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1.
J Sleep Res ; : e14110, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38030221

RESUMEN

This study investigated the impact of comprehensive sleep patterns on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes (T1D). Thirty subjects with type 1 diabetes (aged 13-25) without chronic complications participated. For 1 week, glucose levels were monitored by real-time continuous glucose monitoring (CGM) and sleep was simultaneously assessed by actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Flow-mediated dilatation (FMD) measured endothelial function at the brachial artery. Insulin sensitivity was determined by calculated estimated glucose disposal rate (eGDR). Glycaemic control was assessed using haemoglobin A1C (HbA1C) levels. To address potential confounding by metabolic syndrome on the FMD results, three affected subjects were excluded from FMD correlation analyses. Participants with PSQI scores >5 had a lower %FMD compared with those with scores ≤5 (4.6 ± 3.7% vs. 7.6 ± 3.0%, p = 0.03). Multivariate analysis indicated that lower sleep efficiency and higher sleep duration variability were associated with higher HbA1C levels (ß = -0.076, 95%CI [-0.145, -0.008], p = 0.029; ß = 0.012, 95%CI [0.001, 0.023], p = 0.033). Irregular sleep timing and lower sleep efficiency were related to decreased insulin sensitivity (sleep midpoint irregularity ß = -1.581, 95%CI [-2.661, -0.502], p = 0.004, and sleep efficiency ß = 0.147, 95%CI [0.060, 0.235], p = 0.001). No significant associations were found between glycaemic parameters and FMD. Our study demonstrated that sleep irregularity in type 1 diabetes was associated with glycaemic control and insulin resistance, while poor subjective sleep quality was linked to endothelial dysfunction. Promoting healthy sleep habits, including consistent sleep timing could benefit metabolic and cardiovascular health in type 1 diabetes.

2.
BMC Endocr Disord ; 23(1): 249, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37974071

RESUMEN

BACKGROUND: There is minimal data of health outcomes for Type 1 Diabetes (T1D) in Southeast Asia (SEA) where government funding of insulin and blood glucose monitoring either do not exist or is limited. The full impact of Covid-19 pandemic on the national economies of SEA remain unknown. In the midst of the pandemic, in 2021, HelloType1 was developed by Action4Diabetes (A4D), a non-government organisation charity in collaboration with Southeast Asia local healthcare professionals as an innovative digital educational resource platform of T1D in local languages. HelloType1 was launched in Cambodia, Vietnam, Thailand and Malaysia in 2021 to 2022 with Memorandums of Understandings (MOUs) signed between A4D and each country. Internet data analytics were undertaken between the 1st of January 2022 to 31st of December 2022. AIMS: The aims of this study were to explore the usability and internet data analytics of the HelloType1 online educational platform within each country. METHODS: The data analytics were extracted Google analytics that tracks data from the website hellotype1.com and Facebook analytics associated with the website. RESULTS: There was a 147% increase in the number of HelloType1 users between the first 6 months versus the latter 6 months in 2022 and a 15% increase in the number of pages visited were noted. The majority of traffic source were coming from organic searches with a significant increase of 80% growth in 2022. CONCLUSIONS: The results of the analytics provide important insights on how an innovative diabetes digital educational resource in local languages may be optimally delivered in low-middle income countries with limited resources.


Asunto(s)
Diabetes Mellitus Tipo 1 , Internet , Humanos , Asia Sudoriental/epidemiología , Glucemia , Automonitorización de la Glucosa Sanguínea , Atención a la Salud , Diabetes Mellitus Tipo 1/epidemiología , Pandemias , Educación del Paciente como Asunto
3.
Pediatr Int ; 64(1): e15356, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36564347

RESUMEN

BACKGROUND: Emerging adults with type 1 diabetes (T1D) have several challenges regarding diabetes management and care transition from pediatric to adult services. In this study we aimed to assess the effectiveness of the newly established transition clinic for emerging adults with T1D. METHODS: We conducted an observational study of emerging adults with T1D treated in a transition clinic jointly operated by a pediatric and adult multidisciplinary care team during 2019-2021. A retrospective chart review of hemoglobin A1c (HbA1c), frequency of clinic attendance, acute diabetes-related complications, assessment of gaps in knowledge and behavior, and psychosocial outcomes was analyzed. RESULTS: A total of 21 patients with T1D were included. Median age at the transfer to the transition clinic was 24 years (range 21-34). Fifteen patients (71%) were successfully transferred to adult services; mean duration of follow-up at the transition clinic was 9.2 months (SD 3.9). None of the patients was lost to follow-up or experienced serious diabetes related complications. Mean (95% confidence interval) HbA1c levels decreased from 8.97% (7.87-10.07) at baseline to 8.25% (7.45-9.05) at the most recent visit (p = 0.01). A proportion of patients achieving the glycemic target (HbA1c < 7.5%) was increased from 24% at the first visit to 38% at the most recent visits. Patients' HbA1c levels at the adult clinic continued a favorable trend. Seven patients (33%) were identified as having symptoms of depression. Knowledge and behavioral gaps were identified and counselled by clinical care team. CONCLUSION: The multidisciplinary transition clinic has shown to be beneficial in terms of improving glycemic control, maintaining continuity of care and clinic attendance.


Asunto(s)
Diabetes Mellitus Tipo 1 , Transición a la Atención de Adultos , Adulto , Humanos , Adulto Joven , Diabetes Mellitus Tipo 1/terapia , Hemoglobina Glucada , Grupo de Atención al Paciente , Estudios Retrospectivos
4.
J Pediatr ; 230: 32-37.e1, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33250172

RESUMEN

OBJECTIVES: To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) and its associated risk factors in children and young adults with type 1 diabetes (T1D). STUDY DESIGN: A cross-sectional study was conducted at a tertiary care center in children and young adults with T1D. Liver fat quantification and hepatic fibrosis were assessed by magnetic resonance imaging proton density fat fraction and magnetic resonance elastography (MRE). Logistic regression analysis was performed to examine the associated risk factors for NAFLD. RESULTS: Fifty patients with T1D (28 females, 13 with overweight/obesity) were included. The median age and duration of T1D were 16.9 years (IQR, 13.6-20 years) and 6.5 years (IQR, 4-11 years), respectively. The prevalence of NAFLD was 10%. Four out of 5 patients with NAFLD were overweight/obese, and 2 had an and elevated alanine aminotransferase (ALT) level. None had liver fibrosis (defined as MRE >2.9 kPa). Compared with patients without NAFLD, patients with NAFLD had significantly higher body mass index standard deviation score (BMI-SDS) (median, 0.94 [IQR, 1.30-2.62] vs 0.13 [IQR, -0.69 to 0.84]; P = .01), ALT (median, 17 IU/L [IQR, 16-52 IU/L] vs 12 IU/L [IQR, 10-14 IU/L]; P = .02), and lower high-density lipoprotein cholesterol (median, 49 mg/dL [IQR, 41-51 mg/dL] vs 57 mg/dL [IQR, 52-69 mg/dL]; P = .039). Multivariate logistic regression analysis identified high BMI-SDS as the sole independent risk factor associated with NAFLD (OR, 5.79; 95% CI, 1.04-32.18). CONCLUSION: The prevalence of NAFLD in children and young adults with T1D was comparable to that in the general population. Our study suggests that routine screening for NAFLD in patients with T1D might not be necessary but should be performed in those patients with T1D who are overweight/obese.


Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adolescente , Adulto , Estudios Transversales , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/complicaciones , Prevalencia , Factores de Riesgo , Adulto Joven
5.
Pediatr Int ; 60(11): 1002-1007, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30151912

RESUMEN

BACKGROUND: Type 1 diabetes mellitus (T1DM) is caused by autoimmune destruction of islet ß-cells of the pancreas. There are overlapping phenotypes in a significant proportion of youth with type 1 and 2 diabetes. Thus, positive pancreatic autoantibodies are helpful to diagnose T1DM. Zinc transporter 8 antibody (ZnT8A) is a recently identified autoantibody in T1DM and no data on ZnT8A in the Thai population have been reported. The aim of this study was therefore to estimate the prevalence of ZnT8A in Thai juvenile-onset T1DM and to evaluate its diagnostic value relative to glutamic acid decarboxylase and insulinoma-2 antigen antibodies (GADA and IA2A). METHODS: In this cross-sectional study, patients with T1DM diagnosed before age 15 years, and disease duration <10 years were enrolled. Serum ZnT8A, GADA, and IA2A were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: The subjects consisted of 81 youths (30 boys, 51 girls) aged 12.3 ± 4.5 years with T1DM. The median diabetes duration was 3 years (range, 0-10 years). The prevalence of ZnT8A, GADA, and IA2A was 54.3%, 75.3%, and 45.7%, respectively. ZnT8A were detected in 16% of T1DM patients negative for both GADA and IA2A. A combination of ZnT8A, GADA and IA2A could detect 80.2% of patients with T1DM. Combined use of ZnT8A and GADA identified 100% of antibody-positive patients. CONCLUSION: The prevalence of ZnT8A in Thai juvenile-onset T1DM appears to be higher than in previous studies from Asia. ZnT8A could replace IA2A as an autoimmunity marker in Thai pediatric T1DM patients, with better diagnostic performance.


Asunto(s)
Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Transportador 8 de Zinc/inmunología , Adolescente , Biomarcadores/sangre , Niño , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inmunología , Femenino , Humanos , Masculino , Tailandia
6.
Eur J Pediatr ; 176(4): 537-545, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28224294

RESUMEN

Patients with congenital adrenal hyperplasia (CAH) appear to have adverse cardiovascular risk profile and other long-term health problems in adult life, but there are limited data in young CAH patients. We aim to evaluate the cardio-metabolic risk factors in adolescents and young adults with classical 21-hydroxylase deficiency (21-OHD). We performed a cross-sectional study of 21 patients (17 females) with classic CAH detected clinically and not through newborn screening, aged 15.2 ± 5.8 years, and 21 healthy matched controls. Anthropometric, biochemical, inflammatory markers, and body composition using dual-energy X-ray absorptiometry were measured. Obesity was observed in 33% of the CAH patients. The waist/hip ratio and waist/height ratio were significantly higher in CAH patients. Five out of 21 patients (24%) had elevated blood pressure. Silent diabetes was diagnosed in one patient (4.8%), but none in the control group. Serum leptin and interleukin-6 levels were not different between groups, but hs-CRP levels tended to be higher in CAH patients. Other metabolic profiles and body composition were similar in CAH and controls. CONCLUSION: Adolescents and young adults with CAH appear to have an increased risk of obesity and cardio-metabolic risk factors. Close monitoring, early identification, and secondary prevention should be implemented during pediatric care to improve the long-term health outcomes in CAH patients. What is Known: • Lifelong glucocorticoid (GC) replacement is the main treatment modality in patients with congenital adrenal hyperplasia which predispose to an adverse metabolic profile. • Adult CAH patients have adverse cardiovascular risk profile and other long-term health problems. What is New: • Adolescents and young adults with CAH appear to have an increased risk of obesity and cardio-metabolic risk factors.


Asunto(s)
Hiperplasia Suprarrenal Congénita/complicaciones , Enfermedades Cardiovasculares/etiología , Síndrome Metabólico/etiología , Obesidad/complicaciones , Adolescente , Hiperplasia Suprarrenal Congénita/metabolismo , Composición Corporal , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Humanos , Leptina/sangre , Masculino , Factores de Riesgo , Adulto Joven
7.
Asian Pac J Allergy Immunol ; 35(2): 82-85, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27543737

RESUMEN

BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) have an increased risk of celiac disease (CD). Both diseases have a common genetic susceptibility locus in the human leukocyte antigen (HLA) class II alleles. Testing for tissue transglutaminase antibodies (anti-tTG) is highly accurate for a CD diagnosis. OBJECTIVE: To determine the frequency of HLA-DQB1*0201/02 and DQB1*0302 alleles and anti-tTG seropositivity in children with T1DM. METHOD: Forty-six children with T1DM (male:female=24:22; mean age 12±3.7 years) without significant digestive symptoms were enrolled. The mean duration of diabetes was 5±3.5 years. Serum anti-tTG IgA and IgG as well as HLA-DQ2 (DQB1*0201/02) and -DQ8 (DQB1*0302) alleles were analyzed. The allele frequencies were compared with those in controls, which included 124 normal Thai individuals, as reported in our previous study. RESULTS: All subjects were negative for anti-tTG IgG. Only one patient (2.2%) was positive for anti-tTG IgA (38.5 U/mL; cut-off 15 U/mL). Although this patient was also heterozygous for HLA-DQ2 and was asymptomatic for CD, he declined endoscopic confirmation. Twenty-nine of 46 patients carried HLA-DQ2 and/or -DQ8 heterodimers. HLA-DQB1*0201/02 and HLA-DQB1*0302 allele frequencies were significantly higher (27% and 14%) in T1DM patients compared with normal controls (13.3% and 7.3%; P<0.001 and P=0.002, respectively). CONCLUSIONS: A significantly greater frequency of DQB1*0201/02 and DQB1*0302 alleles were present in children with T1DM compared with the control group. This indicates a potentially important role of these alleles in the development of T1DM. The prevalence of CD screening by serologic testing is negligible in Thai children with T1DM.


Asunto(s)
Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Proteínas de Unión al GTP/inmunología , Cadenas beta de HLA-DQ/genética , Transglutaminasas/inmunología , Adolescente , Alelos , Enfermedad Celíaca/inmunología , Niño , Preescolar , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-DQ/genética , Haplotipos , Prueba de Histocompatibilidad , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Proteína Glutamina Gamma Glutamiltransferasa 2
8.
BMC Endocr Disord ; 16(1): 37, 2016 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-27316665

RESUMEN

BACKGROUND: Congenital adrenal hyperplasia (CAH) due to steroid 11ß-hydroxylase deficiency (11ß-OHD) is a rare form of CAH associated with low renin hypertension, hypokalemia, hyperandrogenemia and ambiguous genitalia in affected females. Herein we describe the clinical, hormonal and molecular characteristics of two Uzbekistan siblings with 11ß-OHD and analyze the effects of a splicing mutation. CASE PRESENTATION: A 46,XX girl presented with genital ambiguity and low renin hypertension; her 46,XY brother presented with precocious puberty. Hormonal studies suggested 11ß-OHD. Mutation analysis was performed by PCR followed by Sanger sequencing of the entire coding regions and their flanking introns of the CYP11B1 gene. Mutation analysis showed that both patients were compound heterozygous for IVS7 + 1G > A, and c.421C > T. Although the identified mutations have been previously described, this is, to our knowledge, the first report of these mutations in compound heterozygotes. A minigene assay was used to determine the effects of the splicing mutation. The constructs containing either the wild-type or the splice-site mutant CYP11B1 genomic DNA of exons-introns 6-9 were transfected into COS-7 cells; subsequently, RNA splicing was assessed by reversed transcribed-PCR of CYP11B1 complementary DNA. The minigene assay revealed that the IVS7 + 1G > A mutation resulted in two shorter incorrectly spliced products; one skipping the exon 7 and the other skipping the exons 7-8. The c.421C > T mutation leads to the introduction of a premature stop codon at residue 141 (p.R141X). These mutations are expected to code non-functional proteins. CONCLUSION: Compound heterozygous mutations (IVS7 + 1G > A and p.R141X) in the CYP11B1 gene were found to cause 11ß-OHD. The IVS7 + 1G > A mutation causes aberrant splicing of CYP11B1 leading to exon skipping. This finding could facilitate the future novel therapies targeted on splicing modulation to treat human disease.


Asunto(s)
Hiperplasia Suprarrenal Congénita/genética , Empalme Alternativo , Mutación , Esteroide 11-beta-Hidroxilasa/genética , Preescolar , Codón sin Sentido , Análisis Mutacional de ADN , Femenino , Tamización de Portadores Genéticos , Humanos , Lactante , Masculino , Sitios de Empalme de ARN
9.
Artículo en Inglés | MEDLINE | ID: mdl-39113399

RESUMEN

Objective: To study the national incidence of admission for diabetic ketoacidosis (DKA) in Thai children and adolescents with type 1 diabetes (T1D) and characterize risk factors for DKA admission. Methods: Admission records of children and adolescents with T1D during the years 2015-2019 were retrieved from the Thai health coverage system of all schemes. Hospitalization was categorized according to patients' age groups (<1, 1-5, 6-12 and 13-17 years), sex and geographical regions (Bangkok, Central, Northeast, North and South). DKA admission incidence and rate were calculated and compared among subgroups. Results: The annual incidences of T1D and DKA admissions progressively increased over the study period (T1D: 12.0 to 15.0, p<0.001 and DKA: 4.8 to 7.3 per 100,000 child-years, p<0.001). About half of DKA admissions (52%) were recurrent episodes. DKA admission rate was 1.49 admissions/patient. The incidence of DKA admission was greatest in individuals aged 13-17 years (13-17 years: 10.3; 6-12 years: 6.3; 1-5 years: 1.7; and <1 year: 0.6 per 100,000 child-years, p<0.001). DKA admission incidence was greater in females than males (7.6 vs. 4.3 per 100,000 child-years, p<0.001). Among 5 geographical regions, greatest percentage of recurrent DKA (57%), rate of increased annual incidence of DKA admission (3.8 to 7.8 per 100,000 child-years), and DKA admission rate (1.64 admissions/patient) were found in the Northeast region. Conclusions: During the years 2015-2019, rising annual incidences of T1D and DKA admissions among Thai youth were observed. Individuals older than 6 years, being females, and resided in the Northeast region had higher risk for DKA hospitalization.

10.
Ren Fail ; 35(1): 98-100, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23113652

RESUMEN

Renal hemodynamic study was performed in eight patients associated with type 1, early childhood diabetes mellitus (DM) and seven patients associated with type 2, early childhood DM. The results in both types of DM revealed a significant reduction in peritubular capillary flow and a high value of glomerular filtration rate (GFR) in the presence of reduced renal perfusion characteristic of glomerular hyperfiltration. These findings imply that renal ischemia has already developed in both types of early stage childhood DM and GFR is overestimated in DM, which may mislead to improper interpretation of renal function.


Asunto(s)
Diabetes Mellitus/fisiopatología , Riñón/irrigación sanguínea , Flujo Sanguíneo Regional/fisiología , Circulación Renal/fisiología , Adolescente , Diabetes Mellitus/orina , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/fisiopatología , Magnesio/orina , Masculino , Pronóstico
11.
Ann Pediatr Endocrinol Metab ; 28(1): 20-25, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36731507

RESUMEN

PURPOSE: Diabetic neuropathy (DN) is a serious complication in diabetes mellitus. We aimed to determine the prevalence of DN in pediatric-onset diabetes in a tertiary care center and to assess the sensitivity and specificity of monofilament testing and noninvasive screening to diagnose DN compared with the gold standard nerve conduction study (NCS). METHODS: Sixty-five Thai children and adolescents (39 females) diagnosed with diabetes before 15 years of age were included. All subjects were screened for DN by foot and neurological examinations, light touch sensation by 10 g Semmes-Weinstein monofilaments, and the Michigan Neuropathy Screening Instrument (MNSI). NCSs were used as the gold standard for diagnosis of DN. RESULTS: Fifty-eight patients had type 1 diabetes ( T1D), 5 patients had type 2 diabetes, and 2 patients had other types of diabetes. The mean age was 17.7±4.6 years (8-33 years). The prevalence of DN in this cohort was 12.3% by NCS. All subjects were asymptomatic. Mean diabetes duration did not differ between the groups (with DN 8.0±3.0 years vs. no DN 8.2±5.0 years). Notably, one patient with T1D developed DN within 3 years after diagnosis. Poor glycemic control was a significant risk factor for DN. Glycosylated hemoglobin was higher in the DN group (10.6%±2.3% vs. 8.5%±1.6%, P=0.008). The occurrence of diabetic nephropathy was associated with DN (prevalence rate ratio, 4.97; 95% confidence interval, 1.5-16.46). Foot and neurological examinations, monofilaments, and the MNSI failed to detect DN in all subjects with abnormal NCS. CONCLUSION: The prevalence of DN in pediatric-onset diabetes is not uncommon but mainly is subclinical. Poor glycemic control is the main risk factor. Noninvasive screening tests for DN exhibited poor diagnostic sensitivity in the pediatric population.

12.
Eur J Pediatr ; 171(10): 1559-62, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22801770

RESUMEN

UNLABELLED: Aldosterone synthase (P450c11AS) deficiency is a rare autosomal recessive disorder, presenting with severe salt-losing in early infancy. It is caused by inactivating mutations of the CYP11B2 gene. Here, we describe three unrelated Asian patients who have clinical and hormonal features compatible with aldosterone synthase deficiency and identify their CYP11B2 mutations. Patient 1 was a Thai female infant. Patient 2 was an Indian boy, and patient 3 was a Thai male infant. All subjects presented at the age of 1-2 months with diarrhea, failure to thrive, and severe dehydration. Their plasma electrolytes showed hyponatremia, hyperkalemia, and acidosis. All patients had normal cortisol response and had elevated plasma renin activity with low aldosterone levels. The entire coding regions of the CYP11B2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a previously described mutation, p.T318M. Patient 2 was homozygous for a novel c.666delC mutation inherited from both parents resulting in p.223F>Sfsx295. No CYP11B2 mutation was detected in patient 3. CONCLUSIONS: We report the first CYP11B2 defects in Southeast Asian families responsible for aldosterone synthase deficiency and identified a novel CYP11B2 mutation. However, the affected gene(s) responsible for primary hypoaldosteronism other than CYP11B2 remain to be determined.


Asunto(s)
Citocromo P-450 CYP11B2/deficiencia , Citocromo P-450 CYP11B2/genética , Hipoaldosteronismo/genética , Secuencia de Bases/genética , Femenino , Humanos , Hipoaldosteronismo/fisiopatología , Lactante , Masculino , Mutación , Reacción en Cadena de la Polimerasa
14.
J Clin Endocrinol Metab ; 107(7): 1939-1947, 2022 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-35363313

RESUMEN

CONTEXT: Congenital adrenal hyperplasia is most commonly caused by 21-hydroxylase deficiency (21-OHD), an autosomal recessive disorder resulting from biallelic pathogenic variants (PVs) in CYP21A2. With a highly homologous pseudogene and various types of single nucleotide and complex structural variants, identification of PVs in CYP21A2 has been challenging. OBJECTIVE: To leverage long-read next-generation sequencing combined with locus-specific polymerase chain reaction (PCR) to detect PVs in CYP21A2 and to determine its diagnostic yield in patients with 21-OHD. METHODS: Forty-eight Thai patients with 21-OHD comprising 38 sporadic cases and 5 pairs of siblings were enrolled. Two previously described locus-specific PCR methods were performed. Amplicons were subject to long-read sequencing. RESULTS: Ninety-six PVs in CYP21A2 in the 48 patients were successfully identified. The combined techniques were able to detect 26 structural chimeric variants (27%; 26/96) in 22 patients with 18 having monoallelic and 4 having biallelic chimeras. The remaining PVs were pseudogene-derived mutations (63%; 60/96), entire gene deletions (2%; 2/96), missense variants (3%; 3/96), a splice-site variant (2%; 2/96), frameshift variants (2%; 2/96), and a nonsense variant (1%; 1/96). Notably, a splice-site variant, IVS7 + 1G > T, which was identified in a pair of siblings, has not previously been reported. CONCLUSIONS: Our approach exploiting locus-specific PCR and long-read DNA sequencing has a 100% diagnostic yield for our cohort of 48 patients with 21-OHD.


Asunto(s)
Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Humanos , Mutación , Esteroide 21-Hidroxilasa/genética , Esteroides , Tailandia
15.
J Diabetes Investig ; 13(5): 796-809, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34890117

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insulinas , Adulto , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Recién Nacido , Insulinas/uso terapéutico , Sistema de Registros , Estudios Retrospectivos , Síndrome , Tailandia/epidemiología , Adulto Joven
16.
J Diabetes Investig ; 13(8): 1448-1457, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35394118

RESUMEN

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.


Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Telemedicina , COVID-19/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa , Humanos , Insulina/uso terapéutico , Persona de Mediana Edad , Pandemias , Aislamiento de Pacientes , Estudios Retrospectivos , Tailandia/epidemiología
17.
Eur J Pediatr ; 170(6): 763-9, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21107605

RESUMEN

INTRODUCTION: Children after craniopharyngioma surgery often develop rapid weight gain and hyperphagia. We investigate the metabolic syndrome features, risk factors, and the insulin dynamics in these patients. MATERIALS AND METHODS: Standard oral glucose tolerance tests (OGTT) were performed in 12 subjects, aged 7.7-18.1 years, after surgical removal of craniopharyngioma and their healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Blood samples were obtained for measurement of levels of plasma glucose, insulin, lipids, liver enzymes, baseline hormonal profiles with calculation of insulin secretion, and insulin sensitivity indices derived from OGTT. RESULTS AND DISCUSSION: Nine of 12 subjects were severely obese. All patients exhibited significant weight gain after surgery. The waist to hip ratio was higher in subjects compared to controls (P = 0.023). Subjects had higher fasting triglycerides (P = 0.019) and lower HDL/total cholesterol ratio (P = 0.012). Five of 12 subjects met the criteria for the metabolic syndrome, compared with one of 12 in controls. One patient had prediabetes and another patient had overt type 2 diabetes. Six of 12 subjects had nonalcoholic steatohepatitis. No significant risk factors were found between each group of patients with and without the metabolic syndrome. There were no differences of insulin secretion and insulin sensitivity indices between craniopharyngioma and control subjects. CONCLUSION: Children after craniopharyngioma surgery are at risk of rapid weight gain and the development of metabolic syndrome. Further studies to better understand the mechanism are required to design effective treatment and prevention.


Asunto(s)
Craneofaringioma/complicaciones , Craneofaringioma/cirugía , Insulina/metabolismo , Síndrome Metabólico/etiología , Obesidad/etiología , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Craneofaringioma/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Hígado Graso/sangre , Hígado Graso/etiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hiperfagia/sangre , Hiperfagia/etiología , Masculino , Síndrome Metabólico/sangre , Obesidad/sangre , Factores de Riesgo , Triglicéridos/sangre , Relación Cintura-Cadera , Aumento de Peso
18.
J Diabetes Investig ; 12(4): 516-526, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32815278

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Control Glucémico/estadística & datos numéricos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Sistema de Registros , Adolescente , Adulto , Automonitorización de la Glucosa Sanguínea/estadística & datos numéricos , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Estudios Retrospectivos , Tailandia/epidemiología , Adulto Joven
19.
J Pediatr Endocrinol Metab ; 33(3): 331-337, 2020 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-29389666

RESUMEN

Background Hypothalamic damage may alter glucagon-like peptide-1 (GLP-1) secretion and be involved in the pathogenesis of obesity. We aim to evaluate the metabolic features and the dynamic changes of GLP-1 levels during an oral glucose tolerance test (OGTT) in children with hypothalamic obesity (HO) compared with simple obesity controls. Methods Subjects included eight patients (six females, aged 9-16 years) with hypothalamo-pituitary tumors who later developed obesity and eight controls with simple obesity matched for age, body mass index (BMI), gender and puberty. We assessed the metabolic syndrome features, fat mass, severity of hyperphagia using a standardized questionnaire, and measured glucose, insulin and GLP-1 levels during a standard 75 g OGTT. Results Age, gender distribution, pubertal status and BMI-Z scores were not significantly different. Subjects with HO had higher fasting triglycerides (TG) than controls (128 vs. 94 mg/dL; p=0.05). Four HO subjects and three controls met the criteria for the metabolic syndrome. Fasting and 120 min post-glucose load GLP-1 levels were significantly higher in HO patients than in controls (21.9 vs. 19.7 pg/mL; p=0.025, 22.1 vs. 17.7 pg/mL; p=0.012). Patients with HO had significantly higher hyperphagia scores than in simple obese controls (13 vs. 2.5; p=0.012). Conclusions Patients with HO appear to have more metabolic complications and hyperphagia than controls with simple obesity. Impaired satiety may play an important role in HO. Fasting and glucose-induced serum GLP-1 concentrations seem to be altered in HO patients and could be a part of the pathogenesis of HO.


Asunto(s)
Péptido 1 Similar al Glucagón/sangre , Glucosa/farmacología , Enfermedades Hipotalámicas/metabolismo , Obesidad/metabolismo , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Niño , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Hiperfagia/metabolismo , Enfermedades Hipotalámicas/sangre , Neoplasias Hipotalámicas/sangre , Neoplasias Hipotalámicas/metabolismo , Insulina/sangre , Masculino , Síndrome Metabólico/metabolismo , Obesidad/sangre
20.
Clin Endocrinol (Oxf) ; 70(4): 623-8, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18681856

RESUMEN

OBJECTIVE: To describe clinical and genetic features of a Thai family with non-autoimmune hyperthyroidism (NAH) caused by an activating germline mutation in the thyrotropin receptor (TSHR) gene. PATIENTS: Three affected individuals from the same family (a father and his two children) were studied. Clinical and imaging findings were reviewed and compared. GENETIC ANALYSIS: Genomic DNA was extracted from peripheral blood leukocytes and mutation analysis of the entire coding sequence of the TSHR gene was performed in both children and their parents by direct DNA sequencing. RESULTS: A heterozygous germline T to C transition in exon 10 of the TSHR gene (c.1358T-->C) resulting in the substitution of methionine (ATG) by threonine (ACG) at codon 453 (p.M453T) was identified in the father and his two children. They presented with different clinical severity and variable age of onset. In addition to hyperthyroidism, ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers were consistently found in all affected individuals. CONCLUSIONS: Ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers might be characteristic features of NAH because of an activating TSHR germline mutation. In addition, the shortening of the middle phalanges of the fifth fingers has never been previously described, expanding the phenotypic spectrum of the disease.


Asunto(s)
Mutación de Línea Germinal/genética , Hipertiroidismo/genética , Receptores de Tirotropina/genética , Adulto , Preescolar , ADN/genética , Femenino , Falanges de los Dedos de la Mano/anomalías , Cardiopatías Congénitas/etnología , Cardiopatías Congénitas/genética , Ventrículos Cardíacos/anomalías , Humanos , Hipertiroidismo/etnología , Lactante , Masculino , Linaje , Fenotipo , Tailandia
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