PURPOSE: Most childhood diabetes mellitus (DM) is usually thought of as type 1 DM (T1DM), but the incidence of type 2 DM (T2DM) in childhood is increasing. Sometimes, it might not be easy to determine which type of DM a patient has and to choose the best treatment. The purpose of this study is to evaluate the usefulness of autoantibody test and clinical characteristics for the specific diagnosis of DM in childhood. METHODS: In this study, we retrospectively reviewed the medical records of 42 patients who were diagnosed with DM and followed at the department of pediatrics, Dankook University Hospital from January 2002 to October 2010. RESULTS: The patients were grouped as T1DM, T2DM, or T1.5DM (unclassified) according to the clinical and laboratory findings. T1DM had an earlier onset age compared to T2DM. Diabetic ketoacidosis (DKA) was the presenting symptom in 57% of T1DM, but there was no DKA in T2DM. Initial serum insulin and C-peptide levels were lower in T1DM than T2DM. Thirty nine percent and 70% of the patients had a family history of DM, respectively. The average body mass index (BMI) in T2DM was higher than that in T1DM. At least one of autoantibodies was positive in 80% of T1DM. But no antoantibody was detected in T2DM. During follow up, higher levels of HbA1c and more frequent microalbuminuria were detected in the female adolescents. CONCLUSION: We can confirm that the autoantibody test is very valuable in diagnosing specific types of DM. And adolescent period was thought as a very vulnerable period to manage the diabetes requiring more intensive emotional support including family cooperation.
Adolescent ; Age of Onset ; Autoantibodies ; Body Mass Index ; C-Peptide ; Child ; Diabetes Mellitus ; Diabetic Ketoacidosis ; Female ; Follow-Up Studies ; Humans ; Incidence ; Insulin ; Medical Records ; Pediatrics ; Retrospective Studies

OBJECTIVETo investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features.

METHODSGenomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations.

RESULTSFamily members on the maternal side all harbored the tRNALeu(UUR) A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980 (P = 0.02). Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found.

CONCLUSIONSThe main cause of diabetes in this pedigree is the tRNALeu(UUR) A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNALeu(UUR) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.

Adolescent ; Adult ; Age of Onset ; Aged ; Asian Continental Ancestry Group ; genetics ; China ; Diabetes Mellitus, Type 1 ; diagnosis ; genetics ; Female ; Hearing Loss ; genetics ; Humans ; Middle Aged ; Mitochondria ; genetics ; Pedigree ; Point Mutation ; genetics ; Polymorphism, Single Nucleotide ; genetics ; RNA, Transfer ; genetics ; RNA, Transfer, Leu ; genetics ; Young Adult

PURPOSE:Worldwide incidence of type 2 diabetes mellitus in youth is increased for last 3 decades. We reviewed the clinical characteristics of the patients and their long term complications. METHODS:We reviewed the medical data of 69 patients who were diagnosed type 2 diabetes mellitus at Seoul National University Children's Hospital before the age of 18 years between January 1991 and December 2007. RESULTS:Forty seven patients (68.1%) developed after 2000. The mean age of onset was 13.1+/-2.0 years. Forty seven (69.1%) patients had family history of diabetes mellitus and forty six (66.6%) patients had overweight or obesity. Thirteen (22.4%) patients were small for gestational age but their body mass index wasn't increased compared to that of appropriate for gestational age at the onset of disease. There were 7 patients who had microvascular complication and the mean disease duration was 9.1+/-3.3 years. Hemoglobin A1c was not increased in the complication group compared to the complication-free group. CONCLUSION:The number of childhood and adolescence onset type 2 diabetes mellitus was increased. The proportion of small for gestation age was high and the long term complication developed in adolescence or early adult life. Early intervention of the risk factors and regular evaluation of the complications are needed and systematized follow-up of small for gestational age is also necessary.
Adolescent ; Adult ; Age of Onset ; Body Mass Index ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Early Intervention (Education) ; Follow-Up Studies ; Gestational Age ; Hemoglobins ; Humans ; Incidence ; Infant ; Obesity ; Overweight ; Pregnancy ; Risk Factors

BACKGROUND/AIMS: The prevalence of diabetes in Korea is reported to be approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are rare in Korea. A diagnostic technique for autosomal dominant MODY is being actively sought. In this regard, we used a DNA chip to investigate the frequency of mutations of the MODY3 gene (hepatocyte nuclear factor-1alpha) in Korean patients with early-onset type 2 diabetes. METHODS: The genomic DNA of 30 normal individuals [age, 24.9+/-8.6 years] and 25 patients with early-onset type 2 diabetes (age, 27+/-5.9 years) was extracted, and the MODY3 gene was amplified. The amplified DNA was hybridized onto a MODY3 chip, which has oligonucleotides of 15-25 bases, representing wild-type and mutant MODY3 sequences in both forward and reverse orientations, immobilized on its surface. RESULTS: Among the normal subjects, there was no mutation of MODY3. Among those with early-onset type 2 diabetes, there was one case of MODY3 mutation. CONCLUSIONS: Our results indicate that MODY3 mutations are not rare in Korean early-onset type 2 diabetes patients in Korea and suggest that MODY3 mutations in patients with early-onset type 2 diabetes need to be further evaluated.
Adolescent ; Adult ; Age of Onset ; Asian Continental Ancestry Group/genetics/*statistics & numerical data ; Case-Control Studies ; Cohort Studies ; Diabetes Mellitus, Type 2/*epidemiology/*genetics ; Female ; Hepatocyte Nuclear Factor 1-alpha/*genetics ; Humans ; Korea ; Male ; Mutation/*genetics ; Prevalence ; Young Adult

Background: Adolescent onset diabetes is currently showing different facets as far as phenotypic and autoimmune characteristics, clinical course, age at onset of the disease and prevalence of its different types are concerned. Alarming increase in the prevalence of type 2 diabetes (T2DM) has been reported from pediatric diabetes centers in North America and elsewhere in the world. Autoimmunity has been identified not only in type 1 adolescent diabetics but also among patients diagnosed clinically as type 2. Previous studies have shown that race or ethnic differences in this population can be identified. With the foregoing studies, we strongly believed that if significant associations can be made among the clinical, immunological and biochemical variables in this study, these associations can serve as guide for physicians in the management of adolescent onset diabetes.Objectives: To describe the phenotypic and immuno-biochemical characteristics of adolescent onset Filipino diabetic. Specifically to correlate the body mass index, acanthosis nigricans and age at onset of diabetes with C-peptide and anti-GAD antibody levels and to find association between anti-GAD and C-peptide levels.Study Design: Descriptive AnalyticalParticipants: Twenty six adolescent diabetics from Makati Medical Center, camp COPE, and Philippine General Hospital Section of Pediatric Endocrinology service patients were included in the study.Results: A total of 26 subjects were included in the study. The mean age was 15.2 years old with male preponderance (17/26; 65%). Mean age at onset of diabetes mellitus was 12.34 years (range 10 - 18 years) BMI ranged from 13.95 to 39.5 (mean 32.4 kg/m2). Seven (27%) were obese and two (8%) were overweight. The waist circumference ranged from 54 - 126 cm (mean of 73.2), the hip circumference ranged from 54 to 114 cm while the waist to hip ratio ranged from 0.85 to 1.1 cm (mean of 0.97). In six cases (23%) acanthosis nigricans was present while 2 subjects has elevated pressure (8%). Using the NCEP III Criteria, only three subjects (11.5%) fulfilled the criteria for metabolic syndrome. Nine subjects were positive for the anti-GAD antibody while 17 subjects (65%) had normal values. C-peptide values and anti-GAD titers did not significantly vary among obese/ overweight adolescents and non obese. A statistically higher ne underweight / normal BMI than those who are obese had low C-peptide values (13 versus 6), while those with high C-peptide values, a higher frequency were overweight (6 versus 3). (p=0.41). There is a negative or inverse statistical correlation between C-peptides and anti-GAD titers, although the relationship is weak. (r = .127, p=.06).Conclusion: The mean BMI of the adolescent onset Filipino diabetics is 21.4 kg/m2, with mean waist circumference of 73.2cm and mean waist to hip ratio of 0.97cm. Eleven percent of the population has metabolic syndrome. Body mass index has no statistically significant correlation with anti-GAD antibody and C peptide level. However, higher number of patients who are underweight or with normal BMI has low C-peptide levels. Twenty three percent of the population has acanthosis nigricans and 75% of them are obese diabetics with elevated C peptide. A trend towards inverse relationship between anti-GAD antibody levels and C-peptide levels has been identified which needs further studies.
Human ; Adolescent Onset Diabetes ; Diabetes Mellitus

PURPOSE: The incidence of type 1 diabetes mellitus is increasing worldwide, the complications such as growth impairment, thyroid dysfunction, microvascular disease can be accompanied in type 1 diabetes mellitus. So, it is important to study initial clinical characteristics of type 1 diabetes mellitus for long-term managements of such complications. METHODS: Forty children and adolescents with type 1 diabetes mellitus who had been followed up in the department of pediatrics, Ajou university hospital from December 1997 to June 2006 were enrolled in this study. Sex, Onset Age, onset season, body mass index, family history, serum blood glucose, urine ketone, admission duration, HbA1c, serum and 24 hours urine C-peptide, islet cell antibody, daily insulin dose, insulin like growth factor-I, thyroid function test, lipid profile, bone age of patients were reviewed retrospectively. RESULTS: Forty patients were enrolled:19 boys and 21 girls. The mean age of diagnosis was 9.2+/-3.5 years. There were no seasonal variation in onset time. The body mass index were 15.9+/-2.7 kg/m2. In family history, 1 patient had type 1 and 16 patients (40%) had type 2 diabetes. Blood glucose was 509+/-172 mg/dL. Urine ketone was positive in 77.8% of patients. HbA1c was 12.5+/-2.4%. Serum C-peptide was 0.76+/-0.65 ng/mL and there was statistically significant positive relationship between patient's age and serum C-peptide level (P<0.05). Daily insulin dose was 0.89+/-0.28 unit/kg/day and negatively correlated with serum C-peptide level (P<0.05), but there were no differences in daily insulin dose between prepubertal and pubertal patients. In 82.4% of patients, at least one of 3 antibody (glutamic acid decarboxylase antibody, islet cell antibody, insulin auto antibody) were detected. Serum C-peptide were higher in GAD Ab positive group than in negative group (P<0.05). In 63.6% of patients, Insulin like growth factor-I levels were lower than normal control group. Thyroid dysfunction were found in 7.5% of patients. 48.7% of patients were accompanied with dyslipidemia. In 51.9% of patients, bone age was advanced by at least 6 months. CONCLUSION: For the most part, our results were consistent with previous studies. But some points like, 1) there was no seasonal variation in onset time, 2) serum C-peptide was not low, 3) there were no differences in daily insulin dose between prepubertal and pubertal patients, differed from previous studies.
Adolescent ; Age of Onset ; Blood Glucose ; Body Mass Index ; C-Peptide ; Child ; Diabetes Mellitus, Type 1* ; Diagnosis* ; Dyslipidemias ; Female ; Humans ; Incidence ; Insulin ; Islets of Langerhans ; Pediatrics ; Retrospective Studies ; Seasons ; Thyroid Function Tests ; Thyroid Gland

OBJECTIVETo investigate the positive frequency and distribution of glutamic acid decarboxylase antibody(GAD-Ab) in phenotypic type 2 diabetic(T2DM) patients.

METHODSSera of 2035 phenotypic T2DM patients were screened for GAD-Ab with radioligand assay. The positive frequency of GAD-Ab and its relation with clinical features were analyzed.

RESULTS(1) The positivity of GAD-Ab in clinic-based, phenotypic T2DM patients was 7.1% (145/2035), comparable to that of data from Caucasians as shown by UKPDS(8.7% vs. 9.8%, P = 0.391) and ADOPT (8.0% vs. 4.2%, P = 0.000) but higher than that of Japanese in Ehime study(7.1% vs. 3.8%, P = 0.000). (2) The positive frequency and distribution of GAD-Ab titer were related to clinical features, including age at onset, body mass index (BMI) and fasting C peptide levels. Patients with younger age at onset (0.33 vs. 0.11, P < 0.05), less BMI (0.34 vs. 0.10, P < 0.05) and lower C peptide levels (0.38 vs. 0.11, P < 0.05) would have higher GAD-Ab titers.

CONCLUSION(1)The positivity of GAD-Ab in adult-onset phenotypic T2DM in Chinese was similar to that of Caucasians but higher than that of the Japanese. (2) The distribution of GAD-Ab titers was associated with clinical features, with high GAD-Ab titers for those having younger age at onset, less BMI and lower C peptide levels.

Adolescent ; Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Antibodies ; immunology ; metabolism ; Body Mass Index ; Case-Control Studies ; Child ; Child, Preschool ; Diabetes Mellitus, Type 2 ; diagnosis ; metabolism ; pathology ; physiopathology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Infant ; Male ; Middle Aged ; Phenotype ; Young Adult

OBJECTIVETo evaluate the associations of human leukocyte antigen (HLA) DQB1 gene with onset age and autoantibodies in type 1 diabetes mellitus(T1DM) in Chinese Han population in Sichuan area.

METHODSForty-six type 1 diabetic patients and 52 healthy control subjects were involved in this study. HLA-DQB1 typing was performed by polymerase chain reaction-sequence specific primer(PCR-SSP). Glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) were qualitatively analyzed by enzyme linked immunosorbent assay (ELISA).

RESULTSThe positive rate of DQB1*0201 was higher in T1DM than in controls (OR=18, P<0.005), but those of DQB1*0601, *0602 were higher in controls than in T1DM(OR=0.07, 0.31 respectively, both P<0.05).The positive rate of DQB1*0602 in type 1 diabetic patients with onset age>or=20 years was higher than that in the patients with onset age <20 years (P<0.05). GADA was more frequent in DQB1*0201(+) patients than in DQB1*0201 (-) patients (P<0.025).

CONCLUSIONThe findings show that DQB1*0201 is susceptible to T1DM, whereas DQB1*0601, *0602 are protective in Chinese Han population in Sichuan area. DQB1*0602 may delay the onset of T1DM. The positive rate of DQB1*0201 correlates positively with that of GADA.

Adolescent ; Adult ; Age of Onset ; Autoantibodies ; immunology ; Child ; Child, Preschool ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; epidemiology ; genetics ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Genetic Predisposition to Disease ; genetics ; Glutamate Decarboxylase ; immunology ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Middle Aged ; Polymerase Chain Reaction ; Young Adult