Socio-economic factors influencing the development of end-stage renal disease in people with Type 1 diabetes - a longitudinal population study.

AIMS: The development of end-stage renal disease (ESRD) in Type 1 diabetes is multifactorial. Familial socio-economic factors may influence adherence to and understanding of diabetes treatment, and also general health behaviour. We investigate how parental and personal education level and exposure to low economic status, indicated by the need for income support, influence the development of ERSD caused by Type 1 diabetes. METHODS: Participants were retrieved from the nationwide Swedish Childhood Diabetes Registry, which was linked to the Swedish Renal Registry, to find people with ESRD caused by Type 1 diabetes, and to Statistic Sweden to retrieve longitudinal socio-economic data on participants and their parents. Data were analysed using Cox regression modelling. RESULTS: Of 9287 people with diabetes of duration longer than 14 years, 154 had developed ESRD due to diabetes. Median diabetes duration (range) for all participants was 24.2 years (14.0-36.7 years). Low maternal education (≤ 12 years) more than doubled the risk of developing ESRD, hazard ration (HR) = 2.9 [95% confidence interval (95% CI): 1.7-4.8]. For people with a low personal level of education HR was 5.7 (3.4-9.5). In an adjusted model, the person's own education level had the highest impact on the risk of ESRD. If at least one of the parents had ever received income support the HR was 2.6 (1.9-3.6). CONCLUSIONS: Socio-economic factors, both for the parents and the person with diabetes, have a strong influence on the development of ESRD in Type 1 diabetes. It is important for caregivers to give enough support to more vulnerable people and their families.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature.

BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation. OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008. METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends. RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ± 11 to ± 38% (median ± 17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours. CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.

Impact of childhood-onset type 1 diabetes on schooling: a population-based register study.

AIMS/HYPOTHESIS: We investigated the impact of type 1 diabetes on educational achievements in compulsory and upper secondary school, as well as potential long-lasting effects. METHODS: Altogether 2,485 individuals with type 1 diabetes, diagnosed at the age of <15 years and born in 1972-1978, were selected from the Swedish Childhood Diabetes Register, which was linked to national population registers including the Swedish Education Register. For each individual, four controls from the general population, matched for year of birth and residence at the time of diagnosis, were selected by Statistics Sweden (n = 9,940). We analysed the impact of diabetes on final school grades at 16 years (compulsory school) and 19 years (upper secondary school) and on participation in the labour market at 29 years using linear, logistic, ordered logistic and quantile regression analyses, controlling for demographics and socioeconomic background. RESULTS: Diabetes had a negative effect on mean final grades (scale of 1-5) in compulsory school (-0.07, p < 0.001) and theoretical programmes in upper secondary school (-0.07, p = 0.001). Children with early-onset diabetes (0-4 years) suffered a greater disadvantage as a result of the disease (-0.15, p = 0.001 in compulsory school). The strongest effect was seen in the lowest deciles of the conditional distribution on mean final grades. At age 29, individuals with diabetes were less likely to be gainfully employed (OR 0.82, 95% CI 0.73, 0.91). CONCLUSIONS/INTERPRETATION: The small but significant negative effect of type 1 diabetes on schooling could affect opportunities for further education and career development. Attention must be paid in school to the special needs of children with diabetes.

Socioeconomic factors, rather than diabetes mellitus per se, contribute to an excessive use of antidepressants among young adults with childhood onset type 1 diabetes mellitus: a register-based study.

AIMS/HYPOTHESIS: Mood disorders, including depression, are suggested to be prevalent in persons with type 1 diabetes and may negatively affect self-management and glycaemic control and increase the risk of diabetic complications. The aim of this study was to analyse the prevalence of antidepressant (AD) use in adults with childhood onset type 1 diabetes and to compare risk determinants for AD prescription among diabetic patients and a group of matched controls. METHODS: Young adults ≥ 18 years on 1 January 2006 with type 1 diabetes (n = 7,411) were retrieved from the population-based Swedish Childhood Diabetes Registry (SCDR) and compared with 30,043 age- and community-matched controls. Individual level data were collected from the Swedish National Drug Register (NDR), the Hospital Discharge Register (HDR) and the Labor Market Research database (LMR). RESULTS: ADs were prescribed to 9.5% and 6.8% of the type 1 diabetes and control subjects, respectively. Female sex, having received economic or other social support, or having a disability pension were the factors with the strongest association with AD prescription in both groups. Type 1 diabetes was associated with a 44% (OR 1.44, 95% CI 1.32, 1.58) higher risk of being prescribed ADs in crude analysis. When adjusting for potential confounders including sex, age and various socioeconomic risk factors, this risk increase was statistically non-significant (OR 1.11, 95% CI 0.99, 1.21). CONCLUSIONS/INTERPRETATION: The risk factor patterns for AD use are similar among type 1 diabetic patients and controls, and socioeconomic risk factors, rather than the diabetes per se, contribute to the increased risk of AD use in young adults with type 1 diabetes.

Trends in childhood type 1 diabetes incidence in Europe during 1989-2008: evidence of non-uniformity over time in rates of increase.

AIMS/HYPOTHESIS: The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989-1998) and second (1999-2008) halves of the period. METHODS: All registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture-recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied. RESULTS: Ascertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half. CONCLUSIONS/INTERPRETATION: The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3-4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.

Glutamate decarboxylase-, insulin-, and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children.

Most autoimmune diabetes occurs in those without a diabetic relative, but few cases are identifiable prospectively. To model general population prediction, 491 consecutive newly diabetic children from all of Sweden were tested for autoantibodies to glutamate decarboxylase (GAD65ab), insulin (IAA), and islet cells (ICA), and for HLA-DQ genotypes by PCR; 415 matched control children were tested in parallel. GAD65ab sensitivity/specificity was 70/96%, versus 84/96% for ICA, 56/97% for IAA, 93/93% (any positive), 39/99.7% (all positive), and 41/99.7% (GAD65ab plus IAA). The latter's 25% predictive value was not improved by requiring concomitant high-risk HLA genotypes. GAD65ab were associated with DQA1*0501/B1*0201 (DQ2; P = 0.007) but not DQA1*0301/B1*0302 (DQ8), and IAA with DQA1*0301/B1*0302 (DQ8; P = 0.03) but not DQA1*0501/B1*0201 (DQ2). GAD65ab were more prevalent in females than males (79 vs. 63%; P < 0.0001) but did not vary with onset age nor season. Combining the three antibody assays yielded sufficient sensitivity for screening. GADab were relatively sensitive/specific for diabetes, but even with HLA marker combinations yielded predictive values insufficient for early immunointervention in the low-prevalence general population.

Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM patients.

It has been suggested that hereditary risk for hypertension and cardiovascular disease (CVD) as well as intrauterine growth may be involved in the pathogenesis of diabetic nephropathy. In the present study, we investigated the influence of familial and perinatal risk factors on the occurrence of micro- and macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with > or =5 years' duration of IDDM was screened for microalbuminuria. Data on family history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth weight, gestational age, and duration of breastfeeding; and maternal education, smoking, hypertension, and proteinuria during pregnancy were collected. We identified 75 patients with an albumin excretion rate > or =15 microg/min in more than two overnight urinary samples and compared them in a nested case-control study with three normoalbuminuric control subjects per patient from the same cohort, matched for diabetes duration. Perinatal factors were analyzed in all patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225 control subjects. In univariate analysis, hypertension in parents (odds ratio [OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were significantly associated with the development of micro- and macroalbuminuria. When adjusted for other familial and perinatal factors, current mean blood pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration, using logistic regression analyses, only parental hypertension in all patients and maternal smoking during pregnancy and low level of maternal education in full-term patients were independent risk factors. When patients with poor glycemic control were analyzed separately, familial CVD, poor metabolic control, parental hypertension, maternal smoking during pregnancy, and level of maternal education were independent risk factors, with the adjusted OR markedly increased, compared with the matched subgroup with better HbA1c. In conclusion, familial hypertension and CVD, maternal smoking during pregnancy, and low level of maternal education may independently increase the risk for incipient nephropathy in full-term offspring who later develop IDDM. Current poor glycemic control seemed to increase the effect of these risk factors.

Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case-control study.

Using the nationwide childhood-onset diabetes register in Sweden, we were able to trace children who contracted diabetes before the age of 15 years and who were born at a specific hospital in Sweden where maternal sera from delivery had been stored during the years 1969-1989. Sera obtained at delivery from 57 mothers of diabetic children were compared with sera from 203 mothers of control subjects who were delivered at the same hospital during the same time period. The sera were analyzed blindly using a group-specific enzyme-linked immunosorbent assay for enteroviral IgG and IgM antibodies before and after urea wash as an avidity test. On the same plates, IgG antibodies to herpes, mumps, and toxoplasmosis were analyzed. The mean absorbance values of enteroviral IgG antibodies against enteroviral antigens (echo30, coxsackie B5, and echo9) were significantly higher among mothers whose children later developed diabetes (P = 0.002, P = 0.02, and P = 0.04, respectively). When reduction in activity after urea wash, indicating recently formed antibodies, was compared, the differences were even more pronounced (P < 0.001 for all three antigens). No significant differences were found for antibodies against herpes (all types), herpes type 2, mumps, or toxoplasmosis. When IgM activity and/or a significant decrease in avidity index, an indication of recent enterovirus infection, was used as a risk exposure, the odds ratio standardized for year of birth (95% confidence interval) was 3.19 (1.39-7.30). We conclude that the results of this study indicate that enteroviral infection during pregnancy is a risk factor for childhood-onset diabetes in the offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphic amino acid variations in HLA-DQ are associated with systematic physical property changes and occurrence of IDDM. Members of the Swedish Childhood Diabetes Study.

The association between human leukocyte antigen (HLA) and insulin-dependent diabetes was studied in a large population-based investigation using genotyping of 425 new-onset patients, 0-14 years of age, and 367 matched control subjects. As many as 97% of patients compared with 75% of control subjects were positive for one or several of DQA1*0301, DQA1*0501, DQB1*0302, or DQB1*0201. Asp-57 DQB was present among 28% of patients, indicating that this residue alone does not confer protection. Combining Asp-57 DQB1 with either Arg-52 DQA1 or Leu-69 DQA1 did not explain susceptibility or protection either. DQA1*0301-DQB1*0302 (DQ8) and DQA1*0301-DQB1*0301 (DQ7) are identical except for four amino acid substitutions in the beta-chain, but DQ8 was positively (odds ratio 8.07; P < 0.001) and DQ7 negatively (odds ratio 0.38; P < 0.001) associated with the disease. Molecular modeling was used to determine whether physiochemical properties such as steric factors and surface electrostatic potentials also differ in a systematic way for various DQ molecules. Amino acids were substituted systematically at the four polymorphic sites, and the solvent-accessible surfaces and electrostatic potentials were computed for each molecule. Dramatic alterations in electrostatic potential were seen for double substitutions at position 45 (G45E) and 57 (A57D) of DQB1. The variation of physicochemical properties due to polymorphic substitutions may be significant to the mechanism of HLA-DQ association with insulin-dependent diabetes, via the effect these property variations have on peptide antigen binding selectivity and subsequent interactions with specific T-cell receptors.

Primary and secondary prevention strategies of pre-type 1 diabetes. Potentials and pitfalls.

Over the past decade, a large part of type 1 diabetes research has focused on the possibility of preventing the disease. The objective of this article is to analyze which potential and pitfalls different preventive strategies may involve from the individual, epidemiological, and ethical perspectives. Two potential prevention strategies are considered: l) to try to arrest or delay an already ongoing immune destruction of the beta-cells, and 2) to try to intervene with exposures that may initiate this process. In addition to the potential effects of immune modulation, this prevention strategy depends on screening for risk markers. There are inherent ethical problems with screening because of the introduction of awareness of risk in healthy individuals and also because false positivity, the rate of which differs tremendously in high- and low-risk groups. Because of these latter circumstances, the most promising low-risk preventive treatments presently used in trials, i.e., nicotinamide and insulin, will probably only be feasible in high-risk groups, such as family members, though this group covers only 10-15% of potential cases. The second strategy aiming at eradicating environmental initiators of the beta-cell destruction will avoid the problem of screening and approach a total population at risk. Potential risk factors, such as food components (cow's milk proteins, gliadin or nitroso products) or different viruses, are indicated by animal and epidemiological studies. So far, however, no single environmental risk factor has been proven to be necessary and certainly not sufficient for the disease causation, and the etiological fractions estimated in population-based studies are low. It is concluded that more basic research is warranted before effective and safe prevention can be introduced for type 1 diabetes. Most probably, different preventive strategies must be applied to different groups and populations and in different phases of the beta-cell destruction.

Determinants of progression of microalbuminuria in adolescents with IDDM.

OBJECTIVE: To evaluate the significance of microalbuminuria in adolescents with IDDM and to study the relative importance of blood pressure (BP), metabolic control, and albumin excretion rate (AER) on progression of microalbuminuria. RESEARCH DESIGN AND METHODS: A cohort of 155/156 children and adolescents followed from onset up to 18.3 years of IDDM participated. In a previous follow-up in July 1991 (up to 15 years of duration), 17 patients had developed persistent microalbuminuria (> or = 20 micrograms/min). In these adolescents, we analyzed whether microalbuminuria had progressed (in mean > or = 5% per year), had remained unchanged, or had normalized (< 20 micrograms/min) after another 3 years. The predictive values of mean HbA1c, diastolic blood pressure (dBP), systolic blood pressure (sBP), overnight AER, sex, age, and duration of diabetes for the progression of microalbuminuria were determined using multiple regression modeling. RESULTS: Seven of 17 patients with microalbuminuria in July 1991 had normalized, 6 of 17 patients had progressed, and 4 of 17 patients had remained unchanged after 3 years. Progressors had higher mean HbA1c during the first 5 years of IDDM and higher mean sBP in 1991 than nonprogressors. Patients with normalized microalbuminuria all had AER < 30 micrograms/min in 1991, were younger at onset of microalbuminuria, had lower mean HbA1c, and had lower dBP before normalized AER than nonregressors at the same duration of microalbuminuria. In multivariate analysis, independent significant predictors for progression were first 5-year mean HbA1c, mean AER, and mean sBP in 1991 (R2 = 0.76, P = 0.001). CONCLUSIONS: Progression of microalbuminuria in adolescents with IDDM is predicted by early sustained hyperglycemia, later elevated sBP, and increased AER per se. Microalbuminuria is frequently normalized in adolescents, and this is associated with better prevailing metabolic control, younger age, and lower dBP.

Clinical onset characteristics of familial versus nonfamilial cases in a large population-based cohort of childhood-onset diabetes patients.

OBJECTIVE: To compare characteristics at clinical onset of childhood-onset diabetes patients with and without a first-degree relative with childhood-onset insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: In a nationwide continuous incident diabetes register covering patients from 0 to 14 years of age with a high level of ascertainment, we compared 687 patients who at onset had at least one first-degree relative with insulin-treated diabetes with 5,137 patients without such relatives. RESULTS: The pattern of change over the 15-year period was similar among familial- and sporadic-case patients. The seasonal pattern, with a lower incidence during the warmer period of the year, was similar in both groups. Age at clinical onset was also similar in both groups in either sex. When the proband had a sibling who already had the disease, the mean age at onset was significantly higher when compared with sporadic-case or other familial-case patients. CONCLUSIONS: This analysis of a very large set of population-based cases of childhood diabetes showed that patients who had one first-degree relative with insulin-treated diabetes at onset shared the onset characteristics of those without such family members, including age at onset, sex ratio, seasonality, and secular trend. The findings may indicate that the complex interactions between genetic and nongenetic risk factors subsequently leading to IDDM are mainly shared by familial- and sporadic-case patients.

Time-space clustering of date at birth in childhood-onset diabetes.

OBJECTIVE: To investigate whether there was a temporal and geographical clustering of time of birth for infants with childhood-onset diabetes. RESEARCH DESIGN AND METHODS: The nationwide Swedish Childhood Diabetes Registry, which ascertains 99% of children with recent-onset diabetes (0-14 years), was linked with the Swedish Medical Birth Registry. Clustering of 3,725 patients as to place and time of birth was studied compared with the general population. For each municipality (and in the three large cities of Sweden for each parish), the observed number of patients was compared with the expected number calculated from the average total rate and the number of births in that municipality. Clustering in time of birth within municipality was analyzed using a modification of a set technique by Chen (14). RESULTS: There was no consistent variability in diabetes risk by calendar birth month, but for specific years, the risk varied during the year. When geographic localization for place of birth was studied on a municipality level, four municipalities showed a statistically significant case excess while one would have been expected by chance. When we looked for clusters in both time and space for date of birth, clearly more clusters than expected were identified (P < 0.01). Of the total of 198 primary clusters, 42 included three or more patients being born in the same municipality within an unlikely short period always < 2 years. CONCLUSIONS: This is the first study indicating a clustering according to place and time of birth for later risk to develop type I diabetes. Such a phenomenon would agree with the hypothesis that infections in early life, including fetal infections, can increase the risk for diabetes.

Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentration of zinc.

OBJECTIVE: Zinc deficiency has shown to increase the risk for diabetes in diabetes-prone experimental animals. Low concentrations of zinc have also been shown in serum of recent onset cases with IDDM. The present study examines the hypothesis that exposure to a low concentration of zinc in drinking water could increase the risk for future onset of IDDM. RESEARCH DESIGN AND METHODS: Using the Swedish childhood diabetes registry and data on residence 3 years before the onset of disease, a case-control study was designed comparing cases and control subjects with estimates of groundwater contents of zinc obtained in biogeochemical samples from areas of residence. RESULTS: A high groundwater concentration of zinc was associated with a significant decrease in risk (odds ration [OR] = 0.8; 95% CI = 0.7-0.9). The same OR was obtained when the model included information of other metals that might act as possible confounders (chromium, vanadium, cobalt selenium, cadmium, lead, and mercury). In small rural areas, in which drinking water is taken from local wells and thus is closely associated with the groundwater content within the area, an even stronger association between zinc and diabetes (OR = 0.6; 95% CI = 0.4-0.9) was found. CONCLUSIONS: It is concluded that this study for the first time provides evidence that a low groundwater content of zinc, which may reflect long-term exposure through drinking water, is associated with later development of childhood onset diabetes.

Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group.

OBJECTIVE: To explore whether perinatal factors are associated with the development of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied hospital records from 892 cases of childhood type 1 diabetes compared with 2,291 population-based control subjects in seven study centers in Europe. RESULTS: In a pooled analysis incorporating stratification by center, we confirmed the previous findings that older maternal age, maternal preeclampsia, neonatal respiratory disease, and jaundice caused by blood group incompatibility are significant risk factors for type 1 diabetes, whereas being a firstborn child, having a low birth weight, or having a short birth length were protective. Cesarean section delivery and neonatal infectious diseases were not significantly associated with the risk of type 1 diabetes in this study. The strongest association was found for blood group incompatibility (AB0 and Rh factor) with an odds ratio (OR) of 2.96 (95% CI 1.88-4.65). AB0 incompatibility (OR = 3.92) was a more common and also a stronger risk factor than Rh incompatibility (OR = 1.62). The effect of AB0 blood group incompatibility was independent of treatment effects in logistical regression analysis. CONCLUSIONS: Different perinatal events are associated with an increased risk of type 1 diabetes. The effect of maternal-child blood group incompatibility is strong and indicates a true effect that must be further explored.

Cumulative incidence of childhood-onset IDDM is unaffected by pertussis immunization.

OBJECTIVE: To identify a possible effect of pertussis vaccination in infancy on the risk for developing human IDDM. RESEARCH DESIGN AND METHODS: A comparison was made of the cumulative incidence of IDDM in children age 0-12 years between two birth cohorts born before pertussis vaccination and two birth cohorts born after pertussis vaccination had been excluded from the Swedish national immunization program. The Swedish Childhood Diabetes registry was used to identify cases of IDDM. Yearly nurse reports on administered vaccines were used to determine coverage for diphtheria/tetanus/pertussis (DTP) and diphtheria/tetanus (DT) vaccines. Pertussis vaccine coverage was estimated based on number of doses of vaccine made available on license. RESULTS: No difference in cumulative incidence rate of IDDM up to the age of 12 years was found when the birth cohorts for 1978 and 1979 with high DTP vaccination coverage were compared with the cohorts of 1980 and 1981 with low pertussis vaccination coverage. CONCLUSIONS: The comparison of the cumulative incidence of IDDM, up to the age of 12 years, in birth cohorts with high and low exposure to pertussis vaccine does not support the hypothesis that pertussis could induce autoimmunity to the beta-cell that may lead to IDDM.

Higher intakes of fish protein are related to a lower risk of microalbuminuria in young Swedish type 1 diabetic patients.

OBJECTIVE: To examine the influence of dietary intake from various protein and fat sources on the occurrence of microalbuminuria in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: In this nested case control study, 1,150 patients with diabetes duration >5 years reported dietary habits for the previous 12 months and submitted urinary samples for the analysis of albumin excretion rate (AER). A total of 75 cases of albuminuria (overnight AER > or = 15 microg/min) were identified and compared with 225 duration-matched control subjects. RESULTS: Neither mean protein, fat intake, average fish protein intake (control subjects 4.56 +/- 3.83 g/day and cases 3.82 +/- 2.87 g/day; P = 0.12), nor intake of meat and vegetable protein differed between the cases of albuminuria and the control subjects. High consumers of fish protein (greater than the 75th percentile) (12 cases and 63 control subjects, mean intake 9.35 g fish protein/day, i.e., approximately 53 g fish/day) had lower odds ratios (ORs) for microalbuminuria than individuals consuming less fish protein (mean 2.72 g/day) (crude OR 0.49 and 95% CI 0.25-0.97). When adjusted for known confounding factors, such as HbA1c, mean arterial pressure, diabetes duration, age, sex, smoking, BMI, country region, and total energy, individuals with a high intake of fish protein and fish fat showed a reduction in the risk for microalbuminuria (OR 0.22 and 0.31, respectively; 95% CI 0.09-0.56 and 0.13-0.76, respectively). When fish protein and fat were adjusted for each other, a high intake of fish protein but not of fish fat was still significantly associated with a decrease in the risk for microalbuminuria. CONCLUSIONS: Total protein and fat intake were not associated with the presence of microalbuminuria, but a diet including a high amount of fish protein seemed to lessen the risk.

Predictors of renal morphological changes in the early stage of microalbuminuria in adolescents with IDDM.

OBJECTIVE: To evaluate the impact of glycemic control, blood pressure, lipid levels, glomerular filtration rate (GFR), age, and duration of IDDM on the degree of structural glomerular changes in the transitional stage of microalbuminuria. RESEARCH DESIGN AND METHODS: Fifteen adolescents (seven boys and eight girls) with > 5 years of duration of IDDM and with low-grade microalbuminuria (15-30 micrograms/min) participated. Seventeen living kidney donors served as healthy control subjects. Five-year mean HbA1c; 5-year mean systolic and diastolic blood pressure; GFR, cholesterol, and triglycerides 2-5 years before renal biopsy; age; and duration of IDDM were investigated and related to basement membrane thickness (BMT), mesangial and matrix volume fractions, and the overall glomerulopathy index [(BMT/10 + mat/glom, %) + matrix star volume]. RESULTS: BMT and the overall diabetic glomerulopathy were increased in diabetic patients as compared with control subjects (P < 0.001), whereas matrix volume fraction, but not mesangial volume fraction, tended to be increased (P = 0.11). In multivariate analysis, BMT was predicted by 5-year mean HbA1c, diabetes duration, and previous GFR (R2 = 0.71, P = 0.003). With matrix volume fraction as the dependent variable, BMT and diabetes duration were the only significant determinants (R2 = 0.63, P = 0.003). Diabetes duration, 5-year mean HbA1c, and GFR were the variables with an independent influence on the overall diabetic glomerulopathy index (R2 = 0.72, P = 0.003). Preceding blood pressure and lipid levels or age had no significant independent influence on these morphometric measures. CONCLUSIONS: In the very early stage of microalbuminuria in IDDM adolescents, a high percentage of the variation in BMT and overall severity of glomerulopathy is explained by prolonged hyperglycemia and diabetes duration. Previous glomerular hyperfiltration may also add to the prediction of these morphological changes.

Psychological stress and the onset of IDDM in children.

OBJECTIVE: The purpose of the study was to determine whether psychosocial stress during different life periods could be a risk factor in the etiology/pathogenesis of insulin-dependent diabetes mellitus (IDDM) in children. RESEARCH DESIGN AND METHODS: In a population-based sample of 67 case patients 0-14 years of age and 61 matched healthy control subjects, life events during the entire lifespan before the onset of IDDM were recorded as well as measures of child behavior before onset, social support, and family function. RESULTS: Negative life events occurring during the first 2 years of life, life events with difficult adaptation, child behavioral deviances, and a more chaotic family function were more common in the case group. A stepwise logistic regression indicated that negative life events in the first 2 years increased the risk of IDDM and that premorbid child behavior as well as dysfunctional hierarchical family pattern affect the risk. CONCLUSIONS: Stress early in life may increase the risk for IDDM, presumably by affecting the autoimmune process. To confirm these results, it is necessary to make a truly prospective study.

Metabolic control in 131 juvenile-onset diabetic patients as measured by HbA1c: relation to age, duration, C-peptide, insulin dose, and one or two insulin injections.

Glycosylated hemoglobin A (HbA1c), considered to reflect long-term metabolic control of diabetes, was analyzed in 131 patients, aged 2 5/12-19 6/12 yr, with juvenile-onset diabetes. Using stepwise multiple regression HbA1c, fasting blood glucose and plasma 3-hydroxybutyrate were analyzed as dependent variables versus independent variables such as age of the patients, duration of the disease, level of plasma immunoreactive C-peptide (IRCP), insulin dose, and number of insulin injections (one or two) per day. HbA1c was inversely related only to IRCP concentration. A low but significant, positive correlation was found between HbA1c and the duration of diabetes. Stepwise addition of the other independent variables did not further increase the fraction of explained variance. HbA1c was also correlated with a subjective rating score of the metabolic control performed by the treating physician. Fasting plasma glucose was significantly related to HbA1c but not to any of the independent variables. Fasting 3-hydroxybutyrate showed an inverse correlation to the age of the patient. The present study showed that in juvenile-onset diabetic patients, endogenous insulin secretion as reflected by IRCP was the factor best correlated with a low level of HbA1c. After the cessation of endogenous insulin secretion, there is a progressive deterioration of metabolic control and multiple injections of insulin rather than one or two per day may be needed to reach optimal control in the patients.