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  • 1
    ISSN: 1432-0428
    Keywords: Prediction ; Type 1 (insulin-dependent) diabetes ; autoimmunity ; autoantibodies ; prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetic determination as well as prospective analysis of islet cell autoantibodies and autoantibodies to insulin were conducted in a population of 479 first degree relatives of 174 Type 1 (insulin-dependent) diabetic patients. Analysis of HLA haplotypes within families illustrated the high frequency of DR3 and DR4 alleles with preferential transmission from parent to both affected and unaffected offspring. DR4 was preferentially associated with DQw3.2 (TA10−) in 60/73 (82.2%) patients and 101/127 (79.5%) relatives. Relatives have been followed for a period of 800 subject-years. Twenty-two out of 430 relatives (5.1%) were found islet cell antibodies (ICA-IgG) positive. Seven sera with low titres became negative 6 months later at two different determinations. Fifteen sera ICA-IgG and ICA-protein A positive with high titres remained positive thereafter. Half of the ICA positive relatives were also found insulin autoantibodies (IAA) positive. All but 3 ICA negative relatives did not have IAA in their sera. Analysis of IAA specificity with competition experiments indicated that most antibodies recognised epitopes shared between human and pork insulins while four were specific for human insulin determinants. Analysis of class I and class II HLA antigen distribution indicated no particular allelic restriction in antibody positive individuals. Metabolic status of antibody positive relatives was determined with oral and intravenous charge of glucose. Two haplo-identical DR3-DQw2 brothers became diabetic during the study. One child and one mother both with DR4-DQw3.2 became intolerant to glucose. Each of these relatives had high titre ICA prior to metabolic deterioration. Taken together, these data indicated that ICA and IAA may be present in first degree relatives of diabetic patients. Individualisation of markers of the ongoing autoimmune process and accurate evaluation of the residual B-cell mass are necessary steps before further immune interventions in the early phases of the disease.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Dawn phenomenon ; Type 1 (insulin-dependent) diabetes ; adolescent ; growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to reassess the role of growth hormone in the dawn phenomenon, we studied eight C-peptide negative diabetic adolescents, who are likely to exhibit important nocturnal growth hormone surges. The insulin infusion rate necessary to maintain euglycaemia was predetermined in each patient from 22.00 hours to 01.00 hours, and then kept constant until 08.00 hours resulting in stable free insulin levels. Blood glucose rose from 4.3±0.7 mmol/l at 01.00 hours to 7.1±1.1 mmol/l at 08.00 hours (p〈0.01) secondary to an increased hepatic glucose production. All the subjects presented an important growth hormone secretion, ranging from 20 to 66 ng/ml (peak values) and from 3619 to 8621 ng·min· ml−1 (areas under the curve). The insulin infusion rate selected for each patient was positively correlated with the nocturnal growth hormone secretion (area under the curve) (r=0.87, p〈0.01). On the other hand, there was no relationship between the nocturnal growth hormone secretion and the magnitude of the early morning blood glucose rise (r=−0.48, p〉0.2). We conclude that, in Type 1 (insulin-dependent) diabetic adolescents, the dawn phenomenon exists but is moderate despite important growth hormone surges; the nocturnal growth hormone secretion influences the nocturnal insulin requirements but not the dawn phenomenon itself, if insulinisation is adequate.
    Type of Medium: Electronic Resource
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