Fluctuations in GAD65 antibodies after clinical diagnosis of IDDM in young children

in Diabetes Care (1997), 20(4), 642-644

OBJECTIVE - To investigate whether the presence of GAD antibodies at onset of IDDM correlates to a more aggressive rate of β-cell destruction after clinical onset. RESEARCH DESIGN AND METHODS - We studied ... [more ▼]

OBJECTIVE - To investigate whether the presence of GAD antibodies at onset of IDDM correlates to a more aggressive rate of β-cell destruction after clinical onset. RESEARCH DESIGN AND METHODS - We studied GAD antibodies at onset of disease, after 1 year, and after 6 years in 33 consecutively referred children (mean age 8.08, range 1.7-16.3). In a subset of 11 patients, GAD antibodies were studied very frequently. The correlation between GAD antibodies and clinical parameters, including glycosylated hemoglobin, residual insulin secretion, and insulin dosage, was evaluated. RESULTS - GAD antibody titers were highly variable. Four patients became GAD antibody positive weeks to years after clinical onset. Other patients switched between testing positive and negative for GAD antibodies shortly after clinical onset. No correlation was found between the presence of GAD antibodies and the rate of β-cell destruction, but patients with high GAD antibody indexes at onset had significantly higher glycosylated hemoglobin levels. CONCLUSIONS - GAD antibodies at clinical onset do not predict the rate of β-cell destruction in young children with newly diagnosed IDDM. The highly variable GAD antibody levels suggest variation of the autoimmune process. [less ▲]

Psychological impact of continuous subcutaneous insulin infusion pump therapy in non-selected newly diagnosed insulin dependent (type 1) diabetic children: Evaluation after two years of therapy [IMPACT PSYCHOLOGIQUE D'UN TRAITEMENT PAR PERFUSION SOUS-CUTANEE CONTINUE D'INSULINE DES LE DIAGNOSTIC CHEZ LES ENFANTS DIABETIQUES NON SELECTIONNES: EVALUATIONS APRES DEUX AND DE TRAITEMENT]

in Diabete et Metabolisme (1990), 16(4), 273-277

Thirty type 1 (insulin dependent) diabetic children were treated from diagnosis onwards in a random order (using a table of random permutations) with either continous subcutaneous insulin infusion pump ... [more ▼]

Thirty type 1 (insulin dependent) diabetic children were treated from diagnosis onwards in a random order (using a table of random permutations) with either continous subcutaneous insulin infusion pump therapy (CSII), or with conventional injection therapy (CT). After two years of therapy psychosocial measurements were obtained of fifteen CSII children (8 boys, 7 girls; mean age: 12+/-4 years) and thirteen CT children (6 boys, 7 girls; mean age: 10+/-4 years) and their parents. Two families of the CT group refused to participate. The examination consisted of six tests (for the children: junior dutch personality test, WISC-R intelligence test, family relation test, diabetes questionnaire; for the parents: family interaction scale and assessment of acceptance scale). Parents (and pediatricians) rated CSII children higher on compliance and better on metabolic control. Acceptance of diabetes, physical and psychological condition was rated equally by parents and doctors. Except for the diabetes questionnaire, the children of the two groups scored not significantly different. The CSII group expressed significantly less physical complaints and physical restrictions. CSII children showed a tendency to score higher on recalcitrance compared with CT children. How adequate this coping of CSII children may be, is discussed. [less ▲]

Insulin antibodies in diabetic children before treatment: A marker for islet B-cell destruction?

in Diabetic Medicine: A Journal of the British Diabetic Association (1988), 5(5), 441-443

Insulin antibodies were measured in the sera of 28 newly diagnosed diabetic children (age 8.0 ± 4.0 (±SD) years) prior to insulin therapy and after 3, 6, 9, and 12 months. The levels at diagnosis and ... [more ▼]

Insulin antibodies were measured in the sera of 28 newly diagnosed diabetic children (age 8.0 ± 4.0 (±SD) years) prior to insulin therapy and after 3, 6, 9, and 12 months. The levels at diagnosis and after 12 months were compared to endogenous insulin production at onset and after 12 to 14 months. Endogenous insulin production was evaluated through the measurement of 24-h urinary C-peptide excretion, fasting plasma C-peptide levels and plasma C-peptide levels after glucagon stimulation. Insulin antibodies were detected in 29% of the patients (8 out of 28). In all but one patient antibodies binding porcine and human insulin were detected. No relationship was found between the presence of antibodies binding human or porcine insulin at diagnosis and age. After 1 year 27 out of 28 patients presented insulin antibodies. No relationship was found between the presence of insulin antibodies before therapy and 1 year after therapy. Insulin antibodies prior to diagnosis showed no relationship with the urinary C-peptide excretion at diagnosis (with antibodies 67 ± 27%, without antibodies 76 ± 11%). However, after 1 year significantly lower urinary C-peptide excretions were found in patients with insulin antibodies prior to therapy (with antibodies, 17 ± 7%, without antibodies, 31 ± 5%, p < 0.02). Peak plasma C-peptide levels after 1 year were possibly lower in patients with insulin antibodies before treatment (with antibodies 0.17 ± 0.06 nmol/l, without antibodies 0.26 ± 0.04 nmol/l, p < 0.1). Fasting C-peptide levels did not differ significantly between the two groups after 1 year of therapy (with antibodies 0.11 ± 0.03 nmol/l, without antibodies 0.14 ± 0.02 nmol/l). Thus, insulin auto-antibodies may be a marker for islet B-cell destruction in Type 1 diabetes. [less ▲]

Antibodies to a 64,000 M(r) human islet cell antigen precede the clinical onset of insulin-dependent diabetes

in Journal of Clinical Investigation (1987), 79(3), 926-934

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (M(r)) 64,000. Since IDDM seems to develop ... [more ▼]

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (M(r)) 64,000. Since IDDM seems to develop after a prodromal period of β-cell autoimmunity,, this study has examined whether 64,000 M(r) antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered β-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 M(r) membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 M(r) immunoreactivity, at a time where a commencement of a decline in β-cell function was detected. 64,000 M(r) antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 M(r) antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the M(r) 64,000 human islet protein are an early marker of β-cell autoimmunity and may be useful to predict a later development of IDDM. [less ▲]

Overnight metabolic profiles in very young insulin-dependent diabetic children

in European Journal of Pediatrics (1986), 145(1-2), 73-76

The magnitude of the disturbance of metabolic control in diabetes mellitus in very young children has been recognised, but seldom studied. Limitations to studies are set by the difficulty of obtaining ... [more ▼]

The magnitude of the disturbance of metabolic control in diabetes mellitus in very young children has been recognised, but seldom studied. Limitations to studies are set by the difficulty of obtaining control data and until recently the lack of alternative therapies. Recently "mini" pumps for continuous subcutaneous insulin delivery have become available and may offer an alternative therapeutic possibility. The present investigation has been undertaken to collect overnight metabolic data of very young diabetic children (<6 years) controlled by standard injection therapy. During one admission to hospital frequent blood samples were collected for free insulin, glucose, alanine, lactate, glycerol and 3-hydroxybutyrate determinations. In all children (n=9) the profiles showed a steep rise in glucose from 04.30h (6.2±1.3 mmol/l) to 09.30h (17.8±2.4 mmol/l) (the so-called "dawn-phenomenon"). The nature of the changes in the intermediary metabolites suggested that rise in blood glucose was caused by insufficient insulin. We have attempted to explore the time relationship between the overnight drop in free insulin levels and the rises in blood glucose by a distribution-free statistical analysis, correlating successive changes in time between the two profiles. The analysis suggested a delay of 2-6 h between free insulin levels and their effects. In conclusion: a clear "dawn phenomenon" is seen in very young diabetic children, and contributes to their poor glycaemic control. More stable and higher insulin concentrations in the early morning, obtained perhaps by continuous subcutaneous insulin infusion, might ameliorate the overall glycaemic control in the very young diabetic child. © 1986 Springer-Verlag. [less ▲]