G. Dahlquist

The Swedish childhood diabetes study — results from a nine year case register and a one year case-referent study indicating that Type 1 (insulin-dependent) diabetes mellitus is associated with both Type 2 (non-insulin-dependent) diabetes mellitus and autoimmune disorders

SummaryFrom 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). Odds ratios were also significantly increased (p(0.05) when thyroid or rheumatic diseases were reported among relatives.It is concluded that although the majority of incident Type 1 diabetic children lack family history, parental Type 1 diabetes may influence the age at onset of the disease but has no effect on sex distribution of these children. An increased risk for Type 1 diabetes in children is also indicated when Type 2 diabetes, (non-insulin-treated) thyroid or rheumatic disease is reported in relatives.

The swedish childhood diabetes study: social and perinatal determinants for diabetes in childhood

SummaryUsing 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. In conclusion, breast-feeding habits and probably other factors dependent on maternal age and the social status of the family may further increase the risk for Type 1 diabetes in genetically susceptible individuals.

A high linear growth is associated with an increased risk of childhood diabetes mellitus

SummaryInsulin 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 1 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 1 diabetes in childhood, and may be either a promoter of Type 1 diabetes or else a marker of a physiological mechanism that affects both growth and the pathogenesis of Type 1 diabetes.

The Swedish childhood diabetes study

SummaryIn a nationwide incident case referent study we have evaluated vaccinations, early and recent infections and the use of medicines as possible risk determinants for Type 1 (insulin-dependent) diabetes mellitus in childhood. A total of 339 recently onset diabetic and 528 referent children, age 0–14 years, were included. Information about infections was collected from a mailed questionnaire and about vaccinations from childhood health care centres and schools. When vaccinations were considered as possible risk factors for diabetes, a significant decrease in relative risk estimated as odds ratio (OR) was noted for measles vaccination (OR=0.69; 95% confidence limits 0.48–0.98). For vaccination against tuberculosis, smallpox, tetanus, whooping cough, rubella and mumps no significant effect on OR for diabetes was found. The odds ratios for Type 1 diabetes for children exposed to 0, 1–2 or over 2 infections during the last year before diagnosis of diabetes revealed a linear increase (OR = 1.0,1.96 and 2.55 for 0, 1–2 and over 2 infections, respectively). The trend was still significant when standardized for possible confounders such as age and sex of the children, maternal age and education and intake of antibiotics and analgetics. In conclusion, a protective effect of measles vaccination for Type 1 diabetes in childhood is indicated as well as a possible causal relationship between the onset of the disease and the total load of recent infections.

The Swedish childhood diabetes study — a multivariate analysis of risk determinants for diabetes in different age groups

SummaryIn 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 1 (insulin-dependent) diabetes. Possible interactions between the risk determinants and differences in risk profiles with different ages at onset were also examined. Reported familial insulin-treated 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 1 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.

The Swedish childhood diabetes study : indications of severe psychological stress as a risk factor for type 1 (insulin-dependent) diabetes mellitus in childhood

SummaryThis study is part of a nationwide case-referent study. All recent-onset Type 1 (insulin-dependent) diabetic children aged 0–14 years in Sweden were invited to participate. Referent subjects matched for age-, sex- and geographical distribution were selected. In all, 338 patients and 528 referent subjects took part. Life events during the last year prior to clinical onset of Type 1 diabetes were recorded on a questionnaire. The total frequency of life events did not differ between diabetic and referent children. However, qualitatively the life events reported by diabetic children revealed a tendency to increased severity. Events related specifically to actual or threatened losses within the family — events that may affect children differently in different age groups — were reported with a significantly higher frequency by diabetic patients than by referent subjects, aged 5–9 years. The relative risk that such events in fact comprise a risk factor for Type 1 diabetes was 1.82 (95% confidence limits 1.09, 3.03). The relative risk was significantly increased even when standardized for possible confounding factors such as age, sex and indices of social status of the family. We conclude that stressful life events, related to actual or threatened losses within the family, occurring in the vulnerable age group of 5–9 years, are associated with the onset of childhood Type 1 diabetes. Such stressful events may in fact be a risk factor for the disease.

Prevalence of diabetic retinopathy in children and adolescents with IDDM. A population-based multicentre study.

Summary Vision-threatening diabetic retinopathy can be prevented if it is diagnosed before becoming too advanced. Since diabetic retinopathy has been reported to occur only rarely before the end of pubertal development, children and adolescents are seldom included in screening programmes. We invited 780 children and adolescents with insulin-dependent diabetes mellitus diagnosed before the age of 15.0 years (disease duration of < 12 years) and who were older than 9.0 years at the time of examination from eight regions of Sweden. Retinal examination was performed with stereoscopic fundus photograph. The photograph were rated according to a modified Airlie House classification. The dropouts (223/780, 28.6 %) were significantly older and with a longer duration of diabetes than the examined children (p < 0.001 and 0.001, respectively). Photographs from 557 patients aged (median [interquartile range]:14.6 [12.4–17.0]) years and with a diabetes duration of 8.0 (5.5–9.9) years were evaluated. Retinopathy was demonstrated in 81 patients (14.5 %):66 with background retinopathy, 2 with microaneurysms and hard exudates, 12 with preproliferative retinopathy, 1 with proliferative retinopathy. Preproliferative retinopathy was diagnosed in a 12.8-year-old girl in pubertal stage 3 and an 11.8-year-old boy in pubertal stage 2, and proliferative retinopathy was found in a 21.5-year-old girl. Retinopathy was demonstrated in 6 % and 18 % of patients in pubertal stages 1 and 5, respectively. The overall prevalence of retinopathy in this population may even be higher since the dropouts were older and had a longer duration of diabetes. Since background and preproliferative retinopathy were found in children before puberty, we recommend including children and adolescents in screening programmes for diabetic retinopathy from the age of 10 years. [Diabetologia (1997) 40: 307–310]

The Swedish childhood diabetes study III: IgM against coxsackie B viruses in newly diagnosed Type 1 (insulin-dependent) diabetic children — no evidence of increased antibody frequency

SummarySera from essentially all Swedish children aged 0–14 years with Type 1 (insulin-dependent) diabetes mellitus with onset during an autumn period (October–December 1985) and a late spring period (May–June 1986) were selected. In all, 98 patients were analysed for IgM antibodies against coxsackie B virus serotypes 1 through 5 by a μ-antibody capture radio immunoassay technique. Sera from 94 referent children matched for age, sex and residential area, collected during the same period, were also analysed. During the autumn period, 10 out of 67 (15%) diabetic children were IgM positive while 14 out of 75 (19%) of the healthy referent children demonstrated positivity. During the late spring period only one out of 31 (3%) children with diabetes and two out of 19 (10%) referent children were IgM positive. In the diabetic patients, five were coxsackie B2 positive while coxsackie B1, 3, 4 and 5 were represented by one to three patients each. Eight referent children were coxsackie B4 positive, six were B3 positive and two B2 positive, while no referent children were positive against coxsackie B1 and 5. During these two periods in late 1985 and early 1986 these data demonstrate no evidence of increased antibody frequency against coxsackie B virus 1 through 5 at the onset of childhood diabetes in Sweden.

Plasma Amino Acids in Relation to Metabolic Control in Insulin-Dependent Diabetic Children

ABSTRACT. The influence of metabolic control (estimated by blood glucose, 3‐hydroxybutyrate and glycosylated hemoglobin levels) on plasma amino acids was determined in a group of 56 insulin‐dependent diabetic children. A multiple correlation analysis revealed significant positive partial correlations between most amino acids and blood glucose. Alanine, methionine, tyrosine, phenylalanine and arginine showed negative partial correlations to the 3‐hydroxybutyrate level. The results are consistent with the postulate that ketone body inhibition of muscle proteolysis is one of the factors regulating substrate flows during insulin deficiency.

Validity of a Questionnaire Measuring Food Frequency Compared to a 7‐Day Record

ABSTRACT. A questionnaire measuring food frequency was validated against 7‐day records of food intake in a group of 30 children, 2–16 years of age. Special emphasis was given to the ability of the questionnaire to estimate frequency of intake of foods of particular interest in diabetes mel‐litus. Fifteen children had insulin‐dependent diabetes; 15 were healthy. Comparison of the two methods regarding frequency of foods with high content of sucrose, protein, fat, fibres, nitrite or vitamin C showed a correlation of 0.52–0.76. The frequency of intake of some staple foods was often overestimated by the questionnaire, while the frequency of meat, sausage and some sweet snacks was underestimated. The use of the questionnaire to identify high or low consumers of the mentioned nutrients showed a rather low sensitivity (0.38–0.50), but a high specificity (0.86–1.0) when compared with results of the 7‐day record. In our limited sample of subjects no systematic differences were found comparing sexes or diabetic and healthy children. A food frequency questionnaire may, in spite of some important reservations, be a useful tool for screening purposes when more time‐consuming and resource‐demanding methods cannot be used.