Using the Swedish childhood diabetes register, a nationwide, case-referent study was performed from September 1, 1985 to August 31, 1986. Based on the information from a mailed questionnaire sent to all incident diabetic children and for each diabetic child - two referent children matched according to age, sex, and county, we have analysed perinatal events and aspects of the social environment as possible risk factors for Type 1 (insulin-dependent) diabetes in childhood. A significantly larger proportion of the mothers of the diabetic children were older than 40 years compared to those of the referent children (33% and 24%, p = 0.01 respectively). A smaller percentage of mothers of the diabetic children had a high educational level compared to mothers of referent children (10% and 15%, p = 0.03 respectively) and 39% of the fathers of the diabetic children were manual workers compared to 31% of the fathers of referent children (p = 0.03). Perinatal events did not differ between diabetic and referent children. In children 0-6 years, the duration of breast-feeding was significantly shorter in diabetic children than among referent children (median duration for diabetic children 5 months compared to 6 months for referent children p = 0.03). When considering the presence of Type 1 diabetes among relatives, maternal age over 40 years, low educational level of the mother, and the father being a manual worker as risk factors, the presence of 1 to 4 of any of these risk factors increased the relative risk for Type 1 diabetes cumulatively from 1.2-7.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Since 1 July 1977, all newly diagnosed diabetic children in Sweden aged 0-14 years have been reported to a central register. During the first 6 years, 2300 newly diagnosed diabetic children out of a population of 1.6 million children were registered. The degree of certainty was close to 100%. The mean of the yearly incidence rate for the whole 6 year period was 23.6 per 100000. The prevalence of insulin dependent diabetes mellitus on 1 July 1980 was 1.48 per 1000 and 1.52 on 1 July 1983. Comparing the first and second 3-year periods, an increase was found (22.7-25.1 per 100000). This increase was consistent when analyzing incidence rates by age, sex, and geographical distribution. Cumulative incidence rates revealed a risk of developing diabetes by the age of 15 years of 3.6 per thousand for boys and 3.2 per thousand for girls. The higher incidence for boys was consistent throughout the study period. Seasonal variations in the incidence rate were also consistent, showing yearly incidence peaks in the autumn and winter months. Incidence peaks were noted for both sexes in the pubertal ages. Age- and sex-standardized morbidity ratios varied significantly within the country. 12.8% of the probands had a first degree relative with Type 1 diabetes, and it was twice as common that this relative was a father as a mother. The high and rapidly increasing incidence of Type 1 diabetes in a genetically stable population such as Sweden calls for case-control studies directed towards the identification of environmental pathogens.

From July 1, 1977 to July 1, 1986, 3,503 incident cases of Type 1 (insulin-dependent) diabetes mellitus were registered in the Swedish childhood diabetes study. Using data from this register and from a case-referent study, including all incident Type 1 diabetic children in Sweden during one year and, for each patient, two referent children matched according to age, sex and county, we have studied the associations between Type 1 diabetes and familial Type 1 and Type 2 (non-insulin-dependent) diabetes, thyroid, adrenal, allergic, rheumatic, heart and bowel disease. The mean annual incidence per 100,000 during the nine year period was 25.1 for boys and 23.5 for girls. In 8.5% of the patients, one parent had Type 1 diabetes, 73% of whom were fathers. Fifty-six of the patients (1.7%) had a parent with Type 2 diabetes. The prevalence of parental Type 1 diabetes tended to be higher in patients with younger age at onset; whereas, the opposite was found for patients with parental Type 2 diabetes. In the case-referent study, the age-adjusted odds ratio for Type 1 diabetes when a first and/or second degree relative had Type 1 diabetes was 5.5 (95% confidence limits 4.0-7.7), and in accordance with the findings of the case register, the odds ratio tended to be highest in patients with the youngest age at onset. Season at onset of the patients was not associated with parental Type 1 diabetes. The odds ratio for Type 1 diabetes was significantly increased 3.3 (95% confidence limits: 2.3-4.6) when Type 2 diabetes was reported in relatives (three generations).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective-To study different nutrients and food additives as risk factors for insulin dependent diabetes mellitus in childhood.Design-Prospective case-control study. Parents of the children being studied were asked to fill in a questionnaire regarding the children's frequency,of consumption of various foods. Parents of children with diabetes were asked about the period before onset of the disease.Setting-Population based study throughout Sweden.Subjects-339 Children aged 0-14 who had recently developed insulin dependent diabetes mellitus and 528 control children matched for age, sex, and county of residence who were traced through the official Swedish population register.Main outcome measures-Foods were classified according to their content of protein, fat, carbohydrates, monosaccharides or disaccharides, nitrosamines, nitrates or nitrites, vitamin C, and fibres. The frequency of intake was categorised as high, medium, and low and the relative risk for developing insulin dependent diabetes was estimated for the three frequencies of intake and calculated as odds ratios.Results-Significant linear trends for dose response in odds ratios by frequency of intake were shown for solid foods containing high amounts of protein (odds ratio for low frequency of intake 1 0; medium 2-3; and high 5.5), and nitrosamines (1.0; 1-7; 2.6) and significant but non-linear trends were found for carbohydrates (1 0; 1 3; 4 4) and nitrates or nitrites (1-0; 0-8; 2-4). The significant trends were not affected when the results were standardised for possible confounders. No significant increases in odds ratios were found for protein, monosaccharides and disaccharides, vitamin C, and fibres.Conclusion -Nutrients and food additives such as protein, carbohydrate, and nitrosamine compounds may influence the risk of developing insulin dependent diabetes in childhood and significant trends in odds ratios indicate a causal relation.

Summary. Insulin release and growth are intimately connected. The aim of the present study was to investigate height and weight in diabetic children from birth to onset of Type 1 (insulin-dependent) diabetes mellitus compared to that in referent children. Data on height and weight were collected from mailed questionnaires and from growth records obtained from the child health clinics and schools in 337 recentonset diabetic children, 0-14 years old, and from 517 age-, sex-, and geographically matched referent children. A total of 9002 paired height and weight observations were collected. The anthropometric development of the children was expressed as standard deviation scores using the National Center for Health Statistics/Centers for Disease Control (NCHS/CDC) growth reference material. On the average, the diabetic children were consistently taller than the referent children, a finding more pronounced among the boys. The diabetic boys were significantly taller from 7 to i years before the clinical onset of the disease, regardless of age at onset. A similar tendency was found for the girls. When mean height from 5 to 1 years before onset was used as a possible risk factor for diabetes, a linearly increasing trend in the odds ratio was found for diabetes in boys (odds ratio = 1.0; 1.57; 2.46 for height standard deviation score values < 0; 0-1 and > 1, respectively;p = 0.002 for trend). A similar, but statistically not significant, tendency was found for girls (odds ratio = 1.0; 1.44; 1.43). As regards height increment from birth similar trends in odds ratios were found. Weight-for-height was similar among diabetic and referent children of both sexes. We conclude that diabetic boys tend to be taller and grow faster than referent boys for several years preceding the disease. A similar, but not statistically significant tendency was found among diabetic girls. Our findings indicate that rapid linear growth is a risk factor for Type I diabetes in childhood, and may be either a promoter of Type i diabetes or else a marker of a physiological mechanism that affects both growth and the pathogenesis of Type 1 diabetes.

The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p less than 0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+-ATPase (3%) were all increased in the patients compared with the control children, being 2% (p less than 0.001), 2% (p less than 0.01), and 0.3% (p less than 0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.

Summary.In a nationwide incident case-referent study stepwise univariate analysis has revealed several risk determinants for childhood diabetes mellitus. In a multivariate analysis we have determined the set of risk determinants that would independently predict childhood Type i (insulindependent) diabetes. Possible interactions between the risk determinants and differences in risk profiles with different ages at onset were also examined. Reported familial insulintreated and non-insulin-treated diabetes were significant risk factors in all age groups, as was also a low frequency of milk intake. The frequency of infections and a high intake of foods rich in nitrosamine tended to interact (OR 11.8,p = 0.053) indicating a synergistic effect. A Cox regression analysis revealed that stressful life events during the last year was the only variable that tended to affect the age at onset (p = 0.055). This indicated that psychological stress may rather precipitate than induce Type i diabetes. A short breast-feeding duration (OR = 3.81), and an increased body height (OR = 3.82) contributed significantly to the predictive model in only the youngest age group (0-4 years). An increased frequency of infections in the year preceding onset (OR = 2.15) and no vaccination against measles (OR = 3.33) contributed significantly to the model only in the age group 5-9 years. Various nutrients had different impacts on the risk of developing Type 1 diabetes in different age groups. It is concluded that in the genetically susceptible child, risk factors which are associated with eating habits, frequency of infections, vaccination status, growth pattern and severe psychological stress affect the risk of developing diabetes independently of each other. The set of risk determinants varies with the age at onset. A high frequency of infections and a high frequency of nitrosamine-rich food intake seem to have a synergistic effect on the risk of developing diabetes in childhood.

Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10% of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99% of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0-14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986-1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96%) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84% (415 of 494), insulin autoantibodies 43% (145 of 334); 40% (135 of 334) were positive for both and 88% (294 of 334) were positive for one or both. Among control children, 3% (14 of 420) had islet cell antibodies, 1% (4 of 390) insulin autoantibodies, and 4% (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4% of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38%. None of the autoantibody-positive (n = 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.