Organ-specific antibodies in young diabetics.
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Biomedical subjects
Publications and source records attributed to H Dorchy.
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The measurement of HbA1 gives an "objective" estimate of the degree of metabolic control of diabetes during the erythrocyte lifespan. 333 assays in 85 young diabetics aged three to twenty-three years showed a mean HbA1 of 10.9 +/- 2.6% (controls: 7.4 +/- 1.4%). HbA1 levels parallel the clinical evaluation of the degree of control. HbA1 concentrations are correlated with the duration of diabetes (r = 0.26; p less than 0.001), triglyceridemia (r = 0.22; p less than 0.001), cholesterolemia (r = 0.26; p less than 0.001) and glycemia (r = 0.50; p less than 0.001). The HbA1 glycemia correlation grows stronger as glycemia increases. This probably reflects the existence of a labile form of HbA1. HbA1 concentrations measured repeatedly over one year were not significantly different in diabetics with and without retinopathy, probably because the study period was too short. Measurement of HbA1 is also of value in diagnosing non-compliance.
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Monoclonal antibodies of the OKT series were used to identify total T lymphocytes (OKT3+) and their helper (OKT4+) and suppressor-cytotoxic (OKT8+) and suppressor-cytotoxic (OKT8+) subsets in 34 insulin-dependent diabetic children and in 39 young healthy controls. The diabetics have a moderate but significant reduction of the proportions of total T lymphocytes at the expense of the T helper subset; the proportion of suppressor-cytotoxic cells are normal. These abnormalities of the lymphocyte subpopulations are not related to the duration of diabetes, the control of the disease nor to the presence of autoimmune phenomena. The latter were found in 51.4% of patients.
The study included 75 young diabetics, having a mean age of 13.7 (+/- 3.4) years, and whose diabetes duration was 5.0 (+/- 3.1) years. All of the subjects were insulin dependent, and none had developed insulin resistance. Injections of either conventional or purified insulin were used. The subjects' diets were "spontaneously balanced", and their physical exercise was similar to non-diabetic school-age children. The 75 diabetics were arbitrarily divided into two groups, A and B, according to their average insulin dose/kg, either less than 1 U/kg or greater than 1 U/kg. Groups A and B were comparable according to their age, age of diabetic onset, degree of diabetic control, frequency of retinal complications, proportion of different insulin types, and concentration of beef or pork insulin antibodies. Insulin antibodies were therefore not responsible for any modification in insulin needs. Insulin needs per kg were very significantly correlated to residual secretion of endogenous insulin (r = -0.34; p less than 0.001). They were equally dependent on the duration of diabetes probably because of the progressive beta cell exhaustion. Insulin needs were also weakly negatively correlated to weight, therefore the heaviest diabetics injected an insulin/kg dose relatively less than the lighter diabetics.
This study concerned 74 diabetic children and adolescents, ages ranging from 3 to 21 years. Duration of the disease ranged from 1 month to 15 years. Blood samples were taken during a 12 month period of observation. 292 immunoreactive C-peptide (CPR) evaluations showed a residual endogeneous secretion of insulin in 57% of cases. CPR and duration of diabetes were negatively correlated (r = -0.35; p less than 0.01); however, even 5 years after onset of the disease, a residual beta-cell activity could be observed. CPR was not related with blood glucose, triglyceride, cholesterol or glycosylated hemoglobin levels. On the other hand, CPR was statistically higher in patients whose diabetes had been well-controlled from the onset of the disease, according to clinical criteria, and in those who did not present with retinopathy: however they were also the patients with the shortest duration of disease.
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The prevalence of islet-cell antibodies and of 10 organ-specific auto-antibodies was determined in 71 diabetic children and adolescents whose mean duration of diabetes was 4 1/2 years. Forty-four p. cent of the patients had autoantibodies; 15% had islet-cell antibodies and 31% had organ specific antibodies. The prevalence of antinuclear, gastric parietal cell and striated muscle antibodies was significantly higher in diabetics than in controls. There was no relationship between prevalence of antibodies and age of the diabetics nor age at the onset of the disease. The frequency of circulating islet-cell antibodies tended to decrease with the duration of diabetes while organ-specific antibodies remained stable. The study failed to demonstrate any correlation between measurable C-peptide and the presence of autoantibodies. Diabetic retinopathy, diagnosed by fluorescein angiography, was not related to the presence of autoantibodies.
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In order to ascertain the first vascular lesions responsible for juvenile diabetic retinopathy, 408 fluorescein angiographies were performed in 114 diabetic children and adolescents whose diabetes became clinically apparent before the age of 14 years. Compared with regular ophthalmoscopy, fluorescein angiography doubles the frequency of the diagnosis of incipient retinopathy. In addition to the classical diabetic lesions, fluorescein leakages are demonstrated in 50% of diabetic eyes with initial retinopathy. They probably reflect early changes in capillary permeability. They appear often before microaneurysms. Duration of diabetes as well as insufficient and poor metabolic control considerably increase the frequency of retinopathy.
The effect of diabetic control upon EEG has seldom been studied. In the present investigation, a significant positive correlation between EEG abnormalities and degree of diabetic control was found, but no definite increase was noted in relation to the duration of diabetes. Eighty per cent of our patients having more than 5 severe hypoglycemic attacks showed evidence of abnormal EEG, suggesting that hypoglycemic coma or convulsions are closely related to EEG abnormalities (minor hypoglycemic episodes had no effect on the EEG). With the sensitive technique of fluorescein angiography, we demonstrated a clear correlation between incipient retinal angiopathy and EEG abnormalities. The factors that most positively relate to pathologic electrocerebral (EEG) activity in diabetic children are frequent and severe hypoglycemic attacks, comas and/or convulsions, and vascular changes in the retina.
Three children with features of the Mauriac syndrome have been studied. Ocular complications, mainly characterized by increased capillary permeability have been demonstrated by fluorescein angiography. A decreased proximal tubular beta 2-microglobulin reabsorption has been found in one patient, and in another one, there was a slowed sensory nerve condition velocity. A liver biopsy, performed in one patient, has shown numerous fat filled cells and intralysosomal lipofuscin storage. No hormonal disturbance, which could explain the growth reardation, has been found. Bad metabolic control of diabetes could be responsible for all the anomalies of Mauriac syndrome.
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