Association of Cytotoxic T Lymphocyte Antigen-4 Gene Polymorphisms and HLA Class II Alleles with the Development of Type 1 Diabetes in Korean Children and Adolescents

We studied the association of cytotoxic T lymphocyte antigen-4 gene (CTLA4) polymorphisms with the development of type 1 diabetes (T1D) in Korean children and adolescents. A total of 176 Korean subjects (92 females and 84 males) with childhood-onset T1D were studied. The A/G polymorphism at position 49 in CTLA4 exon 1 and the C/T polymorphism at position -318 in the CTLA4 promoter were analyzed by PCR-RFLP methods. The genotype and allele frequencies of the CTLA4 polymorphisms in the T1D patients were not different from those in the controls. These polymorphisms were not associated with the clinical characteristics or the development of autoimmune thyroid disease in the T1D patients. The frequency of the A allele was significantly higher in the patients that did not have two out of the three susceptible HLA-DRB1 alleles, which were DRB1*0301, *0405 and *09012, compared to the controls (P<0.05). These results suggest that CTLA4 polymorphisms do not directly confer any susceptibility to T1D. However, a CTLA4-mediated susceptibility effect on the development of T1D might be significant in children and adolescents that do not have susceptible HLA class II alleles.Steck AK, 2005, DIABETES, V54, P2482Yu J, 2004, CLIN IMMUNOL, V113, P318, DOI 10.1016/j.clim.2004.08.009Ueda H, 2003, NATURE, V423, P506, DOI 10.1038/nature01621Mochizuki M, 2003, DIABETES CARE, V26, P843Field LL, 2002, DIABETOLOGIA, V45, P21Abe T, 2001, DIABETIC MED, V18, P726Ligers A, 2001, GENES IMMUN, V2, P145Takara M, 2000, DIABETES CARE, V23, P975Park YJ, 2000, THYROID, V10, P453Lee YJ, 2000, CLIN ENDOCRINOL, V52, P153Abe T, 1999, DIABETES RES CLIN PR, V46, P169Park MH, 1999, HUM IMMUNOL, V60, P901Yanai K, 1999, CLIN EXP ALLERGY, V29, P29Gonzalez-Escribano MF, 1999, TISSUE ANTIGENS, V53, P296Badenhoop K, 1999, EXP CLIN ENDOCR DIAB, V107, pS89Heward JM, 1998, CLIN ENDOCRINOL, V49, P331Donner H, 1998, DIABETES, V47, P1158Djilali-Saiah I, 1998, DIABETES, V47, P125Yanagawa T, 1997, THYROID, V7, P843Marron MP, 1997, HUM MOL GENET, V6, P1275Owerbach D, 1997, DIABETES, V46, P1069Donner H, 1997, J CLIN ENDOCR METAB, V82, P143Lane P, 1997, ANN NY ACAD SCI, V815, P392Deichmann K, 1996, BIOCHEM BIOPH RES CO, V225, P817Nistico L, 1996, HUM MOL GENET, V5, P1075Walunas TL, 1996, J EXP MED, V183, P2541WALUNAS TL, 1994, IMMUNITY, V1, P405BANNAI M, 1994, EUR J IMMUNOGENET, V21, P1LUCASSEN AM, 1993, NAT GENET, V4, P305EISENBARTH GS, 1986, NEW ENGL J MED, V314, P1360

The effect of overweight on the luteinizing hormone level after gonadorelin stimulation test in girls with idiopathic central precocious puberty

Purpose We investigated the effect of overweight on luteinizing hormone (LH) levels after a gonadorelin stimulation test in Korean girls with idiopathic central precocious puberty (CPP). Methods Medical records of 234 girls diagnosed with idiopathic CPP were reviewed retrospectively. CPP was diagnosed when the peak LH levels after gonadorelin stimulation was >5.0 U/L. The enrolled girls had a peak LH level >5.0 U/L after a gonadorelin stimulation test. Selected girls were classified as normoweight (body mass index [BMI] below the 85th percentile with respect to age) and overweight (BMI greater than the 85th percentile with respect to age). Results The peak LH (8.95±2.85 U/L vs. 11.97±8.42 U/L, P<0.01) and peak follicle-stimulating hormone (9.60±2.91 U/L vs. 11.17±7.77 U/L, P=0.04) after gonadorelin stimulation were lower in overweight girls with idiopathic CPP than in normoweight girls with idiopathic CPP. Being overweight was negatively associated with peak LH levels after gonadorelin stimulation test (odds ratio, 0.89; 95 % confidence interval, 0.81–0.98, P=0.02). Conclusions In girls with idiopathic CPP, being overweight led to a lower LH peak after gonadorelin stimulation. Further research is needed to better understand the role of overweight on gonadotropin secretion in precocious puberty

Evaluation of changes in random blood glucose and body mass index during and after completion of chemotherapy in children with acute lymphoblastic leukemia

PurposeImproved survival of patients with childhood acute lymphoblastic leukemia (ALL) has drawn attention to the potential for late consequences of previous treatments among survivors, including metabolic syndrome. In this study, we evaluated changes in 3 parameters, namely, random blood glucose, body mass index (BMI), and Z score for BMI (Z-BMI), in children with ALL during chemotherapy and after completion of treatment.MethodsPatients newly diagnosed with ALL from January, 2005 to December, 2008 at Saint Mary's Hospital, The Catholic University of Korea, who completed treatment with chemotherapy only were included (n=107). Random glucose, BMI, and Z-BMI were recorded at 5 intervals: at diagnosis, before maintenance treatment, at completion of maintenance treatment, and 6 and 12 months after completion of maintenance treatment. Similar analyses were conducted on 2 subcohorts based on ALL risk groups.ResultsFor random glucose, a paired comparison showed significantly lower levels at 12 months post-treatment compared to those at initial diagnosis (P<0.001) and before maintenance (P<0.001). The Z-BMI score was significantly higher before maintenance than at diagnosis (P<0.001), but decreased significantly at the end of treatment (P<0.001) and remained low at 6 months (P<0.001) and 12 months (P<0.001) post-treatment. Similar results were obtained upon analysis of risk group-based subcohorts.ConclusionFor a cohort of ALL patients treated without allogeneic transplantation or cranial irradiation, decrease in random glucose and Z-BMI after completion of chemotherapy does not indicate future glucose intolerance or obesity

Hepatic glycogenosis in type 1 diabetes mellitus mimicking Mauriac syndrome

Hepatic glycogenosis in type 1 diabetes mellitus (DM) can be caused by poor glycemic control due to insulin deficiency, excessive insulin treatment for diabetic ketoacidosis, or excessive glucose administration to control hypoglycemia. Mauriac syndrome, which is characterized by hepatomegaly due to hepatic glycogenosis, growth retardation, delayed puberty, and Cushingoid features, is a rare diabetic complication. We report a case of hepatic glycogenosis mimicking Mauriac syndrome. A 14-year-old girl with poorly controlled type 1 DM was admitted to The Catholic University of Korea, Seoul St. Mary's Hospital for abdominal pain and distension. Physical examination revealed hepatomegaly and a Cushingoid face. The growth rate of the patient had decreased, and she had not yet experienced menarche. Laboratory findings revealed elevated liver enzyme levels. A liver biopsy confirmed hepatic glycogenosis. Continuous glucose monitoring showed hyperglycemia after meals and frequent hypoglycemia before meals. To control hyperglycemia, we increased insulin dosage by using an insulin pump. In addition, we prescribed uncooked cornstarch to prevent hypoglycemia. After strict blood glucose control, the patient's liver functions and size normalized. The patient subsequently underwent menarche. Hepatic glycogenosis is a complication of type 1 DM that is reversible with appropriate glycemic control