Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group.

OBJECTIVE: To study the characteristics of type 1 diabetes in very young children. RESEARCH DESIGN AND METHODS: Clinical outcome, islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies against GAD (GADA), IA-2 antibodies (IA-2A), and HLA-DQB1-defined genetic risk were analyzed in 35 children diagnosed with type 1 diabetes before 2 years of age and compared with those in 146 children who were diagnosed between 2.0 and 4.9 years of age and with those in 620 children diagnosed between 5.0 and 14.9 years of age. RESULTS: The youngest age-group had severer metabolic decompensation at clinical onset, and their serum C-peptide levels, compared with those of older children, were lower at the time of diagnosis and during the first 2 years after the diagnosis. The levels of ICA and IAA were highest in children < 2 years of age, but there were no differences in GADA levels among the three age-groups. The youngest age-group had the lowest IA-2A levels. The HLA DQB1*02/*0302 genotype associated with strong genetic susceptibility was more frequent in children diagnosed < 5 years of age, whereas the proportion of children carrying a genotype, which includes protective alleles, was higher among those diagnosed at > or = 5 years of age. CONCLUSIONS: The clinical presentation of type 1 diabetes at a very young age is associated with severe metabolic decompensation, poorly preserved residual beta-cell function, strong humoral autoimmunity against islet cells and insulin, and strong HLA-defined disease susceptibility.

Prepubertal girls with insulin-dependent diabetes mellitus have higher exogenous insulin requirement than boys. Childhood Diabetes in Finland Study Group.

In a population based study, the prescribed insulin dose of 348 prepubertal children with insulin-dependent diabetes mellitus (IDDM) was analysed 2 years after the diagnosis of diabetes. Girls had an insulin dose 13.6% higher than that in boys. When children younger than 5 years of age at diagnosis were analysed separately, the difference in insulin dose between boys and girls remained. The increased insulin dose in girls was not explained by possible differences in endogenous insulin secretion, body mass index, metabolic control or the number of daily insulin injections. Our observations indicate that prepubertal girls with IDDM have a poorer insulin sensitivity than boys.

Autoimmune and clinical characteristics of type I diabetes in children with different genetic risk loads defined by HLA-DQB1 alleles. Childhood Diabetes in Finland Study Group.

1. The impact of different genetic risk loads defined by HLA-DQB1 alleles on the autoimmune and clinical characteristics of 647 children and adolescents with recent-onset Type I diabetes was evaluated in a prospective population-based study. The subjects were divided into four groups based on HLA-DQB1 genotypes: DQB1*0302/0201 (high risk), *0302/x (moderate risk), *0201/y (low risk) and *z/z (decreased risk). 2. Close to two thirds (62.3%) of the subjects possessed a high or moderate risk genotype. A decreased frequency of positivity for islet cell antibodies (ICA) and insulin autoantibodies (IAA) (76.8% compared with 85.3%; P = 0.05, and 30.5% compared with 50.8%, P = 0.0006, respectively) but not of positivity for antibodies to the 65 kDa isoform of glutamate decarboxylase was observed in children with the DQB1*0201/y genotype compared with other children. Among ICA-negative subjects, those with the DQB1*0201/y genotype had higher serum C-peptide levels over the first 2 years after the diagnosis of Type I diabetes than those with other genotypes (P = 0.028). 3. Our data provide some evidence of HLA-DQB1-determined heterogeneity in the autoimmune and clinical characteristics of childhood Type I diabetes at the time of the clinical manifestation. This suggests differences between children with various HLA-DQB1 genotypes in the pace and/or intensity of the beta-cell destructive process leading to clinical Type I diabetes.

Poor beta-cell function after the clinical manifestation of type 1 diabetes in children initially positive for islet cell specific autoantibodies. The Childhood Diabetes in Finland Study Group.

The prognostic significance of islet cell specific autoantibodies at the diagnosis of Type 1 (insulin-dependent) diabetes mellitus for the persistence of residual beta-cell function over the first 2 years of clinical disease was evaluated in a prospective population-based study. Seven hundred and eighty probands, aged 0.8-14.9 years, were examined for islet cell antibodies (ICA) and insulin autoantibodies (IAA), while 769 probands were studied for antibodies to glutamic acid decarboxylase (GAD65A). They were subsequently observed for 2 years. Lower serum C-peptide concentrations and higher requirement of exogenous insulin during the follow-up period were observed in the group of probands positive for at least one of the antibodies, especially for ICA or IAA. We conclude that the residual beta-cell function after the presentation of Type 1 diabetes is less in children initially positive for islet cell specific autoantibodies than in those testing negative at diagnosis. This might reflect possible heterogeneity in the pathogenesis of childhood diabetes. It also demonstrates that ICA and IAA negativity at the diagnosis of Type 1 diabetes is not associated with a smaller amount of functioning beta-cell mass, but the absence of antibodies probably reflects a slower beta-cell destructive process and a longer duration of preclinical disease.

The unchanging incidence of hospitalization for diabetic nephropathy in a population-based cohort of IDDM patients in Finland.

OBJECTIVE: Finland has the highest documented incidence of childhood IDDM in the world, but the incidence of diabetic nephropathy in Finland is unknown. The aim of the present study was to determine the incidence of hospitalization for diabetic nephropathy in a population-based cohort of Finnish IDDM patients and to analyze the prognostic effect of sex, age at diagnosis, and calendar year of diagnosis of IDDM. RESEARCH DESIGN AND METHODS: We included all Finnish patients who had onset of IDDM before age 18 years, were diagnosed between January 1965 and December 1979 (n = 5,149), and were traced for hospitalizations between January 1970 and the end of December 1989 in the Hospital Discharge Register, using the unique personal identification code given to all Finnish citizens. The development of diabetic nephropathy was defined as the first hospitalization with a diagnosis of nephropathy (International Classification of Diseases-8th Revision [ICD-8] 250.04, or 9th Revision [ICD-9] 2503B/2503X). RESULTS: Among the 5,149 patients included, we identified 446 cases of diabetic nephropathy. The incidence of hospitalization for diabetic nephropathy was very low during the first 8 years of diabetes duration, and after that increased to a maximum of 1.6-2.0% per year. Female subjects developed nephropathy slightly earlier than male subjects, but the cumulative risk was independent of sex. Patients diagnosed at ages 5-14 years had the highest risk of hospitalization for diabetic nephropathy. We observed no effect of calendar year of diagnosis. CONCLUSIONS: We found a 20% cumulative incidence of hospitalization for diabetic nephropathy during a total 24 years of IDDM duration. This finding is compatible with the cumulative incidence of hospitalization for diabetic nephropathy found in other European populations. The incidence of hospitalization for diabetic nephropathy did not decrease during the 20-year observation period.

Incidence trends in childhood onset IDDM in four countries around the Baltic sea during 1983-1992.

We present secular trends of childhood onset insulin-dependent diabetes mellitus (IDDM) in Finland, Estonia, Latvia and Lithuania during the period of 1983-1992. Incidence data were obtained from the national IDDM registries. The average age-standardized incidence per 100,000/year was 35.0 in Finland, followed by 10.2 in Estonia, 7.1 in Lithuania and 6.5 in Latvia. A male excess in incidence was recorded in Finland (1.15) and Latvia (1.01). In all countries, the highest age-specific risk of IDDM was observed in the 11-13 year age range. The large difference in incidence between Finland and other Baltic countries was see even in 1-2 year-old children. During the 10-year study period overall changes in incidence of IDDM were relatively small in these four countries. The incidence increased in Finland and Lithuania on average by 1% and 1.4% per year, respectively. A statistically significant increase was recorded only in 0-4 year old children in Finland, at 5.6% per year. In Estonia, an 8.3% increase in this age group, however, was not statistically significant. The different trends in the age-group specific incidence rates were confirmed in Finland. In conclusion, from 1983 to 1992 the incidence of childhood onset IDDM was increasingly in Finland and Lithuania, while in Latvia and Estonia it was stable. There are still great differences in IDDM incidence between the countries around the Baltic Sea.

Islet cell-specific autoantibodies in children with insulin-dependent diabetes mellitus and their siblings at clinical manifestation of the disease. Childhood Diabetes in Finland Study Group.

The aim of this work was to characterize both newly diagnosed insulin-dependent diabetic subjects and their siblings with positive tests for islet cell-specific autoantibodies (ICSAA) and to evaluate whether there is an association between the ICSAA levels detected in the diabetic children and siblings. We analysed 781 probands younger than 15 years of age for islet cell antibodies (ICA) and 755 for insulin autoantibodies (IAA) and 610 of their 3-19-year-old non-diabetic siblings for ICA and IAA upon diagnosis of the proband. Islet cell antibodies were observed in 657 of the probands (84.1%) and IAA in 353 (46.8%). The ICA-positive probands were younger in age and had higher IAA levels than the ICA-negative probands, while the IAA-positive probands were younger and had higher levels of ICA than the IAA-negative probands. Islet cell antibodies were detected in 46 (7.5%) and IAA in 16 (2.6%) siblings, and the ICA-positive siblings had higher IAA levels than the ICA-negative siblings. A falling trend was seen in the frequency of ICA > or = 20 Juvenile Diabetes Foundation units in the siblings with decreasing degrees of HLA identity with the index case. Infections during the preceding year, especially respiratory infections, increased the prevalence of both ICA and IAA in the diabetic children at diagnosis and the frequency of IAA in the siblings. There was a significant, although weak, correlation between the IAA levels of the probands and those of their siblings when 594 pairs were tested (r(s) = 0.15; p < 0.001). No association could be seen between the ICA levels of the probands and those of their siblings, not even when including only HLA-identical proband-sib pairs in the analysis. The lack of any relation between ICA levels in the probands and siblings supports the view that there may be multiple exogenous factors capable of inducing ICA formation or else a common factor but variable responsiveness in the index case and the sibling.

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.

Increase in incidence of insulin-dependent diabetes mellitus among children in Finland.

BACKGROUND: In Finland, the incidence of insulin-dependent diabetes mellitus (IDDM) in children aged < 15 years is the highest in the world. The aim of this study was to determine the temporal variation in incidence and the age distribution at diagnosis of IDDM. SUBJECTS AND METHODS: Data on incidence of IDDM in Finland nationwide were obtained from two sources: the Central Drug Registry for the years 1965-1986 (6195 IDDM cases) and the prospective IDDM registry for the years 1987-1992 (2062 IDDM cases). The annual incidence rates were calculated per 100,000 population. The increase in incidence from 1965 to 1992 was estimated by fitting the linear regression with the annual incidence data. RESULTS: The overall incidence of IDDM between 1987 and 1992 was 36 per 100,000/year. During 1965-1992 the increase was almost linear. The regression-based change in incidence was 2.8% per year. In the 1970s the increase in incidence was steepest in 5-9 year olds and since the mid-1980s in those < 5 years old at diagnosis. CONCLUSIONS: The incidence of IDDM in Finnish children seems to increase further. During the last decades the increase in incidence has been almost linear with occasional peaks. The age-at-diagnosis of IDDM has been moving towards the younger ages, and differences in incidence between age groups have now almost disappeared among Finnish children aged 1-14 years.

Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study. The Childhood Diabetes in Finland Study Group.

To study the possible temporal association between primary cytomegalovirus infection and the appearance of islet cell autoantibodies or the development of insulin-dependent diabetes mellitus (IDDM) cytomegalovirus antibodies were analysed from follow-up sera of 46 initially non-diabetic siblings of diabetic children who either manifested clinical IDDM (22 siblings) or turned islet cell antibody positive (24 siblings) during the prospective observation (mean follow-up time 2.9 years). Secondly, cytomegalovirus antibodies were analysed during pregnancy in 96 mothers whose child presented with IDDM before the age of 7 years and in 96 control mothers who gave birth to a non-diabetic child. Thirdly, a case-control series including 90 newly-diagnosed young children with IDDM and their 90 control subjects was analysed. No seroconversions were found in cytomegalovirus antibodies during the follow-up of the 46 siblings indicating no temporal association with islet cell antibody seroconversion or manifestation of clinical diabetes. During the follow-up 17 (37%) siblings were constantly seronegative and 29 (63%) seropositive for cytomegalovirus IgG and there was no difference between islet cell antibody positive and negative siblings. Cytomegalovirus IgG and IgM were not different in pregnant mothers who gave birth to a subsequently diabetic child compared to control mothers, or in newly-diagnosed diabetic children compared to control children. Cytomegalovirus IgA was higher in newly-diagnosed diabetic children than in control children (p < 0.005). This difference disappeared when only cytomegalovirus IgG positive individuals were analysed. No correlation was found between islet cell antibodies and cytomegalovirus antibodies in newly-diagnosed diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrate and nitrite intake and the risk for type 1 diabetes in Finnish children. Childhood Diabetes in Finland Study Group.

The intakes of nitrate and nitrite of children and their parents from food and drinking water were estimated in a Finnish nation-wide case-control study on the epidemiology of Type 1 diabetes. The study population consisted of 684 case and 595 control children; 548 case-control pairs of fathers; and 620 case-control pairs of mothers. The consumption frequencies of foods which are important sources of nitrate and nitrite were assessed by structured questionnaire. Nitrate and nitrite concentration data were collected from Finnish water works. Diabetic children's and their mothers' daily dietary intake of nitrite was greater compared with that of control children and mothers (for case and control children 0.9 mg vs 0.8 mg, for case and control mothers 0.9 mg vs 0.8 mg, p < 0.001). Case mothers compared with control mothers received less (p < 0.05) nitrate from their diet. No differences were observed in the intake of nitrate or nitrite from drinking water. Dietary nitrite intake of children (odds ratios and 95% confidence intervals for the second, third, and fourth quartile 1.16, 0.82-1.65; 1.49, 1.06-2.10; 2.32, 1.67-3.24, respectively) and mothers (odds ratios and 95% confidence intervals for the second, third, and fourth quartile 1.15, 0.76-1.74; 1.29, 0.87-1.91; 1.98, 1.35-2.90, respectively) was positively associated with the risk for Type 1 diabetes independently from length of mother's education, child's or mother's age, place of residence or mother's smoking status.(ABSTRACT TRUNCATED AT 250 WORDS)

Is children's or parents' coffee or tea consumption associated with the risk for type 1 diabetes mellitus in children? Childhood Diabetes in Finland Study Group.

OBJECTIVE: The study was carried out to determine whether coffee or tea consumption by the child before diagnosis of diabetes or consumption by parents at the time of the child's conception or during pregnancy was associated with the risk for childhood type 1 diabetes. DESIGN: Case-control study. SETTING AND SUBJECTS: All diabetic children younger than 15 years, and diagnosed from September 1986 to the end of April 1989, were invited to participate. 600 newly diagnosed diabetic children and 536 randomly selected population-based children, and their parents took part in a nationwide study. RESULTS: The risk for type 1 diabetes was increased in the children who consumed at least 2 cups of coffee daily [odds ratio (OR) 1.94, 95% confidence interval (CI) 1.08-3.47], and in the children who consumed 1 cup of tea (OR 1.69, 95% CI 1.21-2.37) or at least 2 cups daily (OR 2.59, 95% CI 1.60-4.18) when adjusted for mother's education, child's age and child's sex. Parents' consumption of coffee or tea during conception of the child and mother's coffee consumption during pregnancy did not affect the risk for diabetes in the children. CONCLUSIONS: We observed an increased risk for type 1 diabetes in the children who consumed coffee or tea regularly.

Natural history of preclinical IDDM in high risk siblings. Childhood Diabetes in Finland Study Group.

To learn more about the preclinical phase of IDDM we observed for a median period of 46.5 months (range 0.5-69 months) a group of 57 siblings positive for ICA and/or IAA when first screened within 6 months of the diagnosis of the proband. Sequential blood samples and IVGTTs were obtained at intervals of 6-12 months. Seventeen siblings (29.8%) presented with IDDM during the observation period. The duration of the known preclinical period ranged from 0.5 to 51 months (median 29 months). The converters were younger than the other siblings (P < 0.05) and had higher initial ICA levels (P < 0.01). In addition they had a lower FPIR in the first IVGTT (P < 0.001). On all subsequent tests the converters had higher ICA levels and a lower FPIR (P < 0.05 or less), a lower glucose elimination rate from the third test onwards (P < 0.01 or less) and higher IAA levels at 3 years (P < 0.05). Some variation could be observed in the FPIR in the converters with an initial increase and subsequent decrease (P < 0.05 for both). Their levels of complement-fixing ICA increased up to 18 months (P < 0.05) and IAA levels up to 3 years (P < 0.01). Those high risk siblings who progress to clinical IDDM are characterized by young age, strong and increasing signs of islet-cell specific autoimmunity, reduced insulin secreting capacity and emerging glucose intolerance. The present observations seem to be incompatible with the hypothesis of beta-cell destruction occurring at a constant, predictable rate.

Early introduction of dairy products associated with increased risk of IDDM in Finnish children. The Childhood in Diabetes in Finland Study Group.

Associations between infant-feeding patterns and risk of IDDM were investigated in a nationwide Finnish case-control study of 690 IDDM children < 15 yr of age. Each child was matched by date of birth and sex to a randomly selected population-based control child. Univariate analysis revealed that the risk of IDDM was increased by approximately 1.5 in children for whom breast-feeding was terminated at < 2 mo of age, doubled in those who were exclusively breast-fed for < 2 mo, and doubled in those who were introduced to dairy products at < 2 mo of age. In further multivariate analyses of these factors, it was found that introduction of dairy products at an early age was the most important risk factor, and the observed univariate effects of duration of breast-feeding variables were explained by their correlation with this factor. This is the first observational study to show that early introduction of dairy products is independently associated with an increased risk of IDDM. Adjustment for mother's education and age, child's birth order, or birth weight did not affect the results.

Decline of mumps antibodies in type 1 (insulin-dependent) diabetic children and a plateau in the rising incidence of type 1 diabetes after introduction of the mumps-measles-rubella vaccine in Finland. Childhood Diabetes in Finland Study Group.

A nationwide mumps-measles-rubella vaccination was introduced in 1982 in Finland to children aged 1.5 to 6 years and since then mumps has virtually disappeared in the country. We investigated whether this rapid epidemiological change had any impact on antibody activity against mumps virus in Type 1 (insulin-dependent) diabetic children or on the incidence of Type 1 diabetes in Finland. Two case-control series were collected before (series I and II) and three series after (series III-V) the introduction of the vaccination. IgA class mumps antibody levels were significantly higher in Type 1 diabetic children than in matched control children in the first two but not in the three later series. IgG class antibody levels were similar in patients and control subjects in the first two series but significantly lower in patients than in control subjects in the three later series. The overall incidence of Type 1 diabetes in 0-14-year-old children increased until 1987 but remained about the same during 1988-1990. In 5-9-year-old children no further increase in Type 1 diabetes was seen since 1985, whereas in 0-4-year-old children the incidence continued to rise until 1990. The results suggest that the elimination of natural mumps by mumps-measles-rubella vaccination may have decreased the risk for Type 1 diabetes in Finland; a possible causal relationship is substantiated by the observed concomitant decrease in mumps antibody levels in diabetic children. However, further studies are required to determine if the vaccine virus, like natural mumps, could trigger the clinical onset of Type 1 diabetes in young children.

Feeding in infancy and the risk of type 1 diabetes mellitus in Finnish children. The 'Childhood Diabetes in Finland' Study Group.

In a case-control design the feeding in infancy of newly diagnosed 7- to 14-year-old diabetic children (n = 426) was compared with that of age- and sex-matched non-diabetic children (n = 426) randomly selected from the Finnish population registry. All 7- to 14-year-old diabetic children diagnosed from September 1986 to the end of April 1989 from all hospitals which treat diabetic children in Finland were invited to participate in the study. Breast-feeding was initiated in almost all children, but during the birth years of this study population (1972-1982), an increase was observed in the duration of breast-feeding (whether alone or in combination with supplementary feeding) and in the age of introduction of supplementary milk feeding. The risk of Type 1 diabetes was decreased in the children who were totally breast-fed for at least 2 months (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.42-0.98) or 3 months (OR 0.67, 95% CI 0.48-0.95) or exclusively breast-fed for at least 2 months (OR 0.60, 95% CI 0.41-0.89) or 3 months (OR 0.63, 95% CI 0.43-0.93). Those children who were younger than 2 months (OR 1.54, 95% CI 1.08-2.18) or 3 months (OR 1.52, 95% CI 1.11-2.08) at the time when supplementary milk feeding was begun had an increased risk of Type 1 diabetes. These associations remained significant after adjusting for the mother's education. The results suggest that early infant feeding patterns are associated with the risk of Type 1 diabetes developing at the age of 7 to 14 years.

Epidemiology of childhood diabetes mellitus in Finland--background of a nationwide study of type 1 (insulin-dependent) diabetes mellitus. The Childhood Diabetes in Finland (DiMe) Study Group.

A nationwide study of childhood Type 1 (insulin-dependent) diabetes mellitus was established in 1986 in Finland, the country with the highest incidence of this disease worldwide. The aim of the project called "Childhood Diabetes in Finland" is to evaluate the role of genetic, environmental and immunological factors and particularly the interaction between genetic and environmental factors in the development of Type 1 diabetes. From September 1986 to April 1989, 801 families with a newly-diagnosed child aged 14 years or younger at the time of diagnosis were invited to participate in this study. The vast majority of the families agreed to participate in the comprehensive investigations of the study. HLA genotypes and haplotypes were determined in 757 families (95%). Our study also incorporates a prospective family study among non-diabetic siblings aged 3-19 years, and two case-control studies among the young-onset cases of Type 1 diabetes. During 1987-1989, the overall incidence of Type 1 diabetes was about 35.2 per 100,000 per year. It was higher in boys (38.4) than in girls (32.2). There was no clear geographic variation in incidence among the 12 provinces of Finland. Of the 1,014 cases during these 3 years only six cases were diagnosed before their first birthday. The incidence was high already in the age group 1-4-years old: 33.2 in boys and 29.5 in girls. Of the 801 families 90 (11.2%) were multiple case families, of which 66 had a parent with Type 1 diabetes at the time of diagnosis of the proband.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of incidence of IDDM in childhood between Estonia and Finland, 1980-1988.

OBJECTIVE: To compare nationwide incidence of childhood insulin-dependent diabetes mellitus (IDDM) in children aged 0-14 yr between Estonia and Finland during 1980-1988. For Estonia, which has a population genetically and linguistically related to Finland, only limited information was available. Finland has the highest incidence of IDDM in the world. RESEARCH DESIGN AND METHODS: The registration of all new cases of IDDM in Estonia was conducted by the local district pediatricians who reported every newly diagnosed diabetic patient to the Republic Endocrinology Centre. Registration of all new cases of IDDM in Finland was based on the statistics of the Social Insurance Institution, which approves free-of-charge insulin treatment for diabetes. These data were validated with one or more additional data sources. The case ascertainment rate approached 100% in both countries. RESULTS: The average yearly incidence of IDDM standardized for age for the years 1980-1988 in Estonia was approximately 33% of that in Finland. Among males it was 11.3 (95% confidence interval [CI] 10.3-12.3) per 100,000 in Estonia and 35.1 (95% CI 33.4-36.9) per 100,000 in Finland, and among females 10.1 (95% CI 9.2-11.1) per 100,000 in Estonia and 30.4 (95% CI 28.8-32.1) per 100,000 in Finland. When the two periods 1980-1982 and 1986-1988 were compared, the age-standardized incidence in Estonia remained unchanged, whereas in Finland it increased approximately 20%. CONCLUSIONS: The data between two populations who are ethnically and linguistically similar and live geographically close but in a different environment, provides further evidence that both genetic and environmental factors are contributing to the risk of IDDM.

Infant feeding in Finnish children less than 7 yr of age with newly diagnosed IDDM. Childhood Diabetes in Finland Study Group.

OBJECTIVE: We studied associations between the type of feeding in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: We studied 103 newly diagnosed diabetic children less than 7 yr of age and 103 age- and sex-matched population-based control children in a countrywide study. RESULTS: The risk of IDDM was decreased (P less than 0.05) among children breast-fed for at least 7 mo (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24-0.85) or exclusively breast-fed for at least 3 (OR 0.33, 95% CI 0.13-0.84) or 4 (OR 0.43, 95% CI 0.22-0.84) mo. Also, children who were greater than or equal to 4 mo old at the time of introduction of supplementary milk feeding had a lower risk of diabetes (OR 0.48, 95% CI 0.26-0.91). CONCLUSIONS: The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mother's education.

Increasing trend in type 1 (insulin-dependent) diabetes mellitus in childhood in Finland. Analysis of age, calendar time and birth cohort effects during 1965 to 1984.

The Central Drug Registry in Finland ascertained 5,920 incident cases of Type 1 (insulin-dependent) diabetes mellitus diagnosed under the age of 15 years, during 1965-1984. The incidence was higher for males 29.2/100,000 (95% confidence intervals 28.2-30.2/100,000) than for females 26.1/100,000 (25.1-27.1/100,000). A non-linear increase in incidence with age was confirmed, with peaks at ages 2, 9 and 14 years in males and at 3, 5-6 and 11 years in females. A significant temporal variation in incidence was found, adjusting for age and sex. During 1965 to 1984 the incidence rose by about 57% or by 2.4% annually. However, a non-linear curve with two incidence peaks in 1978 and 1983 would better describe the temporal pattern than a linear trend. There was no significant difference in the temporal variation between males and females. The changes in diabetes risk appeared to affect proportionally all age groups under 15 years. Two possible mechanisms were explored: a calendar period effect vs a birth cohort effect. The calendar time period effect was significant alone and also when adjusted for the birth cohort effect. One the contrary, the birth cohort effect was not significant, when adjusted for the calendar period effect. In conclusion, over the past two decades, the incidence of childhood Type 1 diabetes in Finland has increased by about 57%. The pattern of change was a steady rising background incidence superimposed by sudden outbreaks suggesting environmental causative factors.