Down's syndrome in diabetic patients aged <20 years: an analysis of metabolic status, glycaemic control and autoimmunity in comparison with type 1 diabetes.

AIMS/HYPOTHESIS: Intellectual impairment in individuals with Down's syndrome and diabetes mellitus potentially limits the quality of diabetic control. In addition, these patients are at risk of having immunological abnormalities. The present study compared metabolic status and concomitant diseases in young (<20 years old) Down's syndrome patients with diabetes vs young type 1 diabetic patients. METHODS: The Diabetes-Patienten-Verlaufsdaten is a longitudinal follow-up database, which collects data from 298 German and Austrian diabetes centres. Data available on diabetic patients aged <20 years were analysed statistically. RESULTS: We compared data for 159 Down's syndrome patients with diabetes and 41,983 type 1 diabetic patients. The former used less insulin, but showed better glycaemic control (HbA1c). Diabetes onset during the first 3 years of life occurred in 18.9% of Down's syndrome patients with diabetes and in 6.4% of type 1 diabetic patients. Antibody titres indicative of coeliac disease and thyroid peroxidase antibodies were more frequent in Down's syndrome patients with diabetes. No significant differences were found regarding the beta cell autoantibodies studied. CONCLUSIONS/INTERPRETATION: The age-of-onset distribution showed a shift towards younger ages and was bimodal in the Down's syndrome group. The better metabolic control found, despite intellectual impairment, in young Down's syndrome patients with diabetes cannot be conclusively explained by our data, but is likely to be due to a less complex lifestyle. Our data provide further confirmation that coeliac and thyroid antibodies are more prevalent in Down's syndrome. The presence of beta cell autoantibodies supports an autoimmune cause of diabetes in some children with Down's syndrome.

Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database.

AIMS: To analyse and compare clinical characteristics in young patients with maturity-onset diabetes of the young (MODY) and Type 2 diabetes mellitus (T2DM). METHODS: We conducted an observational investigation using the DPV-Wiss database containing clinical data on 40 757 diabetic patients < 20 years of age from Germany and Austria. RESULTS: Three hundred and thirty-nine cases were clinically categorized as MODY (0.83%); 562 patients were diagnosed as T2DM (1.4%). In 20% of cases, the diagnosis of MODY was based on clinical findings only. Of the 272 subjects where genetic testing was available, 3% did not carry mutations in the three examined MODY genes. Glucokinase-MODY was commoner than HNF1A-MODY and HNF4A-MODY. Age at diagnosis was younger in MODY patients. The body mass index of T2DM was significantly higher compared with all MODY subgroups. Macrovascular risk factors such as dyslipidaemia and hypertension were commoner in T2DM, but 23% of MODY patients had dyslipidaemia and 10% hypertension. Glycaemic control was within the therapeutic target (HbA(1c) < 7.5%) in 86% of MODY and 70% of T2DM patients. CONCLUSIONS: The prevalence of MODY in children and adolescents in Germany and Austria is lower than that of T2DM in this age group. Dyslipidaemia and hypertension are less frequent in MODY compared with T2DM patients, but do occur.

Age-specific characteristics of the basal insulin-rate for pediatric patients on CSII.

OBJECTIVE: This study intends to analyse the basal insulin dosage for pediatric patients (0-18 years) with type 1 diabetes on insulin-pump therapy (CSII). RESEARCH DESIGN AND METHODS: In a large German and Austrian prospectively documented data base (DPV) for children with diabetes, patients with CSII were identified. The documented basal rates from patients (0-18 years) were analysed and related to age, gender, duration of diabetes, body weight and type of insulin used in the pump. Data were evaluated for three age groups (0-6; >6-12; >12-18 years). RESULTS: Complete data sets with documented hourly intervals of basal rate were available from 743 patients. Basal insulin dosage in the 3 age groups differed significantly (0-6 years 0.20 IU/kg body weight; >6-12 years 0.34 IU/kg body weight; >12-18 years 0.41 IU/kg body weight p<0.0001). The amount of basal insulin in 24 hours in each group correlates with body weight, age and duration of diabetes. The circadian distribution of the basal rate shows different profiles in each age group. CONCLUSION: Pediatric patients on CSII have age specific characteristics in total amount and circadian distribution of basal rates.

Urinary excretion of albumin in adolescents with type 1 diabetes: persistent versus intermittent microalbuminuria and relationship to duration of diabetes, sex, and metabolic control.

OBJECTIVE: Urinary excretion of albumin is a marker for incipient diabetic nephropathy in adults. The intra-individual variability, as well as the relationship to duration of diabetes, onset of the disease, and long-term metabolic control, have not been evaluated in a large sample of pediatric patients. RESEARCH DESIGN AND METHODS: A total of 5,722 nocturnal urinary albumin excretion rates were determined in 447 children, adolescents, and young adults with type 1 diabetes, comprising 1,821 years of observation. Excretion rates were related to duration of diabetes, age at onset of diabetes, sex, blood pressure, and metabolic control. RESULTS: Based on repeated measurements in individual patients, the positive predictive value of one sample was 76%, the negative 99.5%. After a duration of diabetes of 11 years, 5% of patients displayed persistent microalbuminuria (10% after 13 years). The duration of diabetes until persistent microalbuminuria was identical for patients with prepubertal or pubertal onset of diabetes. In addition to duration, female sex (P < 0.03) and insufficient long-term metabolic control (P < 0.03) contributed significantly and independently to urinary albumin excretion. CONCLUSIONS: Determination of urinary albumin excretion rate is useful in pediatric patients. Female subjects with a long duration of diabetes and insufficient metabolic control are especially at risk for microalbuminuria. Even if persistent microalbuminuria usually becomes evident in patients aged > 11 years, the prepubertal duration of diabetes contributes equally to this risk. Good metabolic control therefore should be aspired to from the onset of diabetes.

Objective assessment of smoking habits by urinary cotinine measurement in adolescents and young adults with type 1 diabetes. Reliability of reported cigarette consumption and relationship to urinary albumin excretion.

OBJECTIVE: To examine the relationship of objective smoking status to age, sex, longterm metabolic control, and urinary albumin excretion. Patients with type 1 diabetes who smoke are at increased risk to develop diabetic microvascular and macrovascular complications. While this has repeatedly been demonstrated in adults, smoking habits have rarely been investigated in adolescents. RESEARCH DESIGN AND METHODS: Urinary continine excretion has been determined by radioimmunoassay in 238 adolescents and young adults with type 1 diabetes. This biochemical parameter of nicotine use was related to age, to the number of cigarettes allegedly consumed per day, and to urinary albumin excretion. RESULTS: A total of 46 patients (19.3%) with urinary cotinine values > 500 ng/ml were classified as smokers. In 26 patients (10.9%), cotinine values between 100 and 500 ng/ml were found (infrequent smokers or environmental nicotine exposure), while the remaining 166 patients excreted < 100 ng/ml of cotinine in the urine (nonsmokers). Smokers were significantly older (20.2 +/- 0.6 years [mean +/- SE]) compared with the intermediate group (18.3 +/- 0.7 years) or with nonsmokers (15.9 +/- 0.4 years; P < 0.0001, Wilcoxon's signed-rank test). Of 46 smokers, 12 denied smoking cigarettes entirely, and among biochemically defined smokers, no correlation was present between urinary continine excretion and the reported number of cigarettes consumed per day. Urinary albumin excretion was significantly higher in smokers compared with nonsmokers (P < 0.003). CONCLUSIONS: These data demonstrate that cigarette smoking is common among German adolescents and young adults with type 1 diabetes in this study. Many patients deny nicotine use or refuse to disclose their smoking habits. Increased urinary albumin excretion is consistent with an increased risk of nephropathy in subjects with diabetes who smoke. Pediatricians in charge of adolescents with type 1 diabetes should actively discuss the risk of nicotine consumption with their patients.

Hospitalization among diabetic children and adolescents and the general population in Germany. German Working Group for Pediatric Diabetology.

OBJECTIVE: To compare hospitalization in a multicenter-based cohort of diabetic children and adolescents (aged 1-19 years) in Germany with that of the general population. RESEARCH DESIGN AND METHODS: Based on standardized documentation, hospital stays after manifestation were ascertained in diabetic subjects 1-19 years of age in 1997. Hospitalization data in the general German population were derived from official statistics. Incidence rates and numbers of hospital days were estimated. Ratios of hospitalization incidences and numbers of hospital days between the diabetic and the general population were calculated. Costs for hospital care in the German diabetic population in 1997 were determined. RESULTS: A total of 5,874 patients came from 61 pediatric centers (52% male, age [mean +/- SD] 12.2 +/- 4.3 years, diabetes duration 4.6 +/- 4.4 years). Hospitalization incidence rates and hospital days per person-year (95% CI) were 0.27 (0.25-0.29) and 1.80 (1.75-1.84) in the diabetic population and 0.0948 (0.0946-0.0949) and 0.6416 (0.6412-0.6420) in the general population. The standardized ratio of hospital incidences was 3.1 (2.9-3.2), and the ratio of numbers of hospital days was 2.8 (2.7-2.9). Costs for hospital care after manifestation were estimated to be $506 (U.S. dollars) per person-year and $12.4 million in the whole German diabetic population aged 1-19 years in 1997; including hospital stays at diabetes onset, total annual costs were $24 million ($970 per person-year). CONCLUSIONS: Diabetic children and adolescents in Germany had an approximately three times higher hospitalization risk and three times more hospital days than the age-matched general population. Including hospitalization at diabetes onset, the annual costs of hospital care for the German diabetic population aged 1-19 years amounted to approximately 1% of all costs for hospital care in this age-group. Thus, costs were largely overproportional (diabetes prevalence 0.1%).

Hemoglobin A1c and body mass index in children and adolescents with IDDM. An observational study from 1976-1995.

In adult patients with type 1 diabetes good metabolic control was associated with an undesired weight gain. In the present report the possible association of HbA1c and body mass index (BMI) in children and adolescents with type 1 diabetes (IDDM) was investigated in a long-term retrospective study from 1976 to 1995. Further, the relationship between BMI on one hand and age, gender, duration of IDDM, the number of units of insulin used and the number of injections per day on the other hand were considered. Statistical analysis was performed using repeated measurements analyses of variance. The 208 girls and 201 boys were 5-17 years old and had diabetes for beyond one year. For analysis 2512 data sets, in part measurements on the same patient in the course of the disease, were available. In various statistical models, the results show that age, gender, the daily amount of insulin, and the HbA1c level (p<0.001-0.005) were associated with the BMI. Extremely high HbA1c levels coincided with a remarkably low BMI. Hence, in children and adolescents with IDDM it may be difficult to achieve a constantly good metabolic control accompanied by a normal body weight.

Direct costs of pediatric diabetes care in Germany and their predictors.

INTRODUCTION: Cost-of-illness study to evaluate diabetes-related direct costs for the care of diabetic children and adolescents in Germany from the perspective of the statutory health insurance. MATERIAL AND METHODS: For all continuously treated patients < 20 years of age from 89 pediatric departments (n = 6437, 52 % male, mean age 12.5 [SD 3.8], diabetes duration 5.2 [3.3] years), diabetes-related hospitalization, ambulatory care, insulin management, glucose self measurement, and treatment with antihypertensive drugs in 2000 were ascertained, as well as metabolic control (HbA1c). Costs per patient-year were calculated in Euros (EUR) based on year 2000 prices. Using multivariate regression, the associations between costs and age, sex, diabetes duration, and metabolic control were evaluated. RESULTS: Mean total costs per patient-year were EUR 2611 (interquartile range 1665 - 2807). Blood glucose self measurement, hospitalization, and insulin accounted for 37 %, 26 %, and 21 % of the costs, respectively, followed by ambulatory care (9 %), injection equipment and glucagon sets (7 %), and treatment with antihypertensive drugs (0.1 %). The total costs were significantly increased for higher age, longer diabetes duration, and higher HbA1c (p < 0.01). The costs for hospitalization were significantly associated with pubertal age (10 - 14 years) and poor metabolic control (HbA1c SDS > 5) (p < 0.001). Based on the present estimations, the total direct costs for the care of all diabetic subjects in Germany < 20 years would be EUR 66.8 (95 % CI 65.4 - 68.1) million in 2000. DISCUSSION: Among the direct medical costs of childhood diabetes, the highest economic burden was due to glucose self measurement, hospitalization, and insulin. The costs were considerably higher in adolescents with poor metabolic control, especially the costs for hospitalization. Outpatient education programs in pediatric diabetes care, in particular targeting children with poor metabolic control, should be encouraged, including their evaluation with respect to cost and effectiveness.

Quality of paediatric IDDM care in Germany: a multicentre analysis. German Paediatric Diabetology Group.

Quality management has been applied in recent years to improve the care of children and adolescents with insulin dependent diabetes mellitus (IDDM). In 1995 the German Paediatric Diabetology Working Group published standards on quality control, in which relevant parameters on structure, process and outcome of care were defined. A computer software programme-developed at the University of Ulm under the auspices of the German Secretary of Health-has been used for quality control with central anonymous analysis in a nationwide survey. Data from 23 paediatric centres with 2407 patients seen between January and June 1996 were evaluated. The results showed an admission rate to hospital of 23.8 per 100 patient-years with an average duration of in-patient stay of 2.74 days/year. 80% of the patients were treated with an intensive insulin therapy regimen comprising three or more injections daily. The overall metabolic control was reasonably good with a mean HbA1c value of 7.8%. The rate of severe hypoglycaemia complicated by coma and/or convulsions was six per 100 patient-years and of ketoacidosis one per 100 patient-years. Unfortunately screening for diabetic retinopathy and nephropathy was not carried out consistently. The incidence was 44% and 33% respectively.

Inpatient and outpatient health care utilization of children and adolescents with type 1 diabetes before and after introduction of DRGs.

OBJECTIVE: To analyze the frequency and length of hospital stays as well as the frequency of diabetes-associated outpatient visits of children and adolescents with type 1 diabetes before and after the introduction of DRGs (diagnosis-related groups) in German hospitals. METHODS: For this prospective cohort study, data from 2000 (before introduction of DRGs) to 2008 (after introduction) was extracted from the German diabetes documentation software DPV. Incidence rates of hospitalizations, length of hospital stays as well as the incidence rates of outpatient visits of 21,502 children and adolescents were estimated. The associations between the target parameters and DRG introduction, age, sex, diabetes duration, calendar year and migration background were estimated using generalized linear mixed models. RESULTS: Incidence of hospitalization was 0.45 (95% CI 0.44-0.45) per person-year (PY), mean number of hospital days 2.77/PY (95% CI: 2.76-2.79). Children had 5.3 (95% CI: 5.3-5.3) outpatient visits per PY on average. The number of hospital stays, inpatient days, and outpatient visits decreased significantly between 2000 and 2008. Time of introduction of DRGs was related to a significant rise in the number of hospital stays and outpatient visits (p<0.05). There was no significant relation to the number of hospital days. Compared with children younger than eleven years of age, 11- to 14-year-old children had significantly more, adolescents older than 14 years significantly less hospital stays (RR 1.2, 95% CI: 1.14-1.23 and 0.92, 95%, CI: 0.87-0.97, respectively). Migration background was significantly associated with worse results for all analyzed target variables (RR 1.21 for hospital stays, 1.26 for hospital days, 1.07 number of outpatient visits). CONCLUSIONS: The introduction of DRGs in the care of patients with pediatric diabetes mellitus resulted in a leveling of the reduction of the number of outpatient visits and hospital stays. Especially adolescents at the age of puberty and patients from families with migration background seem to require particular attention in health care.

Socioeconomic conditions and type 1 diabetes in childhood in North Rhine-Westphalia, Germany.

AIMS/HYPOTHESIS: The aim of the study was to investigate the relationships between childhood type 1 diabetes and socioeconomic conditions, which might provide clues to the aetiology of the disease. MATERIALS AND METHODS: In an ecological study, we investigated the relationships between socioeconomic conditions and the incidence of type 1 diabetes incidence among children aged 0-14 years in North Rhine-Westphalia (NRW), Germany, between 1996 and 2000 at the level of the 33 districts. Incidence data were obtained from the population-based NRW diabetes register and regional socioeconomic data from official statistics. Associations were assessed by Poisson regression models and Bayesian conditionally autoregressive regression models (CAR). RESULTS: In simple Poisson regression, population density, proportion of non-German nationals in the population, measures of income, education and professional training, and deprivation scores were significantly associated with diabetes risk (p < 0.01). An increase of about one interquartile range (IQR) in population density, proportion of non-German nationals or household income was associated with a 9-12% decrease in diabetes incidence. A rise of about one IQR in income ratio, measures of education and professional training, or in deprivation score (high values correspond to high deprivation) was associated with an 8-12% incidence increase. There was a significantly 'linear' increasing incidence trend across five deprivation classes (relative risk: 1.06; 95% CI: 1.03-1.09). All associations were confirmed when overdispersion and spatial autocorrelation were accounted for in Poisson and CAR models. CONCLUSIONS/INTERPRETATIONS: The results raise the possibility that the risk for type 1 diabetes is higher for children living in socially deprived and less densely populated areas. Subsequent investigations are necessary to verify the observed ecological relations at the individual level and to identify the causal factors behind the socioeconomic indicators.

Persistent social disparities in the risk of hospital admission of paediatric diabetic patients in Germany-prospective data from 1277 diabetic children and adolescents.

BACKGROUND: Reduction of social inequality in health care is a major target in many countries. The risk of hospital admission is thought to be higher in diabetic children from socially deprived families but actual data are lacking. METHODS: Based on a nationwide prospective computer-based documentation program (DPV), we determined the association between three social parameters (parental professional education, one-parent family vs. complete family, migration background) and the risk for post-onset hospital admission, as well as the number of hospital admission days in children and adolescents < 20 years of age with diabetes onset in 2002-2005 [n = 1277, 56% male, mean age at onset 8.5 (4.1) years]. We estimated relative risks with 95% confidence intervals, adjusting for age, sex, and diabetes centre (cluster), using random effect models. RESULTS: Forty-two per cent of the study subjects were admitted to hospital at least once during follow-up. The incidence of hospital admissions was 0.46 (0.43-0.49) per person year, and there were 2.72 (2.65-2.80) hospital days per person year. Hospital admissions and hospital days were higher in girls than in boys (significant for hospital days, P < 0.05), and significantly lower in adolescents aged 15-19 compared with children aged 0-4 years (P < 0.05 in all models). Hospital admission rates were significantly higher in children from lower-educated parents, single-parent families, and families with a migration background (all P < 0.05). DISCUSSION: We found post-onset hospital admission rates to be higher in diabetic children and adolescents from socially deprived families. In comparison with an analysis in the 1990s, no decrease in social disparity in hospital admission risk was found.

Indications for insulin pump therapy in different age groups: an analysis of 1,567 children and adolescents.

AIMS: The German working group for pump therapy in paediatric patients has defined seven indications for continuous subcutaneous insulin infusion (CSII): dawn phenomenon, reduction of severe hypoglycaemia, improvement of hyperglycaemia, more flexibility, motivation, failure of injection therapy and pregnancy. In this study we analysed age-specific differences for starting CSII in four age groups (group A: 0-4 years; group B: 5-9 years; group C: 10-14 years; group D: 15-19 years). We also investigated whether glycaemic goals could be reached. METHODS: A total of 1567 children and adolescents (mean age 12.4 years, mean diabetes duration 5.2 years) with documented indications for CSII from the DPV-database (December 2005) were included. RESULTS: Dawn phenomenon (27.4%), reduction of hypoglycaemia (20%) and improvement of hyperglycaemia (18.1%) were the commonest indications for starting CSII. Indications differed by age group (P < 0.0001). In infants and toddlers (group A, n = 138) reduction of hypoglycaemia (42.5%) was the commonest indication. For adolescents (group C, n = 789/group D, n = 408) dawn phenomenon (32.1/21.7%) and flexibility (21.7/25.8%) were the main indications. The rate of severe hypoglycaemia with coma in patients commencing CSII in order to reduce hypoglycaemia fell (12.1/100 patient years before CSII vs. 5.8 after 1 year, 4.49 at study end). Glycated haemoglobin (HbA(1c)) in patients with the treatment goal 'improvement of hyperglycaemia' was lowered significantly in the first year of CSII (HbA(1c) start: 8.8%; after 1 year: 8.5%, P < 0.01) and was stable thereafter (8.8% after 36 months). CONCLUSIONS: CSII in children and adolescents is safe and can reduce the rate of severe hypoglycaemia without deterioration in glycaemic control. In patients with poor glucose control, a significant reduction in HbA(1c) can be achieved in the first year.

The 'accelerator hypothesis': relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether either increased weight or BMI are associated with the earlier manifestation of type 1 diabetes mellitus in children. METHODS: We evaluated anthropometric measurements in a large cohort of 9,248 patients of European extraction who were diagnosed in the years 1990-2003 in 116 pediatric clinics throughout Germany and Austria. RESULTS: Patients were divided into four groups according to age (0-4.9 years, 5-9.9 years, 10-14.9 years and 15-20 years). Significantly higher standard deviation scores (SDSs) for weight and BMI at diabetes onset were found for both boys and girls in the three younger age groups (up to 14.9 years of age) compared with the reference population (p<0.00001). In addition, the BMI SDS and the weight SDS were significantly higher in the 0-4.9-years age group than in all other groups (p<0.00001), and BMI SDS at onset gradually decreased with increasing age at manifestation (p<0.0001). Over the >10-year study period, there was a continuous rise in the weight-SDS and the BMI-SDS in the cohort (p<0.0001), especially in the 5-9.9-years and the 10-14.9-years age groups. Multivariate analysis revealed a significant influence of male sex and of year of manifestation on BMI SDS (p<0.0001) and demonstrated a negative association between the patients' BMI SDS and age at diagnosis, with a mean annual decrease in BMI SDS of -0.0248 (95% CI -0.0294 to -0.0202, p<0.0001). CONCLUSIONS/INTERPRETATION: A higher BMI was associated with a younger age at diabetes onset. Increased weight gain could therefore be a risk factor for the early manifestation of type 1 diabetes.

Longitudinal analysis of somatic development in paediatric patients with IDDM: genetic influences on height and weight.

Normal growth and development, as well as the prevention of overweight, are major goals in the treatment of paediatric patients with insulin-dependent diabetes mellitus (IDDM). We therefore evaluated longitudinally the anthropometric measurements of height and weight, as well as bone age, in an unselected group of 389 patients with IDDM treated at one institution. In order to identify genetic influences on these parameters, height and weight were determined in 186 unaffected siblings and 177 pairs of parents. At diagnosis, patients were slightly taller than average (median z score: +0.37). During the subsequent course of diabetes, age-adjusted heights decreased progressively for the first 9 years, catching up again after more than 10 years of diabetes. Bone ages were progressively retarded with increasing duration of diabetes. In 76 patients of 18 years or older, median z-score for height was +0.30, not different from their unaffected siblings (median z-score: +0.22). The correlation with midparental height was identical for diabetic and nondiabetic siblings (r = 0.43). In contrast, children with diabetes were significantly heavier (z-score for weight: +0.74 compared to +0.34 in unaffected siblings; p < 0.002). Obesity developed primarily during and after puberty. We conclude that: 1) during the course of diabetes, longitudinal growth is temporarily reduced and maturation is delayed in children with diabetes compared to unaffected siblings. However, this effect of diabetes is transient and small compared to genetic influences on height in an individual child. 2) As a group, children with IDDM become significantly overweight, which is likely to increase the cardiovascular risk during adulthood.

Age at onset and long-term metabolic control affect height in type-1 diabetes mellitus.

UNLABELLED: Reduced height as a consequence of type-I-diabetes mellitus in childhood has been reported in many studies. However, it is still debated whether good metabolic control can normalize the growth rate. A total of 436 children (204 boys, 232 girls, mean age at diagnosis of diabetes 8.2+/-0.2 years) were followed at our outpatient diabetes centre. Z-scores for height were evaluated in relation to duration of diabetes, age at onset and long-term metabolic control. At diagnosis, height in children with diabetes was significantly above the reference population (+0.43+/-0.09). Standardized height decreased during the subsequent course of diabetes. This likely represents a delay of growth, as the final height (chronological age > 18 years, n = 144) was +0.27+/-0.09. Growth reduction was more pronounced in patients diagnosed before the onset of puberty and final height in patients with a prepubertal onset of diabetes was significantly lower (+0.10+/-0.13) compared to patients with a pubertal/postpubertal onset (+0.52+/-0.14). Among patients with a prepubertal onset, the subgroup with "poor" metabolic control (long-term median HbA(Ic) >7%) lost significantly more height compared to patients with "good" metabolic control. CONCLUSION: Despite modern treatment regimens, reduced longitudinal growth can still be demonstrated in type-I diabetes. This parameter therefore provides a valuable endpoint for quality control in paediatric diabetology.

Contributions of age, gender and insulin administration to weight gain in subjects with IDDM.

Overweight in insulin-dependent diabetes mellitus (IDDM) has been repeatedly reported, especially in girls during adolescence. Potential pathophysiologic factors include tight metabolic control, insulin dose, treatment regimen, puberty and genetics. A standardized data-base from all IDDM patients treated at our institution was evaluated. IDDM patients with hypothyroidism or celiac's disease as well as all records from the first year of diabetes were excluded, resulting in a total of 427 patients (2454 patient-years) available for analysis. BMI and SD-score for BMI based on the Zurich longitudinal growth study were evaluated. Standardized BMI was higher in pubertal children ( + 1.07+/-0.06) compared to prepubertal children (+ 0.68+/-0.07; p < 0.002). This increase was present both for boys and girls. Increasing overweight during puberty was found irrespective of the age at diagnosis of diabetes (prepubertal or pubertal). The daily dose of insulin and the long-term metabolic control had only a minor impact on the development of overweight. In contrast, in pubertal children, SDS-BMI was significantly higher in patients on intensified insulin regimens (3 or 4 daily injections) compared to patients with 2 injections (p < 0.05). These data demonstrate that both boys as well as girls with IDDM develop overweight during puberty. Multiple injection therapy, not daily dose of insulin or the level of metabolic control achieved, was the main predictor of weight gain. This finding may be explained by increased caloric intake due to the flexibility allowed by intensified treatment.

Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Effect of age, gender and HLA type.

Type 1 diabetes is often associated with additional autoimmune phenomena. However, data reported on the frequency of thyroid autoimmunity differ vastly. Therefore, the prevalence of thyroid autoantibodies was evaluated at a large pediatric diabetes center in Southern Germany. 2,305 determinations (TPO and TG, ELISA) were performed in 495 patients with type 1 diabetes (234 boys, 261 girls; age at last measurement: 15.4 +/- 0.3 years, duration of diabetes 7. 5 +/- 0.2 years). The prevalence of elevated thyroid antibodies increased dramatically with age: from 3.7% in patients less than 5 years of age up to 25.3% in the age group 15-20 years (p < 0.0001). For children older than 10 years, girls were significantly more affected than boys (p < 0.0001). Thyroid autoimmunity tended to be more prevalent in the subgroup of patients with the HLA type DR3/DR4 compared to patients with other HLA types (p = 0.08). In children older than 10 years, basal TSH concentrations were significantly elevated in antibody-positive patients (p < 0.05). In conclusion, thyroid autoimmunity is prevalent in children and adolescents with type 1 diabetes. Adolescent girls and young women are especially affected. Yearly routine determinations of thyroid antibodies are therefore recommended.

Diabetic retinopathy in pediatric patients with type-1 diabetes: effect of diabetes duration, prepubertal and pubertal onset of diabetes, and metabolic control.

OBJECTIVE: The objective of this study was to determine the contribution of prepubertal and pubertal onset and duration of diabetes to the development of diabetic retinopathy. STUDY DESIGN: A total of 1391 standardized fundus examinations (stereo fundus-photography) were performed in 441 children or adolescents with type-1 diabetes (median age 15.5 years, median duration of diabetes 6.3 years). RESULTS: Mild nonproliferative retinopathy was present in 72 patients (median age 19.9 years). Life table analysis revealed a median duration of diabetes until retinopathy was first diagnosed at 16.6 years (95% confidence interval: 15.3 to 18.3). Patients were stratified according to diabetes onset before or in puberty (> or = 10.4 years in girls, > or = 12.2 years in boys). In children with a prepubertal onset of diabetes, retinopathy occurred after a pubertal duration of 10.9 years compared with 15.1 years in children with onset of diabetes in puberty (p < 0.01), demonstrating the additional risk conveyed by the prepubertal years of diabetes. Long-term metabolic control had a significant influence on the prevalence of retinopathy: patients with a median HbA1c > or = 7.5% had development of retinopathy on average after 15.5 years compared with 18.3 years in patients with lower HbA1c values (p < 0.05). CONCLUSION: Both prepubertal and pubertal duration of diabetes are relevant for the development of background retinopathy. Good metabolic control should be attempted irrespective of age.