IDDM and early exposure of infant to cow’s milk and solid food

Associations studies were attempted between the type of feeding, duration, and time of starting of solid foods in infancy and the incidence of insulin-dependent diabetes mellitus ( IDDM). The study subjects comprised 52 IDDM patients and 52 control subjects matched for sex, age, social status, country, geographical location and selected from pediatric departments of different hospitals in Tehran. Diabetic children (21 boys, 31 girls) were of the ages of 1.5 to 14 years. Information about the pattern of their feeding at the first two years of life were collected through questionnaires administered to the mothers. The questionnaire was designed to evaluate the duration of complete or partial breast-feeding and the age at which dietary products containing cow’s milk were introduced into the diet. A large proportion of the diabetic children rather than the control children had been breast-fed, and the risk of IDDM among children who had not been breast-fed was below unity. No significant difference in the duration of breast-feeding was observed between diabetic and control group. Our data do not support the existence of a protective effect of breast-feeding on the risk of IDDM, nor do the data indicate that early exposure to cow’s milk and dairy products has any influence on the development of IDDM.     

Initial signs and diagnosis of diabetes, — special considerations of oriental patients

Hyperglycemia and other metabolic derangements resulting from absolute or functional deficiency of insulin are accompanied by typical signs and symptoms of diabetes. The clinical signs and the findings of hyperglycemia over 200 mg/dl should establish a diagnosis of diabetes mellitus. An oral glucose tolerance test (O-GTT) is rarely necessary for diagnosis of diabetes in a. child. A small proportion of children, however, present less severe symptoms, and may require an O-GTT. Approximately 14% of IDDM children were in coma at diagnosis in Tokyo, and 11 onset deaths (0.94%) were observed among the 1172 newly diagnosed IDDM cases in Japan. A significant decline in the onset mortality, however, has been observed in the past 20 years in Japan in association with the improvement of early management of childhood diabetes. The clinical distinction of IDDM from NIDDM is often difficult in diabetic children of Oriental origin without obesity. Japanese IDDM can be divided into two forms, abrupt and slow onset forms, but they may be essentially the same disease. There was no difference in the frequency of being tested positive for circulating ICA between the two groups of the patients. But a difference in the frequency of HLA DR4 and DRW9 was noticed between the two groups. Clinical features of 107 children with NIDDM were studied and about 75% of these cases were obese. All of them can be detected by routine urinalysis for glucose. Diet and exercise therapy in most of the newly diagnosed patients resulted in remission but some of them may require insulin or an oral hypoglycemic agent to get better glycemic control     

HLA-DQA1*05-DQB1*0201 positivity predisposes to coeliac disease in Czech diabetic children

The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLADQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMApositive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%). Conclusion: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity.     

Quantitation of gene expression by real-time PCR disproves a "retroviral hypothesis" for childhood-onset diabetes mellitus.

Children with insulin-dependent diabetes mellitus (IDDM) suffer from a chronic autoimmune beta cell destruction of unknown origin, maybe due to superantigens or retroviral endogenous genes. Recently, a novel endogenous retrovirus designated as IDDMK 22 was proposed to encode for such a candidate autoimmune gene in type 1 diabetes. We therefore analyzed the expression of IDDMK 22 genes in peripheral blood leukocytes and plasma from 55 healthy children and 55 diabetic children including 11 patients with acute disease onset. In our study we applied an improved quantitative and highly specific real-time PCR assay. In contrast to previous data obtained by conventional PCR. IDDMK 22 gene expression did not differ between diabetic and nondiabetic individuals. For this reason, we propose that IDDMK 22 is an ubiquitous endogenous retroviral element in the human genome but not a candidate autoimmune gene for IDDM, especially in childhood-onset disease. Real-time PCR proved to be a highly sensitive and specific method for detection and quantitation of very low amounts of mRNA and will thereby be useful regarding the special demands in pediatric studies dealing with very low amounts of specimen.     

Congenital Malformations in Newborns from Diabetic Mothers*

It has been well known that there is a high incidence of congenital malformations in newborns from diabetic mothers when the mothers' diabetes control before and during pregnancy is poor. We treated 438 pregnant diabetics who bore 443 children between February 1964 and June 1992. Among these children, there were 51 cases (11.5%) with congenital malformations, 21 cases with major anomalies (4.7%) and 30 cases with minor anomalies (6.8%). The type of malformations are not related to special organs; heart malformations and cleft lips are relatively frequent compared to other types of malformations. The mechanism of the congenital malformations in newborns from diabetic mothers remains unclear. However, clinically and experimentally it has been found to be due to fuel-mediated teratogenesis. Since October 1978, HbAi has been used as an index of diabetic control and the relationship between congenital malformations and the mother's diabetes control has been observed. 1) There is no difference in the incidence of malformations in children from IDDM and NIDDM mothers. However, there are more severe malformations in the children from IDDM mothers compared to those from NIDDM mothers. 2) Mothers who bore children with major malformations had all made their first visit to our hospital after pregnancy. HbAi in the IDDM mothers who had children with malformations at the first visit was 11%. 3) In the NIDDM mothers, even if HbAi levels are near normal, children with major malformations were born and there was little relationship between congenital malformations and the mothers' diabetes control. These data suggest that there are two kinds of congenital malformations in children from diabetic mothers, fuel-mediated teratogenesis, and malformations as seen in children from non-diabetic mothers.     

Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.     

Family characteristics and insulin dependent diabetes.

During the calendar year of 1988 a survey of new cases of insulin dependent diabetes mellitus (IDDM) in children under the age of 15 years in the British Isles was conducted. After cases had been confirmed and permission obtained to contact the families, postal questionnaires were sent to the parents of children diagnosed in England, Wales, Northern Ireland, and the Republic of Ireland. Children who developed diabetes were significantly more likely to be heavier at birth in comparison with national reference data. The diabetic children were less likely to have been breast fed, and there were more children than expected whose fathers were in nonmanual occupations. Where there was a first degree relative with IDDM there were positive correlations between the age at diagnosis of the index cases and that of their diabetic fathers and their diabetic siblings, but not their diabetic mothers. A higher proportion of children than expected who were diagnosed under the age of 5 years had fathers with IDDM. Characteristics of family members associated with IDDM in children that might provide pointers to the aetiology of the disease include heavier birth weight, method of infant feeding, the age at onset of IDDM in affected fathers and affected siblings, and the family lifestyle as defined by social class of the father.     

Descriptive Epidemiology of Non-Insulin Dependent Diabetes Mellitus Detected by Urine Glucose Screening in School Children in Japan

During the period from 1974 through 1988, we annually examined approximately 225,000 to 386,400 school children residing in Tokyo for glycosuria to detect juvenile diabetes. If the first test was positive for glucose, glycosuria was confirmed by a second test. In children who gave a positive result in both the first and second tests 0-GTT were performed. All 124 patients were diagnosed as NIDDM according to the criteria of the WHO Report on Diabetes of 1985. The incidence of NIDDM in children in Japan has increased in recent years and from 1984 to 1986 was approximately 3.8 per 100,000 per year. The frequency of NIDDM increases with age up to 14 years. In about 84% of cases, the body weight at diagnosis is more than 20% above the ideal weight and the height is often above average. There is a high frequency in families with a history of diabetes. Diet and exercise therapy in newly diagnosed patients irrespective of the presence or absence of obesity may result in remission, but some cases may require insulin therapy or oral administration of a hypogly cemic drug to obtain a better glycemic control. Children with NIDDM are more likely to be complicated by incipient retinopathy within two years after diagnosis than those with IDDM. Therefore, it is important to keep strict glycemic control to prevent diabetic complications in NIDDM children just as in juvenile onset IDDM.     

Normal stimulated growth hormone secretion but low peripheral levels of insulin-like growth factor I in prepubertal children with insulin-dependent diabetes mellitus

The hypothalamo-pituitary-insulin-like growth factor I (IGF-I) axis was studied in 24 prepubertal children with insulin-dependent diabetes mellitus (IDDM) and 12 non-diabetic children. There were no significant differences between the diabetic and control subjects in basal concentrations of immunoreactive growth hormone releasing hormone (ir-GHRH), growth hormone (GH) or stimulated GH levels, but after exercise ir-GHRH concentrations were higher in the diabetic children. Peripheral IGF-I levels were significantly lower in the diabetic children, and even lower in those with poor metabolic control. A positive correlation was found between IGF-I levels and circulating free insulin concentrations in the diabetic subjects (r = 0.49, p < 0.05). These observations suggest that the GH response to physiological stimulation is normal in prepubertal diabetic children. Exercise-induced GH response may not be mediated by GHRH. IGF-I levels were reduced in prepubertal children with IDDM and even more so in subjects with poor metabolic control. This may be a consequence of transitory hypoinsulineamia, emphasizing the importance of adequate insulinization to facilitate optimal growth in children and adolescents with IDDM.     

Metabolic cataracts in newly diagnosed diabetes

The morphologically distinct diabetic or 'metabolic' cataract is rare in newly diagnosed insulin dependent diabetes. The cases described are of five adolescents (three girls, two boys) with newly diagnosed insulin dependent diabetes who developed metabolic cataracts close to the time of diagnosis (0-16 months). They all had a prolonged duration of symptoms before diagnosis (4-24 months) and high glycated haemoglobin levels at diagnosis (15-21%). The pathogenesis of diabetic cataract is not well understood in humans. An attempt is made to link clinical observations with evidence from experimental animal models to understand the mechanism of cataract formation, with particular reference to the aldose reductase pathway. It is recommended that the lens and retina are examined at the onset of diabetes in all children, especially those who have a prolonged duration of symptoms before diagnosis and who report persistent blurred vision.     

A 5‐yr follow‐up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin‐dependent diabetes mellitus

Lee S‐S, Han H‐H, Kim H. A 5‐yr follow‐up nerve conduction study for the detection of subclinical diabetic neuropathy in children with newly diagnosed insulin‐dependent diabetes mellitus. Pediatric Diabetes 20XX: 00: 000–000 Objective: To investigate the changes of peripheral nerve conduction in children with insulin‐dependent diabetes mellitus (IDDM) prospectively from diagnosis and to know how those results were related to clinical risk factors. Methods: A total of 37 patients (14 males and 23 females) aged 3–19 yr (mean 12.0 ± 3.7) with newly diagnosed IDDM underwent bilateral nerve conduction studies (NCS) of median, ulnar, posterior tibial, peroneal, and sural nerves annually for 5 yr. Results: In all, 12 patients (32.4%) showed electrophysiological evidence of polyneuropathy in at least two different nerves including the sural nerve at the diagnosis of IDDM; 20 patients (54%) had multiple (≥2) abnormalities in parameters of NCS. The most common abnormal parameters at the diagnosis were conduction velocities of peroneal motor and sural nerves. In sequential NCS over 5 yr, the percentage of abnormal nerve conduction velocities rose except within the sural nerve. Poor metabolic control, height, duration of diabetes, and older age of onset were related to the changes of parameters of NCS over 5 yr. Among those risk factors, the duration of diabetes and sustained hyperglycemia affected the parameters of NCS more frequently than others. Conclusions: Children with IDDM frequently have nerve conduction abnormalities without clinical neuropathy at initial diagnosis. The frequency of abnormalities of any attribute of nerve conduction increased over the 5 yr follow‐up. The duration of diabetes and poor glycemic control proved to be more important risk factors over 5 yr as related to the development of subclinical neuropathy.     

Initial coping responses and psychosocial characteristics of children with insulin-dependent diabetes mellitus

School-aged children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) were studied longitudinally in order to document how they adjusted to the medical illness and to assess salient background factors. The extent of life stress and the prevalence of psychiatric disorders that predated the IDDM were within normative ranges, and there was no characteristic preexisting "diabetic personality." The initial strain of living with IDDM elicited two general modes of coping. The prototypical and subdued reaction (seen in 64% of the children) consisted of mild sadness, anxiety, feeling of friendlessness, and social withdrawal. The rest of the children (36%) exhibited reactions that met criteria for a psychiatric disorder; depressive syndromes were the most common presentations. Anamnestic factors and the parents' initial responses to their children's IDDM were unrelated to how the children themselves coped. However, psychiatrically diagnosable reactions were more likely among children whose parents were of low socioeconomic status and had marital distress. Coping with the diagnosis and the early impact of IDDM took no more than 7 to 9 months, no matter how severe the child's response was initially.     

Pregnancy outcome in patients with insulin dependent diabetes mellitus and diabetic nephropathy treated with ACE inhibitors before pregnancy

The preconception and intrapregnancy parameters that are relevant to outcome in women with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy remain controversial. We analyzed the types and frequencies of maternal and neonatal complications in 24 IDDM patients with diabetic nephropathy (24 pregnancies), all with preserved to mildly impaired renal function. All patients received treatment with captopril for at least six months prior to planned pregnancy and were maintained under strict glycemic control from at least three months before pregnancy to delivery. A successful pregnancy outcome (live, healthy infant without severe handicaps two years after delivery) was observed in 87.5% of the patients. Preexisting hypertension was the only parameter found to be significantly predictive of an unsuccessful outcome (p = 0.0004). We conclude that in patients with IDDM complicated by diabetic nephropathy, pre-pregnancy captopril treatment combined with strict glycemic control offers a prolonged protective effect against possible renal deterioration and probably improves pregnancy outcome.     

Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally

The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are still not well defined. We evaluated total bone mineral content (TBMC) and bone mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of 12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation scores (Z-scores) were determined by comparing our results to controls matched for age, sex and pubertal status. BMD and bone formation and resorption markers were determined at the beginning of the study and after one year of follow up. Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26 children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below the mean. Mean lumbar spine Z-score remained unchanged after one year of follow up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or TBMC between groups. No correlation was observed between lumbar spine BMD Z-scores and duration of IDDM or degree of diabetes control, as assessed by the mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our patients initially and after one year of follow up; however, no correlation was obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy-terminal propeptide of type 1 collagen values and levels of urinary cross-linked N-telopeptides of type 1 collagen in the diabetic children were significantly lower than those of the matched controls. Osteoblastic activity as assessed by serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided into males and females and into children with more than or less than 2 yr duration of diabetes since diagnosis, no differences between groups were found. These results suggest that insulin dependent diabetes in children is associated with low bone turnover resulting in a deficit in bone mass which may be manifested as osteopenia in the growing bone. This defect is already present in trabecular bone early on in the disease and seems not to be related to glycemic control.     

Insulin-dependent diabetes mellitus in southern Chinese children: An overview

Thirty-three southern Chinese children with insulin-dependent diabetes mellitus (IDDM) were studied. The patients had a mean follow-up of 5.2 years (range 1.2–8.2). The mean age of onset was 8.3 years (range 1.7–13.5). The mean duration of symptoms before diagnosis was 22 days. Ten patients (30%) presented with diabetic ketoacidosis at diagnosis. Only one patient (3%) was found to have thyroid microsomal antibodies and none was found to have hypothyroidism or hyperthyroidism. Incidence and prevalence were calculated from data recorded retrospectively and prospectively in a population-based registry of IDDM. The prevalence in 1991 and 1992 was 8.3 per 100000 children under 15 years of age. The age-standardized incidence of IDDM was 1.7/100 000 per year with the 95% confidence interval of 1.2–2.4/100 000 per year for children under 15 years of age during the years 1986–93. The incidence for males was 1.1/100 000 per year and for females, 2.4/100 000 per year.     

Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group

The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children.     

Islet cell and other organ-specific autoantibodies in healthy first-degree relatives to insulin-dependent

The presence of organ-specific autoantibodies including islet cell surface, cytoplasmic and cytotoxic as well as thyroid-gastric antibodies were determined in healthy, non-diabetic, first-degree relatives to 30 insulin-dependent diabetic (IDDM) children. Thirty healthy families without family-history of diabetes mellitus served as controls. The prevalence of organ-specific autoantibodies among the healthy members in the diabetic families was increased compared to the control families (p less than 0.005). Islet cell cytoplasmic antibodies were only detected in diabetes families, since 23% (7/30) of the probands and 7% (2/31) of the siblings were positive and all others negative. Organ-specific autoantibodies were associated with HLA DR3 only in the diabetes families (p less than 0.025) while autoantibody positive members in the control families were associated with HLA B7 (p less than 0.01). This study suggests that childhood IDDM occurs in families with an increased prevalence of organ-specific autoantibodies.     

Sympathetic skin response in diabetic children: Do diabetic children have diabetic neuropathy?

BACKGROUND: Abnormal sympathetic skin response (SSR) has been reported in adult patients with diabetic neuropathy. In addition, other studies have revealed abnormal SSR in diabetic patients not having autonomic symptoms and autonomic dysfunctions. These findings have been only obtained from adult patients. There have been few reports on the autonomic functions in diabetic children. Accordingly, it is not clear whether the autonomic neuropathy occurs in diabetic children. The aim of the present study is to clear autonomic function in children with insulin-dependent diabetes mellitus by SSR. METHODS: The SSR was measured in 28 normal healthy children and in eight patients with IDDM not having symptoms of dysautonomia. The SSR was elicited using 10 stimuli on programmed Nihonkoden Neuropack Sigma model machine. Following a single electrical stimulation, four SSR were recorded in both the palms and the soles simultaneously. RESULTS: The SSR were simultaneously obtained in 100% of the two groups. The amplitudes in the palms and soles were not significantly different between the two groups. The mean and shortest latency in the soles were significantly longer in the IDDM group than in the control group (P < 0.01). None of the measurements of SSR revealed correlation with duration of diabetes and onset of illness. CONCLUSIONS: Diabetic neuropathy may not have occurred in young patients having shorter duration of illness. Conversely, assuming that prolonged latency is abnormal, it may even have occurred in them. Follow up on these patients with prolonged latencies would be required.     

Increased frequency of IgM antibodies to cow's milk proteins in Hungarian children with newly diagnosed insulin-dependent diabetes mellitus

We investigated the association between serum antibodies to cow’s milk proteins and insulin-dependent diabetes mellitus (IDDM) in Hungarian children. Forty-eight children 1.0–17.1 years of age with newly diagnosed IDDM and 74 control children 1.0–16.0 years of age were studied for serum IgG, IgA and IgM antibodies to cow’s milk, β-lactoglobulin, bovine serum albumin and ovalbumin by enzyme-linked immunosorbent assays. The specificity of IgM antibodies to β-lactoglobulin and bovine serum albumin was controlled by Western blot. The levels of IgG and IgA antibodies to cow’s milk proteins were similar in children with and without IDDM, with the exception of slightly increased levels of IgA antibodies to β-lactoglobulin in diabetic children (P = 0.05). The levels of IgM antibodies to cow’s milk were significantly higher in IDDM patients than in control children (P = 0.0002). Children with IDDM more often had IgM antibodies to β-lactoglobulin (46.3% vs 18.8%; P = 0.002) and bovine serum albumin (87.8% vs 49.3%, P < 0.0001) than control children. Neither the levels of IgG or IgA antibodies to ovalbumin nor the frequency of IgM antibodies to ovalbumin differed between diabetic and control children. Conclusion In Hungarian children, clinical manifestation of IDDM is often associated with IgM antibody response to cow’s milk protein and its fractions, β-lactoglobulin and bovine serum albumin, indicating a loss of immunological tolerance to these proteins. IgG and IgA antibodies to cow’s milk proteins, associated with an early introduction of cow’s milk in diet, seem to play a minor role in the development of childhood IDDM in Hungary. Received: 14 November 1995 Accepted: 3 March 1996     

Islet Cell and Other Organ-specific Autoantibodies in Healthy First-degree Relatives to Insulin-dependent

ABSTRACT. The presence of organ-specific autoantibodies including islet cell surface, cytoplasmic and cytotoxic as well as thyroid-gastric antibodies were determined in healthy, non-diabetic, first-degree relatives to 30 insulin-dependent diabetic (IDDM) children. Thirty healthy families without family-history of diabetes mellitus served as controls. The prevalence of organ-specific autoantibodies among the healthy members in the diabetic families was increased compared to the control families ( p <0.005). Islet cell cytoplasmic antibodies were only detected in diabetes families, since 23% (7/30) of the probands and 7% (2/31) of the siblings were positive and all others negative. Organ-specific autoantibodies were associated with HLA DR3 only in the diabetes families ( p <0.025) while autoantibody positive members in the control families were associated with HLA B7 ( p <0.01). This study suggests that childhood IDDM occurs in families with an increased prevalence of organ-specific autoantibodies.