Epidemilogy of Insulin-Dependent Diabetes Mellitus in Korea

The prevalence of diabetes mellitus in the age group5–16 years, determined from 13,152 subjects residing in Kwangju, Chonnam Provice was 0.099 per cent or 98.9/100,000 in a study performed from December, 1976 to June 1977. On the other hand an epidemiologic study carried out on 254,835 subjects in the age groups14–15 and17–18 years from March 1981 to March 1982 in Seoul City revealed on overall prevalence of 7.85/100,000. In a retrospective study, 88.0/100,000 or out of a total of 10,228 pediatric inpatients were confirmed casesw of insulin-dependent diabetes mellitus, during 7 years and 2 months (from january 1974 to March 1981) at a general hospital located in Jeonju City. The wide range in the prevalence and incidence figures of diabetes mellitus in Korean children probably resulted from lack of uniformity in epidemiological methodology and the degree of ascertainment. The adge distribution at onset of diabetes mellitus showed a gradual incdrease and peak incidences at 3,8 and 12 years of age. The4 sex difference in incidence was not obvious, though girls slightly outnumbered boys. Seasonal variation at onset of diabetes mellitus showed the highest frequency of new cases in winter and spring months.     

Report of a Japanese Girl with Marfan Syndrome Associated with Insulin-Dependent Diabetes Mellitus

A 3 year old girl was admitted to hospital in an emaciated condition and with polydipsia in October 1974. Following the diagnosis of diabetes mellitus, she Received treatment with insulin. On the first admission, a systolic murmur was noted at the apex of the heart. In 1981, the murmur was found to be continuous with a systolic click, and echocardiography demonstrated a mitral valve prolapse. In 1982, electrocardiography revealed left ventricular hypertrophy, and the patient's X-ray showed vertebral kyphoscoliosis. Ophthalmological examination revealed slightly impaired visual acuity and a mild case of cataracts in 1986. The patient grew to be tall and thin with arachnodactylia of the hands, fingers, feet and toes. These symptoms and findings were compatible with Marfan syndrome, although the ophthalmological findings are not specific for this disease. This patient is the first case in Japan of Marfan syndrome associated with insulin-dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear.     

The Study of HLA, ICA and Autoantibodies in Japanese Type 1 Diabetes Mellitus

HLA, ICA (islet cell antibody) and autoantibodies were studied in 65 Japanese patients with type 1 diabetes mellitus to elucidate the existence of immuno-genetic heterogeneity. Patients with autoantibodies had increased frequencies of HLA DRw9 antigen and of HLA haplotype of Bw61-DRw9, and a slow decay of ICA, while patients without autoantibodies had increased frequencies of HLA DR4 antigen and of HLA haplotype of Bw54-DR4, and a rapid decay of ICA. These findings support the concept of immunogenetic heterogeneity in Japanese type 1 diabetes mellitus.     

Classification of Type 1 and Type 2 Diabetes Mellitus from Studies of ICA, HLA and Insulin Secretory Capacity

We studied ICA, HLA and insulin secretory capacity in 87 children with positive urinary screening and more than 2 points in the oral glucose tolerance test in order to establish criteria by which they could be classified into type 1 or type 2 diabetes mellitus. Fifty-five non-obese, ketosis-prone insulin dependent diabetic children were used as controls for type 1 diabetes mellitus. Our conclusions were as follows: 1. Type 1 diabetics were non-obese (on insulin therapy), ICA positive, ketosis-prone, had an insulin secretory capacity (Z IRI) of less than 100/nU/ml, and most of them possessed HLA-Bw54-DR4 or DRw9, DRw53 but did not possess Bw52-DR2 haplotype. 2. In the patients who were treated by dietary regimens alone for certain periods, however, insulin secretory capacities gradually deteriorated and they finally became insulin dependent. The children of this group who were not obese during insulin therapy and possessed an HLA haplotype identical to that in type 1 diabetes, regardless of ICA, might be classified as having slowly progressive type 1 diabetes. 3. The major difference between type 1 and slowly progressive type 1 diabetes was a family history of diabetes. Genetic factors might modify the clinical course of type 1 diabetes mellitus. 4. If the sensitivity of ICA or related autoantibodies to islet cells can be detected more readily, it should become easier to distinguish between type 1 and 2 diabetes.     

Characterization of Diabetes Mellitus in Japanese Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is frequently associated with marked obesity and diabetes mellitus (DM). Although the overall frequency of DM in PWS ranges from 7–20%, there is only limited data available on Japanese patients. This study evaluated five factors associated with DM in PWS: 1) frequency, 2) age of onset, 3) risk factors, 4) long-term complications and 5) treatment. Sixty-five patients, ranging in age from 10 to 53 yr, were studied retrospectively. The frequency of DM in patients over 10 yr of age was 26.2% (17/65 patients). The age of DM onset ranged from 10 to 29 yr with a median age of 15 yr. The body mass index (BMI) was significantly higher in the DM group in comparison with the non-DM group. The number of patients using growth hormone (GH) in the DM group was significantly lower than the number that did not. Proteinuria (urinary excretion of albumin/creatinine at spot collection: U-Alb/Cr ≥300 mg/gCr) was observed in 1/17 patients (5.9%), microalbuminuria (U-Alb/Cr 30–300 mg/gCr) was observed in 4/17 patients (23.5%) and nonproliferative retinopathy was observed in 2/17 patients (11.8%). Among oral hypoglycemic agents, alpha-glucosidase inhibitors (α-GI) were most often used in our patients (10/17, 58.8%). Eleven out of 17 patients (64.7%) had been treated with insulin.     

Residual Pancreatic Beta-Cell Function in Insulin-Dependent Diabetes Mellitus

It is recognized that residual pancreatic /3-cell function may play a role in the control of blood glucose in patients with insulin-dependent diabetes mellitus (IDDM). Since modern therapy is concerned with the possibility of recovery of pancreatic β-cell function, we need to identify the secretagogue of choice in the various phases of IDDM. Eleven patients with IDDM underwent four different stimulation tests of (3-cell function over two weeks. The tests were i.v. arginine (ATT), oral glucose (o-GTT), i.v. glucagon (GCT) and i.v. tolubutamide (TTT). One patient had the tests repeated four times over two years after the onset. Among the tests, ATT and o-GTT produced the largest response ofC-peptide. The response to GCT was small in comparison. TTT had no significant effect. The present study suggests that ATT or o-GTT or both are useful in the evaluation of endogenous insulin secretion during follow-up of IDDM. On the other hand, GCT can only be used as a simple screening method for residual ß-cell function and is not sufficient for quantitative measurement in IDDM.     

Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (DIDMOAD Syndrome): A Clinical Study in Two Sudanese Families

ABSTRACT. Four Sudanese children with DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) are reported. They were two boys (aged 15 and 16 years) in one family and a boy and a girl (aged 16 and 6 years, respectively) in another family. Diabetes mellitus was first to appear (at 3–8 years) followed by deafness and visual failure; and the disease ended fatally in one patient (aged 20 years). In the other three, diabetes insipidus was confirmed using water deprivation test for 8 hours. The maximum urine osmolality ranged between 131–523 mOsm/kg, whereas the corresponding plasma osmolality ranged between 315–332 mOsm/kg. Slight further improvement in urine concentration was observed in 2 of the patients following the use of desmopression (DDAVP, 20 μg intranasally). Intravenous pyelography, voiding cystourethrography and ultrasound revealed severe bilateral hydronephrosis, dilated ureters and distended bladder without vesicoureteral reflux in the three patients. With the high rate of consanguinity prevalent in North Africa and the Middle East, we recommend examining children who present with diabetes mellitus in this region for features of DIDMOAD syndrome.     

Metabolic Control in Children and Adolescents with Insulin-Dependent Diabetes Mellitus

ABSTRACT. The metabolic control, assessed from the mean daily glucosuria, mean daily glucosuria index based on home tests, and mean haemoglobin A₁ (HbA₁) concentrations during 1980, and the influence of various factors on the control were analysed in 177 diabetic children and adolescents. The mean daily glucosuria was 21 % of the carbohydrates in the subscribed diet, and the mean glucosuria index 55 %. The mean HbA] was 14.0 %. Boys had better metabolic control than girls. Good motivation towards treatment was associated with better metabolic control. There was a negative correlation between metabolic control and both the age of the child and the duration of diabetes. Prepubertal children were better controlled than those in puberty. Adherence to the dietary regimen was related to better control, as was the patient's endogenous insulin secretion, measured by serum C-peptide concentration. There was also an association between the season and the metabolic control, the control being better in the spring than during the other seasons. On the basis of these results male sex, a good motivation towards treatment, residual beta-cell function and adherence to the prescribed diet favor good metabolic control, while a long duration of the disease, the presence of puberty and relatively high age in childhood are factors impairing the metabolic control.     

HLA A Class II (DR, DQ) in Japanese Patients with Type 1 Diabetes Mellitus

DNA restriction fragment length polymorphism (RFLP) typing of HLA-DR and DQ alleles of 60 Japanese type 1 (insulin dependent) diabetic patients and 115 controls was performed. RFLP typing of DRB1 showed increased frequency of DR9 and decreased frequencies of DR2 and DRW6 among patients compared to controls. In the RFLP typing of BamHI- digested DNA to DQ β probe (BamHI-DQB1), the incidence of the 10.26 kb fragment, which represents either DQW4, DQW8 or DQW9, was markedly elevated in the patients, whereas the incidence of DQW6 was reduced. The predicted DR-DQ haplotype study revealed that DR4-DQW4 or DQW8, DRW8-DQW4 or DQW8 and DR9-DQW9 may contribute to susceptibility to type 1 diabetes. When serological typing of the 13 DRW8 patients was performed, all the 11 DRW8 patients carrying DQW4 or DQW8 (BamHI-10.26 kb) were positive for DQW3.
These results indicated that the HLA-DQ locus may play an important role in the development of type 1 diabetes in the Japanese as well as other ethnic groups and that the DRW8- DQW8 haplotype may predispose to the disease in Japan.     

Circulating Class II Transplantation Antigen-Expressing T Lymphocytes in Children with Insulin-Dependent Diabetes Mellitus at Diagnosis

ABSTRACT. The occurrence of circulating class II antigen-expressing T lymphocytes was examined in 25 children with insulin-dependent diabetes mellitus using an indirect double immunofluorescence assay on prefixed cell samples. In order to exclude sensitization to heterologous insulin as a possible factor affecting the results, the patients were investigated at the day of clinical onset, before receiving insulin. An increased percentage of T cells (CD3+ cells) expressing class II antigens was seen in 19 out of 25 patients and class II expression was observed on cells within both the CD4+ and CD8+ T cell subsets. No correlation was found between the levels of class II expressing T cells and the individual degree of metabolic derangement or indicators of recent infection. Re-testing of 16 patients after one year on insulin treatment revealed a significant decrease of class II expressing T cell levels. Our data suggest that the increased levels of class II expressing T cells seen in IDDM of recent onset directly reflects immune reactions that are related to the disease process.     

Autoimmunity of Insulin-Dependent Diabetes in Japan

In this paper some findings concerning autoimmunity have been studied in young Japanese patients with diabetes. Patients diagnosed before 30 years old were classified carefully into new categories recommended by WHO in 1980: insulin-dependent (IDDM), non-insulin-dependent (NIDDM) and other types of diabetes. HLA antigen types, islet cell antibodies (ICA) and islet cell surface antibodies (ICSA) were checked in the sera. HLA-Bw54 and -DR4 were found in a significantly high percentage of IDDM patients, especially in those with Insulin-Dependent Diabetes Mellitus with Special Reference to acute onset of the disease. Positivity of ICA was remarkably high in IDDM Viral Infections patients within one year after the onset, and then decreased very rapidly. ICSA had the same tendency, but the rate of decrease of positivity seemed slower than that of ICA Apparent autoimmune diseases were rare among our patients, and persistent positivity of ICA was found only in a few cases. At this time we have notenough evidence concerning autoimmunity as a major cause of IDDM.     

Clinical Significance of Urinary C-Peptide Excretion in Children with Insulin-Dependent Diabetes Mellitus

ABSTRACT. In order to evaluate the accuracy of urinary C-peptide determination and the clinical significance of C-peptiduria for the early course of insulin-dependent diabetes (IDDM), the rate of urinary excretion of C-peptide was determined in 32 children and adolescents with IDDM and correlated with serum C-peptide concentration, urinary excretion of albumin and β-mic-rogloublin and with the glomerular filtration rate (GFR) measured in terms of the clearance of ⁹⁹mTc-DTPA. The age of the subjects ranged from 9.1 to 17.1 years (mean 13.1) and the duration of diabetes from 0.3 to 11.9 years (mean 4.6). There was a good correlation between postprandial serum C-peptide concentration and the 24-hour urinary C-peptide excretion rate ( r =0.81; p <0.001). GFR and urinary albumin excretion were slightly elevated in the diabetic patients as compared with non-diabetic subjects ( p <0.05 and p <0.001, respectively), but C-peptide excretion was unrelated to the degree of hyperfiltration or albuminuria, neither was there any correlation between the excretion rate of β₂-microglobulin and C-peptide. Glycaemic control was poorer in the diabetic children who had only trace amounts of C-peptide in their urine (<0.05 nmol/m²/24 h) than in those with minimal (0.05–1.0 nmol/m²) or moderate 24-hour urinary C-peptide excretion (>1.0 nmol/m²). It is concluded that urinary C-peptide excretion serves very well to reflect residual β-cell function and is unrelated to the slight renal hyperfunction and albuminuria often seen in diabetic subjects. Even minimal C-peptide excretion ranging from 0.05 to 1.0 nmol/m²/24 h still seems to indicate clinically significant insulin secretion.     

儿童糖尿病198例

目的 探讨儿童糖尿病(DM)的临床特点,为临床诊治提供理论依据.方法 对1999年1月-2009年3月在本院住院的198例DM患儿的临床表现和实验室检查进行回顾性临床分析.结果 198例DM患儿中,男97例,女101例.均为首诊病例;发病高峰年龄为5～6岁及9～11岁;首诊例数逐年增加,2008年较1999年增加了3.7倍;其中1型糖尿病(T1DM) 174例(占88.9％),2型糖尿病7例(占3.5％),新生儿DM 14例(占7.1％),其他3例(占1.5％).首诊的TlDM患者中,酮症酸中毒(DKA)的发生率为42.0％;发病前有感染史者55例,与无感染史者比较,DKA的发生率有统计学差异(P＜0.01).有DM家族遗传史者23例.并甲状腺功能亢进症2例;并暂时性甲状腺功能减低症31例;并肝功能异常30例,肾功能异常12例,血脂异常48例,尿蛋白阳性27例.糖化血红蛋白为(12.0±1.8)％;共分析了25例T1 DM患者的自身抗体,胰岛细胞抗体阳性率为28％,胰岛素自身抗体的阳性率为20％,谷氮酸脱羧酶自身抗体(GADA)阳性率为72％.结论 首诊的儿童DM逐年增加,以T1DM为主;新生儿DM增加明显;DKA是T1DM患者就诊的重要原因;首诊的T1DM者中,感染是发生DKA的重要诱因;儿童DM常合并暂时性甲状腺功能减低症、肝肾功能异常及血脂异常;糖尿病自身抗体中GADA的阳性率最高.     

Psychological Problems in the Families of Japanese Insulin-Dependent Diabetes Mellitus (IDDM) Patients

Emotional stability of insulin-dependent diabetics is closely related to their metabolic control. We have already presented the psychological features of diabetic children at the 5 th International Beilinson Symposium. These results indicate that psychological problems are usually interactions with the patient's family. Family troubles derived from impaired interrelation are significant. From these points of view, counselling with the family based on a proper understanding of their relationship is absolutely necessary. We have had regular meetings for mothers with diabetic children in our clinic to discuss their psychological troubles. In this study we examined the frequency of poorly controlled patients in our clinic and analyzed the nature of their problems. We further summarized the opinion of family members which had been discussed in the above-mentioned meeting. Frequency of constantly poorly controlled patient was 8.1% (3/37) in male and 16.3% (8/49) in female. We report on our method' of approach to them.     

Delayed Management of Insulin-Dependent Diabetes Mellitus in Children

IntroductionDiabetic ketoacidosis (DKA) is a common presentation for pediatric new-onset insulin-dependent diabetes mellitus (IDDM). Delayed diagnosis is the major risk factor for DKA at disease onset.MethodTwo pediatric endocrinologists independently reviewed the admission records to assess the appropriateness of preadmission management in various health care settings.ResultsEighteen percent (n = 45) of patients with new-onset IDDM had a delayed diagnosis. Twenty-eight were misdiagnosed (respiratory [n = 9], nonspecific [n = 7], genitourinary [n = 4], gastrointestinal [n = 8] issues) and 17 were mismanaged. One child died within 4 hr of hospitalization, presumably because of a hyperosmolar coma. Forty-six percent (n = 21) of patients with delayed diagnosis presented with DKA, comprising 18% of all DKA cases.DiscussionA significant number of patients with new-onset IDDM were either misdiagnosed or mismanaged. All providers must be appropriately trained in diagnosing new-onset IDDM and follow the standard of clinical care practices.     

Growth Hormone Treatment and Diabetes: Survey of the Kabi Pharmacia International Growth Study

Out of a total of 8136 children registered in the Kabi Pharmacia International Growth Study, 12 have been reported to have diabetes either before or during treatment with growth hormone (GH). Two of these have non-insulin-dependent diabetes mellitus (NIDDM), of whom one had risk factors for the development of his condition, namely gross obesity and familial occurrence of NIDDM. One is a rare case of McCune-Albright's syndrome with insulin-dependent diabetes mellitus (IDDM), and 9 other patients have IDDM. Of these 9, 6 have idiopathic GH deficiency. In 8 of the 9 patients with IDDM, the condition was diagnosed before GH therapy was commenced, at ages ranging from less than 2 years to 16 years. The association is probably fortuitous, however, as the onset of IDDM in 7 patients was immediately before or during puberty, as often occurs in IDDM in general.     

C-Peptide/Creatinine Ratio in Early Morning Urine as an Indicator of Residual B-Cell Function in Insulin-Dependent Diabetes

The C-peptide/creatinine (Cr) ratio in early morning urine was evaluated to assess B-cell function. The subjects were 12 boys and 36 girls with insulin-dependent diabetes mellitus (IDDM). The controls were 130 boys and 137 girls aged 4–15 years. There was a significant inverse correlation of this ratio with the duration of insulin therapy (r = -0.5807, P<0.01). The daily insulin dose in U/kg was significantly different among the following groups: 1.22 ± 0.31 U/kg in group 1 with undetectable C-peptide, 0.94 ± 0.37 in group 2 with a decreased ratio and 0.45 ± 0.28 in group 3 with a normal ratio. HbAl levels were 11.3 ±1.6% in group 1 and 9.2 ± 1.1% in group 3. The difference was significant. The result shows that the C-peptide/ Cr ratio in early morning urine is useful for assessing B-cell function in diabetic children.     

Clinical significance and time course of antibodies to glutamic acid decarboxylase in Japanese children with type I (insulin-dependent) diabetes mellitus

Although anti-glutamic acid decarboxylase antibodies (GADAb) have been reported to be a useful diagnostic and predictive marker of insulin-dependent diabetes mellitus (IDDM, type 1 DM) in Caucasians, a precise analysis of GADAb in Japanese children has not been reported. We examined the clinical significance and time course of GADAb in Japanese IDDM children, who have different genetic backgrounds from Caucasians. Twenty-three of 34 (67.6%) sera from recent-onset (<6 months) IDDM, and 16 of 49 (32.7%) sera from long-standing (≥2 years) IDDM patients were positive for GADAb. This prevalence of GADAb in IDDM patients was significantly higher than in normal controls and the other groups including non-insulin-dependent DM. autoimmune thyroid disease and congenital hypothyroidism, and was also significantly higher in recent-onset than in longstanding IDDM. Time course analysis suggested that autoimmune response against GAD could follow different courses in individual cases after the initiation of insulin therapy. The incidence of GADAb was significantly higher in females than in males in the older age group (11 15 years). Other clinical features including residual pancreatic β-cell function after diagnosis were demonstrated to be similar between GADAb-positive and -negative patients. In conclusion, this study using the newly established radioimmunoassay (RIA) for GADAb revealed a high prevalence of autoimmune reactivity to GAD in Japanese IDDM children. These results, using this RIA procedure, might assist in laying the groundwork for future trials of immunomodulation therapy for IDDM in Japan.     

Does Control Affect Growth in Diabetes Mellitus?

ABSTRACT. Factors affecting the growth of 67 diabetic children were analysed retrospectively. The effects of age, sex, three year average glycosylated haemoglobin (Hb A₁) levels, time since diagnosis and age at diagnosis were assessed on the change in the child's height standard deviation score (SDS) over three years, as well as the change in height SDS from diagnosis. No correlation between these factors was noted over a three year period; however, there was a strong correlation ( p <0.001) in the change in height SDS from diagnosis with the age of the child and time from diagnosis. Multiple regression analysis revealed that the younger the child at original diagnosis, the less the height SDS loss, and also that in younger children the age of the child and not the time from diagnosis was the more important variable in deciding the loss in height SDS. No correlation existed between HbA₁ levels and either the short or long term growth of patients in this study.