The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycaemia.

In non insulin dependent diabetics (N.I.D.D.) of normal body weight, the acute insulin response to glucose is defective while that to pharmacologic agents such as tolbutamide is less impaired. This specific B-cell insensitivity to glucose results from unknown and perhaps multiple mechanisms. Hyperglycemia may be itself aggravate this phenomenon. To test this hypothesis acute insulin release (delta I: sum of increment at 2, 5, 10 min) after intravenous and tolbutamide injection was studied in 5 N.I.D.D. with fasting blood glucose averaging 12.1 mM/I (range 10.7-13.7) before and after 20 hours of glycemic normalization by an artificial pancreas. Intravenous injection of .3 g/k glucose did not elicit an acute insulin or C-peptide response, but following Tolbutamide (20 mg/kg) delta I was 44 +/- 21 microU/ml and delta C-peptide 0.84 +/- 0.37 nM/I. After 20 hr of normoglycemia a response to glucose was apparent (delta I 60 +/- 24 and delta CP 0.86 +/- 26) that to Tolbutamide was unchanged (delta I 58 +/- 26 and delta CP 0.97 +/- 0.27). These results suggest that 20 hr of normoglycemia improve significantly the "glucoreceptor" function of the B-cell in N.I.D.D.

Effects of insulin on erythrocyte deformability in diabetics--relationship between erythrocyte deformability and platelet aggregation.

Erythrocyte deformability was studied by the filtration technique of Reid & Dormandy using whole blood and washed erythrocytes from insulin-dependent diabetics (IDD) under insulin delivery by an artificial pancreas (AP). The same technique was employed to study deformability in vitro using normal erythrocytes incubated in the presence of insulin. Results of this study show that in IDD the initially poor erythrocyte deformability is improved within hours of insulin administration. Improved deformability was accompanied by increased levels of intra-erythrocyte ATP but without changes in levels of HbG and 23 DPG. Incubation of erythrocytes in medium containing glucose showed that deformability was significantly improved in the presence of insulin. These results indicate that insulin favourably affects erythrocyte deformability in IDD. Before and after 24 hours treatment by AP, platelet aggregation was studied in IDD by the technique of Born using platelet-rich plasma (PRP) and by a modified Breddin technique using PRP, whole blood or whole blood treated by chlorpromazine and mixtures of erythrocytes from IDD with normal PRP. Platelet hyperaggregation was only found in the presence of erythrocytes from untreated diabetics. Chlorpromazine, at a dose (10 mumole) which inhibits haemolysis without inducing platelet hyperaggregation, eliminated the above anomaly. In conclusion, it is conceivable that the insulin-induced correction of poor erythrocyte deformability eliminates excessive fragility of erythrocytes and their haemolysis wit release of ADP, thus avoiding platelet hyperaggregation.

[Specific immunologic resistance to bovine insulin in an insulin-dependent diabetic]. / Résistance d'origine immunologique spécifique à l'insuline bovine chez un diabétique insulino-dépendant.

A 60-year old male diabetic patient treated with insulin for 6 years developed ketosis whenever an attempt was made to replace porcine insulin by mixed bovine and porcine insulin. That this resistance was specific to bovine insulin and of immune origin was demonstrated by in vivo and in vitro studies. The in vivo study used a Biostator artificial pancreas: rapid decrease of plasma glucose concentrations was observed under insulin infusion at a constant rate of 200 mU/min with either porcine or semi-synthetic human insulin despite maximum glucose infusion rate (400 mg/min), but not with bovine insulin and a low glucose infusion rate (150 mg/min). In the in vitro study, high levels of anti-insulin antibodies (11.4 m U/ml, Christiansen method) were found in the plasma, and the curves of competitive binding of radiolabelled insulin to the patient's IgG in the presence of unlabelled porcine or bovine insulin showed a 50% decrease of total binding with 0.12 ng/ml of bovine insulin and 25 ng/ml of porcine insulin, suggesting that the affinity of these antibodies for the former was 200 times higher than for the latter.

[Treatment of solar urticaria: advantage of terfenadine]. / A propos du traitement de l'urticaire solaire: intérêt de la terfénadine.

Solar urticaria is a rare photodermatosis, but it is extremely incapacitating and therapy is usually ineffective. Three patients who took a daily dose of 240 mg terfenadine were able to be normally exposed to sunlight. This efficacy was confirmed by photobiological tests. The minimal dose necessary to induce urticaria was increased at least three times. These results confirming recently published ones. Terfenadine at 240 mg per day seems to be the treatment of choice for solar urticaria because of its efficacy and excellent tolerance-especially as there is no sedative effect.

[Self-modifying automata. Models allowing the understanding of the properties of self-programming of life and of the nervous system (some basic theorems)]. / Les automates automodificateurs. Modèle permettant la compréhension des propriétés d'autoprogrammation du vivant et du système nerveux (quelques thérorèmes de base).

In an attempt to discover the properties of the nervous system, we imagined the conditions under which a machine would be able to construct its own program and from which emerged the model of Self Modifying Automata (SMA). We demonstrated the unicity of the SMA model, their convergence in a p-cycle and, in this case, the SELFREFERENCE of a stabilised SMA (it then generates its own program), their adaptability when connected to a deterministic world. The SMA reaches its p-cycle very quickly and the most probable length of the -cycle is 1.

Modifiable automata self-modifying automata.

One of the most important features of living beings that seems universal is perhaps their ability to be modified in a functional way. In order to modelize this characteristic, we designed automata with a finite number of instantaneous internal descriptions, with input(s) and output(s) and which are able to be functionally modified. The rules which govern the evolution of these automata (and the initial conditions) are randomly chosen at the beginning and once and for all. When such an automaton is linked by its input and output to a deterministic process, it always stabilizes and it then has the property to rebuild itself. Thus it made a function which is inverse of the external function. We demonstrate the prevalence of p = 1 length period and of tau = 0 transient length for automata with m instantaneous internal descriptions.

Self-programming machines (II): Network of self-programming machines driving an Ashby homeostat.

The progress in artificial intelligence enables us to conceive adaptive systems whose characteristics are nearer and nearer to those of living beings. These characteristics though depend on ingenious choices by the designer of these systems: Initial conditions, parameters, optimisation functions, gradient and measure of fitness within the environment. Nevertheless, in living systems which are non-finalist, there are no programmers or designers to conceive of such ingenious choices. Our paper "Self-Programming Machines (I)" presents a non-finalist model since initial states and functions are randomly chosen at the beginning and once and for all. In spite of the fact that they are non-finalist, these machines always stabilise at fixed points when they are connected to an external process. This paper studies the dynamics of a mono-layered network of self-programming machines driving a real device. "the Ashby homeostat", and shows the striking properties of such networks. This system stabilises only at fixed points even if it is subjected to small perturbations or intentional breakdowns such as a reversal of power supply or disconnection of one or several motors. Real and simulated experiences are compared and theoretical results are demonstrated.

[Initial remission period in insulin-dependent diabetes in the young subject]. / La phase de rémission initiale du diabète insulinodépendant du sujet jeune.

Occurrence of a remission after initiation of insulin treatment in insulin dependent diabetes (type I) of recent onset is a well known phenomenon. It may be more or less complete up to insulin withdrawal. In newly diagnosed IDD requiring insulin for ketoacidosis or primary failure of oral agents and with a duration of symptoms of less than 6 months, initiation of optimized insulin therapy was followed by suppression of insulin (with or without the use of oral agents) in two thirds of cases for a mean period of 12 months while blood glucose and glycosylated haemoglobin remained normal. As therapeutic reversal of the etiopathological mechanism of IDD is foreseen it is relevant to define the characteristics of cases with remission induced by intensified insulin treatment, and the mechanisms by which they may be explained. Current knowledge on these questions will be analysed in this review. Furthermore it appears that withdrawing insulin for a mean period of 12 months does not hamper the subsequent control of diabetes.

[Blood typing of a Hansen population in Guadeloupe (F.W.I.)]. / Etude hémotypologique d'une population hansénienne en Guadeloupe (F.W.I.).

The target of this survey carried out in Guadeloupe (F.W.I.) is to search for eventual relationship between leprosy forms and ethnic features--Made in people subjected to same environmental factors, such a study avoids usual bias of investigations on the epidemiological aspect of "racial" factors. The 1522 investigated patients have been divided into 2 categories: allergic paucibacillary (Mitsuda +), and anergic multibacillary (Mitsuda -) patients. -). Three parameters were studied: morphological type empirically determined according to cutaneous pigmentation; ABO blood groups; and Rhesus phenotype. The results bring to the fore: Significant linkage between clinical forms and morphotype: the dominant Caucasian morphological typed subjects, with integument poor in melanin, are more numerous among multibacillary patients. This might confirm high sensitiveness of Caucasians to leprosy. No significant linkage between clinical forms and ABO blood groups. Nevertheless, variations are found already reported in more homogeneous populations: predominance of A group in multibacillary patients, of B and O groups in paucibacillary patients. Significant linkage between clinical forms and Rhesus phenotype. But this link does not seem to be imputable to ethnic factors because clinical forms distribution is the same in ccDee sub-population (the most frequent in West Africa), and in ccddee subpopulation (quite frequent phenotype in West Europe). In fact, only the ccDEe phenotype sub-population is significantly different from all the others, because multibacillary forms are particularly frequent (49.3%) and strike evenly women and men in this sub-population.

[The artificial pancreas in surgery. An attempt to simplify intra- and post-operative insulin therapy]. / Le pancréas artificiel en chirurgie. Recherche d'une simplification de l'insulinothérapie per et post-opératoire.

The insulin requirements of 10 insulin-dependent diabetic patients were evaluated during and after surgery (including 4 caesarian sections) by connecting the patients with an artificial pancreas. Considerable variations were observed in the intra-operative period. In contrast, the amounts of insulin released during the immediate post-operative period were more regular and reproducible (mean: 2.36 U/h for a glucose intake of 200-250 g/24 h). A satisfactory control of glycaemia was obtained with this dosage in 7 insulin-dependent post-operative patients without using an artificial pancreas. It would therefore seem that in most cases continuous insulin infusion combined with direct measurement of capillary glycaemia could replace an artificial pancreas and make the intra- and post-operative care of diabetic patients simpler and more effective.

Sustained initial remission induced by intensive insulin treatment in type I diabetes. Possible role of the genetic background.

A remission defined by the possibility of temporarily discontinuing insulin therapy while blood glucose remains normal is not infrequently observed after intensive insulin therapy in newly diagnosed acute type I diabetes in the South of France. In order to analyze possible factors of such a remission, 47 newly diagnosed ketotic diabetics under 35 years of age and of Caucasian origin were enrolled in a prospective study. They were given continuous s.c. insulin infusion for two weeks and oral agents were introduced on day 8. In 16 patients insulin could not be withdrawn. In 31 insulin was stopped for more than 3 months (mean 12.3, range 3-35) while blood glucose remained below 6 mmol/l fasting (mean 5.3) and 7.8 post-prandial (mean 5.1) and glycosylated Hb below 8.5% (mean 6). At presentation, diabetics who later went into remission and those who did not, showed no difference in age (22.3 vs 23.1 years), sex ratio, apparent duration of symptoms (1.4 vs 1.6 months), glycosylated hemoglobin (12.0 vs 13.1%) and basal or post-prandial C-peptide values or presence of islet cell antibodies. No differences were observed in the frequency of DR3 and DR4 antigens in the two groups but diabetics who developed a remission bore the A 19.2 antigen (9/31 vs 1/16) and the B18 one (11/31 vs 1/16) more frequently, A 19.2 and B18 being associated in 7 cases of this group. This increased frequency in the remission group of HLA antigens, more often observed in diabetics of Mediterranean origin, suggests that differences in the genetic background may be associated with a difference in the evolution of the disease.

[Whited Addison's disease. Eight cases (author's transl)]. / La maladie d'Addison "blanchie". Huit cas apparemment guéris.

In 8 cases of Addison's disease due to adrenal tuberculosis, the substitutive treatment appeared unnecessary since more than one year. Urinary 17-OHCS were in the normal range but did not rise after ACTH injection except in two cases. In all the cases, plasma ACTH was elevated but lower than in severe adrenal insufficiency, and in the range of those observed in congenital adrenal hyperplasia. The nycthemeral variation of plasma ACTH were maintained. Therefore, an apparently normal basal cortico-adrenal function was obtained by an excessive stimulation by endogenous ACTH. The one year prescription of anti-tuberculosis chimiotherapy to 6 of these patients was possibly responsible for the partial reversal of adrenal insufficiency. However the substutive therapy appears needless in every day life, such a treatment would eventually be necessary during stress conditions.

Abnormalities of erythrocyte deformability and platelet aggregation in insulin-dependent diabetics corrected by insulin in vivo and in vitro.

Erythrocyte deformability is lower than normal in uncontrolled insulin-dependent diabetics and returns towards normal after 24 h treatment with a feedback-controlled insulin infusion. Deformability of normal erythrocytes is reduced by incubation in plasma from uncontrolled insulin-dependent diabetics but is normal in plasma from insulin-dependent diabetics controlled by 24 h insulin infusion, or in plasma from uncontrolled insulin-dependent diabetics with insulin added in vitro. Therefore, insulin has a direct action on erythrocyte deformability. Platelet aggregation measured in whole blood is raised in uncontrolled insulin-dependent diabetics and returns to normal after 24 h treatment with a feedback-controlled insulin infusion. Aggregation of normal platelets rises in the presence of erythrocytes from uncontrolled insulin-dependent diabetics, but not erythrocytes from the same patients after 24 h treatment with insulin. The effect of insulin on platelet aggregation therefore seems to be at least partly mediated by erythrocytes. The enhanced platelet aggregation seen in uncontrolled insulin-dependent diabetics can be explained either by a direct effect of erythrocyte rigidity or by an increased release of nucleotides (ADP) by the erythrocytes.

[Evaluation of the acceptability of 2 methods for self monitoring of blood sugar by a group of insulin-dependent diabetic patients]. / Evaluation de l'acceptabilité de deux méthodes d'autosurveillance glycémique par un groupe de diabétiques insulinodépendants.

In order to evaluate the advantages and disadvantages of two methods of blood glucose self-monitoring (either direct semi-quantitative reading on Haemoglukotest 20-800 or quantitative reading of Dextrostix strips using a reflectance-meter, Glucometer) 20 insulin-dependent diabetics selected according to the quality of the management of their own diabetes were asked to try both methods for 3 months and then fill a questionnaire assessing their acceptance. Analysis of the responses shows that home blood glucose monitoring is well accepted even after one year by patients aware of the necessity of a good glycemic control. It is specially useful for the adaptation of insulin doses and less so for identification of hypoglycemic attacks. Haemoglukotest 20-800 is appreciated for its easy utilization specially during professional life and outside leisure. However, the reflectance-meter Glucometer is preferred by most patients because they feel it is more reliable and safe.