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

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

Single measurement of intact parathyroid hormone after thyroidectomy can predict transient and permanent hypoparathyroidism: a prospective study.

OBJECTIVE: Immediate postoperative hypocalcemia is the most common complication of bilateral thyroidectomy. Although hypocalcemia is usually transient, it can be fatal. This study aimed to find a predictor of immediate postoperative hypocalcemia by using intact parathyroid hormone (PTH) level at 4 hours after thyroidectomy (iPTH4hr) compared with the decline in the percentage of intact PTH (%iPTH). We also followed the subjects for evaluation of permanent hypoparathyroidism. METHODS: This was a prospective study of 65 patients (86.2% female, mean age: 43±15 years) who planned to undergo total or subtotal thyroidectomy. Preoperative and iPTH4hr were measured. RESULTS: Thirty-nine patients (60%) were diagnosed with papillary thyroid carcinoma, while the rest were multinodular goiter (21.5%) and Graves' disease (7.7%). Significant immediate hypocalcemia was observed in 25 (38.5%) patients. Both iPTH4hr <12.5 pg/mL and %iPTH decline >72% could accurately predict significant immediate hypocalcemia. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for iPTH4hr were 92%, 87.5%, 82.1%, and 94.6%, respectively. The %iPTH decline was equal in accuracy, with sensitivity, specificity, PPV, and NPV of 84%, 90%, 84%, and 90%, respectively. At 6 months after surgery, 19 patients (29.2%) displayed permanent hypoparathyroidism. The iPTH4hr <12.5 pg/mL and %iPTH decline >72% could also predict permanent hypoparathyroidism, with sensitivity, specificity, PPV, and NPV of 100%, 80.4%, 67.9%, and 100%, and 94.7%, 84.8%, 72%, and 97.5%, respectively. CONCLUSIONS: Only a single measurement of iPTH4hr could be helpful in identifying patients at risk of significant immediate hypocalcemia in need prompt treatment, and subsequently facilitating early discharge of patients. Also, this parameter can precisely predict permanent hypoparathyroidism.

The association of soluble IGF2R and IGF2R gene polymorphism with type 2 diabetes.

The aim of this study is to investigate the insulin-like growth factor type 2 (IGF2R) gene and circulating soluble IGF2R in relation to type 2 diabetes (T2DM). Six hundred fifty-four subjects without history of diabetes were screened for diabetes by oral glucose tolerance test. In addition, 145 subjects with known diabetes were recruited from a local diabetes clinic. Circulating IGF2R levels were measured by ELISA method; plasma glucose was measured by colorimetric method; insulin levels were determined by chemiluminescent method; IGF2R gene rs416572 was genotyped using real-time PCR. The distributions of IGF2R genotypes were 69.2% CC, 27.8% CT, and 3.0% TT. The C allele was more commonly found in diabetes subjects, with a significant difference (P < 0.01). In the presence of the T allele, circulating IGF2R levels were significantly lower (P < 0.05). There was no significant difference in other potential confounders including age, sex, and BMI. Only circulating IGF2R, age, and BMI were independently associated with the degree of insulin resistance, as assessed by the HOMA model. It was found that age, sex, and BMI were associated with beta cell function. In conclusion, IGF2R gene polymorphism and circulating IGF2R are associated with T2DM.

Copy number variation in Thai population.

Copy number variation (CNV) is a major genetic polymorphism contributing to genetic diversity and human evolution. Clinical application of CNVs for diagnostic purposes largely depends on sufficient population CNV data for accurate interpretation. CNVs from general population in currently available databases help classify CNVs of uncertain clinical significance, and benign CNVs. Earlier studies of CNV distribution in several populations worldwide showed that a significant fraction of CNVs are population specific. In this study, we characterized and analyzed CNVs in 3,017 unrelated Thai individuals genotyped with the Illumina Human610, Illumina HumanOmniexpress, or Illumina HapMap550v3 platform. We employed hidden Markov model and circular binary segmentation methods to identify CNVs, extracted 23,458 CNVs consistently identified by both algorithms, and cataloged these high confident CNVs into our publicly available Thai CNV database. Analysis of CNVs in the Thai population identified a median of eight autosomal CNVs per individual. Most CNVs (96.73%) did not overlap with any known chromosomal imbalance syndromes documented in the DECIPHER database. When compared with CNVs in the 11 HapMap3 populations, CNVs found in the Thai population shared several characteristics with CNVs characterized in HapMap3. Common CNVs in Thais had similar frequencies to those in the HapMap3 populations, and all high frequency CNVs (>20%) found in Thai individuals could also be identified in HapMap3. The majorities of CNVs discovered in the Thai population, however, were of low frequency, or uniquely identified in Thais. When performing hierarchical clustering using CNV frequencies, the CNV data were clustered into Africans, Europeans, and Asians, in line with the clustering performed with single nucleotide polymorphism (SNP) data. As CNV data are specific to origin of population, our population-specific reference database will serve as a valuable addition to the existing resources for the investigation of clinical significance of CNVs in Thais and related ethnicities.

Reference ranges of serum TSH, FT4 and thyroid autoantibodies in the Thai population: the national health examination survey.

OBJECTIVE: Data on reference intervals of thyroid functions in Southeast Asia are limited. The aim of this study was to provide reference ranges of thyroid functions and thyroid autoantibodies in Thais. DESIGN AND METHODS: Serum samples from 2545 apparently healthy non-pregnant subjects, aged ≥14 years, from the fourth Thai National Health Examination Survey were measured for TSH, FT4, antithyroperoxidase (TPO Ab), antithyroglobulin (Tg Ab) and antithyrotrophin receptor antibodies (TRAb). A reference population was selected from the disease-free population by excluding those who had thyroid autoantibodies and TSH > 20 mIU/l. RESULTS: For the total population, median TSH and FT4 levels were 1·94 mIU/l and 1·35 ng/dl, respectively. TSH was higher and FT4 was lower in females than in males. Based on National Academy of Clinical Biochemistry criteria, the reference intervals (2·5th-97·5th percentile) were: TSH, 0·34-5·11 mIU/l; FT4, 0·98-1·79 ng/dl; TPO Ab, 5-84·88 IU/ml; Tg Ab, 10-118·2 IU/ml; and TRAb, 0·3-1·24 IU/l. With the new reference ranges, hypothyroidism was found in 4·16% of the total population (0·78% overt and 3·38% subclinical hypothyroidism) and hyperthyroidism was found in 3·18% (0·94% overt and 2·24% subclinical hyperthyroidism). Positive TPO Ab, Tg Ab and TRAb were found in 8·96%, 12·26% and 5·93%, respectively. The upper normal limit of TSH tended to increase with age, particularly for those aged 80 years and older. CONCLUSIONS: The reference interval for TSH needs to be derived from each specific population. Slightly elevated TSH concentrations in the elderly could be considered acceptable, with no need for thyroxine treatment.

Aspirin non-responder in Thai ischemic stroke patients.

BACKGROUND: An important cause of recurrent ischemic stroke is failure to prevent secondary stroke due to poor control of important stroke risk factors. One of the proposed important risk factor is aspirin resistance. The prevalence of aspirin resistance varied widely. It depended on heterogeneity in studied populations and methods of platelet functional assessment. OBJECTIVE: To describe the prevalence of aspirin resistance based on optical platelet aggregometry in stroke patients who attended the Neurological Institute and investigate the clinical risk factors associated with aspirin resistance. MATERIAL AND METHOD: Three hundred stable ischemic stroke patients, whose aspirin dosage varied between 60 to 325 mg/day for at least 14 days before enrollment were recruited in the present study. Demographic data, modifiable risk factors, and treatment were collected by interview and from medical records. Aspirin resistance was determined by optical platelet aggregation technique, using arachidonicacid (AA) and adenosine diphosphate (ADP) as agonists. RESULTS: The patients were classified into two groups based on their platelet aggregatometry tests (PAT). The cases group (n = 40, 13.3%) included both patients with aspirin resistance (n = 2, 0.6%) and aspirin semi-responsiveness (n = 38, 12.7%). The control group was aspirin non-resistance (n = 260, 86.7%). The cases were older (64.8 year vs. 61.26 year, p = 0.049), higher proportion of females (60% vs. 41.5%, p = 0.029), and shorter in height (159.9 CM vs. 164.1 CM, p = 0.007) than the control group. Dosage and duration of the aspirin therapy were the same in both groups. The multivariate analysis showed old age was associated with aspirin resistance. CONCLUSION: The prevalence of aspirin resistance in the present study is 0.6% (95% CI, 0.18%-1.38%). The risk factor for aspirin resistance in post stroke patients is aging. No association between duration and aspirin dosage with aspirin resistance was found. The proportion of aspirin resistance was similar to a previous study done in post myocardial infarction patients.

A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis.

Several lines of evidence have pointed out that genetic components have roles in thyrotoxic hypokalemic periodic paralysis (TTPP). In this study, for the first time we performed genome-wide association study (GWAS) in male hyperthyroid subjects in order to identify genetic loci conferring susceptibility to TTPP. We genotyped 78 Thai male TTPP cases and 74 Thai male hyperthyroid patients without hypokalemia as controls with Illumina Human-Hap610 Genotyping BeadChip. Among the SNPs analyzed in the GWAS, rs312729 at chromosome 17q revealed the lowest P-value for association (P=2.09 × 10(-7)). After fine mapping for linkage disequilibrium blocks surrounding the landmark SNP, we found a significant association of rs623011; located at 75 kb downstream of KCNJ2 on chromosome 17q, reached the GWAS significance after Bonferroni's adjustment (P=3.23 × 10(-8), odds ratio (OR)=6.72; 95% confidence interval (CI)=3.11-14.5). The result was confirmed in an independent cohort of samples consisting of 28 TTPP patients and 48 controls using the same clinical criteria diagnosis (replication analysis P=3.44 × 10(-5), OR=5.13; 95% CI=1.87-14.1; combined-analysis P=3.71 × 10(-12), OR=5.47; 95% CI=3.04-9.83).

Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis.

Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis.

The association between vitamin D status and circulating adiponectin independent of adiposity in subjects with abnormal glucose tolerance.

Vitamin D status assessed by serum 25-hydroxyvitamin D levels (25(OH)D) has been shown to be inversely associated with insulin resistance. The underlying basis for such association is less clear. In the present study, we assessed the prevalence of inadequate vitamin D levels and its relationship to glucose tolerance status and circulating adiponectin in healthy Thai population. The cohort of 246 subjects was classified into two groups according to 75 g oral glucose tolerance test (OGTT) results. There were 86 subjects and 160 subjects in normal glucose tolerance group (NGT) and abnormal glucose tolerance group (AGT), respectively. Anthropometric variables were recorded for each individual. Fasting blood samples were assayed for 25(OH)D, adiponectin, glucose, and insulin levels. Insulin resistance (HOMA-IR) and insulin secretion index (HOMA-B) were calculated by the homeostasis model assessment. Pearson and partial correlation analyses were performed. There were 35 males and 211 females with a mean age of 62.4 +/- 7.2 years in this study. The mean levels of 25(OH)D were 21.4 +/- 6.6 ng/ml. The prevalence of vitamin D deficiency defined by 25(OH)D levels less than 20 ng/ml and vitamin D inadequacy defined by 25(OH)D levels less than 30 ng/ml were 44.3 and 91.9%, respectively. The mean levels of 25(OH)D obtained from samples collected in the rainy season (19.4 +/- 4.6 ng/ml) were significantly lower than those collected in the winter (22.6 +/- 8.3 ng/ml) and summer period (23.1 +/- 4.6 ng/ml). AGT subjects had slightly lower average 25(OH)D levels than the NGT group (21.0 +/- 6.8 vs. 22.1 +/- 6.2 ng/ml, P = 0.09). 25(OH)D levels were positively associated with adiponectin levels (r = 0.20, P < 0.05) and negatively associated with HOMA-IR and BMI (r = -0.22, P < 0.01 and r = -0.22, P < 0.01, respectively) only in AGT subjects. An independent association between 25(OH)D and adiponectin levels was demonstrated after controlling for BMI (r = 0.17, P < 0.05). High prevalence of vitamin D inadequacy and seasonal variation of vitamin D status are found in Thai population. We demonstrated an association between insufficient vitamin D status and lower circulating adiponectin in subjects with abnormal glucose tolerance independently of adiposity which may indicate the role of adiponectin as a link between vitamin D status and insulin resistance.

Differences in insulin sensitivity, pancreatic beta cell function and circulating adiponectin across glucose tolerance status in Thai obese and non-obese women.

Although adiponectin levels are associated with obesity and insulin insensitivity, the role of adiponectin in the progression to diabetes in non-obese subjects is unclear. Therefore, 289 women aged 50-80 years without previous history of diabetes or impaired glucose tolerance (IGT) were studied. They were classified as normal glucose tolerance (NGT), IGT or diabetes based on WHO criteria. Insulin sensitivity (S) and beta cell function (B) indices were calculated using homeostasis model assessment (HOMA). In obese women with BMI > or = 25 kg/m(2) (n = 161), there were declines in HOMA-%S (P < 0.001), HOMA-%B (P < 0.05) and circulating adiponectin (P < 0.001) across glucose tolerance status. In non-obese women with BMI < 25 kg/m(2) (n = 128), there was no significant change in HOMA-%S in women with IGT and diabetes as compared to women with NGT. However, HOMA-%B (P < 0.05) and serum adiponectin levels (P < 0.001) were significantly decreased across glucose tolerance. Serum adiponectin levels were correlated to HOMA-%S in both obese and non-obese women while negative correlations between circulating adiponectin and HOMA-%B were demonstrated only in obese women. We have demonstrated in the present study the predominant role of beta cell dysfunction as compared to that of insulin resistance in the deterioration of glucose tolerance in non-obese women. Circulating adiponectin appears to be inversely related to beta cell dysfunction in addition to insulin resistance only in obese women.

Association of genetic variants in GABRA3 gene and thyrotoxic hypokalaemic periodic paralysis in Thai population.

BACKGROUND: Genetic predisposition has been suggested to play role in the pathogenesis of thyrotoxic hypokalaemic periodic paralysis (THPP). OBJECTIVES: In this study, we assessed the differences of single-nucleotide polymorphisms (SNP) allelic frequency between THPP patients and well-characterized controls in order to find the susceptibility genetic variants related to THPP using microarray-based assessments on pooled DNA. METHODS: Fifty cases of THPP and 50 male hyperthyroid patients without hypokalaemia as controls were recruited. Equal amounts of individual genomic DNA were pooled from each group. Estimated allele frequencies of SNPs were derived by averaging relative allele signal score obtained by Affymetrix GeneChip(R) Mapping 10K Arrays. RESULTS: Sixty-nine loci that display robust allele frequency differences between THPP and controls were identified. SNP rs750841 (A > T) in intron 3 of the gamma-aminobutyric acid (GABA) receptor alpha3 subunit (GABRA3) gene possessed the most significant difference in allele frequency (27% in THPP case and 5% in controls, P = 0.007). Actual allele frequencies obtained from genotyping in each individual were very similar to the estimated frequency from the pools (28% in THPP and 2% in controls, and P = 0.0002). Nearby DNA sequences of GABRA3 were sequenced and an additional two SNPs were found (A > C at exon 1 and G > T of rs12688128). Allele A of rs750841 and allele G of rs12688128 in intron 3 were predominantly found in THPP with significant genetic relative risk of 19 (P < 0.0002; 95%CI 2.4-151.6). CONCLUSIONS: Whole-genome scanning on pooled DNA provides an accurate, useful screening tool for elucidating genetic underpinnings of THPP. SNPs at intron 3 of GABRA3 are found to be associated with THPP.

Advancing age and renal impairment as important predisposing factors of gatifloxacin-induced hyperglycemia in non-diabetes patients.

There have been case reports about adverse effects to glucose homeostasis related to gatifloxacin use. The authors report an elderly, non-diabetic patient who developed severe hyperglycemia after receiving oral gatifloxacin 400mg/d. He was a 73-year-old male, patient with a history of hypertension, cured vesical pheochromocytoma, idiopathic dilated cardiomyopathy, chronic renal insufficiency (baseline serum creatinine of 1.7 mg/dL), and gouty arthritis admitted to the hospital with a diagnosis of acute bronchitis. Seven days after initiating gatifloxacin, his symptoms were improved. Subsequently he developed polyuria, polydipsia, and fatigue with an increase in serum creatinine to 2.8 mg/dL, and random plasma glucose levels elevated to 903 mg/dL. Gatifloxacin was stopped. Intravenous regular insulin infusion was administered. Euglycemia was achieved within 8 hours after fluid rehydration and only low dose insulin was required He maintained normal glucose levels without any antidiabetic drugs afterward. Old age and renal impairment were considered significant contributing factors for this hyperglycemic adverse event from gatifloxacin.

Insulin and C-peptide levels, pancreatic beta cell function, and insulin resistance across glucose tolerance status in Thais.

Impaired pancreatic beta cell function and insulin sensitivity are fundamental factors in the pathogenesis of type 2 diabetes; however, the predominant defect appears differ among ethnic groups. We conducted a cross-sectional study to evaluate the contribution of impaired beta cell function and insulin sensitivity at different stages of the deterioration of glucose tolerance in Thais. The study involved 420 urban Thais of both sexes, 43-84 years old. A 75-g oral glucose tolerance test was performed on all of the subjects. Indices of insulin resistance and beta cell function were calculated with the use of a homeostasis model assessment. The subjects were classified as having normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG and IGT, or type 2 diabetes mellitus according to the American Diabetes Association (ADA) criteria. There were no differences between groups with regard to gender and age. The percentage of obesity was significantly greatest in the diabetic group. Fasting serum insulin and C-peptide levels progressively increased from the NGT to the diabetic subjects. Serum C-peptide was more strongly associated with newly diagnosed diabetes than insulin, and was an independent factor associated with newly diagnosed diabetic subjects. The insulin resistance index progressively increased when the glucose tolerance stage changed from NGT through diabetic subjects. Beta cell function did not change significantly in any other group compared to the NGT group. An increase in fasting serum C-peptide may be a risk factor for type 2 diabetes. Obesity and insulin resistance are the predominant features in the deterioration of glucose tolerance in Thais.

The relation between parameters from homeostasis model assessment and glycemic control in type 2 diabetes.

OBJECTIVE: To determine the association of insulin sensitivity and pancreatic beta-cell function parameters assessed by the homeostasis model assessment (HOMA) and glycemic control, and their potential utilization in the clinical care of patients with type 2 diabetes mellitus. MATERIAL AND METHOD: The HOMA indices were assessed in 204 (62 males, 142 females) type 2 diabetic outpatients aged 60.7 +/- 10.9 years. All patients were non-insulin treated for their diabetes. The correlation between variables including logarithmically transformed HOMA-%S and HOMA-%B, body mass index (BMI) and duration of diabetes to glycemic control were assessed The value of the disposition index (HOMA-%SxHOMA-%B) that best discriminated patients with good glycemic control (HbA1C < 7%) from those without (HbA1C > or = 7%) was determined. RESULTS: Both log (HOMA-%S) and log (HOMA-%B) were inversely related to HbA1C with comparable degrees of association (beta = -0.62, p < 0.001 and beta = -0.61, p < 0.001, respectively). The log-transformed disposition index of at least 3.57 had a sensitivity of 74.2% and a specificity of 67.6% in classifying patients as having HbA1C < 7%. The result suggested that in order to achieve acceptable glycemic control, oral hypoglycemic agents should be adjusted to maximize the likelihood of the log-transformed disposition index reaching 3.57. CONCLUSIONS: Glycemic control in diabetic patients partially depends on both insulin sensitivity and pancreatic beta-cell function. Assessing both parameters with the HOMA model is likely to result in a more rational approach for achieving better glycemic control in type 2 diabetic patients.

Prevalence of thyroid dysfunction in Thai HIV-infected patients.

Increasing prevalence of thyroid function abnormality has been reported in HIV-infected patients. We aim to evaluate the prevalence and assess risk factors of thyroid dysfunction in Thai HIV-infected patients. A cross-sectional study was conducted. Serum thyroid hormone concentrations (FT4, FT3, and TSH) and thyroid autoantibodies (TgAb and TPOAb) were measured by electrochemiluminescence immunoassay. A total of 200 HIV-infected outpatients were included. Ninety-seven patients (48.5%) were men (mean age of 36.3 +/- 8.3 years). Duration of HIV infection was 49.6 +/- 35.1 months and 53% had previous opportunistic infections (OI). Mean CD4 cell count was 340.6 +/- 173.1 cells/mm(3). Of these, 167 patients (83.5%) received antiretroviral therapy (ARV). Abnormal thyroid function test was detected in 32 patients (16%). Twenty-seven patients (13.5%) had decreased thyroid function (primary hypothyroidism 3, subclinical hypothyroidism 12, and low FT4 with low or normal TSH 12) whereas 5 patients had increased thyroid function (overt hyperthyroidism 1, subclinical hyperthyroidism 1, and isolated high FT3 3). None had clinical features of thyroid hormone dysfunction. Thirteen patients (6.5%) had thyroid antibody positive. Patients who received ARV had higher mean FT3 levels than those who were naïve to ARV (p = 0.017). History of previous OI was found to be an independently significant risk factor for decreased thyroid function with the odds ratio of 3.28 (95% CI =1.183-9.099; p = 0.022). Hypothyroidism was common among Thai HIV-infected patients, especially in those who had history of previous OI. It is therefore suggested that screening and/or monitoring of thyroid hormone in HIV-infected patients should be considered.

Similarity of the allele frequency and linkage disequilibrium pattern of single nucleotide polymorphisms in drug-related gene loci between Thai and northern East Asian populations: implications for tagging SNP selection in Thais.

The similarity of the marker allele frequency and linkage disequilibrium structure between two populations are major factors for the determination of the transferability and efficiency of haplotype tagging SNP derived from one population to use for an indirect association study in another population. To prove the similarity between northern East Asian populations in Hapmap and Thais, 861 SNP in 166 drug-related genes shared between Thais, Han Chinese and Japanese were analyzed for their correlation statistics. Allele frequency, Fst statistics and linkage disequilibrium statistics (r (2)) showed a high correlation between these populations. TagSNP sets derived by an aggressive tagging algorithm from these 861 SNP in Japanese and Chinese were used to test the coverage of East Asia-derived tagSNP in Thais. TagSNP derived from Japanese and Chinese are comparable in the percentage of coverage of the alleles captured with tagSNP at r (2)>or=0.8 (93% vs. 93%) in these drug-related gene loci. Additional tagSNP sets derived from the combination of Japanese- and Chinese-derived tagging SNP sets were used to test the coverage in Thais. The later set improved the percentage of coverage of alleles captured with tagSNP at r (2)>or=0.8-98% for these sites. High similarity between Thais and northern East Asian allele frequency and linkage disequilibrium statistics supported that tagSNPs derived from the northern East Asian population should be useful for an indirect association study in Thais. The combination of non-overlapping Japanese derived tagSNP and Chinese-derived tagSNP improved the percentage of genomic coverage in Thais, at least in these drug-related gene loci.

Efficacy of intermittent low dose alendronate in Thai postmenopausal osteoporosis.

Alendronate has been proven to be effective in the prevention and treatment of postmenopausal osteoporosis with the recommended daily dose of 10 mg. However, a constraining requirement for dosing limited its general acceptance in treatment. Since alendronate is potent and has a long half-life, weekly administration of alendronate in lower total doses might be safer and more convenient. The purpose of this study was to determine the efficacy of low dose once-weekly 20 mg alendronate in Thai postmenopausal women with osteoporosis. Thirty-nine postmenopausal women with osteoporosis received alendronate 20 mg once a week plus 750 mg elemental calcium daily. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at baseline and 6 and 12 months after treatment. Serum C-terminal telopeptide of type I collagen (CTx-I) was measured by electrochemiluminescence immunoassay at baseline and 3 months after treatment. By the end of 1 year, once weekly 20 mg alendronate significantly increased vertebral BMD (+6.2%, p < 0.001 vs baseline) from baseline whereas there was a reduction of 60.7% in serum CTx-I at 3 months. However, the BMD at femur did not increase significantly (+0.64%). Conclusion. Low-dose intermittent once-weekly 20 mg alendronate was effective, cost saving and had a good safety profile in increasing vertebral BMD and stabilizing BMD at the femoral neck in postmenopausal osteoporosis.

Effect of alendronate on bone mineral density and bone turnover in Thai postmenopausal osteoporosis.

Alendronate has recently been approved for the prevention and treatment of postmenopausal osteoporosis, and its efficacy has been demonstrated in many Western countries. Our present study was performed to evaluate the effect of alendronate on bone mineral density (BMD) and its tolerability in Thais. Eighty postmenopausal women with osteoporosis participated in this study. After giving informed consent, the subjects were randomly allocated either 10 mg alendronate or placebo in a double-blind fashion. All patients received a supplement of 500 mg elemental calcium daily. BMD at the lumbar spine, femoral neck, and distal forearm was measured at baseline and 6 and 12 months after treatment. Biochemical markers of bone resorption were determined at baseline and 6 months after treatment. Baseline characteristics were similar in both alendronate- and placebo-treated groups. Ten subjects discontinued the study. Of 70 subjects, 32 received 10 mg alendronate daily and the remaining subjects received placebo. At 1 year, BMD in the alendronate-treated group had increased from baseline by 9.2%, 4.6%, and 3.1% at lumbar spine, femoral neck, and distal forearm, respectively. These percentages were greater than those in controls (4.1%, 0.6%, and 1.0%, respectively). Urinary N-terminal telopeptide (NTx)-I and serum C-terminal telopeptide (CTx)-I levels decreased in both groups after 6 months of treatment. However, more reduction was demonstrated in the alendronate-treated group (71.9% vs. 28.4%, P < 0.01, and 84.7% vs. 33.1%, P < 0.01, respectively). Compliance with treatment and drug tolerability were good in both alendronate and placebo groups. We concluded that treatment with alendronate 10 mg daily for Thai postmenopausal women with osteoporosis significantly increased BMD at all skeletal sites and reduced biochemical markers of bone resorption. It was well tolerated without any serious side effects.