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OBJECTIVE To analyze the efficacy of ECPII and the factors responsible for technical problems often encountered. This treatment has been in use with IDDM patients since 1980. RESEARCH DESIGN AND METHODS Forty-four IDDM treated by ECPII for 42–78 mo (mean, 53 mo). patients were RESULTS Glycemic equilibrium was improved during treatment (mean plasma glucose level, 7.6 mM; mean GHb level, 8%). Catheter blockage was the main reason for ECPII failure (74%). Mean catheter survival of each catheter, determined by actuarial analysis, was 11.7 mo and significantly decreased with subsequent implantation. SEM of the catheter tips showed deposits composed of fibrin and cells occluding the inner lumen. Factors such as age, sex, local infection, and low insulin basal rate were not found to have any incidence on the catheter survival. Placement of the catheter in the upper part of the peritoneum, however, increased catheter survival. Anti-insulin antibodies did not seem to be directly involved in blockage. CONCLUSIONS We conclude from this long-term experience that during ECPII, catheter blockage remains the major recurring complication, probably involving a local immune-inflammatory response in the peritoneum.

Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study.

La fatigue, sous ses formes neuropsychique ou neuromusculaire, est une composante semiologique de nombreuses pathologies. L’experience clinique des maladies endocriniennes permet de retenir le role de perturbations hormonales dans sa constitution. Differents mecanismes physiopathologiques hormonodependants sont impliques, tant au niveau musculaire qu’au plan du systeme nerveux central pour concourir a la fatigue. Inversement, la fatigue chronique de nature endogene telle qu’observee dans les etats depressifs est a l’origine de modifications neuro-endocriniennes, confirmant ainsi l’etroite intrication des processus. La boucle d’interdependance entre les desordres endocriniens et l’etat de fatigue chronique conduit a envisager la possibilite de terrains propices a l’installation d’un tel cercle vicieux. L’approche genetique et l’analyse moleculaire de la biochimie cellulaire peuvent s’averer des voies nouvelles pour apprehender la fatigue sur un mode uniciste plutot qu’a travers ses differents aspects sectoriels attaches a un organe ou a un appareil.

The aim of the present study, a pilot trial, was to find out if nicotinamide (50 mg kg-1 day-1) in combination with cyclosporin A favours remission in recently diagnosed Type 1 diabetic patients, and if it postpones relapse even when cyclosporin A is administered in decreasing doses (trough blood level 300-500 micrograms l-1 until month 4, and 100-300 micrograms l-1 until month 9) and then discontinued. The criteria for inclusion in the study and the follow-up protocol were the same as those used in the Cyclosporin Diabetes France (CDF) programme in which all five of the centres involved in this study participated. The data of the present preliminary open study were therefore compared retrospectively with those of the placebo (CDF-placebo) and cyclosporin (CDF-active) group of the CDF programme. Clinical remission (fasting plasma glucose less than 7.8 mmol l-1, postprandial plasma glucose less than 11.1 mmol l-1, HbA1c less than 7.5% with neither insulin nor oral hypoglycaemic agents) was achieved within 6 months in 12 out of 35 patients (34%) vs 16 out of 63 (25%) in CDF-active and 11 out of 59 (19%) in CDF-placebo. Remission was achieved by month 9 in 6 out of 35 patients (17%) vs 13 out of 54 (24%) in CDF-active and 3 out of 52 (6%) in CDF-placebo. By 12 months remission persisted in 3 out of 35 patients (9%) vs 11 out of 63 (17%) in CDF-active and 0 out of 52 (0%) in CDF-placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged pulsatile exogenous GnRH allows differentiation between hypothalamic and pituitary causes of hypogonadotrophic hypogonadism and is able to induce ovulation and pregnancy in most of women with hypothalamic amenorrhea (HA). When compared with human menopausal gonadotropin, GnRH appears to be a more efficient therapy of HA but yields inferior results in chronic anovulatory patients with persistent LH secretion. Pulsatile GnRH following a GnRH-analog suppression represents a new promising treatment of infertile women with polycystic ovarian syndrome. However such a combined therapy is time-consuming and only permits to attempt 3 to 4 stimulated cycles during a year. Therefore the successful preliminary reports need to be confirmed by a further randomized study.

The aim of this study was to determine which candidates were suitable for immunotherapy among adult insulin dependent diabetic patients of recent onset. A statistical analysis was performed using the results of a multicentre randomized trial of cyclosporine versus placebo after nine months of treatment. When the baseline characteristics of the patients in remission were compared with those not in remission, there was no difference observed either in initial residual beta-cell function (glucagon stimulated C-peptide level), or in immunological markers (T4 and T8 lymphocytes counts, Interleukin 2). The parameters showing the most difference were, in addition to treatment group, the duration of diabetes symptoms and body mass index at inclusion, and the HLA-DR phenotype. This was confirmed using a logistic regression analysis, in which these variables were found to be significantly related to remission. The probability of remission in each individual patient was then calculated using these variables in the mathematical function provided by the logistic model. Ninety eight out of 110 patients were correctly classified using this method. In addition, it must be noted that only subjects adequately treated by cyclosporine were still in complete remission after a one year follow-up. Conversely, it appeared that immunosuppression in subjects having a predicted probability of remission lower than 0.35 using the mathematical function, and being non-DR3, non-DR4 has to be avoided. These results will be useful in optimizing the recruitment of patients in on-going or future trials of immunotherapy in early diabetes.

The aim of therapeutic research is to find out an effective medication against the disease without any dangerous toxic action. The delicate problem is that very often the dose of drug confines with toxicity. The solutions are numerous: transformation of supports, change of the introduction route, adaptation of the concentration. It has been realised that, in certain disease, continuous infusion of medication was much more effective than repeated intermittent injections. The general technic of drug contribution by a pump supposed a drug reservoir with sufficient volume to prevent the frequent manipulations, a source of energy assuring the circulation of the drug and a control of the speed of the drug delivery. These attempts are not exceptional in our practice, being very often utilized in the treatment of difficult diabetes by insulin infusion, the thrombosing diseases be heparin infusion, some forms of diffused cancers by specific chemotherapeutic agents, acute polyhormonal insufficiencies... It is also possible to use infusion pumps in intensive cares with administration of antibiotics, of antalgic drugs, in cardiology for the management of atrial fibrillation, atrial and/or ventricular tachycardias, etc. The most common are the portable pumps and the implantable.

ACE inhibition is widely used for treatment of arterial hypertension or congestive heart failure. No change occurs in glucose metabolism either in diabetic or non diabetic subjects. No change occurs in glucose metabolism in patients with chronic renal failure. Glucose intolerance induced by diuretics is attenuated when ACE inhibitor is associated with thiazides. In some very rare circumstances (with high plasmatic levels of norepinephrine), insulin sensitivity seems to be enhanced by captopril. Then, in clinical use, no adverse effect occurs with ACE inhibition in non diabetic or diabetic subjects. Under thiazide treatment, ACE inhibitors protect against glucose intolerance.

Diabetic cheiroarthropathy (DCA) or pseudosclerodermatous hand of the diabetic is characterized by nonpainful limited extension of the proximal metacarpophalangeal and/or interphalangeal joints with spontaneous flexum of the fingers. The mechanism of lesion formation is poorly known but apparently associates neurogenic, vascular and cutaneous phenomena. Fifteen patients with DCA (9 men, 6 women; range 20-74 years) were studied by capillaroscopy, photoplethysmography and skin biopsy. Eleven had type 1 diabetes and 4 type 2 over periods ranging from 1 to 42 years (mean 19.9 years). Diabetic retinopathy was noted 10/15 times, nephropathy 5/15 times and neuropathy of the lower limbs 13/15 times. All patients had at least one of these abnormalities. In capillaroscopy, "Shoal of fish" features of diabetic microangiopathy were found only 4 times, but minor dystrophy was noted in 12 cases. In digital photoplethysmography, a drop in digital systolic pressure or an increase in pulse time was noted in 5 cases. The Hillestad test was less than or equal to 2 in 8 patients. Histological study showed constant dermal collagenous fibrosis in diseased skin, which was also found in normal skin in 6/13 patients. PAS staining showed a thickening of vascular basal membrane 14/15 times in diseased skin and 11/13 times in normal skin. The relation between DCA and microangiopathy is discussed in terms of collagen metabolism abnormalities observed during diabetes.

Methods for detection and characterization of episodic fluctuations in circulating hormone levels are frequently used for endocrine investigations, related to the physiological importance of the pulsatile nature of hormone secretion in modulating target-cells response. Several sophisticated methods of pulse analysis have been recently developed and validated, aiming to minimize the false-positive and false-negative error rates. The present report mainly devoted to the clinician aims to analyze and discuss the main features of the most widely used methods for pulse detection.

The best route of insulin administration by infusion pumps remains a subject of controversy. For that reason plasma lipids and apolipoproteins were compared in three groups of nine patients who had been treated for several months or years with conventional treatment (group I), continuous subcutaneous insulin infusion (CSII, group II) or continuous intraperitoneal insulin infusion (CPII, group III). Plasma cholesterol and apolipoprotein B remained increased on CPII compared with CSII even when similar satisfactory or even tight diabetic control was achieved with both techniques. This study suggests that cholesterol and perhaps apolipoprotein B biosynthesis by the liver is increased in patients treated with CPII compared to those treated with CSII.

Plasma Antithrombin III (At III), a natural inhibitor of coagulation, was determined using a single radial immunodiffusion technique. In 116 diabetics, plasma At III levels were significantly decreased (26.6 +/- 0.4 mg/100 ml) compared with those in 64 controls (31.0 +/- 0.3 mg/100 ml, P less than 0.001). An elevation of plasma fibrinogen degradation products in 42 per cent of our patients, and a positive linear relationship between platelet counts and At III levels ( r = 0.29, P less than 0.01), provided additional evidence for chronic disseminated intravascular clotting in diabetes mellitus. Diabetic retinal complications were more frequent in patient with low plasma At III levels (50.6 per cent of cases) than in those exhibiting At III concentrations within a normal range: 32.4 per cent of cases (X2 = 6.09, P less than 0.02). It is postulated that the low levels of At III encountered in diabetes result from excessive consumption, and that the deficiency may be responsible for the onset and/or aggravation of intravascular clotting. At III deficiency may therefore contribute to vascular degenerative complications, particularly those leading to diabetic retinopathy.

Seven stable and 10 labile insulin-dependent diabetic patients were submitted to 2 dietary regimens which were given in random order and maintained for 10 to 15 days. During one period (“control”) patients were given their usual diets. During the other period patients received a fibre supplemented diet (“test”). The fibre supplementation was calculated to provide 1 g dietary fibre per 15 g available carbohydrate. For each period, diabetic control was estimated from: (i) daily glycosuria; (ii) % glycosylated haemoglobin, (iii) insulin requirements, (iv) frequency of hypoglycaemic episodes and (v) circadian blood glucose levels.. Dietary fibre supr plementation resulted in: (i) decreased glycosuria in both stable (12.8±5.6 g/day vs 25.5±6.9 P < 0.01) and labile diabetics (35.8±10.5 g/day vs, 52.5+7.1, P < 0.02); (ii) a significant decrease in blood glucose at 1430h (P < 0.02) in stable and at 1430 h (P < 0.05) and 2030h (P < 0.01) in labile diabetics. The percentage of glycosylated haemoglobin was identical in stable (10.8±1.0%) and labile diabetics (10.7±1.0) and was slightly depressed with the fibre supplemented diet (9.5±0.8 and 9.3±0.6 respectively). The mean blood glucose during the control period was not significantly different in stable (186+28 mg/100 ml) and labile diabetes (221±24 mg/ 100 ml) and did not change significantly with fibre treatment. The results show that the control of stable and labile diabetes is improved to a similar degree by dietary fibre. This effect results mainly from a decrease in post prandial hyperglycaemia after lunch and dinner.

We compared the fractional absorption of calcium (FACa, 6 h, % TD) and the radiocalcium transit (% TD per min) in seven glucocorticoid-treated patients (10-25 mg prednisolone per day) and in seven normal subjects, in the basal state and 12 h after an oral dose of synthetic 1,25-(OH)2D (3 micrograms). In the basal state, the radiocalcium transit was significantly decreased (P less than 0.02) at 15 min in patients treated with prednisolone, but FACa at 6 h was not significantly decreased (51 +/- 5 vs. 60 +/- 5% TD). 12 h after an oral dose of 1,25-(OH)2D which resulted in supraphysiologic plasma levels, FACa increased significantly (P less than 0.02) in both groups but the peak absorption rate of Ca remained lower in the corticoid-treated patients than in controls (P less than 0.02). The results suggest that glucocorticoids decrease the 1,25-(OH)2D-dependent transport of calcium across the proximal small intestine.

The intestinal absorption and the urinary excretion of calcium were compared in two groups of diabetic patients during periods of satisfactory and poor control. In a first group of ten patients, periods of isolated high glycosuria were obtained by giving an oral glucose load. The second group consisted often patients with a severe endogenous insulin deficiency. The subjects of this latter group were investigated before and after a few days of insulin therapy. In group I, the oral glucose load induced a significant increase in the intestinal calcium absorption and had a tendency to lower the urinary calcium excretion. Furthermore, an inverse relationship was found between the changes in the intestinal calcium absorption and the variations of the urinary calcium excretion. In group II, both intestinal absorption and urinary excretion of calcium fell significantly after recovery of satisfactory metabolic control by insulin therapy. From the results as obtained in group I one can conclude that glucose enhances the calcium transfer from the luminal to the serosal pole of both intestinal and renal tubular cells. During severe ketosis as observed in group II, calcium metabolism is considerably accelerated and the increase in the intestinal calcium absorption rate may be interpreted as a compensatory mechanism for the high urinary loss of calcium.

The hypoglycemic activities of NPH biosynthetic human and pork insulins were compared in eight insulin-dependent diabetic patients using continuous blood glucose monitoring. After an overnight normalization of blood glucose levels, either human or pork NPH were injected subcutaneously in random order. Blood glucose was continuously recorded during 9.5 h while patients were consuming their usual diet. After NPH biosynthetic human insulin, blood glucose levels from the 2nd to the 9th h post-injection were lower as well as the glycemic nadir. The area under the curve was smaller after human than after pork insulin. But, in the last half-hour of the experiment, blood glucose was falling after pork insulin, while it was rising after human insulin. Under the conditions of this study, our results demonstrate that NPH biosynthetic human insulin may be more effective than NPH pork insulin, due to more rapid subcutaneous absorption but its duration is shorter than after porcine NPH insulin. These data may be of importance in the treatment of insulin-dependent diabetes mellitus.

The stability of a new insulin formulation (lyophilized U100 insulin, Organon) was investigated in vitro in conditions reproducing those of in vivo implanted devices, i.e., constant horizontal agitation at 37°C for 4 wk in various containers and 8 wk in different solvents. Physical stability was assessed by ultraviolet absorption, chemical stability by HPLC, and biological stability by hypoglycemia tests in mice. Insulin precipitated in glass vials but remained clear and active in polyethylene reservoirs and after passage through catheter and pumps in motion, although only 83–90% of insulin was delivered chemically intact. In acidic solvent, insulin showed a major gradual transformation into deamidized derivatives (up to 78% after 8 wk), although still fully active and clear, as expected from previously published excellent in vivo results with acidic insulins. Heparin addition to neutral insulin solution (500 IU/ml) did not alter the properties of the two compounds and might thus be tried to prevent in vivo catheter obstruction due to fibrin deposition.

The infusion of periodic intravenous insulin for the equilibrium of the diabetic state is proposed for cases of non-insulin-dependent diabetes mellitus (NIDDM) that have become resistant to oral treatment. In order to re-establish the efficacy of oral antidiabetic treatment, 37 patients with NIDDM presenting secondary failure to diet and oral antidiabetic therapy were subjected to sessions of continuous intravenous insulin infusion, resulting in transitory normal blood sugars. With a diminution of symptoms, an increase in the efficacy of oral treatment was noted in 18 cases (48.6%), allowing the continuation of treatment without disturbance of the equilibrium over periods of 6 and 12 months. This improvement is not concurrent with the rise in glucagon-stimulated insulin secretion as evidenced by C-peptiduria and basal C-peptidemia. An improvement in insulin sensitivity (not investigated in this study) might explain this beneficial effect. Periodic intravenous infusions of insulin, based on the diabetic equilibrium, are proposed for the treatment of NIDDM patients that have become resistant to oral therapy.

Remission of diabetes was attempted in 12 recent acute onset ketosis-prone juvenile diabetes after short term (5 +/- 1 days) but excellent blood glucose control by the external artificial beta-cell. The comparison group comrised patients undergoing traditional treatment (n = 28). Nine (75%) persistent (over 3-14 months of duration) although partial (oral drugs required) remissions were obtained in the former group as compared to 3 (11%) in the latter group (p less than 0.05). Cases which showed remissions after insulin infusion had a plasma insulin response to IV glucagon still present before insulin infusion, and a daily urinary C-peptide excretion significantly enhanced after (p less than 0.01). Urinary C-peptide/blood glucose remained improved during the remission period. Thus, early effective treatment by means of the artificial pancreas may break the vicious circle hyperglycaemia-insulin depletion-hyperglycaemia and lead to frequent and sustained remissions of juvenile diabetes.

Circulating lymphocytes from 39 juvenile insulin dependent diabetics of recent onset were studied by six membrane marker techniques and mitogen stimulation. Well controlled (n = 14) were grouped separately from poorly controlled (n = 25) patients. The total lymphocyte counts were not different from 50 control subjects. The percentage of T-cells detected by erythrocyte rosettes and B-cells detected by erythrocytes--antibody--complement rosettes was significantly decreased only in poorly-controlled diabetics (64.1 +/- 1.3 and 9.7 +/- 1.8, vs 71.0 +/- 1.0 and 15.3 +/- 0.6 in controls). Cells bearing receptors for the Fc fragment of IgG immunoglobulins were decreased in both groups. Mitogen stimulation was not different from controls but was significantly lower in poorly controlled than in well controlled diabetics. Optimal blood glucose control for 5 +/- 2 days using an external artificial pancreas led to a rapid normalisation of membrane marker values and mitogen responsiveness of lymphocytes from previously poorly controlled diabetics. Separate in vitro experiments showed that glucose had an inhibitory effect on mitogen stimulation at concentrations greater than or equal to 8.3 mmol/l and on T- and B-lymphocyte numbers at concentrations greater than or equal to 55.6 mmol/l. DL 3-hydroxybutyrate tested at 17.1 and 34.2 mmol/l only depressed mitogen responsiveness. Such results suggest a rapidly reversible T-cell defect closely linked to the existing metabolic disturbances.

Ten patients who had been totally duodeno-pancreatectomized and totally (N = 1) or partially gastrectomized (N = 9) for chronic pancreatitis (N = 9) or pancreatic carcinoma (N = 1) were investigated. None had a measurable basal level of either plasma C-peptide or a C-peptide response to i.v. glucagon. Immunoreactive glucagon (IRG) was present in all patients, and the mean level (69 ± 8 pg/ml) was not significantly different from the mean observed in normal subjects (81 ±16 pg/ml). Plasma IRG was unequivocally stimulated by arginine in 2 of the 10 subjects. The effect of somatostatin on plasma glucose and IRG during an oral glucose tolerance test was studied in 5 of the 10 patients. The effects of somatostatin on spontaneous hyperglycemia, plasma growth hormone, and IRG after withdrawal of insulin treatment was studied in 4 patients. Somatostatin blunted both the hyperglycemic and paradoxical IRG responses to the glucose challenge, and reduced the spontaneous rise of blood glucose that occurred after insulin withdrawal. This latter effect was not related to clear-cut changes in plasma growth hormone or in IRG. These data confirm the existence of circulating IRG in pancreatectomized patients and demonstrate the presence of circulating IRG in a completely gastrectomized and pancreatectomized patient. The somatostatin-induced improvement in glucose tolerance in the oral glucose tolerance test seems to be related to a reduction of the paradoxical IRG response. In contrast, the inhibition by somatostatin of the rise in blood glucose which occurs after insulin withdrawal does not seem to be mediated through IRG or growth hormone.

The intestinal absorption of iron was measured in 13 patients suffering from idiopathic hemochromatosis by using a double radiotracer technique. For each patient, iron absorption was determined in the fasting state, i.e., under basal conditions, and after an oral indigestible fiber load (9 g/m2 of body surface) with either pectin (group I: eight patients) or cellulose (group II: five patients). The results were compared with those from a group of seven normal control subjects investigated under basal conditions. The patients with haemochromatosis (groups I and II) had a significant increase in the basal value of fractional iron absorption as compared with controls. In the patients of group I, the pectin induced a significant fall in fractional iron absorption (P less than 0.02). In group II, iron absorption rates remained unchanged whether or not cellulose was given. Furthermore, we found in vitro that pectin had a high iron binding activity, while cellulose bound none. From the present study, we conclude that pectin but not cellulose reduces iron absorption by forming unabsorbable complexes with dietary iron. Thus, enrichment of the diet with foods providing significant amounts of noncellulosic dietary fibers, such as pectin, may be useful in the management of hemochromatosis patients.

Ninety five patients with Graves' disease were studied before and at three months intervals after antithyroid drugs (ATD) (31 cases) or radioiodine (64 cases) therapy until recovery. Before treatment, the T4 maxima binding capacity of TBPA was significantly decreased 253.5 +/- 11.4 mug/100 ml)(mean + se) (control values: 287 +/- 10.4 mug/100 ml) (alpha = 0.04), especially in 53.7% of patients (m = 177 +/- 8 mug/100 ml). The mean of TBG (m = 20.7 +/- 0.9 mug/100 ml) was not different from euthyroid subjects (m = 19.7 +/- 1.7 mug/100 ml) except in 51.2% of patients who had a low TBG (m = 14.3 +/- 1.1 mug/100 ml). An inverse linear correlation was found between TBG-DFT4 (alpha = 0.05) and DF T 3 (alpha = 0.002), TBPA-log DF T4 (alpha = 0.05) but not between TBG and TBPA. The physiological relationship between DFT3, DFT4, TT3, TBG and TBPA was studied in vitro; after adding increased quantities of T4 to a pool of sera collected from eu, hypo or hyperthyroid patients, DFT4, DFT3, FT3 index increased in linear positive relationship with TT4 concentrations, the kinetic of this phenomena was inversely correlated with T4 maximal binding capacity of TBG or TBPA for T4. Addition of T3 to the same sera did not show any effect on the previous parameters. DFT3 depended on the level of T4 in serum more than T3 concentration and was in inverse relationship with the maximal binding capacity of TBG. This data might explain the paradoxal normal or slightly increased values of DFT3 found in T3 thyrotoxicosis. In patients treated with ATD or radioiodine, TBPA but not TBG increased significantly on year after. However, in subjects with an initial very low TGB or TBPA, this phenomenon occurred on the third month after radioiodine or ATD. During the same period, DF T4 and DF T3 were inversely correlated to TBG and TBPA. In conclusion, important changes in T4 binding proteins and free fractions of thyroid hormones were observed in Graves' disease but were corrected by antithyroid therapy. All these data were in good agreement with the normalisation of thyroid function.

A l'aide de 68 observations de diabetes sucres evolues (20 cas), latent avec obesite (12 cas), chimique avec malaises (26 cas) et de 10 observations d'obesite sans diabete, les AA. analysent les differentes modalites de riposte insulino-secretrice lors des charges en glucose, veineuse et orale. La riposte s'avere totalement effondree dans le diabete evolue, mais susceptible de repondre encore a la stimulation par le glucagon. Dans les deux autres formes de diabete ici decrites, la stimulation par charge veineuse est reduite par rapport au sujet normal alors qu'elle est majoree apres charge orale, mais l'insuline ainsi secretee parait inefficace dans l'obesite et efficace puisque hypoglycemiante lors de malaises sans obesite.

L'etude des vitesses d'ascension et de descente glycemique par la technique de l'enregistrement continu de la glycemie permet de mesurer avec une grande precision leur acceleration tres franche dans les formes instables de la maladie. En outre, dans tous les diabetes insulines, l'insuline-retard s'avere insuffisamment efficace le matin et l'insuline ordinaire le soir. Les vitesses les plus regulieres sont obtenues avec les insulines demi-retard. Les differences de vitesses, a apport calorico-glucidique equivalent, au cours de la journee, posent le probleme d'un rythme d'efficacite de l'insuline exogene.

The authors analyze the effects of a protein overload prolonged over 3 days in 16 diabetics, 10 of whom were treated with three daily injections of standard insulin and 6 with a single injection of sustained-action insulin. The protein load appears to act as a hyperglycemic when taken at breakfast and at the evening meal. Following the noonday meal, however, it seems to have an antidiabeticeffect. It is possible that the difference in physical muscular activity after the midday andevening meal has an influence on the results.

This study reports our first total implantation of an insulin minipump in a severely unstable 23-year-old female insulin-dependent diabetic. The implantable unit includes a stepping motor, a per-cutaneously refillable insulin reservoir (10 ml, U 100 special insulin), a battery with a life span of one year, and a method for prevention of overdosage. Variable continuous basal and superimposed 1-hour high rates are programmed and checked via an external remote controller. The pump was inserted in the lateral muscles of the abdomen and the insulin delivery catheter terminated in the peritoneal cavity. Excellent glycemic control was reached rapidly and has continued seven months after implantation (mean blood glucose is 123 ± 62 mg/dl; glycosylated hemoglobin is 7.0 ± 1.2%), with the unit providing the only source of insulin. The only negative aspects were a chronic lymphorrhea in the first two months, and a need for frequent and laborious insulin refills (every 20 days). Only slight local discomfort was experienced. Thus, although further miniaturization and autonomy are expected, these preliminary results show that with careful instruction and followup, implanted pumps could represent a reliable and safe alternative to conventional insulin therapy for selected diabetics.

Twenty-five children born of 23 diabetic mothers, 17 of whom were treated with insulin, underwent glucose tolerance tests with estimation of blood insulin levels. These tests were performed on a regular basis before the age of five years, then every two years. Blood glucose and insulin disturbances were slight but appeared frequently since they were present in 56% of our cases. Our data show that blood glucose disturbances in children of diabetic mothers are more common if the diabetes of the mother suggests a maturity onset type on the basis of accompanying symptoms and treatment, and hence not insulin dependent. In this case, the chances that the child will become diabetic are much greater and this may be detected very early by a minor disturbance in the oral glucose tolerance test.

HLA typing has been carried out in 100 caucasions with Graves' disease and compared with 270 healthy controls. 25 HL-A antigens were characterized using a lymphocytotoxicity micro-technique. Analysis of the results reveals an increased incidence of HLA-B8 antigen (35% in patients as compared to 16.3% in controls) with a high degree of statistical significance: p = 0.0002 and corrected p (X 25) = 0.005. We did not observe a clear-cut correlation between the presence of HLA-B8 and different characteristics of the disease: sex, age of onset, familial history, exophtalmia, goiter, severity. The knowledge of the relationships between the HLA B8 gene and several auto-immune diseases is a strong argument in favor of the auto-immune nature of Graves' disease. The association between HLA B8 and Graves' disease could be explained by a close linkage between the second HLA locus and one or several Ir-IrG loci, occupied in predisposed individuals by "predisposing" alleles. In these subjects, an antigenic contact with an exogenous etiological agent would induce a pathological immune response, with production of thyroid stimulating IgG.

Long term experience with the use of sulfonylurea and/or biguanide oral hypoglycemic agents in patients under the age of 30 years shows the following results: 1) Oral treatment under 30 years of age is effective only for a limited period of time, in the large majority less than 24 months;--2) The success of oral treatment of diabetics and the period of effectiveness is increased if the subject is overweight at the time of discovery of the diabetes mellitus;--3) The type of antidiabetic treatment, i.e., insulin only, oral only, or oral and insulin, does not influence the susceptibility to the complications likely to appear in this age group, such as retinopathy, coronary disease, neuropathies and urinary and dental infections;--4) Poteinuria, peripheral vascular disease and various abnormalities of plasma lipids involving cholesterol and triglycerides, are significantly more common in patients under oral therapy than in those receiving insulin. These findings suggest the necessity for serious reconsideration of therapy as soon as any of these pathological events appear, especially the proteinuria or the lipid anomalies;--5) The duration of the oral treatment preceding therapeutic insulin does not have influence on the subsequent metabolic disturbance (hypoglycemia, deto-acidosis) and thus on the ultimate control of the diabetic state;--6) The somatic growth of the diabetic child is maintained regardless of the type of treatment as long as it is effective. Growth is interrupted however very early if oral treatment becomes ineffective with regard to control of the diabetes. Monitoring of somatic growth during oral antidiabetic treatment is of obvious importance. An interruption in growth is an indication for insulin therapy even if the diabetic control appears satisfactory;--7) The course and the outcome of pregnancy do not appear to be affected by the use of oral therapy at the time of conception. This holds true also for cases in which oral treatment precedes the use of insulin, the pregnancy having commenced during the course of insulin therapy.

Peripheral T lymphocyte subsets were investigated, using monoclonal antibodies, in 14 patients with acute diabetes of duration less than 1 month (before insulin treatment) and after prolonged strict blood glucose control, and also in 40 healthy volunteers. At the time of diagnosis, the percentage total T cells was decreased (67.6 +/- 8.4 versus 72.8 +/- 6.6%), but T4 'helper' cells and T8 'suppressor/cytotoxic' cells were in the normal range. The T4/T8 ratio was not significantly higher than in the control group and B-cell percentages were increased (IgS: 18.3 +/- 7.1 versus 12.4 +/- 4.9%). The second T cell enumeration, performed after sustained normoglycaemia, showed a normal total T cell percentage and a decrease in the T4/T8 ratio depending on a decrease of T4 cells (38.3 +/- 12.8 versus 49.3 +/- 13.4), without any change of T8 lymphocytes; B cells remained elevated. These results suggest that insulin deficiency/metabolic derangement was responsible for an imbalance of circulating lymphocytes and underlines the importance of metabolic control in the assessment of such immunological parameters.

The effect of an insulin-induced hypoglycemia was examined in 14 type I diabetic patients. After an overnight blood glucose normalization, each patient received an additional intravenous bolus of 3 U regular insulin at 0900 h (time 0). Blood glucose was continuously recorded up to 180 min. Plasma samples were assayed for beta-thromboglobulin (beta TG, ng/ml), pancreatic glucagon (pg/ml), cortisol (microgram/dl), and growth hormone (ng/ml) 30 min before the insulin stress, at time 0, at blood glucose nadir, and at 180 min. The blood glucose fell from a baseline level of 85.0 +/- 3.2 mg/dl to a nadir value of 39.2 +/- 1.9 mg/dl (P less than 0.001) reached at an average time of 41.4 +/- 4.9 min. Plasma beta TG increased significantly (P less than 0.05) during the insulin stress: 93.4 +/- 23.7 ng/ml at nadir versus 42.5 +/- 5.9 at time 0. Plasma cortisol and growth hormone were significantly increased (P less than 0.02 and P less than 0.01) at nadir compared with time 0 values. Plasma pancreatic glucagon was higher at nadir than at time 0, but the difference was not significant. The present results indicate that in vivo platelet activation can be triggered by hypoglycemic episodes in insulin-treated diabetic patients.

Remission of juvenile insulin-dependent diabetes is a rare, temporary, and partial phenomenon which seems to be related to an improvement of the residual insulin secretion supported by prompt and rigorous insulin therapy. Thus, remissions allowing the replacement of insulin by oral drugs were attempted in 23 insulin dependent ketotic juvenile diabetics (age 10 +/- 2 years) of recent onset (apparent duration of diabetes 71 +/- 5 days) treated by an external artificial pancreas during 5 +/- 1 days and compared with 10 control diabetics treated by a less effective technique (preprogrammed insulin pump without feedback control) during 6 +/- 1 days. 18 (78%) remissions of long duration (1-26 months) occurred after artificial pancreas compared with 3 (30%) in the control group. Measurement of daily urinary C-peptide excretion confirmed the improvement of the residual insulin secretion in patients with insulin-induced remissions. Thus, the excellent blood glucose control given by an artificial pancreas seems necessary to lead to much more frequent remissions of diabetes than usually reported.