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.

DUOX2 variants are a frequent cause of congenital primary hypothyroidism in Thai patients.

OBJECTIVE: To identify the genetic etiologies of congenital primary hypothyroidism (CH) in Thai patients. DESIGN AND METHODS: CH patients were enrolled. Clinical characteristics including age, signs and symptoms of CH, pedigree, family history, screened thyroid-stimulating hormone results, thyroid function tests, thyroid imaging, clinical course and treatment of CH were collected. Clinical exome sequencing by next-generation sequencing was performed. In-house gene list which covered 62 potential candidate genes related to CH and thyroid disorders was developed for targeted sequencing. Sanger sequencing was performed to validate the candidate variants. Thyroid function tests were determined in the heterozygous parents who carried the same DUOX2 or DUOXA2 variants as their offsprings. RESULTS: There were 118 patients (63 males) included. Mean (SD) age at enrollment was 12.4 (7.9) years. Forty-five of 118 patients (38%) had disease-causing variants. Of 45 variants, 7 genes were involved (DUOX2, DUOXA2, TG, TPO, SLC5A5, PAX8 and TSHR). DUOX2, a gene causing thyroid dyshormonogenesis, was the most common defective gene (25/45, 56%). The most common DUOX2 variant found in this study was c.1588A>T. TG and TPO variants were less common. Fourteen novel variants were found. Thyroid function tests of most parents with heterozygous state of DUOX2 and DUOXA2 variants were normal. CONCLUSIONS: DUOX2 variants were most common among Thai CH patients, while TG and TPO variants were less common. The c.1588A>T in DUOX2 gene was highly frequent in this population.

Growth hormone treatment in adolescent males with idiopathic short stature: changes in body composition, protein, fat, and glucose metabolism.

CONTEXT: Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH. OBJECTIVE: Our objective was to assess longitudinally the effects of short-term GH supplementation in adolescent males with non-GH-deficient idiopathic short stature (ISS) on body composition, substrate metabolism, and insulin sensitivity. Children with ISS were studied to simulate the pubertal increase in GH secretion. PARTICIPANTS AND SETTING: Eight males with ISS (10.8-16.5 yr) were recruited from pediatric endocrinology clinics at an academic medical center. STUDY DESIGN: Participants were evaluated in the General Clinical Research Center before and after 4 months of GH supplementation (0.3 mg/kg.wk). Body composition was assessed with dual-energy x-ray absorptiometry. Whole-body glucose, protein, and fat turnover were measured using stable isotopes. In vivo insulin action was assessed during a 3-h hyperinsulinemic (40 mU/m(2).min) euglycemic clamp. RESULTS: GH supplementation led to 1) increase in hepatic glucose production and fasting insulin levels, 2) increase in lean body mass and decrease in fat mass, and 3) improvement in cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with insulin levels. CONCLUSIONS: Four months of GH supplementation in adolescent males with ISS is associated with significant body composition changes and hepatic insulin resistance.

Short-term pharmacologically induced growth study of ontogenetic allometry of oxygen uptake in children.

BACKGROUND: A range of allometric coefficients have been proposed in describing the maximal oxygen uptake (VO2max): body mass relation in children using weight-bearing ergometry. However, a wide deviation in the allometric coefficients for VO2max may be apparent when selected pediatric cohorts are studied in conjunction with clinical intervention for growth abnormalities. AIM: The purpose of this study was to determine the allometric coefficients for VO2max after short-term pharmacologically induced growth in pre- and early pubescent children. SUBJECTS AND METHODS: The treatment group consisted of nine subjects with non-growth hormone (GH)-deficient short stature and one with GH-deficient short stature (mean age: 13.7+/-1.7 years). Ten pre- and early pubescent children matched for age, height, weight, VO2max and body mass index (BMI) were controls. The treatment group were evaluated before (Pre-GH) and after (Post-GH) 4 months of subcutaneous GH therapy (0.05 mgkg(-1)day(-1) x 6 days week(-1)). RESULTS: The mean ontogenetic coefficient for the treatment group was 1.50+/-0.20 and for the control group was 0.77+/-0.34. The mean allometric coefficient for body mass relative to VO2max was significantly higher in the treatment group compared with the control group (p<0.05). Height, weight, fat free mass (FFM), VO2max indexed to body mass (mLkg(-1)min(-1)) and FFM (mLkgFFM(-1)min(-1)) increased (p<0.05) with GH therapy. GH therapy also increased insulin-like growth factor-I (IGF-I) and served as a biochemical marker of GH therapy (p<0.05). The control group had no significant differences in all the variables tested (p<0.05). CONCLUSION: The scaling for oxygen uptake (VO2) for body mass varies with GH treatment and the increase in VO2max that commonly occurs in conjunction with physical growth in the pre-and early pubescent individual may be linked to an increase in FFM and linear size.

Evaluation of the bedside glucose monitoring system in neonatal units.

OBJECTIVE: To evaluate the performance of a commercial reader compared with a laboratory method in neonates with a variety of diseases and conditions. PATIENTS AND METHOD: A total of 175 patients were included in the present study. Venous whole blood samples were analyzed with a commercial reader by trained nurse. Through the same sampling site, specimens were collected, spun and plasma were sent to the laboratory for measurement of plasma glucose. RESULTS: The regression analysis between the results of a commercial reader and laboratory glucose were significantly correlated (r = 0.97; p < 0.001) with the result as follows: A commercial reader = Laboratory glucose - 0.17 (n = 175). A positive slope of 0.04 was found between hematocrit and difference between a commercial reader and laboratory plasma glucose. However, this correlation was of little clinical significance. CONCLUSIONS: A commercial reader showed a good correlation with the standard laboratory method for the measurement of plasma glucose in neonates with a variety of diseases and conditions.

Deadspace: a potential error in concentration of medication during dilutional process in neonates.

OBJECTIVE: To evaluate the volume of deadspace (DS) and degree of errors in concentration of medications during medication dilution with needle removable syringe (NRS) compared to needle nonremovable syringe (NNRS). MATERIAL AND METHOD: 300 syringes were tested and divided into 3 groups as follows: The first group was 100 syringes of needle removable insulin 1 ml syringe (NRIS) with a 27 gauge needle (Terumo), the second group was 100 syringes of NRIS with a 27 gauge needle (Nipro) and third group 3 was 100 syringes of needle non removable insulin syringe (NNRIS) with a 27 gauge needle (Terumo). All syringes with needle sets (without needle cover) were weighed with a Mettler electronic balance. Volume of DS was measured and calculated using a standard method. 10 syringes of each group were randomly selected to test for degree of errors in concentration of medications during the dilutional process using standard insulin (310 micro unit per ml) as a medication for dilution. All specimens were collected by ejecting all diluents into collecting tubes and insulin concentrations were measured using radioimmunoassay technique (insulin-CT biointernational, France) twice in each sample. Concentration was then calculated back and the results were noted and analysed. RESULTS: Means of DS in group 3 (2.4 +/- 0.8 microl) was significantly less than group 1 (49.7 +/- 00.9 microl) and group 2 (65.3 +/- 0.7 microl) (median = 2 microlitre). All three groups were significantly different from each other with the largest DS in group 2. After dilution, insulin concentrations from diluents in group 3 were still close to standard insulin (335 +/- 28 vs 310 microunits/ml), whereas group 1 and 2 were significantly higher than group 3 (1.7 and 1.9 times) and standard insulin (1.8 and 2 times). CONCLUSIONS: DS in NRIS is not negligible and is considered a potential source of error in the concentration of medications when it is used to dilute parenteral medications in the neonatal intensive care unit (NICU).

Detection of symptoms by adolescents and young adults with type 1 diabetes during experimental induction of mild hypoglycemia: role of hormonal and psychological variables.

OBJECTIVE: To identify hormonal, psychological, and demographic predictors of symptom detection and accuracy of blood glucose estimation during mild hypoglycemia in adolescents and young adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: During an insulin-glucose clamp study, 53 adolescents and 19 young adults estimated blood glucose levels and reported symptoms at euglycemia and after 30 min of mild hypoglycemia (3.3 mmol/l). Epinephrine and pancreatic polypeptide were measured, and both change in anxiety level during hypoglycemia and baseline level of anxiety were measured with the Spielberger Anxiety Inventory. Elevated levels of anxiety during euglycemia were used as an indicator of the psychological trait "negative affectivity." Previous studies have suggested that individuals with higher negative affectivity are more internally focused and, therefore, more likely to report somatic and visceral changes. RESULTS: During mild hypoglycemia, 42% of the sample subjects reported an increase in autonomic symptoms; 29% reported an increase in neuroglycopenic symptoms, and 28% estimated blood glucose levels accurately (within 10% of actual). Hormonal excursions did not predict any outcome, but higher anxiety levels during the euglycemic baseline were associated with better detection of hypoglycemic symptoms and more accurate estimation of blood glucose values after controlling for change in anxiety level during hypoglycemia. CONCLUSIONS: Psychological factors such as elevated anxiety levels ("negative affectivity") can influence blood glucose estimation and symptom detection in adolescents and young adults and may explain why some individuals are more adept than others at reducing their risk of severe hypoglycemia after participation in a formal blood glucose awareness training program.