[Detection of subjects at risk of type 1 diabetes. GOFEDI. Groupe Ouest-France pour l'Etude du Diabète Insulino-dépendant]. / Dépistage des sujets à risque de diabète de type 1. GOFEDI. Groupe Ouest-France pour l'Etude du Diabète Insulino-dépendant.

The so-called type 1 (insulin-dependent) diabetes is an autoimmune disease occurring in genetically predisposed subjects. The clinical onset of the disease is preceded by a subclinical period during which insulin-producing cells are progressively destroyed by immunological effectors. This prediabetic phase can be detected by the presence of autoantibodies directed against islet cells and sometimes associated with anti-insulin antibodies in children, and later on by the disappearance of the early insulin secretion peak in response to intravenous glucose. It is at this prediabetic phase that immunomodulators specific to the antipancreas process and devoid of side-effects will be used, when available, and that an early insulin therapy will be instituted.

[Synthetic antithyroid drugs and Basedow's disease or the choice of a therapeutic strategy]. / Antithyroïdiens de synthèse et maladie de Basedow ou le choix d'une stratégie thérapeutique.

We present the conclusions of two prospective studies of patients examined at their first manifestation of Graves' disease and treated with antithyroid drugs (ATD). The purpose of the first study was to investigate the effects of long-term treatment: the patients were given carbimazole in degressive doses without hormone replacement for 18 months, the followed up for 2 to 6 years after drug withdrawal. The second study was designed to determine the effect of treatment duration on the prognosis: the patients were given an ATD according to the same protocol for a duration randomly set at either 6 or 18 months, then seen again 2 years after ATD withdrawal. The results showed that after 18 months of treatment at least 50 percent of the patients could be expected to remain in remission for 6 years. Remissions were less frequent when treatment was shorter (41.7 percent after the 6 month treatment versus 61.8 percent after the 18 month treatment, with a 2 years' follow-up; P less than 0.05). The relapses that occurred came early: 70 percent of them took place within the first post-treatment month. This article also provides evidence of high T3 and/or T4 levels without signs of thyrotoxicosis during the post-treatment clinical course; these exclusively biochemical relapses spontaneously disappeared and may have been expressing epidoses of active thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-cell cytoadherent lymphocytes in some subjects at risk for type 1 (insulin-dependent) diabetes: progression to diabetes within 2 years.

The increased binding in vitro of CD3 CD4 T-lymphocytes from type 1 (insulin-dependent) diabetic patients to beta-cell membrane antigens compared to lymphocytes from control subjects was previously shown to be a marker of cell-mediated immunity, called diabetic rosettes. In the present study diabetic rosettes were detected in some subjects at risk for type 1 diabetes (first degree relatives of type 1 diabetic patients or nondiabetic subjects with previous transient hyperglycaemia). The mean number of lymphocytes adherent to beta-cells (beta-CL) was significantly higher in subjects at risk for type 1 diabetes than in age- and sex-matched control blood bank donors (P less than 10(-6]. This number of beta-CL was higher in type 1 diabetic patients than in subjects at risk (P less than 10(-6], and one-way analysis of variance by rank (Kruskal-Wallis) revealed that the three populations (controls, diabetics, and risk subjects) were different in terms of beta-CL values (P less than 0.001). The percentage of subjects at risk that had a positive test (arbitrarily defined as a beta-CL value higher than the 95th percentile of 228 controls) was 20%. No difference was observed between the two subgroups of subjects at risk in terms of either mean +/- SEM of beta-CL or percentages of individuals with a positive test. These diabetic rosettes were slightly associated with acute insulin response to iv glucose lower than the 5th percentile of controls (immunoreactive insulin at 1 +/- 3 min, 250 pmol/L; by chi 2, P = 0.04) and with HLA DR 3/4 heterozygosity (by chi 2, P = 0.04). They were not associated with islet cell antibodies (regardless of the threshold for positivity, expressed in Juvenile Diabetes Foundation units), insulin autoantibodies, activated (HLA DR+) T-lymphocytes, or sex. A statistical association was detected between HLA DR 3/4 heterozygosity and a low acute insulin response to iv glucose (by chi 2, P less than 0.003). The preliminary (2-yr) longitudinal follow-up revealed that out of five islet cell antibody-positive subjects who progressed to type 1 diabetes, three displayed beta-CL values higher than the 90th percentile of controls. Diabetic rosettes could, thus, be detected in some individuals at risk for type 1 diabetes as a marker of cell-mediated immunity.

["Diabetic rosettes": a cellular immunity marker in subjects at risk for type I diabetes]. / Les "rosettes diabétiques": un marqueur d'immunité cellulaire chez des sujets à risque de diabète de type I.

The authors have previously described a marker of cell-mediated, called "diabetic rosettes", revealed by the increased binding of CD3 CD4 lymphocytes from type I diabetic patients to beta-cell membrane antigens, as compared to lymphocytes from control subjects. In the present study, they have detected such "diabetic rosettes" in some subjects at risk for type I diabetes. The mean value of lymphocytes adhering to beta (RINm5F)-cells (beta-CL) was statistically higher in those subjects at risk than in control blood bank donors (p = 0.003). When a positive test was arbitrarily defined as a value of beta-CL higher than the 95th percentile of controls, 20 p. cent of the subjects at risk were classified as beta-CL+. No difference was observed between two subgroups of subjects at risk: first degree relatives of type I diabetic patients, and non-diabetic subjects with transient hyperglycaemia. "Diabetic rosettes" were associated with HLA DR 3/4 heterozygosity (p less than 0.04) and with a "low" acute insulin release to IV glucose (p = 0.05). They were not associated with islet-cell antibodies, insulin autoantibodies, or "activated" (HLA DR+) T-lymphocytes. The authors suggest that "diabetic rosettes" represent a marker of cellular immunity in some subjects at risk for type I diabetes.