Continuous glucose monitoring in children, adolescents, and adults with type 1 diabetes mellitus: analysis from the prospective DPV diabetes documentation and quality management system from Germany and Austria.

OBJECTIVE: To determine frequency, duration, and relationship of continuous glucose monitoring (CGM) to glycemic control and rate of hypoglycemia in children and adults in Germany and Austria. RESEARCH DESIGN AND METHODS: From 59,920 patients documented in the DPV (Diabetessoftware zur prospektiven Verlaufsdokumentation) database, 144,385 sensor days of 2874 patients using CGM between January 2008 and September 2010 were analyzed. RESULTS: Overall, 4.8% of patients used CGM. In pediatric patients, study period (p = 0.0309), age (p = 0.0140), insulin dose (p < 0.0001), and use of insulin analogs (p < 0.0001) significantly influenced hemoglobin A1c (HbA1c), but duration of diabetes, sex, and CGM use did not. In contrast, adults with longer CGM use (>30 d) had significantly lower HbA1c (p < 0.0016). Severe hypoglycemia was not reduced in patients using CGM for <30 d. CONCLUSIONS: CGM is still rarely used in Germany and Austria. CGM use is associated with a significant reduction of HbA1c in adults but not in children. Hypoglycemic events were not reduced, irrespective of age.

Sensor augmented pump therapy from onset of type 1 diabetes: late follow-up results of the Pediatric Onset Study.

AIM: To evaluate the metabolic control and ß-cell function 1 yr after the end of the European multicentre randomized Pediatric Onset Study. METHODS: Of 154 study patients, 131 were re-examined 24 months after type 1 diabetes onset (49.6% boys, age at onset 8.9 ± 4.3 yrs). Of which, 62 patients belonged to the primary group of the main study applying a sensor-augmented pump system during the first yr and 69 patients to the control group performing conventional insulin pump therapy with self-monitoring blood glucose. HbA1c, fasting blood glucose, and C-peptide were centrally measured (Clinical Trail Registration Number: ISRCTN05450731). RESULTS: At 24 months, i.e., 1 yr after the end of the interventional study, 52.4% of the patients used the sensor-augmented pump system, 46.0% conventional pump, and 1.6% multiple daily injections. HbA1c was 7.6 ± 1.3% in the primary and 7.7 ± 1.2% in the control group (p = 0.493). Frequent sensor use during the first yr was associated with statistically insignificant lowering of the HbA1c at 24 months (p = 0.236) as compared with irregular or no sensor use (7.4 ± 1.0% vs. 7.7 ± 1.3%). Although fasting C-peptide was not clearly different between the primary and control group (0.13 ± 0.17 vs. 0.09 ± 0.10 nmol/L, p = 0.121), patients with frequent sensor use had significantly less C-peptide loss within 24 months (C-peptide reduction 0.02 ± 0.18 vs. 0.07 ± 0.11 nmol/L, p = 0.046). There was no difference between the groups regarding daily insulin requirements. CONCLUSION: Sensor-augmented pump therapy from onset of diabetes may lead to better long-term glycemic control and help to preserve endogenous ß-cell function, if patients comply with frequent use of continuous glucose monitoring.

Low levels of asymmetric dimethylarginine in children with diabetes mellitus type I compared with healthy children.

OBJECTIVE: Although high levels of asymmetric dimethylarginine (ADMA) are associated with an increased risk for vasculopathy in adults, elevated ADMA concentrations also have been found in healthy young children. Patients with diabetes mellitus type 1 (DM1) are at risk for vasculopathy, and because the function of ADMA in the development of vascular symptoms is incompletely understood, we investigated ADMA concentrations in pediatric patients with DM1 compared with healthy age- and sex-matched individuals. STUDY DESIGN: This cross-sectional study included 85 pediatric patients with DM1 and 89 age- and sex-matched healthy controls. RESULTS: ADMA concentrations were significantly lower in the patients with DM1 and were inversely correlated with hemoglobin A1c concentrations. CONCLUSIONS: Besides its vasoprotective function, nitric oxide itself may exert oxidative stress by generating free radicals. In these circumstances, ADMA would protect the system from nitric oxide overproduction and perpetuation of oxidative stress. This theory is supported by the physiologically higher ADMA concentrations in healthy children. Thus, low ADMA concentrations in children with DM1 may be an indicator of impaired protection against oxidative stress.

Prevalence of intentional under- and overdosing of insulin in children and adolescents with type 1 diabetes.

OBJECTIVE: The aim of this study was to evaluate the prevalence of insulin under- and overdosing in paediatric patients. RESEARCH DESIGN AND METHODS: Cross-sectional study including 241 patients (age 14.0 + 2.7 yr, 42.5% males) with type 1 diabetes from 21 diabetic outpatient clinics. Haemoglobin A1c (HbA1c), height, and weight were available from clinical records. Patients were interviewed with the Diabetes Self-Management Profile (DSMP) interview. T test, U test, and chi-squared test were used for comparison. RESULTS: On the basis of the DSMP, 103 (42.7%) patients (group A) showed adherence to the therapeutic insulin regimen, while 71 (29.5%) patients (group B) confessed intentional over and/or under-dosing of insulin. Sixty-seven (27.8%) adolescents (group C) reported management problems leading to unintended inappropriate insulin dosages. In group B, 55 (22.8%) injected higher insulin doses and 58 (24.1%) omitted insulin. Patients of group B compared to group A were older 15.0 (±2.5) vs. 14.0 (±2.5) yr (p < 0.01), older at onset 9.5 (±3.6) vs. 8.3 (±3.8) yr (p = 0.05), were more often girls (69 vs. 45.6%), had a higher actual HbA1c (8.7 ± 1.7 vs. 7.8 ± 1.2%), and a higher average HbA1c in the previous year (8.3 ± 1.6 vs. 7.9 ± 1.2%) (p < 0.01). No significant differences could be found between group A and group C. CONCLUSION: Intentional overdosing of insulin is almost as prevalent in children and adolescents as insulin omission. Females are more at risk.

Type 1 diabetes and epilepsy: efficacy and safety of the ketogenic diet.

Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD.

Incidence and time trend of type 1 and type 2 diabetes in Austrian children 1999-2007.

OBJECTIVE: To analyze the time trend of the nationwide incidence of type 2 diabetes in children and adolescents < or = 15 years of age compared with type 1 diabetes between 1999 and 2007 in Austria. STUDY DESIGN: In a prospective, population-based incidence study, all newly diagnosed patients with diabetes < or = 15 years of age were registered by the Austrian Diabetes Incidence Study Group. The Diabetes type was classified on the basis of clinical and laboratory findings according to ADA criteria. Time trends were estimated by linear regression models. RESULTS: During the observation period, 1881 patients with type 1 diabetes and 34 patients with type 2 diabetes could be identified. Sixty-two percent of patients with type 2 diabetes were female, 56% had a positive family history for type 2 diabetes, and 74% presented with diabetes-specific symptoms. The incidence of type 1 diabetes in Austria increased from 12.0 to 18.4/100,000 (P < .001) and the incidence of type 2 diabetes remained stable below 0.6/100 000 (P = .706). CONCLUSIONS: The incidence of type 2 diabetes in Austrian children is 10-fold lower than reported in other regions and did not increase over the last 8 years. During the same time period, a significant rise in the incidence of type 1 diabetes was observed.

Dermatological side effects and complications of continuous subcutaneous insulin infusion in preschool-age and school-age children.

OBJECTIVE: The objective of this study was to evaluate whether very young children develop more dermatological complications during insulin pump treatment compared with school children. STUDY DESIGN: Cross-sectional study in 78 consecutive children using insulin pump treatment >4 months. RESULTS: Children in group A [n = 40, 28 males (M) and 12 females (F)] were 2.3 +/- 1.3 yr (+/-SD) and those in group B (n = 38, 13 M and 25 F) were 11.0 +/- 2.9 yr old at the start of continuous subcutaneous insulin infusion (CSII). The mean duration of CSII was similar in both groups (23.6 +/- 16.5 months in group A and 21.8 +/- 16.1 in group B). The most common dermatological complications were scars <3 mm (50% in group A vs. 71% in group B, p < 0.05) and lipohypertrophic areas at the insertion sites (45% in group vs. 47% in group B). Local abscesses and blisters were rare findings in both groups (7.5-12%), none leading to interruption or stop of CSII. CONCLUSIONS: Dermatological side effects during CSII are not more frequent or severe in very young diabetic children compared with diabetic children in school age.

Perinatal risk factors for early childhood onset type 1 diabetes in Austria - a population-based study (1989-2005).

BACKGROUND: To investigate the rapid increase in incidence of type 1 diabetes mellitus (T1DM) in children <5 yr in Austria. METHODS: Data of children born between 1989 and 2005 (n = 444) from the T1DM children incidence registry were linked with birth certificates (n = 1 407 829). RESULTS: Age of mother, level of education, birth weight, birth length, body mass index, and APGAR score at 10 min were not significant. Boys have about 25% higher risk than girls [hazard ratio = 0.75, 95% confidence interval (CI): 0.62-0.91]. The risk of developing diabetes increases over time significantly (1989-1991 vs. 2001-2005, hazard ratio = 2.86, 95% CI: 2.07-3.94). The linear effect of parity is borderline significant (p = 0.045), with lower risks for second and later born siblings. Marital status is significant [hazard ratio = 0.73, 95% CI: 0.57-0.90)]. Native-born children exhibit twice as high risk as non-native children (hazard ratio = 0.51, 95% CI: 0.37-0.71). Birth weight shows a positive but not significant effect on risk of T1DM. CONCLUSIONS: In this very young and rapidly increasing cohort of diabetic children <5 yr of age, no association with birth weight but with year of birth, gestational age, nationality and parity could be observed.

Long-term follow-up of patients with congenital hyperinsulinism in Austria.

AIM: To assess the neurological and clinical long-term outcome of patients diagnosed with congenital hyperinsulinism (CHI) in Austria. PATIENTS AND METHODS: Fourteen patients diagnosed with CHI (1978-2000) were investigated retrospectively by reviewing hospital records. Thirteen of them were evaluated with either a questionnaire or clinical, neurological and biochemical investigations (age at evaluation 4.2-25.5 years) in a follow-up study in the year 2004. RESULTS: Fifty percent of the patients needed a pancreatectomy. The prevalence of mental retardation was 31%, of epilepsy 15% and of pancreatic insufficiency 14%. None of our patients had developed diabetes mellitus. Additionally the prevalence of obesity was 43% in patients after pancreatectomy. Sixty-nine percent of the patients had no further treatment at the time of follow-up. CONCLUSION: Despite early diagnosis and intensive treatment, 31% of the patients presented with mental retardation.

Small area variation in childhood diabetes mellitus in Austria: links to population density, 1989 to 1999.

We analyzed the associations of environmental factors with the regional distribution of Type 1 diabetes mellitus in Austria. All newly diagnosed cases (n=1449) from 1989 to 1999 were allocated to districts using the postal code. Nitrate content of the water was measured by the Austrian Federal Environmental Agency. Data on infant mortality, population density, and percentage of employment by industry were derived from Statistics Austria. An inverse effect was seen between the proportion of children younger than 15 years of age and the risk ratio (P<.01). Infant mortality, population density, and percentage of persons with employment in industry were not of significant influence. The mean nitrate level was positively associated (P=.07). In regions with a higher percentage of children younger than 15 years of age, fewer children developed diabetes, which is in agreement with the observation that early social mixing is a protective factor. Nitrate levels may have a confounding effect.

[CGM-continuous glucose monitoring - statement of the Austrian Diabetes Association]. / Positionspapier des Insulinpumpenausschusses der OEDG zur kontinuierlichen Glukosemessung (CGM - Continuous Glucose Monitoring).

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes mellitus, based on current evidence.

Steep increase of incidence of childhood diabetes since 1999 in Austria. Time trend analysis 1979-2005. A nationwide study.

In a prospective population-based incidence study all newly diagnosed type 1 diabetic patients 0-<15 years of age were registered by the Austrian Diabetes Incidence Study Group. The nationwide incidence of type 1 diabetes between 2000-2005 was compared with the previously published incidence rates. Long-term trends as well as seasonal trends were estimated by Poisson regression models. A total of 3,599 incident cases (1,908 boys; 1,691 girls) were identified. Case ascertainment was >92%. The overall incidence rate doubled from 7.3 (95% CI; 6.8-7.9)/100,000 in the period 1979-84 to 14.6 (95% CI, 13.7-15.4)/100,000 in the time period 2000-2005. A significant increase during the observation period of 26 years could be demonstrated in all age groups and both sexes (p<0.01), with the steepest increment during the last 5 years. Until 1994 the incidence rate in children 0-<5 years was rather stable, but afterwards increased dramatically with 9.2% (95% CI, 5.2-13.4) annually. Despite this steep increase in time trend, we did not observe a seasonal variation in this age group (0-<5) in contrast to significant seasonal variations in the groups 5-<10 and 10-<15 years of age. Over the past 26 years incidence of type 1 diabetes in childhood increased clearly in Austria. The steepest rise was observed in the last 5 years and in the younger age groups.

Recent trend in overweight and obesity in male adolescents in Austria: a population-based study.

OBJECTIVE: The aim of the study was to provide current estimates of the prevalence of overweight and obesity in young Austrian men and to determine both the trend over the study period and regional differences. METHOD: Data extracted from the database containing the nation-wide compulsory conscription health examinations were analysed. Four cohorts of 18-year-old males (1986-1990: n=252,799; 1991-1995: n=209,266; 1996-2000: n=208,427; 2001-2005: n=209,168) were investigated. Measurements of height and weight were taken and, and body mass index (BMI) was calculated. Overweight was defined as a BMI >or=25.00 kg//m2 and obesity as a BMI >or=30.00 kg//m2. Information on place of residence of the young men was also collected. The t-test and Cochran-Armitage test were used for statistical analysis. RESULTS: During the study period, the prevalence of overweight among the study population increased from 12.9 to 15.5%, while that of obesity increased from 2.5 to 5.8%. A significant regional trend was found, with the highest proportion of overweight and obesity occurring among young male residents of the eastern part of Austria (p<0.001). Mean BMI was 22.38+/-3.05 kg/m2 in 1986-1990, increasing significantly (p<0.001) during the study period to 22.89+/-3.88 kg/m2. Overweight and obesity increased remarkably in young males in Austria between 1986 and 2005. The prevalence of obesity doubled during the whole study period. CONCLUSION: Even in a small country as Austria, significant regional differences with respect to overweight and obesity can be found. Although limited to just one gender and a single age group, data from the nation-wide compulsory conscription health examinations could be a useful tool for public health monitoring.

Telemedical support to improve glycemic control in adolescents with type 1 diabetes mellitus.

INTRODUCTION: In this paper, we evaluated the feasibility of a telemedical (TM) support program and its effect on glycemic control in adolescents with type 1 diabetes mellitus (T1DM). Thirty-six adolescents (m=20, median age at the start of the study: 15.3 years (range: 10.7-19.3 years), median age at diagnosis: 9.3 years (2.1-13.8 years), median duration of disease: 6.4 years (1.0-12.8 years), HbA1c>8%, all on intensified insulin therapy) were randomized in a crossover trial over 6 months (3 months with TM, 3 months with conventional support and paper diary (PD)). During the TM phase, the patients sent their data (date, time, blood glucose, carbohydrate intake, insulin dosage) via mobile phone, at least daily, to our server and diabetologists sent back their advice via short message service (SMS) once a week. RESULTS: Glycemic control improved during the TM phase, while it deteriorated during the PD phase: TM-PD group HbA1c (%, median (range)): 9.05 (8-11.3) (at 0 months), 8.9 (6.9-11.3) (at 3 months), and 9.2 (7.4-12.6) (at 6 months), and PD-TM group: 8.9 (8.3-11.6), 9.9 (8.1-11), and 8.85 (7.3-11.7) (p<0.05). Patients rated the TM support program to be a good idea. Technical problems with General Packet Radio Service (GPRS) data transmission led to data loss and decreased patient satisfaction. CONCLUSION: Our telemedical support program, VIE-DIAB, proved to be feasible in adolescents and helped to improve glycemic control.

Screening detected celiac disease in children with type 1 diabetes mellitus: effect on the clinical course (a case control study).

OBJECTIVE: To investigate clinical and metabolic characteristics of diabetic children with screening detected celiac disease in a multicenter case-control study. CASES: 98 diabetic patients were diagnosed as having silent celiac disease by screening with endomysial antibodies and subsequent biopsy. CONTROLS: two controls in the same center were chosen, (stratified by age and age-at-diabetes onset) who were negative for endomysial antibodies (n = 195). Height, weight, HbA1c, insulin dosage and acute complications were documented for at least 1 year of follow up. RESULTS: Mean age of diabetes manifestation was 6.5 +/- 4.1 years and diagnosis of celiac disease was made at 10.0 +/- 5.4 years. Biopsy showed total or subtotal mucosal atrophy in 74 patients. The mean observation period after the diagnosis of celiac disease was 3.3 +/- 1.9 years. Mean HbA1c levels were similar between cases and controls (8.63% +/- 1.45% versus 8.50% +/- 1.39%; P = 0.35). There was also no difference in the frequency of severe hypoglycemia, ketoacidosis and the applied insulin dosage (P = 0.45). Body mass index-standard deviation score at celiac disease diagnosis (0.57 +/- 1.24 versus 0.52 +/- 1.07) and height-standard deviation score (0.14 +/- 1.13 versus 0.30 +/- 0.95) did not differ between cases and controls. After diagnosis of celiac disease, weight gain was diminished in boys with celiac disease compared with their controls (P < 0.05). Female cases also had a lower body mass index than female controls (P = 0.067). CONCLUSION: In a cohort of diabetic children, silent celiac disease had no obvious effect on metabolic control but negatively influenced weight gain.

Regional distribution of risk for childhood diabetes in Austria and possible association with body mass index.

UNLABELLED: This study was performed to investigate whether the body mass index (BMI) of diabetic children at manifestation is related to the non-random risk distribution in Austria and whether there is an association with the BMI of the background population. All newly diagnosed cases aged <15 years (n=1644) from 1989 to 2000 were allocated to districts using the postal code. BMI at the time of diagnosis was derived from the Austrian incidence data sheet in 99.3% of the registered cases. Data on BMI of the whole population >14 years of age for the year 1991 and birth weight for the years 1989-1999 were derived from Statistics Austria. Linear regression as well as ecological regression (Poisson) models with correction for non-linearity were used. BMI at diabetes manifestation was positively associated with year of diagnosis (P<0.05) and the age at diagnosis (P<0.01). An increase in BMI when moving from West to East (P<0.01) and a higher BMI at diagnosis in boys than girls (P<0.01) was observed. The ecological regression model showed a positive significant association of BMI in newborns and a positive trend of BMI in the background population with incidence rates. CONCLUSION: our data support the hypothesis that obesity may be a risk factor not only for type 2 but for type 1 in children acting as an accelerator for the clinical manifestation.

Coeliac disease in children and adolescents with type 1 diabetes mellitus: to screen or not, to treat or not?

Coeliac disease is more prevalent in individuals with type 1 diabetes mellitus than in the normal population. It often presents in an atypical or silent form. Specific autoantibodies are found in almost all cases. Untreated coeliac disease may be associated with long-term health risks, so screening and early treatment with a gluten-free diet seem to be justified. However, extended follow-up is needed to document the clinical benefits of screening and treatment in diabetic patients.

Type 2 diabetes mellitus is rare but not absent in children under 15 years of age in Austria.

UNLABELLED: Until recently, most children with diabetes mellitus had type 1 diabetes (T1DM). The prevalence of type 2 diabetes (T2DM) is on the rise in North America, especially in risk populations such as the American Indians. Few epidemiological data on the incidence of the disease exist in Europe. In a prospective population-based epidemiological study, all newly diagnosed cases of diabetes mellitus in patients under 15 years of age were registered nation-wide in Austria between 1999 and 2001. Differential diagnosis (according to the American Diabetes Association diagnostic criteria) was based on clinical case definition. During the 3 years of the study period, 529 cases of DM <15 years were documented, of which 510 were clinically assigned to T1DM (271 boys, 239 girls) resulting in an incidence rate of 12.4/100,000. In the same network, eight cases were diagnosed as T2DM (one boy, seven girls) and two cases with an atypical form of T2DM (two girls). The age of onset of T2DM was 12-15 years and all patients were overweight (body mass index >90th percentile). The calculated incidence for T2DM <15 years in Austria was 0.25/100,000. CONCLUSION: at present, type 2 diabetes mellitus is rare but exists in children aged under 15 years in Austria. Follow-up of this registration will help to describe the secular trend.

Growth data in large series of 587 children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: Discordant data were found in recent growth studies in children with type-1 diabetes mellitus. This study focuses on growth data and final height in the largest cohort of diabetic children studied so far. METHODS: 7598 growth data collected in a longitudinal/cross sectional way between 1971 and 1996 in 587 diabetic subjects (317 males, 270 females) were available for analysis of height and BMI, together with 3889 HbA1c measurements. Final height data were correlated with target height in 123 subjects. The individual growth and BMI linear regression curve of each patient was compared to growth standards and correlated with HbA1c. RESULTS: Children of both sexes were taller at the first observation (males, SDS 0.15 +/- 1.10, mean +/- SD, P=0.02, females, SDS 0.74 +/- 1.46, P<0.001) and tended to lose height afterwards (males, P<0.001, females, n.s.). Males reached a final height of 176.5 cm (n=62, target height 176.8, n.s.) and females 167.0 cm (n=61, target height 165.6, n.s.). Children of both sexes had a higher than normal BMI at first observation (males, SDS 0.32 +/- 1.31, P<0.001, females, SDS 0.10 +/- 0.52, P=0.02). Females but not males gained weight over-proportionally afterwards. HbA1c did not predict any of the variables. CONCLUSION: Diabetic children are taller close to the diabetes onset, which may be due to the synchronization of onset of diabetic symptoms with the mid-childhood growth spurt or the pubertal growth spurt accompanied by elevated growth hormone and/or androgen levels and increased insulin resistance. The subsequent growth deceleration may represent a physiological lag-down growth. This concept is supported by normal adult heights following growth deceleration.