Letter: Propranolol in treatment of migraine in children.
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Biomedical subjects
J Ludvigsson
Publications and source records attributed to J Ludvigsson.
[Phimosis in 19-year-olds].
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[Is the hospital environment hostile to children?].
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Treatment with antioxidants at onset of type 1 diabetes in children: a randomized, double-blind placebo-controlled study.
BACKGROUND: In recent years different types of immune interventions have been tried at the onset of type 1 diabetes. Although some have shown effects, none have proven to be sufficiently effective to justify the inherent risks and side effects. Antioxidants have no or minimal side effects. If they can protect the beta cells against free oxygen radicals during the inflammatory process this would be a safe and cheap intervention. To evaluate this hypothesis a combination of various antioxidative agents was employed in a double-blind randomized study. METHODS: The study group comprised 46 children aged 1-17 years at diagnosis. They were followed for 3 years: 2 years whilst taking the tablets and 1 year of follow-up. Twenty-four children were randomly allocated to active treatment with high doses of antioxidants and 22 children to placebo tablets. The tablets were the same size and tasted identical. RESULTS: Twenty patients had for more than 1 month an insulin dose <0.5 U/kg in parallel with a normal HbA(1c) value and stable blood glucose values, but with no difference observed between those with and without active treatment. Nor was any significant difference observed regarding C-peptide values, fasting as well as stimulated. Whilst the antioxidants demonstrated no positive effect, they also had no negative side effects. CONCLUSION: At diagnosis of type 1 diabetes in children, high doses of antioxidative agents have no effect either on the preservation of beta cell function or on metabolic balance.
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Family history in classical juvenile onset diabetes in relation to severity of the disease.
A group of 100 patients with juvenile diabetes, age at onset 1-15 years (7.1 +/- 3.9), was studied with reference to family history of diabetes (FHD), HLA-types, symptoms at onset of diabetes, and occurrence of partial postinitial remission. No significant relations were seen between HLA-types and FHD. Nor was there any correlation between FHD and age at onset of diabetes, severity of th disease at onset, or occurrence of remission. Patients with a dominant type of inheritance were insulin-dependent to the same extent as those with less pronounced or no known FHD. According to previous results, it is concluded that all children and adolescents with a newly diagnosed diabetes should receive insulin treatment immediately to minimize further loss of B-cell function.
Adolescent↗
Abnormal proinsulin/C-peptide ratio in juvenile diabetes.
B-cell function was studied in 20 diabetic children, with an age at onset of diabetes between 1.16 years (8.8 +/- 4.0). Serum samples were taken before the first insulin injection and after 1, 3, 6, 9 and in a few patients after 18 months. At 3, 9, and 18 months the patients were also given a standardized breakfast load. Serum proinsulin, C-peptide, IRI and insulin antibodies (IgG) were determined. At onset 19 patients had measurable C-peptide (0.22 +/- 0.17 pmol/ml; range 0.05-0.58). Proinsulin varied between 0.000-0.25 pmol/ml (0.069 +/- 0.071) and at onset amounted to 31.3 +/- 29.4 (0.100)% of C-peptide as compared to 3.3 +/- 1.1 (1.7-6.6) in non-diabetics. A long partial remission was significantly correlated to a low proinsulin/C-peptide ratio at onset. In patients with low fasting proinsulin and no insulin antibodies, breakfast stimulation was accompanied by an increased proinsulin release at 3 and 9 months. The results suggest that abnormal proinsulin secretion is a feature of the 'B-cell exhaustion' complex in juvenile-onset diabetes.
Adolescent↗
Immunological aspects on IDDM in children.
Diabetes mellitus in childhood is connected to several immunological phenomena which per se do not prove that immunological mechanisms do cause the beta cell destruction, as such mechanisms could be just secondary. However, there is now evidence which strongly supports the autoimmune hypothesis, like the beta-cell destruction in the transplant given from a healthy twin to the diabetic monozygotic co-twin, the effect in newly-diagnosed diabetes of immunosuppression, the passive transfer in experimental animals of an immune process creating diabetes etc. Several facts such as presence of activated T-cells in the insulitis indicate that the cell-mediated immunity is important, while it is still debatable whether humoral factors, and if so which, alone could be responsible for the beta cell destruction. Recently interleukins and other lymphokines have shown to be of great interest as well as the release of free radicals. This knowledge opens new views on the possibility to put an end to or even prevent the beta cell destruction. Rough immunosuppression with cytostatics or cyclosporin has such severe side-effects that such therapy is contra-indicated at least in children. Until more specific therapies are discovered e.g. vaccination with lymphoblasts or blocking the autoantigens with monoclonal antibodies, supportive measures to protect the beta cells may be one practical way.
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Side effects and indwelling times of subcutaneous catheters for insulin injections: a new device for injecting insulin with a minimum of pain in the treatment of insulin-dependent diabetes mellitus.
For 2 months we observed side-effects and indwelling times when using a subcutaneous catheter (Insuflon, Viggo AB, Sweden) for insulin injections. This method is used by approximately 600 children and adolescents with IDDM in Sweden today. 22 children and adolescents aged 4-19 years with a diabetes duration of 4.0 +/- 3.0 (mean +/- SD) years participated. Their HbA1c was 5.8 +/- 1.0%. All used 4-6 dosages of insulin per day. The catheter was placed subcutaneously in the abdominal wall, and replaced by parents when home tests showed increased blood or urine glucose, when the child experienced pain or when skin changes were observed. The 22 patients used 239 catheters with a mean time between changing catheters of 4.8 +/- 2.2 (range 0.5-17) days (= 1147 catheter days). Noted side effects were (% of catheter days): fixation problems, 5.6%; minor infection/irritation (= redness greater than 1 mm), 5.6%; pain, 2.8%; sore skin from plastic wings, 2.4%; itching/dry skin, 2.0%; eczema from band-aid, 1.7%; blocked catheter/injection needle, 1.6%; leakage of insulin, 1.3%, transient lipohypertrophies, 1.1%; hematoma/blood in catheter, 0.8%, and moist skin, 0.3%. No major infections requiring surgical or antibiotic treatment occurred. In conclusion, the use of indwelling insulin catheters seems to be a safe method to lessen the pain of insulin injections with a low frequency of side effects. The long-term metabolic control was not altered in this group of well-controlled children. We therefore find that we can recommend the use of indwelling catheters to children and adolescents who have difficulties with injections because of needle phobia or pain, particularly when using MIT.
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Genetics of insulin-dependent diabetes mellitus in children.
Insulin-dependent diabetes in children is a heritable disease, although it does not fit into any simple genetic model. Research is not facilitated by the lack of knowledge of the different etiological mechanisms and the inability to classify the disease. Human leucocyte antigens (HLAs) coded for in the major histocompatibility complex on the 6th chromosome have given the most important insights into the genetics of diabetes, and these genes probably provide the majority of genetic susceptibility to type-I diabetes. Several facts indicate that there are at least two loci of importance, one associated with HLA B8, DR3 and another with HLA B15, DR4, which probably are usually included in extended haplotypes in linkage disequilibrium. There seems to be a substantial DNA polymorphism and further studies may detect fragments that are even more strongly associated with diabetes than the DR type. A combination of more detailed immunological, perhaps virological or other environmental investigations on diabetic patients and their families, together with the use of specific DNA probes for the HLA region, might reveal the susceptibility genes.
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