Effect of Vitamin D Supplementation on Muscle Function in Patients With I131-Induced Hypothyroidism: A Pilot Randomized Trial.

Background: There is a lack of data regarding the effect of vitamin D supplements in patients with I131-induced hypothyroidism. The primary aim of this study was to investigate the effect of vitamin D supplements on muscle function, and the secondary aim was to observe the effect on body composition, insulin resistance, and quality of life (QOL) in patients with I131-induced hypothyroidism. Methods: In this pilot randomized placebo-controlled trial, patients with I131-induced hypothyroidism on a stable dose of levothyroxine were enrolled and allocated into 2 groups to receive oral vitamin D 20 000 IU weekly or placebo for 24 weeks. Baseline biochemical values, body composition, handgrip strength, the 5 times sit-to-stand test (5TSTS), homeostatic model assessment for insulin resistance (HOMA-IR), and QOL were measured before intervention and after 3 and 6 months in both groups. Mixed model regression analysis was used to compare the outcomes between the 2 groups. Significance was set at P value of < .05. Results: There were 20 participants in each group. The time taken for 5TSTS in the vitamin D group was significantly lower than the placebo group at 3 (P = .032) and 6 months (P = .006). Other outcomes, including handgrip strength, body composition, HOMA-IR, and QOL, showed no significant difference between the 2 groups. Conclusion: A supplement of vitamin D2 at 20 000 IU per week for 24 weeks could help improve performance in 5TSTS in patients with I131-induced hypothyroidism.

A diagnostic predictive model for secondary osteoporosis in patients with fragility fracture: a retrospective cohort study in a tertiary care hospital.

Identifying secondary causes among osteoporotic patients is crucial. However, there is no simple tool for screening secondary osteoporosis. A predictive model for screening secondary osteoporosis was constructed using simple clinical and biochemical parameters. This predictive model may provide clinicians with guidance to perform further investigations for specific causes of osteoporosis. PURPOSE: Establishing whether a fragility fracture is secondary to a specific cause of osteoporosis is crucial for treatment outcomes. Therefore, this study aimed to develop a simple screening tool for secondary osteoporosis in the elderly initially presented with fragility fractures. METHODS: A retrospective cohort study including 456 patients with fragility hip and vertebral fractures that occurred between January 2017 and July 2022 was conducted. Demographic, clinical, biochemical, and final diagnostic data were retrieved. Potential predictors for secondary osteoporosis were determined by multivariable logistic regression analysis, and a predictive model for secondary osteoporosis was subsequently developed using identified potential predictors. RESULTS: This study included 343 females and 113 males with a mean age of 76.9 ± 11.0 years. One hundred and twenty-one patients (26.5%) were diagnosed with secondary osteoporosis. Vitamin D deficiency (71.9%) was the most common cause of secondary osteoporosis, followed by glucocorticoid-induced osteoporosis (23.9%) and primary hyperparathyroidism (9.9%). The potential predictors for secondary osteoporosis included in the predictive model were age, body mass index (BMI), corrected calcium, phosphate, thyroid stimulating hormone, and a 10-year probability of hip fractures calculated by BMI-based FRAX®. With a cut-off level of 0.22, the proposed predictive model has an AuROC of 0.75 (95% CI 0.69 to 0.81) with a sensitivity of 77%, a specificity of 66%, and an accuracy of 68.9%. CONCLUSION: A predictive model for screening secondary osteoporosis was constructed using simple clinical and biochemical parameters. This newly developed predictive model may provide clinicians with guidance to perform further advanced investigations for secondary causes of osteoporosis.

Glycated hemoglobin variability and the risk of cardiovascular events in patients with prediabetes and type 2 diabetes mellitus: A post-hoc analysis of a prospective and multicenter study.

AIMS/INTRODUCTION: High glycated hemoglobin (HbA1c) variability has been reported to be linked with cardiovascular events in type 2 diabetes patients. Only a few studies have been carried out on Asian patients. This study aimed to investigate the association of prediabetes and type 2 diabetes in Asian patients by performing a post-hoc analysis of a multicenter, prospective, observational study. MATERIALS AND METHODS: Data for prediabetes and type 2 diabetes patients were retrieved from a multicenter national registry entitled "CORE-Thailand study." The primary outcome was 4P-MACE (major adverse cardiovascular events, including non-fatal myocardial infarction, heart failure hospitalization, non-fatal stroke and all-cause death). Patients were stratified according to quartiles of HbA1c standard deviation. The Cox proportional hazards regression model was used to estimate the association of HbA1c variability with incident cardiovascular disease. RESULTS: A total of 3,811 patients with prediabetes and type 2 diabetes were included. The median follow-up duration was 54 months. In the fully adjusted model, the highest quartile of HbA1c variability showed a statistically significant association with 4P-MACE (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.77-4.35), fatal and non-fatal myocardial infarction (HR 6.91, 95% CI 1.90-25.12), hospitalization for heart failure (HR 3.34, 95% CI 1.20-9.26) and all-cause death (HR 3.10, 95% CI 1.72-5.57). All these outcomes were statistically significantly different among four quartiles of HbA1c (log-rank P-value <0.05). Fatal and non-fatal stroke showed no statistically significant association with high HbA1c variability. CONCLUSION: High HbA1c variability in the highest quartile showed a statistically significant association with multiple adverse cardiovascular events in an Asian population. Minimizing HbA1c fluctuation during long-term follow up should be another important objective for type 2 diabetes patients.

Gaps in the Care of Subjects with Familial Hypercholesterolemia: Insights from the Thai Familial Hypercholesterolemia Registry.

AIMS: Familial hypercholesterolemia (FH) is currently underdiagnosed and undertreated. The establishment of a FH registry could facilitate a deeper understanding of this disease. We described the clinical characteristics of subjects with FH from the Thai FH Registry, compared our data with the regional and global data, and identified gaps in the care of these subjects. METHODS: A multicenter, nationwide prospective FH registry was established in Thailand. Our data were compared with those of the European Atherosclerosis Society-FH Studies Collaboration. Multiple logistic regression analyses were performed for variables associated with lipid-lowering medication (LLM) use and the attainment of low-density lipoprotein-cholesterol (LDL-C) goal. RESULTS: The study includes 472 subjects with FH (mean age at FH diagnosis: 46±12 years, 61.4% women). A history of premature coronary artery disease was found in 12%. The percentage of LLM use in subjects with a Dutch Lipid Clinic Network score of ≥ 6 (probable or definite FH) in our registry (64%) was slightly lower than the regional data but higher than the global data. Among those who received statins, 25.2% and 6.4% achieved LDL-C levels of ＜100 mg/dL and ＜70 mg/dL, respectively. Women with FH were less likely to achieve LDL-C ＜70 mg/dL (adjusted odds ratio: 0.22, 95% confidence interval: 0.06-0.71, p=0.012). CONCLUSIONS: FH in Thailand was diagnosed late, and treatment was inadequate for the majority of subjects. Women with FH were less likely to achieve LDL-C goals. Our insights could potentially help raise awareness and narrow the gap in patient care.

The efficacy of alendronate for the treatment of thalassemia-associated osteoporosis: a randomized controlled trial.

Background: With adequate blood transfusion and iron chelation, thalassemia patients have a longer life expectancy and experience long-term metabolic complications, including osteoporosis, fractures, and bone pain. Alendronate, an oral bisphosphonate, is currently used to treat various types of osteoporosis. However, the efficacy for the treatment of thalassemia-associated osteoporosis remains unclear. Methods: We conducted a randomized controlled trial to evaluate the efficacy of alendronate for the treatment of osteoporosis in thalassemia patients. Patients were included if they were males (18-50 years) or premenopausal females with low bone mineral density (BMD) (Z-score < -2.0 SD) or positive vertebral deformities from vertebral fracture analysis (VFA). Stratified randomization was performed according to sex and transfusion status. Patients were 1:1 allocated to receive once weekly alendronate 70 mg orally or placebo for a total duration of 12 months. BMD and VFA were re-evaluated at 12 months. Markers of bone resorption (C-terminal crosslinking telopeptide of type I collagen; CTX) and bone formation (Procollagen type I N-terminal propeptide; P1NP), and pain scores were measured at baseline, 6 months, and 12 months. The primary outcome was the change of BMD. The secondary endpoints were changes in bone turnover markers (BTM) and pain scores. Results: A total of 51 patients received the study drug, 28 patients were assigned to receive alendronate and 23 patients to receive placebo. At 12 months, patients in the alendronate group had significant improvement of BMD at L1-L4 compared to their baseline (0.72 ± 0.11 vs 0.69 ± 0.11 g/cm2, p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm2, p = 0.814). There was no significant change of BMD at femoral neck in both groups. Serum BTMs were significantly decreased among patients receiving alendronate at 6 and 12 months. The mean back pain score was significantly reduced compared to the baseline in both groups (p = 0.003). Side effects were rarely found and led to a discontinuation of the study drug in 1 patient (grade 3 fatigue). Conclusion: Alendronate 70 mg orally once weekly for 12 months effectively improves BMD at L-spine, reduces serum BTMs, and alleviates back pain in thalassemia patients with osteoporosis. The treatment was well tolerated and had a good safety profile.

The trajectory of osteoblast progenitor cells in patients with type 2 diabetes and the predictive model for their osteogenic differentiation ability.

The fate of osteoprogenitor cells along with the progression of type 2 diabetes (T2DM) and factors determining the fate of those cells remains to be elucidated. This cross-sectional study included 18 normoglycemic, 27 prediabetic, and 73 T2DM to determine osteogenic differentiation across the continuum of dysglycemia and to construct a model to predict the fate of osteoprogenitor cells. This study demonstrated a preserved osteogenic differentiation ability of peripheral blood-derived mononuclear cells (PBMC) isolated from normoglycemic and prediabetic but a progressive decline in their osteogenic differentiation during the progression of T2DM. The rate of osteogenic differentiation rapidly declined by 4-7% annually during the first 10 years of diabetes and then slowed down. A predictive model composed of three independent risk factors, including age, duration of diabetes, and glomerular filtration rate, demonstrated an AuROC of 0.834. With a proposed cut-off of 21.25, this model had 72.0% sensitivity, 87.5% specificity, and 78.9% accuracy in predicting the fate of osteoprogenitor cells. In conclusion, this study provided a perspective on the osteogenic differentiation ability of the osteoprogenitor cells across a continuum of dysglycemia and a predictive model with good diagnostic performance for the prediction of the fate of osteoprogenitor cells in patients with T2DM.

The differences of serum lipid profiles between primary aldosteronism and essential hypertension: a meta-analysis and systematic review.

BACKGROUND: The data on lipid profile differences between primary aldosteronism (PA) and essential hypertension (EH) patients are inconsistent and inconclusive. Most studies reported lower levels of lipid profiles in PA than in EH. This meta-analysis aimed to explore differences in serum lipid profiles including triglyceride (TG), total cholesterol (TC), LDL and HDL levels in PA patients and EH patients. METHODS: A search of published studies was performed using PubMed, Embase and Scopus databases from their inception through August 2022. Thirty studies involving 11,175 patients were identified. Inclusion criteria included 1) observational studies which contained data on any of the lipid profiles of interest (TG, TC, LDL and HDL) which could be acquired from baseline data or the outcomes, 2) data which should be compared between adult PA and EH patients and 3) the use of appropriate methods to diagnose PA. Standardized mean difference (SMD) with a 95% confidence interval (95% CI) was calculated to assess effect size by using STATA program version 15.0. Risk of bias was assessed by Joanna Briggs Institute (JBI) Critical Appraisal Tools for cross-sectional, cohort and case-control studies. RESULTS: Levels of the lipid parameters TG (SMD - 0.16 mmol/L; 95%CI (- 0.25, - 0.07)), TC (SMD - 0.30 mmol/L; 95%CI (- 0.41, - 0.19)) and LDL (SMD - 0.17 mmol/L; 95%CI (- 0.27, - 0.08)) were significantly lower in PA than in EH patients. There was no statistically significant difference in HDL between PA and EH patients (SMD - 0.08 mmol/L; 96%CI (- 0.23,0.07)). High levels of heterogeneity for TG, TC, HDL and LDL were observed in all studies. Risk of bias among the studies was low to moderate. CONCLUSION: Lower levels of TG, TC and LDL were observed in PA than in EH patients. Further study should be conducted to address the underlying mechanisms of lipid alteration in PA.

Sesamin protects against neurotoxicity via inhibition of microglial activation under high glucose circumstances through modulating p38 and JNK signaling pathways.

Diabetes mellitus (DM), one of the principal causes of morbidity and mortality worldwide, is implicated in the progression of age-related neurodegenerative diseases (NDDs), in which microglial activation is a crucial mediator. Sesamin, a kind of phytochemical, shows inhibitory effects on microglial activation. The present study studied whether sesamin protects against neurotoxicity triggered by high glucose-induced microglial activation. We firstly demonstrated that high doses of glucose, which mimics hyperglycemia in DM, did induce the activation of murine BV2 microglial cells, increasing inflammatory responses such as the production of ROS or inflammatory mediators like IL-1ß, TNF-⍺, and nitric oxide, through activation of p38 and JNK signaling pathways. Next, conditioned medium (CM) collected from high glucose-activated BV2 cell culture was used to show aggravated neurotoxicity in differentiated PC12 cells, indicating that high glucose-activated microglia could induce neurotoxicity. Interestingly, pretreatment of BV2 cells with sesamin diminished high glucose-induced microglia activation and inflammatory responses. Moreover, neurotoxicity in PC12 cells was found to be decreased in the group treated with CM from the sesamin-pretreated BV2 cell culture, suggesting sesamin inhibited microglial activation, thereby protecting neurons from activated microglia-mediated neurotoxicity. Thus, sesamin might be a potential compound to use in the prevention of diabetic-induced NDDs.

A predictive risk score to diagnose hypocalcemia after parathyroidectomy in patients with secondary hyperparathyroidism: a 22-year retrospective cohort study.

Hypocalcemia is a common complication found in patients with secondary hyperparathyroidism (SHPT) who undergo parathyroidectomy. This study aimed to construct a predictive risk score for the occurrence of hypocalcemia after parathyroidectomy in patients with SHPT who underwent chronic renal replacement therapy (RRT). This 22-year retrospective cohort study enrolled 179 patients with SHPT who had their first parathyroidectomy. Eighty-two percent of patients developed hypocalcemia within 16.9 (95% CI 14.5-19.5) h after parathyroidectomy. This study demonstrated four factors as independent risk factors for post-parathyroidectomy hypocalcemia, including duration of RRT, preoperative serum phosphate, preoperative serum alkaline phosphatase (ALP) and mean difference of serum intact parathyroid hormone (iPTH). By using logistic regression analysis, this study demonstrated cut-off points for these four risk factors for the diagnosis of hypocalcemia after parathyroidectomy: 5 years for the duration of RRT, 5 mg/dL for serum phosphate, 387 U/L for serum ALP, and 97% for the mean difference of serum iPTH. Finally, the predictive risk score was constructed by assigning a score of one to each factor. With a total score of at least 2, the proposed predictive risk score has an AuROC of 0.755 with a sensitivity of 78.2%, a specificity of 71.4%, and an accuracy of 76.9%.

Effectiveness of enhanced recovery after surgery protocol in open gynecologic oncology surgery: A randomized controlled trial.

OBJECTIVE: To examine the effectiveness of applying the recommended enhanced recovery after surgery (ERAS) protocol compared with our usual care in women with gynecologic malignancy undergoing elective laparotomy. METHODS: From June 2020 to May 2021, 93 women with gynecologic cancers (cervix, endometrium, and ovary) undergoing elective laparotomy at our institution were randomly assigned into an intervention group (ERAS protocol, 46 women) or control group (usual care, 47 women). For the intervention group, each woman was brought through the pre-specified ERAS protocol starting from preoperative counseling to postoperative management. For the control group, participants underwent routine standard care. The primary outcomes were length of hospital stay and postoperative pain. RESULTS: The intervention group demonstrated shorter hospital stay by 20 h (47.48 h vs 67.17 h, P = 0.02) with lower postoperative pain score at postoperative day 0 (1.58 vs 4.00, P < 0.01) and day 1 (1.00 vs 2.67, P < 0.01) while having decreased opioid consumption (P < 0.01). The intervention group also had faster recovery of gastrointestinal function. Overall, good compliance to most of the ERAS pathway domains was obtained. CONCLUSION: The ERAS protocol demonstrates benefits on shortening hospital stay, reducing pain, and bowel function recovery without increasing complications in our population. CLINICAL TRIAL REGISTRATION: The present study was registered at clinicaltrials.gov (NCT04201626) on December 3, 2019. Initial participant enrollment began on June 1, 2020. Access through URL of the registration site: https://clinicaltrials.gov/ct2/show/NCT04201626?cond=ERAS&cntry=TH&draw=2&rank=3.

Receptors of Advanced Glycation End Product (RAGE) Suppression Associated With a Preserved Osteogenic Differentiation in Patients With Prediabetes.

Type 2 diabetes is widely documented for osteogenic differentiation defect and impaired bone quality, which is related to the skeletal accumulation of advanced glycation end products (AGEs). Prediabetes is a condition in which hyperglycemia is lower than the threshold for the diagnosis of diabetes. Prediabetic animal models consistently demonstrate impaired osteogenic differentiation and deteriorated bone microarchitecture. However, no evidence shows defects in osteoblast development and skeletal effects of AGEs in prediabetic individuals. Therefore, it remains to be elucidated whether impaired osteogenic differentiation ability and altered cellular response to AGEs occur in patients with prediabetes. This cross-sectional study included 28 patients with prediabetes as defined by impaired fasting glucose criteria, fasting plasma glucose (FPG) between 100-125 mg/dl and 17 age-matched normoglycemic controls to elucidate osteogenic differentiation and AGER expression in the PBMC derived from those individuals. The PBMC-isolated from both groups showed similar rates of expression of osteoblast-specific genes, namely, ALPL, BGLAP, COL1A1, and RUNX2/PPAR (89.3% and 88.2%, p = 1.000), and showed comparable levels of expression of those genes. By using age- and pentosidine-matched normoglycemic individuals as references, the PBMC-isolated from prediabetic patients demonstrated lower expression of both AGER and BAX/BCL2. The expression of AGER and BAX/BCL2 significantly correlated to each other (r = 0.986, p <0.0001). The multivariate analysis demonstrated that serum pentosidine is an independent risk factor for AGER expression. With logistic regression analysis, the area under the ROC curve (AUC) for serum pentosidine at the cut-off level of 2.1 ng/ml and FPG at 100 mg/dl, which is a cut-off point for prediabetes, was significantly higher for predicting AGER expression than that of serum pentosidine alone (0.803 vs 0.688, p = 0.048), indicating that serum pentosidine was a good predictor of AGER expression in prediabetic individuals. In conclusion, this study demonstrated a preserved osteogenic differentiation in the PBMC derived from prediabetic individuals. In addition, those PBMC with preserved osteogenic differentiation potential showed the suppression of both cellular RAGE and apoptotic-related signals. Serum pentosidine was an independent risk factor for cellular RAGE expression and is conceivably a good predictor for AGER suppression in prediabetic individuals.

Young-onset diabetes patients in Thailand: Data from Thai Type 1 Diabetes and Diabetes diagnosed Age before 30 years Registry, Care and Network (T1DDAR CN).

AIMS/INTRODUCTION: There is a lack of current information regarding young-onset diabetes in Thailand. Thus, the objectives of this study were to describe the types of diabetes, the clinical characteristics, the treatment regimens and achievement of glycemic control in Thai patients with young-onset diabetes. MATERIALS AND METHODS: Data of 2,844 patients with diabetes onset before 30 years-of-age were retrospectively reviewed from a diabetes registry comprising 31 hospitals in Thailand. Gestational diabetes was excluded. RESULTS: Based on clinical criteria, type 1 diabetes was identified in 62.6% of patients, type 2 diabetes in 30.7%, neonatal diabetes in 0.8%, other monogenic diabetes in 1.7%, secondary diabetes in 3.0%, genetic syndromes associated with diabetes in 0.9% and other types of diabetes in 0.4%. Type 1 diabetes accounted for 72.3% of patients with age of onset <20 years. The proportion of type 2 diabetes was 61.0% of patients with age of onset from 20 to <30 years. Intensive insulin treatment was prescribed to 55.2% of type 1 diabetes patients. Oral antidiabetic agent alone was used in 50.8% of type 2 diabetes patients, whereas 44.1% received insulin treatment. Most monogenic diabetes, secondary diabetes and genetic syndromes associated with diabetes required insulin treatment. Achievement of glycemic control was identified in 12.4% of type 1 diabetes patients, 30% of type 2 diabetes patients, 36.4% of neonatal diabetes patients, 28.3% of other monogenic diabetes patients, 45.6% of secondary diabetes patients and 28% of genetic syndromes associated with diabetes patients. CONCLUSION: In this registry, type 1 diabetes remains the most common type and the prevalence of type 2 diabetes increases with age. The majority of patients did not achieve the glycemic target, especially type 1 diabetes patients.

Novel Predictive Model for Adrenal Insufficiency in Dermatological Patients with Topical Corticosteroids Use: A Cross-Sectional Study.

PURPOSE: This study aimed to identify predictive factors and to develop a predictive model for adrenal insufficiency (AI) related to topical corticosteroids use. METHODS: The research was conducted using a cross-sectional design. Adult patients with dermatological conditions who had been prescribed topical steroids for at least 12 months by the dermatology outpatient departments of the Faculty of Medicine, Chiang Mai University from June through October 2020 were included. Data on potential predictors, including baseline characteristics and laboratory investigations, were collected. The diagnoses of AI were based on serum 8AM cortisol and low-dose ACTH stimulation tests. Multivariable logistic regression was used for the derivation of the diagnostic score. RESULTS: Of the 42 patients, 17 (40.5%) had AI. The statistically significant predictive factors for AI were greater body surface area of corticosteroids use, age <60 years, and basal serum cortisol <7 µg/dL. In the final predictive model, duration of treatment was added as a factor based on its clinical significance for AI. The four predictive factors with their assigned scores were: body surface area involvement 10-30% (20), >30% (25); age <60 years old (15); basal serum cortisol of <7 µg/dL (30); and duration of treatment in years. Risk of AI was categorized into three groups, low, intermediate and high risk, with total scores of <25, 25-49 and ≥50, respectively. The predictive performance for the model was 0.92 based on area under the curve. CONCLUSION: The predictive model for AI in patients using topical corticosteroids provides guidance on the risk of AI to determine which patients should have dynamic ACTH stimulation tests (high risk) and which need only close follow-up (intermediate and low risk). Future validation of the model is warranted.

Age-Influenced Receptors of Advanced Glycation End Product Overexpression Associated With Osteogenic Differentiation Impairment in Patients With Type 2 Diabetes.

Preclinical studies have found impaired osteogenic differentiation to be associated with type 2 diabetes (T2DM), which is related to skeletal accumulation of advanced glycation end products (AGEs). Our previous study also showed impaired osteogenic differentiation in peripheral blood-derived mononuclear cells (PBMC) isolated from patients with long-standing T2DM, which is conceivably due to the overexpression of receptor of advance glycation end products (RAGE) and the enhancement of cellular apoptosis. However, the existence of RAGE overexpression in earlier stages of diabetes remains unclear, as do the factors influencing that RAGE overexpression. This cross-sectional study enrolled 40 patients with T2DM treated with metformin monotherapy and 30 age-matched non-diabetic controls (NDM) to investigate the overexpression of RAGE in PBMC derived from patients with earlier stage diabetes, as well as to explore its determining factors. Almost all (90%) PBMC-isolated from NDM (NDM-pD) expressed osteoblast-specific genes including ALPL, BGLAP, COL1A1, and RUNX2/PPAR while only 40% of PBMC-derived from diabetic patients (DM-pD) expressed those genes. By using age- and pentosidine-matched NDM-pD as a reference, AGER and BAX/BCL2 expression in PBMC isolated from diabetic patients showing impaired osteoblast-specific gene expression (DM-iD) were 6.6 and 5 folds higher than the reference while AGER and BAX/BCL2 expression in DM-pD were comparable to the reference. AGER expression showed a significant positive correlation with age (r=0.470, p=0.003). The multivariate analysis demonstrated that both age and AGER expression correlated with the potential for osteogenic differentiation in the PBMC isolated from patients with diabetes. In conclusion, this study showed osteogenic differentiation impairment in approximately half of PBMC derived from type 2 diabetic patients receiving metformin monotherapy. Both AGER and BAX/BCL2 overexpression were demonstrated only in PBMC-isolated from diabetic patients with poor osteogenic differentiation. Therefore, this study not only illustrated the existence of RAGE overexpression in PBMC derived from patients with early stages of T2DM but also strengthened the linkage between that RAGE overexpression and the retardation of osteogenic differentiation. Age was also shown to be a positive influencing factor for RAGE overexpression. Furthermore, both age and RAGE overexpression were demonstrated as independent risk factors for determining osteogenic differentiation potential of the PBMC-isolated from T2DM.

A Predictive Risk Score to Diagnose Adrenal Insufficiency in Outpatients: A 7 Year Retrospective Cohort Study.

Background: The diagnosis of adrenal insufficiency (AI) requires dynamic tests which may not be available in some institutions. This study aimed to develop a predictive risk score to help diagnose AI in outpatients with indeterminate serum cortisol levels. Methods: Five hundred and seven patients with intermediate serum cortisol levels (3-17.9 µg/dL) who had undergone ACTH (adrenocorticotropin) stimulation tests were included in the study. A predictive risk score was created using significant predictive factors identified by multivariable analysis using Poisson regression clustered by ACTH dose. Results: The seven predictive factors used in the development of a predictive model with their assigned scores are as follows: chronic kidney disease (9.0), Cushingoid appearance in exogenous steroid use (12.0), nausea and/or vomiting (6.0), fatigue (2.0), basal cortisol <9 µg/dL (12.5), cholesterol <150 mg/dL (2.5) and sodium <135 mEq/L (1.0). Predictive risk scores range from 0-50.0. A high risk level (scores of 19.5-50.0) indicates a higher possibility of having AI (positive likelihood ratio (LR+) = 11.75), while a low risk level (scores of <19.0) indicates a lower chance of having AI (LR+ = 0.09). The predictive performance of the scoring system was 0.82 based on the area under the curve. Conclusions: This predictive risk score can help to determine the probability of AI and can be used as a guide to determine which patients need treatment for AI and which require dynamic tests to confirm AI.

Sesamin suppresses advanced glycation end products induced microglial reactivity using BV2 microglial cell line as a model.

Neuroinflammation-mediated microglial reactivity is a major process, which explains the increased risk of Alzheimer's disease (AD) development in patients with Type 2 diabetes mellitus (T2DM). Advanced glycation end products (AGEs), formed by hyperglycemic condition in diabetes, is characterized as an intermediary of brain injury with diabetes through induction of microglial reactivity. Here, we explored the effect of AGEs on microglial reactivity using BV2 as a model. The NF-κB, p38 and JNK pathways were found to be important mechanism in AGEs-induced BV2 microglial reactivity. NF-κB inhibitor (BAY-11-7082), p38 inhibitor (SB203580) and JNK inhibitor (SP600125) exhibited the potential inhibition of AGEs-induced NO production. We also found that the sesamin, a major lignan found in sesame seed oils, exerts an anti-inflammatory effect under AGEs-induced microglial reactivity via suppressing the phosphorylation of NF-κB, p38 and JNK pathways. Moreover, sesamin also ameliorated AGEs-induced-receptor for advanced glycation end products (RAGE) expression. Taken together, sesamin may be a promising phytochemical compound to delay inflammatory progress by AGEs microglia function. Similarly, inhibition of AGEs-induced microglial reactivity might be potential therapeutic targets of neuroinflammation-based mechanisms in T2DM link progressive AD.

Type 1 diabetes management and outcomes: A multicenter study in Thailand.

AIMS/INTRODUCTION: The Thai Type 1 Diabetes and Diabetes Diagnosed Before Age 30 Years Registry, Care and Network was established in 2014 and involved 31 hospitals. The objective of the registry was to evaluate glycemic control and complications of patients with type 1 diabetes. MATERIALS AND METHODS: Patients' demographics, clinical data, frequencies of daily self-monitoring of blood glucose (SMBG), glycemic control and complications were collected. RESULTS: Among the 1,907 type 1 diabetes patients, the mean age was 21.2 ± 11.3 years. The mean glycated hemoglobin level was 9.35 ± 2.41%, with significant variations among age groups (P < 0.001). Conventional insulin treatment and intensive insulin treatment were used in 43 and 57% of patients, respectively. Mean glycated hemoglobin levels were significantly higher in patients treated with conventional insulin treatment compared to those treated with intensive insulin treatment (9.63 ± 2.34 vs 9.17 ± 2.46%, P = 0.002). Compared to the conventional insulin treatment group, significantly more patients in the intensive insulin treatment group achieved good glycemic control (P < 0.001), and fewer had diabetic retinopathy (P = 0.031). The prevalence of microvascular complications increased significantly with age (P < 0.001). Multivariate analysis showed good glycemic control to be associated with age 25 to <45 years, intensive insulin treatment with SMBG three or more times daily and diabetes duration of 1 to <5 years. CONCLUSIONS: Most Thai type 1 diabetes patients were not meeting the recommended glycemic target. As a result of this study, the national program to improve the quality of diabetes treatment and education has been implemented, and the results are ongoing.

Impact of iron overload on bone remodeling in thalassemia.

INTRODUCTION: Iron overload, a state with excessive iron storage in the body, is a common complication in thalassemia patients which leads to multiple organ dysfunctions including the bone. Iron overload-induced bone disease is one of the most common and severe complications of thalassemia including osteoporosis. Currently, osteoporosis is still frequently found in thalassemia even with widely available iron chelation therapy. STUDY SELECTION: Relevant publications published before December 2019 in PubMed database were reviewed. Both pre-clinical studies and clinical trials were obtained using iron overload, thalassemia, osteoporosis, osteoblast, and osteoclast as keywords. RESULTS: Increased ROS production is a hallmark of iron overload-induced impaired bone remodeling. At the cellular level, oxidative stress affects bone remodeling by both osteoblast inhibition and osteoclast activation via many signaling pathways. In thalassemia patients, it has been shown that bone resorption was increased while bone formation was concurrently reduced. CONCLUSION: In this review, reports on the cellular mechanisms of iron overload-associated bone remodeling are comprehensively summarized and presented to provide current understanding this pathological condition. Moreover, current treatments and potential interventions for attenuating bone remodeling in iron overload are also summarized to pave ways for the future discoveries of novel agents that alleviate this condition.

30-Minute Delta Cortisol Post-ACTH Stimulation Test and Proposed Cut-Off Levels for Adrenal Insufficiency Diagnosis.

The ACTH stimulation test is used to diagnose adrenal insufficiency (AI). This study evaluated the diagnostic performance of serum delta cortisol from ACTH stimulation tests and determined appropriate cut-off levels of serum 30-minute delta cortisol for the diagnosis of AI, allowing a reduction in the number of 60-minute cortisol tests. A 6-year retrospective study in 471 patients was conducted. The performance of the serum delta cortisol in diagnosing AI was assessd using a multivariable logistic regression model and the area under ROC curves (AuROC). Both serum 30-minute and 60-minute delta cortisol demonstrated equally high diagnostic accuracy for AI (AuROC for LDT : 0.91 vs 0.90 ; HDT : 0.91 vs 0.92, respectively). The 30-minute delta cortisol test was chosen to develop proposed diagnostic cut-off levels due to its simplicity. The proposed lower cut-off level for 30-minute delta cortisol was Δ < 1.8 µg/dL for both LDT and HDT. The upper cut-off levels were Δ > 11.8 µg/dL for LDT and Δ > 10.5 µg/dL for HDT. These cut-off levels yielded high sensitivity and specificity > 90%. The 30-minute serum delta cortisol using the proposed cut-off levels provides diagnostic performance for AI equal to that of the 60-minute test and is more convenient, requires less time, less invasive and is cost-saving. 67 : 95-101, February, 2020.

Predictive Factors of Adrenal Insufficiency in Outpatients with Indeterminate Serum Cortisol Levels: A Retrospective Study.

Background and Objectives: To diagnose adrenal insufficiency (AI), adrenocorticotropic hormone (ACTH) stimulation tests may need to be performed, but those tests may not be available in some institutions. In addition, they may not be necessary for some patients. The objective of this study was to identify clinical and biochemical factors that could facilitate AI diagnosis in outpatient departments and decrease the number of unnecessary dynamic tests. Materials and Methods: This seven-year retrospective study was performed in a tertiary care medical center. A total of 517 patients who had undergone ACTH stimulation tests in the outpatient department were identified. AI was described as a peak serum cortisol level of <18 µg/dL at 30 or 60 min after stimulation. The associations between clinical factors, biochemical factors, and AI were analyzed using the Poisson regression model and reported by the risk ratio (RR). Results: AI was identified in 128 patients (24.7%). Significant predictive factors for the diagnosis of AI were chronic kidney disease (RR = 2.52, p < 0.001), Cushingoid appearance (RR = 3.44, p < 0.001), nausea and/or vomiting (RR = 1.84, p = 0.003), fatigue (RR = 1.23, p < 0.001), serum basal cortisol <9 µg/dL (RR = 3.36, p < 0.001), serum cholesterol <150 mg/dL (RR = 1.26, p < 0.001), and serum sodium <135 mEq/L (RR = 1.09, p = 0.001). The predictive ability of the model was 83% based on the area under the curve. Conclusion: The easy-to-obtain clinical and biochemical factors identified may facilitate AI diagnosis and help identify patients with suspected AI. Using these factors in clinical practice may also reduce the number of nonessential dynamic tests for AI.