in obesity. Vitamin D receptor is expressed in adipose tissues and vitamin D regulates multiple aspects of adipose biology including adipogenesis as well as metabolic and endocrine function of adipose tissues that can contribute to the high risk of metabolic diseases in vitamin D insufficiency. We will review current understanding of vitamin D regulation of adipose biology focusing on vitamin D modulation of adiposity and adipose tissue functions as well as the molecular mechanisms through which vitamin D regulates adipose biology. The effects of supplementation or maintenance of vitamin D on obesity and metabolic diseases are also discussed.

Prediabetes among HIV-infected individuals receiving antiretroviral therapy: prevalence, diagnostic tests, and associated factors.

BACKGROUND: Metabolic complications in human immunodeficiency virus (HIV)-infected individuals are common. Prediabetes represents a high risk for future diabetes development. This study aimed to determine the prevalence, diagnostic methods, and associated factors of prediabetes among HIV-infected individuals receiving antiretroviral therapy (ART). METHODS: A cross-sectional study was conducted among HIV-infected adults without a history of diabetes who were receiving ART. Fasting plasma glucose (FPG), 2-hour plasma glucose (2-h PG) after a 75-g oral glucose tolerance test, and hemoglobin A1c (HbA1c) were assessed. RESULTS: A total of 397 patients with a mean age of 47.0 ± 9.8 years and 55.7% male, were studied. All received ART with undetectable plasma viral load. The mean duration of ART was 9.6 ± 5.2 years, and the mean CD4 cell count was 554 ± 235 cells/mm3. Among the patients, 28 (7.1%) had first-diagnosed diabetes, and 133 (33.5%) patients had prediabetes. Glycemia estimation by FPG, 2-h PG, and HbA1c showed a prediabetes prevalence of 17.4%, 14.7%, and 12.5%, respectively. The kappa statistics for the agreement of FPG and 2-h PG, HbA1c and 2-h PG, and HbA1c and FPG were 0.317, 0.429, and 0.396, respectively. In multivariate analysis, hypertension [odds ratio (OR) 3.38; 95% confidence interval (CI), 1.16-9.91; p = 0.026), and triglycerides > 150 mg/dL (OR 2.11; 95% CI, 1.01-4.44; p = 0.047) were factors significantly associated with prediabetes. CONCLUSIONS: Prediabetes among HIV-infected individuals receiving ART is common. The agreements of glycemia estimation methods are minimal to weak. HbA1c may underestimate prediabetes prevalence. Using FPG together with HbA1c increases the detection rate to approximately three-quarters of prediabetes patients. HIV-infected individuals who had hypertension and hypertriglyceridemia should be regularly assessed for prediabetes. Trial registration ClinicalTrial.gov, NCT03545217. Registered 1 June 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03545217.

Vitamin D and Calcium Supplement Attenuate Bone Loss among HIVInfected Patients Receiving Tenofovir Disoproxil Fumarate/Emtricitabine/ Efavirenz: An Open-Label, Randomized Controlled Trial.

BACKGROUND: Antiretroviral therapy (ART), especially with tenofovir disoproxil fumarate (TDF), has been associated with accelerated bone turnover and leads to significant bone loss. OBJECTIVE: We aimed to determine the effect of vitamin D2 and calcium on bone mineral density (BMD) in HIV-infected patients receiving TDF/emtricitabine (FTC)/efavirenz (EFV). METHODS: A prospective, open-label, randomized controlled study was conducted. Eligible patients were ART naïve HIV individuals who initiated TDF/FTC/EFV. The study group received supplementation with vitamin D2 and calcium carbonate, whereas the control group was administered only ART. The primary outcome was the percentage change in total hip BMD at week 24 compared with baseline. RESULTS: A total of 18 patients were randomized (9 in each group). The mean (standard deviation; SD) total hip BMD significantly decreased from baseline in both groups, from 0.96 (0.14) g/cm2 to 0.93 (0.13) g/cm2 in the study group (p = 0.006) and from 0.87 (0.11) g/cm2 to 0.84 (0.11) g/cm2 in the control group (p = 0.004). The mean (SD) lumbar spine BMD significantly decreased from baseline in both groups, from 1.00 (0.13) g/cm2 to 0.97 (0.13) g/cm2 (p = 0.004) in the study group and from 0.90 (0.09) g/cm3 to 0.86 (0.08) g/cm2 in the control group (p = 0.006). At week 24, the mean (SD) lumbar spine BMD was significantly greater in the study group than in the control group (p = 0.042). However, there were no significant differences in the percentage change of total hip, lumbar spine, and femoral neck BMD between both groups. No adverse events were reported. In conclusion, as early as 24 weeks after TDF initiation, a significant decline in BMD was detected. CONCLUSION: Vitamin D2 and calcium supplements should be considered for HIV-infected patients receiving TDF/FTC/EFV in a resource-limited setting where there are limited ART options (Clinicaltrials. gov NCT0287643).

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.

Urinary metabolic profiles after vitamin D2 versus vitamin D3 supplementation in prediabetes.

AIM: To assess the potential biological differences between vitamin D2 and D3 using urinary metabolite profiles in response to vitamin D3 or D2 supplementation. METHOD: Subjects consisted of 29 subjects with impaired fasting glucose and/or impaired glucose tolerance. Subjects were randomized into two groups, vitamin D2 (20,000 IU weekly, n = 14) or vitamin D3 (15,000 IU weekly, n = 15). Urine and serum samples were taken at two different time points for each subject (at baseline and at 12 weeks). Urinary metabolite profiling was performed by liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). Serum calcium was analyzed on an automated biochemical analyzer and serum intact parathyroid hormone was determined by electrochemiluminescence immunoassay. RESULTS: At baseline, there was no statistically significant difference in clinical characteristics including age, gender, body mass index, waist circumference and 25-hydroxyvitamin D (25(OH)D) levels between the 2 groups. Weekly administration of 20,000 U D2 for 12 weeks resulted in comparable 25(OH)D concentrations as compared to weekly 15,000 U D3 supplementation (97.8 ±â€¯305 vs. 96.8 ±â€¯3.4 nmol/L, p = 0.84). No difference in serum calcium (2.3 ±â€¯0.03 vs. 2.2 ±â€¯0.03 nmol/L, p = 0.52) or intact parathyroid hormone (5.3 ±â€¯0.3 vs. 4.9 ±â€¯0.5 pmol/L, p = 0.54) at 12 weeks was found. Principle component analysis did not reveal apparent segregation of metabolites according to D2 or D3 supplementation. Moreover, using partial least square regression, no apparent separation between the D2 and the D3 group was found. No important metabolite influencing the separation of the D2 from the D3 group was found using variables importance on projection analysis. CONCLUSIONS: At comparable circulating 25(OH)D concentrations, vitamin D2 or D3 supplementation does not appear to result in different urinary metabolite profiles. Our finding does not support a biological difference between vitamin D2 and D3.