Overdiagnosis of adrenal insufficiency in children with biliary atresia.

Serum cortisol mainly binds to the cortisol-binding globulin (CBG). Children with biliary atresia (BA) may have low serum CBG levels; thus, low serum total cortisol (TC) levels and adrenal insufficiency (AI) may be overdiagnosed. This study aimed to assess adrenal function in children with BA. All the patients underwent adrenocorticotropic hormone (ACTH) stimulation tests. Plasma ACTH, serum TC, and CBG levels were measured at baseline, with additional TC measurements at 30 and 60 min during testing. Free cortisol (FC) index (FCI) and calculated FC (cFC) were also calculated. AI was defined as peak TC <500 nmol/L (<18 µg/dL), peak FCI <12 nmol/mg, or peak cFC <33 nmol/L (<1.2 µg/dL). This study enrolled 71 children with BA. The Median (IQR) age of the patients was 5.5 (1.7-11.4) years. Twenty-five (35%) patients were diagnosed with AI based on the peak TC. In the AI group, the median serum CBG level was significantly lower than that in the non-AI group (481 vs. 533 nmol/L, p = 0.03). Only eight patients (11%) met all three AI criteria (six secondary AI and two primary AI). In conclusion, low serum CBG levels contribute to reduced peak TC and, consequently, overdiagnosing AI. Peak FCI and cFC could help reduce the overdiagnosis of AI.

Genetic Polymorphisms of Pesticide-Metabolizing Enzymes and Transporters in Agricultural Workers and Thyroid Hormone Levels.

PURPOSE: Chronic exposure to pesticides has been associated with thyroid dysfunction owing to their endocrine disruption ability. Genetic variations in genes encoding phase I and II enzymes and phase III transporters are partly responsible for individual responses to chemical pesticides. This study investigated the association between variations in genes involved in pesticide metabolism and altered thyroid hormone concentrations. METHODS: We assessed thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) in organic agriculture workers (n = 216) and workers who used chemical pesticides (n = 229). A questionnaire was used to collect sociodemographic, pesticide exposure, and health status data. Blood samples were analyzed for TSH, FT3, and FT4. Genomic DNA was extracted and genotyped using the TaqMan real-time PCR genotyping assay and restriction fragment length polymorphism method for 15 metabolically related genes. RESULTS: Significant differences in the TSH (1.58 vs 1.12 µIU/mL) and FT3 (0.34 vs 0.31 ng/dL) concentrations between the chemical and organic worker groups were observed. The frequencies of all single nucleotide polymorphisms were in Hardy-Weinberg equilibrium and were mostly consistent with Asian populations. The findings showed the association between SNPs of enzymes and transporters and TSH, FT3, and FT4. The odd ratio and adjusted odd ratio (with sex, age, smoking status, alcohol consumption and exposure parameters) for subclinical thyroid disease by the variant alleles CYP1A1 rs1048943, CYP2B6 rs2279343, CYP2C19 rs4244285, NAT2 rs1799931, and PON1 rs662 in the chemical workers compared with the organic workers were found (P values < 0.05). CONCLUSION: This is the first study to assess gene-environment interactions in Thai agricultural workers by investigating disruptions of the hypothalamic-pituitary-thyroid axis. The investigated SNP profiles revealed several gene-thyroid hormone associations in which even low levels of pesticide exposure could disturb thyroid homeostasis. These findings provide a foundation for planning future studies investigating associations between complex diseases and occupational pesticide exposure.

Gut Microbiota Characteristics in Children After the Use of Proton Pump Inhibitors.

BACKGROUND/AIMS: Prolonged acid suppression from proton pump inhibitor (PPI) has been shown to cause gut microbiota alteration which may increase risk of various infections in adults. We aimed to characterize gut microbiota profiles in children after a short-term use of PPI. MATERIALS AND METHODS: Children aged 1-18 years who underwent PPI therapy were included during April-December 2017. We excluded children who previously used antibiotics or acid suppressants, had a history of acute gastroenteritis or specific food avoidance one month prior to the enrolment. The stool samples before and after the PPI use were collected for gut microbiota composition. The 16S ribosomal RNA gene sequencing was performed by using Illumina MiSeq. The differences in gut microbiota profile after the use of PPI were compared to pre-PPI period. RESULTS: We completed stool collection in 20 children (median age of 5.8 years and 60% were female). No significant changes in the overall number of species-level taxonomy categories or predominant bacteria phylum (Bacteroidetes) were noted. We found a trend increase in the proportion of phylum Firmicutes among children living in the metropolitan/suburban area (P=.07) and among males (P=.11). In four children with infection-related adverse effects, we noted a non-significant increase in the proportion of phylum Firmicutes after the PPI use (from 35 to 52%, P = .14). CONCLUSION: Even the total number and predominant gut microbiota did not significantly change after a four- to eight-week course of PPI therapy; we found a trend of increased proportion of phylum Firmicutes in certain groups of children.

A reduced serum level of total osteocalcin in men predicts the development of diabetes in a long-term follow-up cohort.

BACKGROUND: Osteocalcin (OC), an osteoblast-specific protein, has been demonstrated to affect glucose metabolism in both animals and humans. Studies in animals have shown an effect of undercarboxylated OC (ucOC) on beta-cell proliferation and insulin resistance. It remains unclear whether OC is associated with the future development of diabetes in humans, as well as the relative importance of ucOC vs OC. OBJECTIVE: The aim of this study was to examine serum OC and its post-translational forms as potential biomarkers for future the development of type 2 diabetes. METHODS: This was a nested case-control study using data from the Electricity Generating Authority of Thailand (EGAT). We identified 63 men without diabetes in the exploratory cohort at baseline who developed type 2 diabetes (DM) during the 10-year follow-up period from 1998-2008, and also 63 men age- and BMI-matched for a non-diabetes control group (non-DM). Serum N-mid OC and ucOC were measured in baseline blood samples. Logistic regression models were used to explore and identify baseline factors, including OC and ucOC, that predicted the subsequent development of diabetes. RESULTS: The mean age and BMI were similar in both non-DM and DM groups (47·2 ± 0·5 vs 47·8 ± 0·8 years and 25·2 ± 0·5 vs 25·9 ± 0·5 kg/m(2) , respectively). Only baseline mean serum N-mid OC (15·2 ± 0·5 vs 13·0 ± 0·5 µg/l, P < 0·05) and fasting plasma glucose (4·92 ± 0·04 vs 5·28 ± 0·07 mmol/l, P < 0·05) were significantly different between the two groups. Multiple logistic regression analysis showed that baseline serum N-mid OC and glucose, but not ucOC, were independent risk factors for the development of diabetes in this long-term study cohort. CONCLUSIONS: Circulating total OC is associated with incident diabetes in men. Further studies to evaluate the potential utility of OC as a biomarker to predict the development of type 2 diabetes are warranted.

The preservation of insulin sensitivity in obese women without diabetes.

OBJECTIVE: To assess insulin sensitivity, pancreatic beta-cell function, and compare circulating levels of adiponectin and ghrelin in obese women with and without diabetes. MATERIAL AND METHOD: Ninety-nine obese women with a body mass index (BMI) > or = 25 kg/m2 and age at least 40 years without previous history of diabetes participated in this study. Oral glucose tolerance test was performed in all subjects. Serum for insulin, adiponectin, and ghrelin were obtained at baseline. Data were expressed as mean +/- SEM. RESULTS: Oral glucose tolerance test revealed 66 non-diabetic (ND) and 33 diabetic (D) subjects. Despite a similar degree of obesity, women without diabetes had near normal insulin sensitivity (ND, 105.7 +/- 6.4%; D, 62.3 +/- 5.9%; p < 0.001) and beta cell function (ND, 95.4 +/- 3.0%; D, 79.0 ++/- 6.1%; p < 0.001) as assessed by the HOMA model. Non-diabetic subjects had higher serum adiponectin levels despite similar BMI (ND, 8.3 +/- 0.4 mg/ml; D, 6.3 +/- 0.4 mg/ml; p < 0.01). Obese subjects with diabetes had lower serum ghrelin levels than obese non-diabetic subjects (ND, 1027.2 +/- 32.0 pg/ml; D, 875.1 +/- 34. 6 pg/ml; p < 0.05). CONCLUSION: Obese women without diabetes have less pancreatic beta cell dysfunction and higher insulin sensitivity than obese women with diabetes. Higher circulating adiponectin may play protective roles in obese non-diabetic subjects, but the significance of higher ghrelin level should be further explored.