Factors associated with venous collaterals in patients with cerebral venous thrombosis.

OBJECTIVES: To identify the factors associated with venous collaterals in Thai patients with cerebral venous thrombosis. MATERIALS AND METHODS: This retrospective 20-year cohort study enrolled patients diagnosed with cerebral venous thrombosis between January 2002 and December 2022. Data was collected from the electronic medical record, and venous collaterals were independently reviewed by two neuroradiologists using the Qureshi classification. Patients with and without venous collaterals were compared. Significant factors (P<0.05) in the univariate analysis were recruited into the multivariate logistic regression analysis to determine independently associated factors. RESULTS: Among 79 patients with cerebral venous thrombosis, the prevalence of venous collaterals at the initial neuroimaging was 25.3%. In the univariate analysis, patients with cerebral venous thrombosis and venous collaterals were significantly younger (37.0±13.9 years vs. 44.9±17.4 years, P = 0.048), more often had occlusion in the superior sagittal sinus (80.0% vs. 54.2%, P = 0.041), and were associated with hormonal exposure (35.0% vs. 6.8%, P = 0.002). Multivariate logistic regression analysis revealed occlusion in the superior sagittal sinus (adjusted odds ratio [aOR] 3.581; 95% confidence interval [95% CI] 1.941-13.626; P = 0.044) and hormonal exposure (aOR 7.276, 95% CI 1.606-32.966, P = 0.010) as independent factors associated with venous collaterals in cerebral venous thrombosis. CONCLUSIONS: In this cohort, the prevalence of venous collaterals was 25.3%. Occlusion in the superior sagittal sinus and hormonal exposure were independently associated with venous collaterals in patients with cerebral venous thrombosis.

Factors associated with the initial intracranial hemorrhage occurrence in patients with cerebral venous thrombosis.

OBJECTIVES: Studies focusing on intracranial hemorrhage (ICH) in patients with cerebral venous thrombosis (CVT) are limited; thus, we aimed to identify factors associated with the occurrence of ICH in Thai patients with CVT. METHODS: This retrospective cohort study recruited patients with CVT admitted to a tertiary university-based hospital between 2002 and 2022. The baseline characteristics, clinical presentations, radiographic findings, and etiologies were compared between the ICH and non-ICH groups. The factors with p < 0.2 in the univariate analysis were further analyzed using multivariable logistic regression analysis to identify independent factors associated with ICH in patients with CVT. RESULTS: Of 228 screenings, 202 patients were eligible. The incidence rate of ICH was 36.63%. The ICH group showed a higher prevalence of focal neurological deficits (63.51% vs. 26.56%, p < 0.001), seizures (68.92% vs. 21.88%, p < 0.001), dependency status at admission (60.81% vs. 39.84%, p = 0.004), superior sagittal sinus thrombosis (71.62% vs. 39.07%, p < 0.001), superficial cortical vein thrombosis (36.49% vs. 10.16%, p < 0.001), and hormonal use (17.57% vs. 7.03%, p = 0.021) than the non-ICH group. In contrast, the ICH group showed a lower prevalence of isolated increased intracranial pressure (10.81% vs. 21.88%, p = 0.048) than the non-ICH group. Seizures (adjusted odds ratio [aOR], 4.537; 95% confidence interval [CI], 2.085-9.874; p < 0.001), focal neurological deficits (aOR, 2.431; 95% CI, 1.057-5.593; p = 0.037), and superior sagittal sinus thrombosis (aOR, 1.922; 95% CI, 1.913-4.045; p = 0.045) were independently associated with ICH in the multivariable logistic regression analysis. CONCLUSIONS: Seizures, focal neurological deficits, and superior sagittal sinus thrombosis are associated with ICH in patients with CVT.

Progression of insulin resistance in individuals with type 1 diabetes: A retrospective longitudinal study on individuals from Thailand.

AIMS: To investigate temporal changes in glycaemic control and weight contributing to insulin resistance (IR), in Thai individuals with type 1 diabetes (T1D). METHODS: Longitudinal data of 69 individuals with T1D were retrospectively collected over a median follow-up of 7.2 years. The estimated glucose disposal rate (eGDR), a marker of IR, was calculated using an established formula. Individuals were assigned as insulin-sensitive T1D (the latest eGDR≥8 mg/kg/min), or insulin-resistant T1D/double diabetes (the latest eGDR<8 mg/kg/min). Generalised linear mixed model was employed to compare the temporal patterns of HbA1c, BMI, and eGDR between the two groups. RESULTS: 26 insulin-resistant T1D had a gradual decline in eGDR, corresponding with increased weight and HbA1c. In contrast, 43 insulin-sensitive T1D had stable insulin sensitivity with an improvement in HbA1c over time, associated with a modest weight gain. Fluctuations of glucose levels were observed during the early diabetes course leading to unstable eGDR, thus limiting the use of eGDR to classify insulin-resistant T1D. CONCLUSION: T1D individuals who eventually develop IR are likely to experience early increasing IR over time. In contrast, those who ultimately do not have IR, maintain their insulin sensitivity throughout their course at least in the medium term.

Assessment of Biological Activities, Acute and Sub-chronic Toxicity of Liang (Gnetum gnemon var. tenerum) Leaves Powder, a Natural Product.

Gnetum gnemon var. tenerum (Gnetaceae) is a shrub plant native to South-East Asia. In Thailand, Liang leaves are commonly consumed in South of Thailand as vegetable. According to literature, they have an antihyperglycemic capacity because of their rich chlorophyll, fiber, and protein. However, there is need to assess the safety since natural food products are not completely devoid of toxicity. This study aimed to assess the biological activities as well as the acute and sub-chronic oral toxicity of Liang leaves powder (LLP). The evaluation of LLP for acute oral toxicity was performed at dose level 2000 mg/kg body weight in Wistar rats while the sub-chronic oral toxicity of LLP was performed at the effective dose (1.47 g/kg) for antihyperglycemic property according to Organisation for Economic Co-operation and Development (OECD)-425. The results showed that LLP demonstrated anti-inflammatory activities. It also showed no clinical signs of toxic effects and mortality in rats throughout 90 d. Thus, LLP could be classified in GHS category 5 which are of relatively low acute toxicity and then the lethal dose, 50% (LD50) cut off at 5000 mg/kg body weight to infinity (∞). Administration of LLP to the experimental rats significantly increased (p < 0.05) the concentration of triglyceride and increased concentration of creatinine as a result of kidney malfunction was also noticed in the experimental rats. Hematological alteration was not noticed in the treated female rats, but red blood cell, hemoglobin and hematocrit concentrations significantly increased in the treated male rats. The study concludes that sub-chronic administration of 1.47 g/kg LLP is relatively safe.

The Antihyperglycemic Effect of Crude Liang (Gnetum gnemon var. tenerum) Leaves Powder on Wistar Rats.

Chlorophyll and chlorophyllin (CHL) demonstrated antidiabetic activity by inhibiting gluconeogenesis and increasing glucose uptake in rats' muscle cells. Liang leaves contain high amounts of chlorophyll and chlorophyllin and may provide an antidiabetic effect. The antidiabetic activity of chlorophyll and CHL contained in Liang leaves, Cu-chlorophyllin (CCL) Liang leaves treated with CuSO4, and untreated crude Liang leaves (CLL) were compared using commercial chlorophyllin (CHL) as a reference. Twelve Wistar male rats were separated into 4 groups (3 rats/group); the first was a normal one (based line group), the second were the diabetic rats treated with CHL, while the third and the fourth were the diabetic rats treated with 0.97 g/kg of CCL and CLL, respectively. Diabetic rats were induced by a high fructose diet, before being taken to administer commercial CHL, CCL, and CLL for 7 days. Nonfasting blood glucose and body weight were checked daily. After euthanasia, organ weight, biochemical, hematological, and histopathological properties were evaluated. CCL treatment showed no antihyperglycemic activity in the rat model but caused some biochemical abnormalities and thrombocytopenia. Commercial CHL gave a higher reduction of nonfasting blood glucose (NFBG) than Liang leaves powder CCL or CLL but also showed some signs of abnormal biochemical parameters. CLL exhibited an antihyperglycemic effect, with higher body weight and increased HDL/LDL ratio and thus could be a promising alternative natural source for diabetes treatment.

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.

Factors associated with acute symptomatic seizure occurrence among patients with posterior reversible encephalopathy syndrome.

OBJECTIVES: We aimed to define the factors associated with acute symptomatic seizure occurrence in posterior reversible encephalopathy syndrome (PRES) in the Thai-Asian population. MATERIALS AND METHODS: We conducted a retrospective cohort study enrolling patients with PRES admitted to the hospital between 2006 and 2019. In addition to seizure characteristics, baseline characteristics, clinical presentations, precipitating factors, neuroimaging characteristics, hospital complications, and hospital outcomes were compared between the seizure and non-seizure groups. Factors with p-value <0.05 in the univariate analysis were entered into the first model of multivariate logistic regression analysis to determine the factors associated with seizure occurrence if the p-value <0.05. The interaction of associated factors was also analyzed in the final multiple logistic regression analysis model. RESULTS: Acute symptomatic seizure, which is mainly based on the clinical documentation without electroencephalography, occurred in 50.0% of 136 patients with PRES. Of these, early seizures within 14 days of PRES occurred in 98.5% which mostly developed at presentation (82.4%) with a single seizure attack (55.9%). Convulsive seizures (77.9%) were the most common seizure semiology. The seizure group was significantly younger (median [interquartile range: IQR] 36.00 years old (21.75-48.50) vs 46.50 years old (31.25-61.00), p = 0.003). In univariate analysis, the seizure group had a higher prevalence of consciousness impairment (61.76% vs 26.47%, p < 0.001), Glasgow coma scale (GCS) score of 0-13 (42.46% vs 13.23%, p < 0.001), preeclampsia (20.58% vs 4.41%, p = 0.004), autoimmune disease (17.65% vs 5.88%, p = 0.033), and frontal lesions (25.00% vs 11.76%, p = 0.046) than those in the non-seizure group. In contrast, the seizure group had a lower prevalence of headache (27.94% vs 61.76%, p < 0.001). In the final multivariate logistic regression analysis which included the interaction terms, the acute symptomatic seizure occurrence directly associated with preeclampsia (adjusted odds ratio (aOR) 6.426, 95% confidence interval (CI) 1.450-27.031, p = 0.016) and autoimmune disease (aOR 4.962, 95% CI 1.283-18.642, p = 0.025), while headache showed a reverse association (aOR 0.310, 95% CI = 0.158-0.721, p = 0.008). CONCLUSIONS: Acute symptomatic seizure occurred in a half of patients with PRES in this cohort. Preeclampsia and autoimmune disease were directly associated with seizure occurrence, while headache showed a reverse association.

Predictors of Hospital Outcomes Among Patients with Posterior Reversible Encephalopathy Syndrome.

OBJECTIVES: We aimed to identify independent predictors of the clinical outcomes of posterior reversible encephalopathy syndrome (PRES) in the Thai-Asian population. MATERIALS AND METHODS: This retrospective cohort study recruited PRES patients admitted in the hospital between 2006 and 2019. The baseline characteristics, clinical presentations, precipitating factors, neuroimaging characteristics, hospital complications, and hospital outcomes were compared between the groups with favourable (modified Rankin scale [mRS] score, 0-2) and unfavourable (mRS score, 3-6) clinical outcomes. Factors presenting with p-values < 0.5 in univariate analysis were analysed in the multiple logistic regression model to determine independent predictors of outcome. RESULTS: Among 136 PRES patients, 22.80% experienced unfavourable outcomes (mRS score, 3-6), and the mortality rate was 7.35%. The common presenting symptoms in the unfavourable clinical outcome group were impairment of consciousness (90.32%) and seizures (67.74%). Sepsis as a hospital complication (adjusted odds ratio [aOR], 32.95; 95% confidence interval [CI], 4.44-244.22, p = 0.001), acute kidney injury as a hospital complication (aOR, 9.94; 95% CI, 1.71-57.66; p = 0.010), and impairment of consciousness (aOR, 10.85; 95% CI, 1.72-68.53, p = 0.011) were independent predictors of unfavourable outcomes. On the other hand, headache was an independent protective factor (aOR, 0.164; 95% CI, 0.03-0.91; p = 0.039). CONCLUSIONS: Impairment of consciousness, sepsis as a hospital complication, and acute kidney injury were independent predictors of unfavourable clinical outcomes, whereas headache showed a preventive effect.

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.

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.

Basal Insulin Dose Titration for Glycemic Control in Patients With Type 2 Diabetes Mellitus in Thailand: Results of the REWARDS Real-World Study.

This multicenter, longitudinal, descriptive, observational study of T2DM adults in Thailand aimed to assess real-world outcomes of basal insulin (BI) dose titration on glycemic control. Three-hundred and twenty-four patients were recruited and followed up over 24 weeks. Basal insulin titration was physician-driven in 58.2% of patients and patient-driven in the rest. During the 24-week study period, the total daily BI dose moved from 20.9 to 25.6 in the physician-driven group, while in the patient-driven group, it increased from 25.3 to 29.7. Thirty-five patients (11.2%) achieved their individualized HbA1c targets, with 18 patients (5.8%) achieving HbA1c ⩽ 7% without documented hypoglycemia. In summary, this study highlights that BI titration is suboptimal in the real world, and patients are unable to achieve their glycemic targets.

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase.

BACKGROUND: Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11ß-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease. METHODS: LINC 3 was a prospective, multicentre, open-label, phase III study with a double-blind randomised withdrawal period, that comprised four periods. Patients aged 18-75 years, with confirmed persistent or recurrent Cushing's disease (defined as mean 24-h urinary free cortisol [UFC] concentration >1·5 times the upper limit of normal [ULN] and morning plasma adrenocorticotropic hormone above the lower limit of normal) who had previously had pituitary surgery or irradiation, or were newly diagnosed and who refused surgery or were not surgical candidates, were recruited from 66 hospital sites and private clinical practices in 19 countries. In period 1, open-label osilodrostat was initiated in all participants and adjusted every 2 weeks (1-30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h UFC concentration and safety until week 12. In period 2, weeks 13-24, osilodrostat was continued at the therapeutic dose determined during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomly assigned (1:1), via an interactive-response technology, stratified by osilodrostat dose at week 24 and history of pituitary irradiation, to continue osilodrostat or switch to placebo for 8 weeks. Participants and investigators were masked to treatment assignment. Ineligible participants continued open-label osilodrostat. In period 4, weeks 35-48, all participants were given open-label osilodrostat until core-study end. The primary objective was to compare the efficacy of osilodrostat versus placebo at the end of period 3. The primary endpoint was the proportion of participants who had been randomly assigned to treatment or placebo with a complete response (ie, mean 24-h UFC concentration of ≤ULN) at the end of the randomised withdrawal period (week 34), without up-titration during this period. The key secondary endpoint was the proportion of participants with a complete response at the end of the single-arm, open-label period (ie, period 2, week 24) without up-titration during weeks 13-24. Analysis was by intention-to-treat for all patients who received at least one dose of osilodrostat (full analysis set; key secondary endpoint) or randomised treatment (randomised analysis set; primary endpoint) and safety was assessed in all enrolled patients who received at least one dose of osilodrostat and had at least one post-baseline safety assessment. LINC 3 is registered with ClinicalTrials.gov, NCT02180217, and is now complete. FINDINGS: Between Nov 12, 2014, and March 22, 2017, 202 patients were screened and 137 were enrolled. The median age was 40·0 years (31·0-49·0) and 106 (77%) participants were female. 72 (53%) participants were eligible for randomisation during the withdrawal phase, of whom 36 were assigned to continue osilodrostat and 35 were assigned to placebo; one patient was not randomly assigned due to investigator decision and continued open-label osilodrostat. More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7-53·4]; p<0·0001). At week 24, 72 (53%; 95% CI 43·9-61·1) of 137 patients maintained a complete response without up-titration after week 12. Most common adverse events (ie, occurred in >25% of participants) were nausea (57 [42%]), headache (46 [34%]), fatigue (39 [28%]), and adrenal insufficiency (38 [28%]). Hypocortisolism occurred in 70 (51%) patients and adverse events related to adrenal hormone precursors occurred in 58 (42%) patients. One patient died, unrelated to study drug, after the core study phase. INTERPRETATION: Twice-daily osilodrostat rapidly reduced mean 24-h UFC and sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. Osilodrostat is an effective new treatment option that is approved in Europe for the treatment of endogenous Cushing's syndrome and in the USA for Cushing's disease. FUNDING: Novartis Pharma AG.

A case report of successful identification of ectopic parathyroid adenomas with a sequence of selective parathyroid venous sampling and 4D-computed tomography in a patient with recurrent hyperparathyroidism.

INTRODUCTION: Recurrent hyperparathyroidism is difficult to manage due to the difficulty in finding the missing adenoma. Herein we present a case of recurrent hyperparathyroidism from ectopic adenomas which basic investigations failed to locate but were finally localized by a 4DCT following selective venous sampling (SVS) of parathyroid hormone (PTH). PRESENTATION OF CASE: A young female presented with recurrent hyperparathyroidism. She had severe primary hyperparathyroidism and temporary normocalcemia after first parathyroidectomy. Her hypercalcemia recurred and required second operation. However, the second operation was unsuccessful due to the pre-operation ultrasound, computed tomography (CT) neck, and sestamibi failed to identify the culprit parathyroid adenoma. After the second operation, positron emission tomography (PET), CT neck and sestamibi failed to identify the tumor but a sequence of SVS PTH and four-dimensional computed tomography (4DCT) successfully identified several ectopic adenomas. DISCUSSION: Ectopic parathyroid tissue is the most common cause of recurrent hyperparathyroidism but precisely locating these ectopic glands is often challenging. Despite modern modalities such as PET scans, the success rate is not impressive. SVS PTH is a good method to regionalize the ectopic source of PTH. With the more specified area, fine-tuning imaging with a 4DCT can identify the specific location of the ectopic parathyroid tissue. CONCLUSION: A sequence of SVS PTH followed by 4DCT could identify the exact location of ectopic parathyroid adenomas in a patient when conventional non-invasive imaging studies failed.

Effects of meal replacement therapy on metabolic outcomes in Thai patients with type 2 diabetes: A randomized controlled trial.

BACKGROUND: A meal replacement (MR) with a low glycemic index (GI) is possibly beneficial for glycemic control. However, the effects of MR on diabetes mellitus have not been studied among Thai patients with type 2 diabetes (T2DM). AIM: To compare metabolic outcomes between T2DM patients receiving the new MR formula (ONCE PRO) and normal controlled diets. METHODS: A multicenter, open-labeled, randomized controlled trial was conducted. Eligible patients received either ONCE PRO for one meal daily with controlled diets or only controlled diets for 3 months. The differences in metabolic profile between the baseline and end point of each group and between groups were measured. RESULTS: 110 participants were enrolled; the mean difference and standard deviation in hemoglobin A1C (HbA1c) (%) from baseline were -0.21 ± 0.78 (p = 0.060) and -0.27 ± 0.60 (p = 0.001) in the MR and control groups, respectively; however, there was no significant difference between groups (p = 0.637). Patients consuming a MR instead of breakfast had a significant decrease in HbA1c (p = 0.040). Body weight (BW) and body mass index (BMI) were significantly reduced in both groups. There were no significant change in waist circumference, fasting plasma glucose, total cholesterol and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was significantly decreased in the MR group compared with the control group (p = 0.049). CONCLUSIONS: Short-term conventional diet control and the low-GI MR product were associated with a decreased BW and BMI. Changes in the other metabolic outcomes, HbA1c, total cholesterol and triglycerides, were comparable despite ONCE PRO as the MR having a better effect on LDL-C lowering.

Effect of phytosterols and inulin-enriched soymilk on LDL-cholesterol in Thai subjects: a double-blinded randomized controlled trial.

BACKGROUND: Hypercholesterolemia, particularly high LDL-c and non-HDL-c levels, is a traditional risk for cardiovascular disease. Ingestion of diets containing phytosterols and inulin can reduce plasma LDL-c and triglyceride levels, respectively. Phytosterols and inulin-enriched soymilk may be an alternative for a supplemental diet to improve both LDL-c and non-HDL-c to reduce the risk of cardiovascular disease. METHODS: Two hundred and forty subjects who were 18 years old or older and had a baseline LDL-c of 130 mg/dl or higher were enrolled into the double-blinded randomized controlled trial study. Subjects were randomly assigned into the study group that received 2 g/day of phytosterols and 10 g/day of inulin-enriched soymilk or into the control group that received standard soymilk. The lipid profile was measured every 2 weeks for 8 weeks. Primary outcomes were 1) to determine the LDL-c reduction after consumption of phytosterols and inulin-enriched soymilk for 8 weeks and 2) to compare the difference of the LDL-c levels between the study and control groups. The secondary outcomes were to compare the difference of TC, TG and HDL-c between the study and control groups. RESULTS: At the end of the study, the median LDL-c levels decreased significantly from 165 (132, 254) mg/dl to 150 (105, 263) mg/dl in the study group (p < 0.001) and from 165 (130, 243) mg/dl to 159 (89, 277) mg/dl in the control group (p = 0.014). The LDL-c reduction was significantly better in the study group (-10.03%, (-37.07, 36.00) vs -1.31% (-53.40, 89.73), p < 0.001). TC also reduced significantly by 6.60% in the study group while it reduced only by 1.76% in the control group (p < 0.001). There were no statistical differences in TG and HDL-c levels between both study groups. The adverse events in the study group and the control groups were not different (RR 1.33 [0.871-2.030, 95 % CI]). CONCLUSION: Daily consumption of soymilk containing 2 g of phytosterols and 10 g of inulin reduced TC and LDL-c better than standard soymilk. It had no effect on TG and HDL-c levels compared to standard soymilk. Both soymilk products were comparably safe. TRIAL REGISTRATION: Thai Clinical Trial Registry: TCTR20150417001 date: April 17, 2015.

Effects of pravastatin, phytosterols, and combination therapy on lipid profile in HIV-infected patients: an open-labelled, randomized cross-over study.

BACKGROUND: To determine the effects of 40 mg of pravastatin, 2 g of phytosterols, and combination therapy on lipid profiles and to compare the reduction of LDL cholesterol between combination therapy and monotherapy. METHODS: Thirty-six HIV-infected patients treated with ARVs who had high LDL cholesterol levels but no current usage of any lipid-lowering agents were enrolled into the open-labelled, randomized, cross-over study. All patients were assigned randomly into one of four intervention groups: (1) pravastatin 40 mg cross-over to the combination of pravastatin 40 mg and phytosterols 2 g (combination group), (2) the combination group cross-over to pravastatin 40 mg, (3) phytosterols 2 g cross-over to the combination group, and (4) the combination group cross-over to phytosterols 2 g. Each active treatment lasted 4 weeks with a wash-out period of 4 weeks. RESULTS: The baseline mean TC, TG, HDL-c, and LDL-c levels in 36 HIV patients were 248.09 ± 34.73, 172.36 ± 125.44, 54.92 ± 16.67, and 175.13 ± 29.00 mg/dl, respectively. Pravastatin, phytosterols, and combination therapy reduced TC and LDL-c but TG and HDL-c were not significantly different from the baselines. The mean LDL-c reductions in the pravastatin, phytosterols, and the combination groups were 28.76 ± 9.32, 9.12 ± 7.84, and 27.08 ± 15.58%, respectively. The LDL-c levels in the pravastatin and combination groups were reduced more than in the phytosterols group (p < 0.01). There was no difference in the LDL-c reduction between the combination and pravastatin monotherapy groups (-25.61 ± 10.43 vs. -28.12 ± 14.07%, p = 0.555). CONCLUSION: Pravastatin had moderate potency on LDL-c lowering in HIV patients but could not bring LDL-c to goal. Adding phytosterols to pravastatin for a 4-week duration could not demonstrate any additional lipid-lowering effect TRIAL REGISTRATION: Thai Clinical Trial Registry: TCTR20150126002 date: January 23, 2015.

Apolipoprotein B as an independent predictor of arterial stiffness in systemic lupus erythematosus patients.

AIM: To determine the relationship of apolipoprotein B (Apo-B) and arterial stiffness determined by brachial-ankle pulse wave velocity (baPWV) in systemic lupus erythematosus (SLE) subjects. METHODS: Eighty-seven Thai SLE subjects with inactive disease activity were studied. Fasting blood was collected for creatinine, glucose, lipid profiles, Apo-B and Apo-A1. Pearson correlation and stepwise-linear regression were used for the analysis. RESULTS: The mean age of the subjects was 36.69 ± 10.85 years; 6.90% of them had stage 3 or more severe chronic kidney disease, 49.40% took anti-hypertensive drugs and 4.60% had abnormal glucose metabolism. The mean value for baPWV was 1332 ± 274.12 cm/s. Thirty-six percent of the subjects had increased arterial stiffness with mean Apo-B levels of 1.05 ± 0.31 g/L compared to 0.94 ± 0.24 in normal arterial stiffness. There were correlations of baPWV with age, systolic blood pressure (BP), diastolic BP and creatinine clearance. Apo-B tended to be associated with baPWV (P = 0.06) whereas low-density lipoprotein cholesterol did not (P = 0.2). By multiple regression analysis, systolic BP, age and Apo-B were the significant predictors of baPWV. CONCLUSION: Apo-B was independently associated with arterial stiffness in SLE subjects.

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.

Acute severe hypercalcemia after traumatic fractures and immobilization in hypophosphatasia complicated by chronic renal failure.

CONTEXT: Hypophosphatasia (HPP) features deficient activity of the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP) due to loss-of-function mutation(s) within the TNSALP gene. Consequently, inorganic pyrophosphate, a TNSALP substrate and inhibitor of mineralization, accumulates extracellularly. This can cause rickets or osteomalacia. OBJECTIVE: We report a 55-year-old man with HPP and chronic renal failure (CRF) requiring hemodialysis who developed severe hypercalcemia acutely after traumatic fractures and immobilization. He manifested HPP in childhood and in middle age received hemodialysis for CRF attributed to hypertension and anti-inflammatory medication. He took 2 g of calcium carbonate orally each day to bind dietary phosphorus, but never aluminum hydroxide or any form of vitamin D. Pretrauma serum levels of calcium spanned 8.4-10.7 mg/dL (normal [Nl], 8.6-10.3), inorganic phosphate 5.8-6.4 mg/dL (Nl, 2.5-4.5), and PTH 63-75 pg/mL (Nl, 10-55). RESULTS: Rapid succession falls fractured multiple major bones. Six hours later, he became confused. Serum calcium was 14.9 mg/dL, ionized calcium was 7.4 mg/dL (Nl, 4.5-5.1), and PTH was 16 pg/mL. Hemodialysis quickly corrected his hypercalcemia and confusion. Low serum alkaline phosphatase persisted, and follow-up skeletal histopathology showed that his osteomalacia was severe. CONCLUSION: Hemodialysis does not heal the skeletal disease of HPP. During sudden fracture immobilization in HPP, sufficient calcium can emerge from bone, perhaps from a rapidly exchangeable calcium pool, to cause acute severe hypercalcemia if the kidneys cannot compensate for the mineral efflux. Hence, we worry that acute hypercalcemia might accompany sudden immobilization in CRF patients without HPP if they have adynamic bone disease.

The association between CYP 2C9 polymorphism and bone health.

PURPOSE: There is a strong scientific rationale to support the view that cytochrome P450 (CYP P450) enzyme-inducing AEDs induce bone loss in patients with epilepsy. However, no study has investigated the association between CYP 2C9 polymorphism and bone mineral density (BMD), 25-hydroxyvitamin D or parathyroid hormone levels in patients with epilepsy. This study sought to determine the association between BMD and CYP 2C9 polymorphism. METHODS: Ninety-three patients taking phenytoin as monotherapy were examined for CYP 2C9 polymorphism, vitamin D level and parathyroid hormone level and underwent basic chemistry testing. The bone mineral density of the lumbar spine and left femur were measured using dual-energy X-ray absorptiometry. RESULTS: The results indicated that about 18.3% of the patients with epilepsy were positive for CYP2C9*3. Furthermore, bone mineral density was associated with CYP 2C9 polymorphism epileptic patients. Specifically, patients with 2C9 polymorphism had higher T-scores and Z-scores of the femoral neck (p=0.02 and 0.04, respectively), but not of the lumbar spine (p=0.27 and 0.06, respectively). There was also a trend of having higher serum PTH levels and statistically significantly lower 25-hydroxyvitamin D levels in patients with wild type than in those compared with CYP 2C9 polymorphism (p=0.05 and 0.03, respectively). Additionally, the patients with CYP 2C9 polymorphism had higher plasma levels of phenytoin, particularly when compared with those with wild type (p=0.01). However, there was no association between serum levels of phenytoin and low BMD at femoral neck or lumbar spine. CONCLUSION: CYP 2C9 polymorphism is associated with higher BMD, independent of plasma levels of phenytoin.