[The 75th anniversary of the discovery of insulin]. / Le 75e anniversaire de la découverte de l'insuline.

When a medical problem is studied intensively by several investigators in the world, a solution may sometimes be found simultaneously in different countries. Seventy-five years after the discovery of insulin, the chronology of this event can be reconsidered objectively and the role of each of the protagonists evaluated. The stubbornness of Banting and Best, the technical abilities of Collip and the active support of Macleod were determinant in the use of insulin for the treatment of diabetic patients. Moreover, in the long line of experimentalists and physicians, Lancereaux and Paulesco also deserve special mention.

[The discovery of insulin]. / La découverte de l'insuline.

When a medical problem is intensively studied by many teams in the world, it is frequent to see the solution found simultaneously in different countries. However that was not exactly the case concerning the extraction of a potent insulin able to cure Diabetes Mellitus. It seems necessary, seventy five years later, when passions are quenched, to reconsider the chronology of the history and put Paolesco but also Collip at the right places much before Banting and Best to whom, by a curious misinterpretation of facts, was attributed the priority of this fundamental discovery.

[Condom: its role in the prevention of AIDS]. / Le préservatif: sa place dans la prévention du SIDA.

Since no effective vaccination is available, protection is our only arm against the spread of the human immunodeficiency virus. For public health officials and associations working against the spread of AIDS, the contraceptive is the ultimate arm and only generalized use will change the course of the pandemia. But because the disease continues to advance regularly it would appear necessary to have a second look at the official position. Actually, there are two sides to the contraceptive picture: 1. a real factor of protection for the healthy man who uses it, 2. a source of possible contamination of a healthy partner by a seropositive man who uses the contraceptive. The user cannot put the contraceptive on without touching his sexual organs which have been humidified by the pre-ejaculatory secretions which are rich in HIV and which are secreted long before complete erection allows him to install the contraceptive correctly. The result is that the inside surface of the contraceptive will always be more or less contaminated. There is therefore a major risk of contamination in certain situations, particularly for the virgin woman, before her first sexual intercourse, since an open wound is created by the rupture of the hymen. If we truly expect to eradicate this disease, the message will have to be changed.

[Evolution of the application of nutrition in French nursing infants. Comparison of two national investigations performed in 1981 and 1989]. / Evolution des apports nutritionnels chez les nourrissons français. Comparaison de deux enquêtes nationales realisées en 1981 et 1989.

A national dietary survey was carried out in 1981 among a representative sample of 499 French infants 1 to 18 months of age. When compared with the French Recommended Dietary Allowances, the diets were found to be well supplied in energy, protein and calcium, and inadequately supplied in iron and linoleic acid, mainly for infants aged 4-10 months. A comparative dietary survey conducted by using the same methodology (food consumption was measured by means of a 3-day food record) in 1989 showed that linoleic acid intake was higher in the 6-month-old group. Similarly, iron intakes were higher in 1989 for infants aged 1-7 months. The mean daily iron intake increased between 1981 and 1989 from 5.0 +/- 1.9 mg to 7.3 +/- 2.6 mg in the 6-month-old group and was similar for the older infants. The data suggest that educational programs were partially efficient but it is clear that more effective efforts are needed.

[Non-enzymatic glycosylation. Biology. Pathology]. / La glycosylation non enzymatique. Biologie. Pathologie.

Enzymatic glycosylation of proteins should be clearly distinguished from non-enzymatic glycosylation or glycation. Both processes occur in normal subjects but are enhanced in patients with hyperglycemia. Increased enzymatic glycation in patients with diabetes mellitus is responsible for thickening and weakening of capillary membranes, resulting in microangiopathy with microaneurisms, bleeding, and circulatory exclusion. Non-enzymatic glycosylation (glycation) affects all the proteins in the body and, if intense enough, may modify the activity or effectiveness of some molecules (apolipoproteins, membrane receptors, or even insulin itself). In everyday practice, glycated serum albumin and, above all, glycated hemoglobin serve as markers to evaluate the effectiveness of therapy in patients with diabetes mellitus.

[Chronic non-insulin deficient hyperglycemia in children]. / Hyperglycémie chronique non insulinoprive chez l'enfant.

Two per cent of "diabetic" children actually exhibit a specific condition which is not a disease in the conventional acceptance of the term. Characteristics of this biologic anomaly, whose pathophysiology is as yet incompletely understood, include the absence of clinical manifestations, with the diagnosis being established upon routine tests (e.g., as part of a school health check-up or during screening tests in family members of diabetics); blood glucose levels or glucose tolerance test results consistently above the 97th percentile of reference values, with some degree of variation over time; normal serum insulin levels; glycosylated hemoglobin levels usually near the upper limit of normal; dominant autosomal inheritance; lack of association with either HLA markers or insulin-dependent diabetes mellitus; lack of microvascular degenerative disease, at least in this study group, even after more than 30 years follow-up; lack of progression towards insulin-dependent diabetes mellitus.

[The socio-professional outlook of children and adolescents with diabetes]. / Le devenir socio-professionnel de l'enfant et de l'adolescent diabétiques.

Intensive medical education programs started in France in 1950 have allowed French patients with diabetes mellitus to assume responsibility for their own management. Obstacles to school attendance and vocational education have been gradually overcome, in large part as a result of the efforts of non-profit organizations such as Assistance to Young Diabetics. At present, diabetics have nearly equal professional opportunities with normal children. However, some professions, such as "security jobs", remain justifiably prohibited; jobs where previous military service is required also remain out-of-bounds for diabetics, although the grounds for this restriction may be questionable. For other government agencies and private corporations, the decision to accept a subject with diabetes mellitus rests with occupational physicians, who are without doubt better informed now than before. Surveys on the long-term social outcome in subjects with diabetes mellitus since childhood have shown that the distribution of occupations is comparable to that seen in the population at large with, however, a higher prevalence of crafts persons, intellectual occupations and health care professionals.

[Degenerative complications of diabetes]. / Complications dégénératives du diabète.

Even optimally treated insulin-dependent diabetes mellitus is responsible for a significant number of complications which impair daily activities and shorten life expectancy in most patients. The cause of these complications has been under investigation for many years. Substantial evidence supports the following 1) a role of high blood sugar levels which lead to glycosylation processes; 2) presence of disorders related to inadequate nutrition, and specifically excessive dietary intake of saturated fatty acids, rather than to insulin deficiency. Furthermore, hereditary factors may play an additional role (HLA haplotypes may promote the development of complications). Antibodies and/or hormonal factors may also be involved. Whatever the mechanisms involved, there is no doubt that every effort should be made to achieve normal blood sugar and lipid levels. But what is the optimal degree of control? What is the ideal diet? Is it necessary to risk severe hypoglycemia? Should insulin pumps be routinely used? Since many of these issues are as yet unresolved, there is a need for collecting valid data on long-term complications with several therapeutic regimens. Unfortunately, most of the many published statistical studies on these complications are virtually invalid. This fundamental issue is discussed. The authors urge diabetes mellitus specialists to use the actuarial method already used by oncologists for many years.

Excess of maternal HLA-DR3 antigens in HLA DR3,4 positive type 1 (insulin-dependent) diabetic patients.

The susceptibility determinants of Type 1 (insulin-dependent) diabetes mellitus are known to be associated with both HLA-DR3 and DR4. In our study we wished to determine if the parental origin of these antigens could influence susceptibility to the disease. We analysed the inheritance of DR3 and DR4 haplotypes from the father or mother (DR3p, DR4p, DR3m and DR4m, respectively), in the index cases and in the affected and non-affected siblings of 246 diabetic simplex and 41 multiplex families without affected parents. An independent series of 80 multiplex families (GAW 5) was also studied. Among the DR3,4 positive index cases and affected siblings, the paternal and maternal DR3 and DR4 antigens were not distributed randomly: 62% and 72%, respectively, had received DR4 from their father and DR3 from their mother (DR4p/DR3m), while only 38% and 28%, respectively, had received a paternal DR3 together with a maternal DR4 (DR3p/DR4m). This differed significantly from the 50% expected ratio (p less than 0.01) and was not observed in unaffected siblings. No excess of maternal DR3 in the absence of DR4 and no excess of paternal DR4 in the absence of DR3 were observed. The finding suggests that some maternal DR3 related event (presumably during pregnancy) might play an enhancing role in the pathogenesis of Type 1 diabetes. It also implies that siblings with both DR4p and DR3m have a significantly higher risk for disease than those with DR3p and DR4m.

[Oral rehydration solution or physiology in public health]. / La solution de réhydratation par voie orale ou la physiologie en santé publique.

Oral rehydratation solution was conceived from physiological concepts to be used in primary health care centers. A new relationship between physiology and public health stems from the clinical use of this solution.

[Yersinia enterocolitica infections and thalassemia major in children]. / Infections à Yersinia enterocolitica et thalassémie majeure chez l'enfant.

We report two cases of severe Yersinia enterocolitica infection in children with homozygous thalassemia. One patient had septicemia and the other had mesenteric adenitis. Two factors can enhance the infectivity of Yersinia enterocolitica in children with thalassemia: iron overload and deferoxamine therapy. Laparotomy and cefotaxime-netilmicin therapy were successful in the patient with mesenteric adenitis. In the patient with septicemia, cefotaxime-netilmicin, then doxycycline-netilmicin failed, and recovery was finally achieved under rifampicin-netilmicin. Because of the possibility of septicemic dissemination secondary to digestive Yersinia enterocolitica infection in children with thalassemia, we advocate immediate discontinuation of deferoxamine and prescription of oral antimicrobial therapy (trimethoprim-sulfamethoxazole for instance) in every thalassemic patient with febrile diarrhea.

[Increased risk of insulin-dependent diabetes for siblings of diabetic children with the DR 3 haplotype of the mother]. / Risque accru de diabète insulino-dépendant pour les germains d'enfants diabétiques ayant reçu l'haplotype DR 3 de la mère.

Among 285 caucasoid families genotyped for HLA-A, B, C, DR including at least one insulin-dependent diabetic child, we have studied the effect of the DR3 and DR4 antigens inherited from the father or the mother (DR3p, DR3m, DR4p and DR4m, respectively) on the recurrence of the disease among siblings; families with affected parents being excluded, a total of 37 affected and 200 non affected siblings have been taken into consideration. Among the DR3, DR4 positive siblings, the DR4p/DR3m genotype was observed at a greater frequency than the DR3p/DR4m genotype among affected, but not among unaffected siblings. Comparing the respective frequencies between affected and unaffected siblings, the relative risk was 8.1 (p less than 10(-6) among DR4p/DR3m positive siblings, but is was not significantly increased among DR3p/DR4m positive siblings. The excess of maternal DR3 among affected siblings of diabetic children could be due to a gestational event associated with HLA-DR3, e.g. education of the fetal immune repertoire or the transmission of a viral infection by the mother to the fetus during pregnancy, after reactivation of the latent viral disease.

[Chronic non-insulin deficient hyperglycemia in children]. / Hyperglycémie chronique non insulinoprive de l'enfant.

We report the clinical records of 45 children with abnormalities regarding glycemic regulation characterized by a non-insulin deficient hyperglycemia (NIDH), known under the different names of chemical diabetes, sub-clinical diabetes and more recently MODY. These 45 children belong to 31 families with 532 relatives comprising 137 cases of NIDH which could have been studied. The symptoms of this biochemical abnormality, the pathophysiology of which is not yet clearly understood, are the following: lack of clinical manifestations, except for a variable and intermittent glycosuria; constant abnormal glucose tolerance tests, above 97 percentiles of the reference value with some variations over time; normal immunoreactive insulin levels; percentage of glycosylated hemoglobin at the upper range of normal; dominant autosomal genetic transmission and no association with HLA markers like in insulin-dependent diabetes; lack of degenerative complications of the micro-angiopathic type, at least on these cases even after more than 30 years of follow-up; finally, no tendency towards insulin-dependent diabetes. The NIDH should not be confused with the slow and progressive beginning of insulin-dependent diabetes for which prolonged delay is needed to affirm the diagnosis. The frequency of the biochemical phenomena is about 1.8% of the cases of authentic diabetes mellitus occurring before the age of 15.

Two distinct HLA-DR3 haplotypes are associated with age related heterogeneity in type 1 (insulin-dependent) diabetes.

Heterogeneity between two haplotypes in linkage disequilibrium with DR3: B8, C4AQOB1,BfS,DR3 and B18,C4A3BQO,BfF1,DR3, with regard to age at onset of Type 1 (insulin-dependent) diabetes mellitus, was investigated in 325 unrelated French patients (146 males and 179 females, age at onset 1 month to 29 years) who were genotyped for HLA-A, B, C, DR and Bf and 225 of whom were typed for the C4A, B complement components. A subgroup of 82 patients and 75 control subjects were tested for DR beta and DQ beta DNA restriction fragment length polymorphism. The distribution according to age at onset and the mean ages at onset were compared between patients bearing B8, DR3 (n = 58), B18,DR3 (n = 62) or other DR3 haplotypes (Bx, DR3, n = 70), the haplotype segments C4AQOB1,DR3 (n = 41) or C4A3BQO,DR3 (n = 52) and the C4 null alleles C4AQO (N = 48) or C4BQO (n = 112) alone. The B8,DR3 haplotype, its smaller segment C4AQOB1,DR3 or C4AQO alone were associated with age at onset after 6 years (p less than 0.01, less than 0.08 and less than 0.02 respectively); on the other hand, the B18,DR3 haplotype, its segment C4A3BQO,DR3 or C4BQO alone were significantly more frequent in patients aged less than 6 years at onset (p less than 0.02, less than 0.01 and less than 0.01 respectively). Accordingly, the mean age of onset was significantly lower in the latter compared with the former patients (p less than 0.02, less than 0.02 and less than 0.01 respectively). No age-related variation was observed in BX,DR3 patients and their mean age of onset was intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)