Childhood Insulin-dependent Diabetes Research Articles

Nutritional Intake of Children and Adolescents with Insulin-Dependent Diabetes Mellitus in Crete, Greece

Background/Aims: The incidence of childhood insulin-dependent diabetes mellitus (IDDM) is rapidly increasing in Greece. The aim of this study was to examine nutrient patterns of children and adolescents with IDDM in Crete. Methods: A case-control survey of eating habits was conducted among 41 children and adolescents, aged 6–17 years, with IDDM (cases) and healthy sex- and age-matched controls, recruited from Heraklion University Hospital and the village of Rouvas, Crete, respectively. Dietary data was based on 24-hour recall records. Results: Dietary intake was similar between the groups. Both groups exceeded the recommendations for total and saturated fat and consumed lower than recommended amounts of dietary fibre and total carbohydrates. Children with IDDM consumed more dairy products and vegetables and less meats and cereals. Vegetables were consumed by a relatively high proportion of children and adolescents in both groups, but there was a higher proportion of fruit consumers amongst the IDDM group. For those who ate fruit and vegetables, intake approximated current recommendations of 400 g/day. Conclusions: The need to increase complex carbohydrates and reduce the consumption of total and saturated fat, in order to approach the traditional dietary pattern of Crete for this population, should be addressed via appropriate nutrition education programmes.

Large incidence variation of Type I diabetes in central-southern Italy 1990-1995: lower risk in rural areas.

To evaluate the relation between the incidence of childhood Type I (insulin-dependent) diabetes mellitus and the degree of urbanization in the central-southern part of Italy. The incidence was determined in two areas: area A encompasses 3 regions of central-eastern Italy (Marche, Abruzzo, Umbria), whereas area B encompasses one southern region (Campania). During 1990-1995, 706 children aged 14 or under with insulin-dependent diabetes mellitus of recent onset were registered. The completeness of the case ascertainment in the registries analysed separately for each region was high, ranging from 96.3 % to 99%. The age-standardized incidence was higher in area A (9.6 per 100000 person per year; 95 % confidence interval: 8.5-10.8) than in area B (5.4 per 100000 person per year; 95% confidence interval: 4.9-6.0). In both areas the standardized incidence ratios increased with the degree of urbanization (chi-squared for trend: area A= 140, p < 0.0001; area B = 79, p < 0.0001). The highest standardized incidence ratios were in the most urban communities. This study showed a statistically significant difference in incidence of childhood insulin-dependent diabetes mellitus among different areas of the continental peninsula of Italy. People living in the rural communities appear to have a lower risk.

Long-term glycemic control influences the onset of limited joint mobility in type 1 diabetes.

Limited joint mobility (LJM) in childhood insulin-dependent (type 1) diabetes is associated with a substantially increased risk of microvascular complications. Cross-sectional studies have not demonstrated a relationship between LJM and metabolic control. This study was designed to determine whether glycemic control, as measured by glycohemoglobin (hgbA1C) levels from the onset of diabetes, is associated with the occurrence of LJM. Probands (n = 18) had hgbA1C values and recorded observation of joint function from soon after onset of their diabetes. Controls (n = 40) were matched to probands for gender and age at diagnosis and had follow-up beyond the age at which the proband was found to have LJM. The odds ratio for occurrence of LJM for the mean hgbA1C from diabetes onset was 1.46, 95% confidence limits 1.07 to 2.00. Thus, for every unit increase in average hgbA1C, there was approximately a 46% increase in the risk of LJM. When hgbA1C was dichotomized, the OR for hgbA1C of more than 8% was 2.55, and the OR was 4.54 if the hgbA1C was greater than 12%. Age at diagnosis and duration of diabetes were not independent prognostic factors for LJM. Glycemic control from onset of diabetes is strongly associated with occurrence of LJM.

Decreased Lumbar Spine Bone Mass and Low Bone Turnover in Children and Adolescents with Insulin Dependent Diabetes Mellitus Followed Longitudinally

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

Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density.

The incidence of insulin-dependent diabetes mellitus (IDDM) incidence varies between and within countries. The origins of this variation are disputed, but they involve both genetic and non-genetic influences. To explore the role of environmental factors in the aetiology of IDDM we have examined the incidence in small geographical areas and related it to variables derived from national censuses. This is an ecological analysis of incidence data from a register of children with IDDM covering the counties of West Yorkshire, North Yorkshire and Humberside in the north of England. All children aged < or = 16, diagnosed with IDDM between 1978 and 1990 were eligible for inclusion. Spatial variation in incidence between electoral wards was investigated using Poisson regression, in relation to socioeconomic status, population density, urban-rural status and measures of geographical isolation. Ward child populations varied in size from 84 to 7197 (mean = 1545). Rates were significantly lower in wards of high population density and with many overcrowded houses. The rate ratio for areas in the upper half of the childhood density distribution was 0.88 (95% confidence interval (CI): 0.78-0.99) and for the two upper tertiles of household overcrowding the rate ratios were 0.84 (95% CI: 0.74-0.95) and 0.68 (95% CI: 0.58-0.79) respectively. The incidence of childhood IDDM was associated with environmental factors including population density and overcrowded homes. A possible inference from these data is that patterns of infection are involved in the occurrence of IDDM. Analytical epidemiological studies will be needed to investigate these ideas further.

Rising incidence of insulin dependent diabetes in children aged under 5 years in the Oxford region: time trend analysis

Objectives: To monitor incidence of insulin dependent diabetes in children in Oxford health region since 1985, and to look for any evidence of disproportionate increase in children aged under 5.Design:...

Antenatal risk factors for childhood diabetes mellitus; a case-control study of medical record data in Yorkshire, UK.

Environmental risk factors for childhood insulin-dependent diabetes mellitus (IDDM) have been investigated using data abstracted from the obstetric records of mothers participating in a population-based case-control study of children (0-15 years) diagnosed with IDDM during 1993-1994. A univariate analysis of 196 age and sex matched sets (129 triplets, 67 pairs) gave significantly raised odds ratios (OR) for mothers over 35 years (OR 2.13, 95%CI 1.04-4.36) and the following exposures in pregnancy: amniocentesis (3.85, 1.34-11.04), oedema, proteinuria and/or hypertensive disorders (1.62, 1.03-2.54), excessive weight gain (7.12, 1.50-33.79) and complications in labour (1.49, 1.00-2.21). The risk previously associated with caesarean deliveries was confirmed and the trend of increasing risk with age was significant. Adjusting separately for mothers with IDDM (4 cases, 0 control subjects), parity and small for gestational age failed to have any influence on the pregnancy risk factors or caesarean delivery. Case mothers undergoing amniocentesis were significantly younger compared to their control counterparts (p = 0.02) and the majority were given the test to determine fetal maturity, late in pregnancy, rather than to identify chromosomal abnormalities. Oedema, proteinuria and/or hypertension conferred an increased risk throughout pregnancy, particularly in the first two trimesters. No specific pattern of risk was present for any age group. Multivariate modelling of the significant OR, using conditional logistic regression, retained excessive weight gain as significant. The overall results present a risk profile of older mothers whose babies may be exposed to adverse intrauterine conditions and delivery by caesarean section.

Serum magnesium and protein concentrations during the first five years of insulin-dependent diabetes in children.

Thirty-four children were followed up prospectively for 5 years from the onset of diabetes regarding serum magnesium, zinc and some proteins. Serum magnesium decreased to significantly lower values (0.76 +/- 0.05 mmol l-1) than those in matched controls after 2 and 5 years, with the lowest mean values in diabetic girls. Serum zinc concentration was higher in the diabetic group than in the control children, and again the diabetic girls differed most from the controls. Serum prealbumin was significantly lower in the diabetic patients after 2 and 5 years than in the controls. Serum albumin was also slightly reduced in the diabetic patients, while orosomucoid was normal. These data indicate chronic magnesium deficiency and insufficient liver synthesis of certain serum proteins in diabetic children.

Growth and subcutaneous fat during the first five years of insulin-dependent diabetes in children.

Thirty-four children were observed prospectively during a period of 5 years from the onset of diabetes regarding height, weight and subcutaneous fat in relation to treatment and diabetes control. Height, weight and body mass index (BMI) did not differ from those in a control group. The girls with diabetes increased their triceps and subscapular fat significantly despite a normal BMI. This increase in relation to control girls was most pronounced during late adolescence. Triceps skinfold and BMI after 5 years were both negatively correlated to insulin dose per kilogram body weight in the diabetic girls. We conclude that girls with diabetes accumulate subcutaneous fat in certain areas rapidly during adolescence in a completely different way from healthy girls.

Long-term patterns in seasonality of insulin-dependent diabetes mellitus diagnosis in Austrian children

The analysis of the seasonal pattern of incidence of childhood insulin-dependent diabetes mellitus in Austria was carried out among cases where the child was under the age of 15 when diagnosed between 1979 and 1993. The cases are registered in the nationwide population-based Austrian insulin-dependent diabetes mellitus registry. Seasonal variation was compared between boys and girls and between three 5-year age groups. We also tested whether the seasonal pattern changed over the 15-year observation period. We found a significant seasonal variation among boys aged 10–14 and girls aged 5–14, while in the 0–4 years age group no seasonal pattern could be demonstrated. Two peaks in incidence were identified during a calendar year (February–March and September–October) for girls aged 5–14. For boys aged 10–14, a yearly cycle was found with a peak in January and October. An extension of the Poisson regression model for testing seasonality by Jones et al. was developed to allow for estimation of a time-dependent amplitude of the seasonal component. The annual incidence rate increased by 36% during the observation period, but no significant change in seasonal pattern could be demonstrated.

Intrauterine growth pattern and risk of childhood onset insulin dependent (type I) diabetes: population based case-control study.

To investigate whether prenatal growth affects the risk of development of childhood onset insulin dependent (type I) diabetes mellitus. Population based case-control study. Data from a nationwide childhood diabetes case register were linked with data from the nationwide Swedish Medical Birth Registry. Data from a total of 4584 diabetic children born after 1973 and diagnosed with diabetes from 1978 to 1992 were studied. For each child with insulin dependent diabetes three control children were randomly selected from among all infants born in the same year and at the same hospital as the proband. Birth weight, gestation, maternal age and parity, number of previous spontaneous abortions, and sex specific birth weight by gestational week expressed as multiples of the standard deviation (SD). There was a clear trend in the odds ratio for childhood onset diabetes according to SD of birth weight. The odds ratio (95% confidence interval) for small for gestational age after stratification for maternal age, parity, smoking habits, and maternal diabetes was 0.81 (0.65 to 0.99) and for large for gestational age after similar stratification was 1.20 (1.02 to 1.42). Intrauterine conditions that affect prenatal growth seem also to affect the risk of development of childhood diabetes in the way previously described for postnatal growth: a poor growth decreases and an excess growth increases the risk. The mechanism for this association is unclear.

Incidence of IDDM in children in urban population in Southern India

This study was carried out to estimate the incidence of childhood insulin dependent diabetes mellitus (IDDM) in an urban southern Indian population. A registry for IDDM has been set up in the city of Madras, South India. Details of newly diagnosed IDDM children, aged less than 15 years, were analysed retrospectively, for a period of 1991–1994. Primary sources were government and service hospitals, large diabetes clinics and secondary sources were diabetes camp, private diabetologists and endocrinologists. A capture-recapture method was used and the estimate of case in the population (1991 census) was calculated. Incidence (case/100 000) was calculated in the total group and then for boys and girls separately. The incidence for the 4 year period was 10.5/100 000/year (CI 5.0). The corresponding values for boys and girls were 12.6 ± 11 and 9.6 ± 4.7 respectively. The peak incidence was between 10 and 12 years. This is the first population based incidence data from India and showed that the incidence of childhood IDDM is not low in urban children.

DR4 subtypes and their molecular properties in a population‐based study of Swedish childhood diabetes

The aim of this study was to determine the association between childhood insulin-dependent diabetes mellitus (IDDM) and HLA-DR4 subtypes and to test in a population-based investigation whether the DR4 association has an effect independent to that of DQ. First, HLA genotyping identified DR4 in 337/425 (79%) patients and 148/367 (40%) controls (Odds Ratio 5.67; p < 0.01). Second, a total of 14 DR4 subtypes were detected by PCR and sequence specific oligo probes. Only two DR4 subtypes, DRB1*0401 (62% patients and 25% controls; OR 4.95, p < 0.01) and *0404 (16% patients and 10% controls; OR 1.67, p < 0.05) were however positively associated with the disease. These two subtypes were positively associated only when linked to DQB1*0302-DQA1*0301 (DQ8) (56% patients and 14% controls; OR 7.69, p < 0.01; 15% patients and 10% controls; OR 1.55, p < 0.05, respectively). When DRB1*0401 was linked to DQB1*0301-DQA1*0301 (DQ7) (6% patients and 11% controls; OR 0.52, p < 0.05), this DR4 subtypes was negatively associated with IDDM. Third, tests of strongest association allowed the following ranking of alleles or haplotypes DQB1*0302-DQA1*0301 (DQ8) > DQB1*0302 > DRB1*0401 > DRB1*0404 and the association of DRB1*0401 has a significant effect in DQ8 positive IDDM patients. We conclude that the DR4 association with IDDM is secondary to DQ by linkage disequilibrium, which support the role of HLA-DQ as a primary genetic risk factor for IDDM.

The clinical approach to thyroid disorders associated with childhood insulin dependent diabetes mellitus.

Article The Clinical Approach to Thyroid Disorders Associated with Childhood Insulin Dependent Diabetes Mellitus was published on March 1, 1996 in the journal Journal of Pediatric Endocrinology and Metabolism (volume 9, issue Supplement).

The frequency of severe hypoglycaemia in children with insulin-dependent diabetes mellitus.

The literature contains numerous reports of the frequency of severe hypoglycaemia in childhood insulin-dependent diabetes mellitus. Unfortunately, most of these data have been collected in such a manner as to make comparisons between them difficult. Most reports have used small, well-defined populations of children who were participants in larger, complex, clinical studies. Additional difficulties are encountered in the standardization of the definition of severe hypoglycaemia. Some studies have required that the child lose consciousness while others also included children who required assistance with treatment. Even when studies clearly define the representative nature of their patient population and include universally acceptable criteria for identifying a severe hypoglycaemic episode, the frequency of severe hypoglycaemia must be qualified. Severe hypoglycaemia is generated by a series of complex biological, psychological, and behavioural processes. Its frequency must be viewed not as a fixed value, but rather as a dynamic dependent variable.

Incidence of diabetes in children

EDITOR,—Emma Wadsworth and colleagues report the incidence of insulin dependent diabetes in children under 5 years in the British Isles.1 Their data suggest that the incidence remained stable over four years. The use of “snapshot” years to address the question of potentially increasing incidence must have limited value, even over a large geographical area, when random variation substantially affects annual numbers. The population based Yorkshire children's diabetes register includes 1650 children and for the years 1978-90 is 97% complete.2 …

Neuropsychological complications of insulin dependent diabetes in children

Abstract Previous research suggests that children with insulin dependent diabetes (IDDM) show selective impairments on neuropsychological tests, with those developing IDDM before 5 years of age appearing to be the most affected. The effect of hypoglycaemia on the developing brain has been suggested as a possible risk factor as has the disruptive effect of chronic hyperglycaemia on myelinisation. A cohort of children (n = 124) with newly diagnosed IDDM, managed at The Royal Children's Hospital, Melbourne has been assembled and evaluated 3 months post diagnosis on standardised tests of general intelligence, attention, memory, new learning, executive functions, and educational achievement. The performance of the children with IDDM has been compared with that of a demographically representative control group (n = 129) of healthy children. At this baseline assessment, the findings strongly support the hypothesis that the neuropsychological and educational profiles of newly diagnosed children are not different ...

Dermatoglyphics, fetal growth, and insulin dependent diabetes in children under 5 years.

Examination of dermatoglyphic patterns in 112 diabetic children under 5 years and matched controls found no difference between the groups. Either those developing diabetes under 5 do not experience the same genetic and environmental conditions that influence its development in later life or the dermatoglyphic abnormalities described in later onset insulin dependent diabetes mellitus reflect the vast number of pattern formations available for study, which has inevitably led to some statistically significant associations.

Variation in HLA-associated risks of childhood insulin-dependent diabetes in the Finnish population: II. Haplotype effects. DiMe Study Group. Childhood Diabetes in Finland.

We fitted models for the main effects of alleles at the HLA-A, B, and DR loci and their haplotypes on the risk of insulin-dependent diabetes mellitus (IDDM). Empirical Bayes methods were used, assuming independent exchangeable normal priors for effects at each locus separately and for haplotype effects. A pure main effects model, pure haplotype effects model, and a combined model were fitted using Gibbs sampling. The main effects model showed that the DR locus had the largest variation in risk between alleles, followed by the B locus; significance tests for each allele in this model were in general agreement with those in the companion paper [Langholz et al. (1995) Genet Epidemiol 12:441-453], although all relative risks were shrunk toward 1.0 in the empirical Bayes analysis. The variance estimate for pure haplotype effects was substantially larger than for any of the three main effects considered in this analysis, but in the combined model, the DR locus showed larger variability than the haplotype deviations. We confirmed that haplotype A2/B56/DR4 previously reported to be common in Finnish diabetics does indeed confer unusually high risk (relative risk = 7.6, P < 0.001), but found this to be only 1.9 times higher than predicted by its component main effects (P = 0.046). All of the other haplotypes could be adequately explained by their main effects. Empirical Bayes methods provide a natural means of dealing with the problems of multiple comparisons, multicolinearity, and sparse data that complicate the analysis of HLA data.

Susceptibility alleles at HLA-DRB1, -DQA1, and -DQB1 loci in Ethiopian childhood insulin-dependent diabetes mellitus

Susceptibility alleles at HLA-DRB1, -DQA1, and -DQB1 loci in Ethiopian childhood insulin-dependent diabetes mellitus