Maria Fritsch

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison

Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries.

Predictors of diabetic ketoacidosis in children and adolescents with type 1 diabetes. Experience from a large multicentre database.

Fritsch M, Rosenbauer J, Schober E, Neu A, Placzek K, Holl RW. Predictors of diabetic ketoacidosis in children and adolescents with type 1 diabetes. Experience from a large multicentre database.

Growth in Children and Adolescents with Type 1 Diabetes

OBJECTIVE To investigate the effect of type 1 diabetes on growth and adult height. STUDY DESIGN Data from 22 651 children (10 494 females) with type 1 diabetes documented at onset of the disease from specialized centers in Germany and Austria were analyzed. Patients of non-German and non-Austrian origin and patients with celiac disease were excluded from the analysis. Near-adult height data were available in 1685 patients. RESULTS At the time of diagnosis of type 1 diabetes, the mean age of the 22 651 children was 8.8 ± 4.2 years, with a mean height SDS of 0.22 ± 1.0. The 1685 patients with diabetes onset before age 11 years reached a mean adult height of -0.16 ± 1.0 SDS. Mean adult height was was 167.1 ± 6.2 cm (-0.16 ± 0.97 SDS) in females (n = 846) and 179.6 ± 7.1 cm (-0.17 ± 1.0 SDS) in males (n = 839). Mean duration of diabetes was 9.1 ± 2.6 years, and mean Hemoglobin A1c concentration was 7.9% ± 1.2% (63 ± 10 mmol/mol). In a multivariate regression model, adult height was positively correlated with height at onset of diabetes (P < .0001) and negatively with mean Hemoglobin A1c (P < .0001) and duration of diabetes (P = .0015). CONCLUSION Height at the time of diagnosis of type 1 diabetes is above average. Even with intensive insulin therapy, growth and adult height remain indicators of metabolic diabetes control in the 21st century.

Diabetic Ketoacidosis at Diagnosis in Austrian Children: A Population-Based Analysis, 1989-2011

OBJECTIVE To analyze the effect of a community-based, poster-focused prevention program on the frequency of diabetic ketoacidosis (DKA) at diabetes onset in Austria. STUDY DESIGN All newly diagnosed patients with diabetes ≤ 15 years of age were registered prospectively by the Austrian Diabetes Incidence Study Group. Registered data included initial blood glucose, pH, and ketonuria. DKA was defined as pH < 7.3 and severe DKA as pH < 7.1. Data between 1989 and 2011 were available. In autumn, 2009, a community-based prevention program similar to the Parma Campaign, in which posters were dispensed broadly, was initiated. The frequency of DKA at the onset of diabetes in the years 2005-2009 and 2010-2011 was compared. RESULTS During the study period, 4038 children were registered. A total of 37.2% presented with DKA; 26% had a mild and 11.2% a severe form. The frequency of DKA was negatively associated with age at onset. In the years before the intervention program, 26% had mild DKA compared with 27% after the intervention (not significant). The prevalence of severe DKA in the years before the campaign was 12% compared with 9.5% thereafter (not significant). No significant change in the DKA rate at onset by the prevention program could be found when we compared age groups <5, 5 to <10, and 10 to <15 years, neither for mild nor for severe DKA. CONCLUSION The frequency of DKA in children with newly diagnosed type 1 diabetes in Austria is high and did not change despite the efforts of a community-based information program.

Bariatric surgery in morbidly obese adolescents: long-term follow-up

OBJECTIVE Morbid obesity is an increasingly common disease in the industrialized world and poses a great challenge to the medical community. Many obese adolescents have undergone various conservative treatment methods without adequate success so that a surgical approach became necessary. We report on 18 patients who underwent bariatric surgery as well as a long-term follow-up program. METHODS Eight patients received a laparoscopic adjustable gastric banding (LAGB). Four of these had to undergo a gastric bypass surgery (GByp) as second procedure due to insufficient weight loss. Nine patients primarily received a gastric bypass. RESULTS LAGB: Mean weight loss after 24 months was 20 ± 6.3 kg. Four of the patients showed a regain in weight leading to a mean weight loss of 9 kg compared to initial weight after 53.3 months mean in this group. These patients had to undergo an additional gastric bypass procedure and lost 31 ± 18.3 kg after 18 months. GByp: Mean weight loss in nine patients after gastric bypass (primary procedure) was 31 ± 10.2 kg after 12 months and 36 ± 30.1 kg at the end of the observation time. Sleeve: Initial weight in this patient was 232 kg with a weight loss of 38 kg after 24 months. DISCUSSION AND CONCLUSION It is remarkable that in four of eight patients who underwent LAGB had to undergo a second surgical procedure (GByp). No previous indicator, neither from a psychological nor from a medical point of view, could be detected. More long-term studies including psychological aspects seem to be necessary.

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

Schober E, Wagner G, Berger G, Gerber D, Mengl M, Sonnenstatter S, Barrientos I, Rami B, Karwautz A, Fritsch M, on behalf of the Austrian Diabetic Incidence Study Group. Prevalence of intentional under‐ and overdosing of insulin in children and adolescents with type 1 diabetes.

Microvascular function is impaired in children with morbid obesity

Children’s obesity is a growing problem in Western societies. We hypothesized that morbid obesity (body mass index [BMI] > 99.5th percentile) might affect microvascular function at an early stage. Therefore, we assessed the microvascular function of 41 obese children (13.2 ± 2.8 years, BMI 32.9 ± 6.6) in comparison to 91 healthy controls (12.7 ± 2.1 years, BMI 18.2 ± 2.5) by post-occlusive reactive hyperemia measured by a laser Doppler: baseline perfusion, biological zero (defined as ‘no-flow’ laser Doppler signal during suprasystolic occlusion), peak perfusion (following occlusion), time to peak perfusion and recovery time (time until resuming baseline perfusion) were recorded and compared between both groups. Peak perfusion was higher in children with morbid obesity than in controls (1.67 ± 0.76 AU [arbitrary units] vs 1.26 ± 0.5 AU, p < 0.001). Consecutively, recovery time was longer in children with morbid obesity (118.21 ± 34.64 seconds) than in healthy children (83.18 ± 35.08 seconds, p < 0.001). In conclusion, higher peak perfusion and prolonged recovery time in children with morbid obesity seem to reflect microvascular dysfunction due to an impaired vasoconstrictive ability of precapillary sphincters.

Fibroblast Growth Factor 21 and Fetuin-A in Obese Adolescents With and Without Type 2 Diabetes

CONTEXT Hepatokines such as fetuin-A or fibroblast growth factor 21 (FGF21) are reasonable candidates affecting the pathophysiology of type 2 diabetes mellitus (T2DM). However, studies in humans at the onset of disease are scarce. OBJECTIVE The objective of the study was to compare FGF21 and fetuin-A levels between adolescents with and without T2DM. DESIGN This was a cross-sectional comparison of adolescents with and without T2DM. SETTING The study was conducted at diabetes and obesity treatment centers. PATIENTS Seventy-four predominantly Caucasian adolescents with T2DM aged 12-18 years and 74 body mass index (BMI)-, age-, and gender-matched controls participated in the study. INTERVENTION There were no interventions. MAIN OUTCOME MEASURES FGF21 and fetuin-A and their correlation to age, BMI, glycated hemoglobin, blood pressure, lipids, adiponectin, and leptin were measured. RESULTS Adolescents with T2DM showed significant higher FGF21 serum concentrations compared with obese controls without T2DM [median 277 pg/mL (interquartile range [IQR] 161-586) vs 200 pg/mL (IQR 116-323), respectively, P = .009] and higher fetuin-A serum concentrations (median 0.30 g/L (IQR 0.27-0.33) vs 0.28 g/L (IQR 0.25-0.30), respectively, P = .005). In a multiple linear regression analysis, fetuin-A was positively associated with glycated hemoglobin [β-coefficient 0.005 (95% confidence interval ± 0.004), P = .013], negatively with adiponectin (β-coefficient -0.004 (95% confidence interval ±0.002, P = .006) but not with BMI, age, gender, ethnicity, or leptin. FGF21 was not associated with any parameter in multiple linear regression analysis. CONCLUSIONS Increased FGF21 serum levels in obese adolescents with T2DM compared with obese adolescents without T2DM suggest a FGF21-resistant state in T2DM because FGF21 improves insulin sensitivity. The increase of fetuin-A levels in obese adolescents with T2DM supports the hypothesis that fetuin-A is involved in the pathogenesis of T2DM because this hepatokine leads to insulin resistance.

Cholecalciferol supplementation improves suppressive capacity of regulatory T-cells in young patients with new-onset type 1 diabetes mellitus - A randomized clinical trial.

It is unknown if cholecalciferol is able to modify defects in regulatory T cells (Tregs) in type 1 diabetes (T1D). In this randomized, double-blind, placebo controlled trial 30 young patients with new-onset T1D were assigned to cholecalciferol (70IU/kgbodyweight/day) or placebo for 12months. Tregs were determined by FACS-analysis and functional tests were assessed with ex vivo suppression co-cultures at months 0, 3, 6 and 12. Suppressive capacity of Tregs increased (p<0.001) with cholecalciferol from baseline (-1.59±25.6%) to 3 (30.5±39.4%), 6 (44.6±23.8%) and 12months (37.2±25.0%) and change of suppression capacity from baseline to 12months was significantly higher (p<0.05) with cholecalciferol (22.2±47.2%) than placebo (-16.6±21.1%). Serum calcium and parathormone stayed within normal range. This is the first study, which showed that cholecalciferol improved suppressor function of Tregs in patients with T1D and vitamin D could serve as one possible agent in the development of immunomodulatory combination therapies for T1D.

Comparison of Cystic Fibrosis–Related Diabetes With Type 1 Diabetes Based on a German/Austrian Pediatric Diabetes Registry

OBJECTIVE The prevalence of cystic fibrosis–related diabetes (CFRD) has increased with improved life expectancy of patients. Clinical and care characteristics were compared with type 1 diabetes mellitus (T1DM) in a multicenter analysis of pediatric data. RESEARCH DESIGN AND METHODS Auxological and treatment data from 47,227 patients aged younger than 21 years with CFRD or T1DM in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by multivariable mixed regression modeling. RESULTS Diabetes onset (mean [interquartile range]) occurred later in individuals with CFRD (14.5 [11.8–16.3] years) than in individuals with T1DM (8.5 [4.9–11.8] years), with female preponderance in CFRD (59.1% vs. 47.5%; P < 0.01). CFRD patients had lower BMI standard deviation scores (−0.85 [−1.59 to −0.12] vs. +0.52 [−0.10 to +1.16]; P < 0.01) and lower HbA1c (6.87% vs. 7.97%; P < 0.01). Self-monitoring of blood glucose was more frequent in patients with T1DM (4.5 vs. 3.5; P < 0.01); 72% of CFRD patients received insulin. In insulin-treated patients, insulin dosage adjusted for age, sex, and diabetes duration differed significantly (T1DM: 0.79 IE per kilogram of body weight; CFRD: 0.83 IE per kilogram of body weight). Use of short-acting and long-acting insulin analogs was significantly more frequent in T1DM (47% vs. 39% and 37% vs. 28%; both P < 0.05). Metabolic control in CFRD patients without insulin was better compared with CFRD on insulin (HbA1c: 6.00 vs. 7.12; P < 0.01), but duration of disease was significantly shorter (0.8 years [0.1–2.4] compared with 2.4 years [0.6–4.6]). There was no significant difference for BMI standard deviations scores between CFRD patients with or without insulin treatment. CONCLUSIONS Pediatric patients with CFRD show clear auxological and metabolic differences from those with T1DM, with different treatment choices.