PARAMETERS BETWEEN LOW AND HIGH DOSES OF PIOGLITAZONE IN TYPE 2 DIABETIC PATIENTS

Pioglitazone (PIO) is highly effective in decreasing blood glucose levels for type 2 diabetes mellitus (T2D), but it can induce serious adverse events such as edema and heart failure (HF). Some previous studies showed that the efficacy on glucose control and lipid levels was not related to the difference in doses of PIO in opposite to the incidence of edema which was doses-dependent of PIO. To compare glucose control, lipid control, adverse events, and pharmacokinetic (PK) parameters between low and high doses of PIO in T2D. Medical chart of 139 diabetic patients using PIO at Ramathibodi hospital were reviewed to compare outcomes and adverse effects between low and high doses of PIO. 38 patients who stabilized dose of PIO and agree to participate were recruited to collect 2 blood samples at 2 appropriated times and were analyzed their PIO concentrations, then, PK parameters were determined. The outcomes of glucose control and lipid control were not differences between low and high dose of PIO, but edema and HF events were significantly higher in high dose of PIO (P=0.010 and P=0.014, respectively). For PK parameters of PIO, elimination rate constant (ke) and clearance rate (CL) values of patients who were stabilized on high dose of PIO were significantly higher (P=0.022 and P=0.031, respectively) while elimination halflife (t1/2) was significantly shorter (P=0.007) than those who were stabilized on low dose of PIO. PK monitoring fo

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 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 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

Copy Number Variation in Thai Population

<div><p>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 <i>Thai CNV</i> 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.</p></div

Thai CNV and CNVR characteristics.

<p>Thai CNV and CNVR characteristics.</p

CNV discovery in the Thai population.

<p>a) Diagram showing Thai CNV discovery workflow; b) % overlap proportion of CNVs identified by both CNV Workshop and PennCNV based on CNV size (bp). The regions shaded in red correspond to CNVs exclusively discovered by CNV Workshop, while regions shaded in blue represent those jointly discovered by CNV Workshop and PennCNV.</p

GWAS studies containing the genomics data of 3,017 Thai individuals after exclusion of low quality samples.

<p>GWAS studies containing the genomics data of 3,017 Thai individuals after exclusion of low quality samples.</p

Hierarchical clustering analysis (HCA) of the 35 genes overlapping CNVs with statistically significantly different allele frequencies across HapMap3 populations as compared with Thais (permutation P-value <0.0002).

<p>The color bar on the right shows the color codes assigned to each frequency range in percent.</p

CNV and CNVR comparison between the Thai and eleven HapMap3 populations.

<p>a) Size distribution of the Thai CNVs and HapMap3 CNVs; b) Allele frequency spectrum of CNVs with frequency of at least 1% across the Thai and HapMap3 CNVRs; c) Degree of match between the Thai CNVRs and HapMap3 CNVRs with reference to allele frequency.</p

Common CNVRs with at least 5% allele frequency in Thai population and their frequencies across HapMap3 populations.

<p>CNVRs covering HLA, immunoglobulin superfamily, and OR genes were excluded due to their multiallelic nature, which might result in inaccuracy of CNV calling in these regions.</p