[Morning hyperglycemia in children and adolescents with type 1 diabetes and different modes of therapy: an evaluation of the DPV data pool]. / Morgenhyperglykämie bei Kindern und Jugendlichen mit Typ-1-Diabetes bei unterschiedlichen Therapieformen: Eine Auswertung des DPV-Datenpools.

Early morning hyperglycemia is frequent among children and adolescents with type 1 diabetes. Reasons are a dawn phenomenon, a Somogyi phenomenon or a lack of insulin in the morning hours. Only few studies are published regarding incidence and relation to different modes of basal insulin treatment in this population.We analyzed all cases recorded in the DPV register from 1995 to 2010. 5 839 patients from 128 centers with at least 3 blood glucose measurements during the last night of a hospital stay were included.24.2% of patients showed a morning hyperglycemia above 200 mg/dl. 8.6% showed a dawn phenomenon, 7.0 % a lack of insulin and 2.0% a Somogyi phenomenon. A dawn phenomenon was significantly less frequent in patients treated with an insulin pump (1.1%) compared to long acting insulin analogs Glargin and Levemir (5.4%) or NPH insulin (8.2%). Lack of insulin was again less frequent during insulin pump treatment compared to other treatments (1.9% vs. 4.9% vs. 5.3%). Median rise of blood glucose levels was 33.4 mg/dl between midnight and 6 a.m. Mode of basal insulin treatment is an important factor: while treatment with an insulin pump led to a blood glucose fall of 28.5 mg/dl between 3 and 6 a.m., treatment with insulin analog or NPH insulin resulted in a rise of 28.5 or 35.9 mg/dl, respectively.This study shows that insulin pump treatment reduces the frequency of morning hyperglycemia caused by the dawn phenomenon or a lack of insulin.

[Clinical parameters for molecular testing of Maturity Onset Diabetes of the Young (MODY)]. / Molekulargenetische Diagnostik bei Verdacht auf Maturity Onset Diabetes of the Young (MODY): Klinische Parameter zur Entscheidungshilfe.

BACKGROUND: Monogenic forms of diabetes are often diagnosed by chance, due to the variety of clinical presentation and limited experience of the diabetologists with this kind of diabetes. Aim of this study was to evaluate clinical parameters for an efficient screening. METHODS: Clinical parameters were: negative diabetes-specific antibodies at onset of diabetes, positive family history of diabetes, and low to moderate insulin requirements after one year of diabetes treatment. Molecular testing was performed through sequencing of the programming regions of HNF-4alpha (MODY 1), glucokinase (MODY 2) and HNF-1alpha/TCF1 (MODY 3) and in one patient the HNF-1beta/TCF2 region (MODY 5). 39 of 292 patients treated with insulin were negative for GADA and IA2A, and 8 (20.5%) patients fulfilled both other criteria. RESULTS: Positive molecular results were found in five (63%) patients (two with MODY 2, two with MODY 3, one with MODY 5). At diabetes onset, the mean age of the 5 patients with MODY was 10.6 ± 5.3 yrs (range 2.6-15 yrs), HbA(1c) was 8.4 ± 3.1 % (6.5-13.9%), mean diabetes duration until diagnosis of MODY was 3.3 ± 3.6 yrs (0.8-9.6 yrs) with insulin requirements of 0.44 ± 0.17 U/kg/d (0.2-0.6 U/kg/d). Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment. CONCLUSION: In patients with negative diabetes-specific antibodies at onset of diabetes, with a positive family history, and low to moderate insulin needs a genetic screening for MODY is indicated. Watchful consideration of these clinical parameters may lead to an early genetic testing, and to an adequate treatment.

[Clinical experiences with the substitution of biosynthetic human insulin in children and adolescents with type I diabetes]. / Klinische Erfahrungen mit der Substitution biosynthetischen Humaninsulins bei Kindern und Jugendlichen mit Typ-I-Diabetes.

The therapeutic efficiacy of biosynthetic human insulin (BHI) is compared to that of porcine insulin into groups of 10 children each with so far untreated type I diabetes. No significant difference between the two groups could be demonstrated throughout the first months of treatment: both the initial substitution dose, and the rate of partial remission were similar. However, the regimen of the BHI treated patients had to be changed to two injections a day earlier, since BHI given subcutaneously results in a faster and shorter lasting response than porcine insulin. Thus, after 9 and 12 months of treatment a higher BHI dose than porcine insulin dose had to be given. Thirty children pretreated with regular and NPH porcine insulin, who were in the post remission period, were transferred to BHI. First, the needed dose of insulin was significantly reduced. Two to three months later, however, the need in insulin increased, so that after 9 and 12 months the original dose had to be given again. The relationship between morning (2/3) and evening (1/3) dose was constant and in the morning as well as in the evening the ratio between regular and NPH-BHI was 40%/60%. There was no significant improvement or deterioration after replacing porcine by human insulin, since both insulins have the same metabolic effects.

Insulin binding to erythrocytes before and after changing from porcine to biosynthetic human insulin in children with type-I diabetes.

The binding of [125I]insulin to isolated erythrocytes from diabetic children (n = 27) before (group a) as well as one and five months after changing from porcine to biosynthetic human insulin (groups b and c) was investigated. An analysis of variance of the binding parameters, determined by a nonlinear regression procedure, yielded statistically significant differences between the receptor affinities Ka as well as between the receptor concentrations Xo of the groups a and b, a and c and b and c. (formula: see text). The results suggest that the change from porcine insulin to biosynthetic human insulin induces a short-term as well as long-term increase in the affinity, and a decrease in the concentration of the erythrocyte insulin receptors.

Insulin binding to erythrocytes in children with type-I diabetes mellitus.

Specific binding of [125I]insulin to isolated erythrocytes was investigated in four groups of children (A) Healthy children under 10 years of age (n = 20) (B) Healthy children over 10 years of age (n = 13) (C) Diabetic children under 10 years of age (n = 12) (D) Diabetic children over 10 years of age (n = 63). In addition, all diabetic children (n = 75) were subdivided into four groups according to the duration of diabetes. (E) less than 2 years, (F) 2--4 years, (G) 4--6 years, and (H) greater than 6 years. By means of a nonlinear regression analysis for the extraction of binding parameters (assuming a single receptor class model with independent receptor sites) and methods of variance analysis, statistically significant differences were observed for the receptor affinities Ka (10(8) l/mol) and the receptor concentrations X0 (nmol/l) between groups A and C, B and D, C and D, but not between A and B. The affinities of groups C and D were found to be higher than the corresponding values of groups A and B, whereas the receptor concentrations exhibited an inverse behaviour. A significant increase of the receptor concentration and decrease of the receptor affinity depending on the duration of diabetes could only be proved to exist during the first 2 years of the disease.