[Insulin therapy during pregnancy: how far and how intensified?].
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Diabetes Mellitus, Type 2↗
Biomedical subjects
E Renard
Publications and source records attributed to E Renard.
[Interrelation of visceral fat and muscle mass in non insulin-dependent diabetes (type II): practical implications].
Insulin resistance, which is found in 85-95% of non-insulin-dependent diabetes mellitus (NIDDM) patients, results from three factors: genetic background (which has been widely investigated), nutritional status (mostly obesity and fat distribution) and exercise. Upper body obesity, which can be found in 85% of these subjects, can increase muscular insulin resistance through several mechanisms, the best known being a free fatty acid-induced decrease in intracellular free CoA/acylCoA that inhibits the stimulatory effect of insulin on glycolysis, glucose transport across cell membrane, and glycogen storage. However, muscle insulin resistance in NIDDM exists before adiposity and is likely to induce it. Actually, muscles of subjects at risk for NIDDM exhibit a very early defect in both glycogen storage ability and free fatty acid oxidation capacity that can impair fuel utilization and increase fat storage. Regular exercise induces muscular metabolic changes which can compensate for those diabetogenic defects and thus prove useful in the management of NIDDM. Moreover, exercise has been shown to prevent subjects at risk for NIDDM from developing overt diabetes.
Abdomen↗
Decreased severe hypoglycemia frequency during intraperitoneal insulin infusion using programmable implantable pumps. Evadiac Study Group.
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Diabetes Mellitus, Type 1↗
Insulin underdelivery from implanted pumps using peritoneal route. Determinant role of insulin pump compatibility.
OBJECTIVE: To evaluate the incidence and investigate determinants of insulin underdelivery events occurring with implanted pumps using peritoneal route from a 103 patient-year experiment. RESEARCH DESIGN AND METHODS: Of the MiniMed (MIP 2001) pumps implanted in 47 type I diabetic patients, 70 were refilled quarterly with four successive batches (A, B, C, D) of U400 Hoechst 21 PH neutral insulin during a 3-year study period. Any reduction of insulin flow rate > 15% was considered as abnormal insulin delivery. Diagnosis of the cause of underdelivery was established according to the response to the following steps: 1) 0.01 mol/l NaOH rinse of pump circuits to solubilize insulin aggregates, 2) surgical examination and replacement of blocked catheters, and 3) postsurgical 0.01 mol/l NaOH rinse of pump. Step 2 was selected first if the increase of insulin requirements or reduction of flow rate were > 50%. Relative contributions of insulin and the implanted system to underdelivery events were analyzed. RESULTS: There were 76 episodes of insulin underdelivery that occurred during the study, resulting in an incidence of 74 events per 100 patient-years. Of 52 NaOH pump rinses, 30 restored normal flow rate. Surgery, performed after rinse failure (n = 22) or as the first step (n = 24), disclosed catheter blockages due to tip obstructions in 28 cases and omental encapsulations in 18 other cases. Five combined severe reductions of pump flow rate requiring pump replacements were diagnosed during surgery, and additional NaOH rinses had to be performed after catheter change in 12 other cases. Analysis of the incidence of underdelivery events indicated that both pump- and catheter-related problems were significantly increased while implanted systems infused batches B, C, and D versus batch A (P < 0.01), whereas the duration of pump implantation had no significant influence. CONCLUSIONS: Underdelivery events constitute serious limiting obstacles to prolonged peritoneal insulin infusion from implanted pumps. Progress in insulin pump compatibility is expected to reduce their occurrence and, thus, to improve the feasibility of this treatment.
Adult↗
[Evolution of blood glucose control and retinopathy during long-term treatment of insulin-dependent diabetes mellitus with intraperitoneal infusion of insulin].
To evaluate the efficacy on blood glucose control of long-term peritoneal insulin infusion and its consequences on the evolution of diabetic retinopathy, we analyzed retrospectively the values of glycosylated haemoglobin measured quarterly and the retinal angiograms obtained after 1, 5 and 9 years from seventeen insulin-dependent diabetic patients treated by this technique during 9.0 +/- 2.2 years. Blood glucose control was significantly improved from the first year of treatment (p < 0.01). Seventy-one per cent of patients had a level of glycosylated hemoglobin below one standard deviation of normal values after five years and ninety-two per cent of 12 patients treated up to nine years remained in the same near-normal range. Glycaemic excursions below 0.5 g/l and over 2 g/l were limited to 5-7% and 15-17% of four times-daily capillary glucose measurements respectively, along the whole IP insulin infusion period. Among 7 patients with no retinopathy (n = 1) or with mild to moderate nonproliferative retinopathy, requiring no specific ophthalmological treatment, (levels 20 to 40 on worse eye according to a simplified version of ETDRS classification, n = 6), 3 remained stable, 2 improved and 2 impaired although remaining under level 50 of the classification, after 5 to 9 years. Nine patients with severe nonproliferative (level 50, n = 1) or proliferative (level 65, n = 8) retinopathy, all treated by panretinal photocoagulation before initiation of IP treatment, improved and one patient with severe nonproliferative retinopathy, incompletely treated by laser photocoagulation, remained stable, after 5 to 9 years. No macular edematous reaction or impairment of existing macular edema occurred after panretinal photocoagulation under IP treatment. These data indicate that a sustained near-normal blood glucose control can be achieved under long-term peritoneal insulin infusion, without significant impairment of diabetic retinopathy when an initial ophthalmological evaluation, and a specific treatment if necessary, are performed.
Adolescent↗
Insulin-dependent phosphatidylinositol 3'-kinase activity co-precipitates with insulin receptor in human circulating mononuclear cells.
In order to establish a working cellular model for the study of post-receptor signaling events, insulin-dependent phosphatidylinositol 3' (PtdIns 3')-kinase activity was investigated in circulating mononuclear cells from normal subjects. The p85 alpha regulatory subunit of PtdIns 3'-kinase co-precipitated with activated insulin receptor as revealed by immunoblotting. Whereas insulin receptor substrate-1 was weakly detected, insulin increased 5.5 +/- 1.5-fold (mean +/- SD) PtdIns 3'-kinase activity in receptor immunoprecipitates. We conclude that insulin-stimulated PtdIns 3'-kinase activity is measurable in circulating mononuclear cells which may constitute an easily available cellular model for the detection of post-receptor defects in insulin-resistant states.
Adult↗
Dupuytren's disease, carpal tunnel syndrome, trigger finger, and diabetes mellitus.
A comparative prospective study of 120 adult diabetics (60 insulin dependent, 60 non-insulin dependent) and 120 non-diabetic adults as controls showed significantly higher incidence of Dupuytren's disease, limited joint motion, carpal tunnel syndrome, and flexor tenosynovitis in the diabetic population. Of the diabetic patients one third had a mild non-progressive form of Dupuytren's disease, which commonly involved the long and ring rays. Limited joint motion was noted in a third of diabetics, and carpal tunnel syndrome was observed in 15-25%, and flexor tenosynovitis in about a fifth. Limited joint motion co-existed with Dupuytren's disease in 57% of insulin-dependent diabetics. Diabetic polyneuropathy was found in two thirds of insulin-dependent diabetics and in one third of non-insulin dependent diabetics. All these hand changes were more marked in insulin-dependent diabetics and they showed a positive correlation with increasing age of the patient, duration of the diabetes, and the presence of a microangiopathy.
Adult↗
Catheter complications associated with implantable systems for peritoneal insulin delivery. An analysis of frequency, predisposing factors, and obstructing materials.
OBJECTIVE: To evaluate catheter survival and identify mechanisms involved in catheter obstructions during a 109.8 patient-year experience with implanted pumps for peritoneal insulin delivery. RESEARCH DESIGN AND METHODS: Fifty-one type I diabetic patients were recruited in feasibility studies of two models of implanted systems for peritoneal insulin delivery. Both systems had a silicone-coated polyethylene catheter and infused Hoechst 21 PH neutral insulin (U400 or U100). Catheter obstruction was suspected each time the increase of insulin flow rate over 50% of usual need was insufficient to correct an impairment of glycemic control in the absence of of intercurrent factors. A laparoscopic examination was then systematically performed under general anesthesia. The disclosed material occluding the catheter was submitted to a pathological analysis. By actuarial analysis, we examined the estimated effects of the potential determinants of the catheters' duration of proper operation on catheter survival. RESULTS: Over an implantation duration of 25.8 +/- 14.0 months (mean +/- SD), 34 catheter obstructions were diagnosed in 24 patients, resulting in an incidence of 31 events per 100 patient-years. Fifty percent survival rate of the first implanted catheter was 27 months (95% confidence interval [CI]: 19-32) on actuarial analysis. Six catheters were cleared under laparoscopy and 24 were replaced, while 2 systems were definitively explanted and 2 combined replacements of pump and catheter were performed because of an associated pump slowdown. In five cases, an alkaline rinse procedure of the pump was necessary after catheter replacement to restore usual insulin needs, suggesting an associated insulin aggregation in the pump. Twenty obstructions were due to a fibrin clot at the catheter tip, and 14 obstructions were created by a tissue encapsulation around the catheter. A previous experience of peritoneal insulin infusion from portable pumps or a longer duration of diabetes ( > 21 years) both appeared as conditions significantly reducing the time of a catheter's proper operation (P < 0.01 and P < 0.05, respectively) either by tip obstructions or by encapsulations. Pathological analysis of catheter encapsulations showed a collagen fibrosis in all studied patients (n = 11), which was associated with a lymphocytic infiltrate in five patients and also with anti-insulin immunoreactive amyloid deposits in four patients. Catheter tip clots were composed of fibrinlike material, nonreactive to anti-insulin antibodies. CONCLUSIONS: Catheter obstruction is a frequent adverse technical event occurring with implanted insulin pumps. Progress is expected in the biocompatibility of catheter material and more specifically in the stability of insulin preparations to prevent immuno-inflammatory reactions and insulin amyloid deposits that appear to be involved in catheter failures.
Actuarial Analysis↗
Feasibility of intraperitoneal insulin therapy with programmable implantable pumps in IDDM. A multicenter study. The EVADIAC Study Group. Evaluation dans le Diabète du Traitement par Implants Actifs.
OBJECTIVE: To report the overall French experience, obtained through the collaboration of seven centers (EVADIAC [Evaluation dans le Diabète du Traitement par Implants Actifs] register), on the safety, feasibility, and efficacy of intraperitoneal insulin therapy by programmable implantable pumps, using three different devices. RESEARCH DESIGN AND METHODS: This is a multicenter prospective study involving 224 type I diabetic patients implanted with a programmable implantable pump (cumulative follow-up: 353 patient-years; mean duration: 1.5 +/- 0.9 years [mean +/- SD]. The Infusaid and the Promedos devices are equipped with a side port and refilled with U100 insulin (Hoechst 21 PH); the Minimed pump is not equipped with a side port and is refilled with U400 insulin (Hoechst 21 PH). Metabolic data and adverse events were recorded in a central register run by EVADIAC. RESULTS: A total of 29 local pump-pocket events (8/100 patient-years) and 9 pump failures (2.5/100 patient-years) occurred. The major technical problems were 1) pump flow rate reduction related to insulin aggregates, reversible after alkaline rinsing of the pump, and 2) 47 catheter obstructions requiring laparoscopic or conventional surgery. Pump therapy was abandoned in only 11 patients. HbA1c (7.4 +/- 1.8 vs. 6.8 +/- 1.0%, P < 0.001), mean glycemia (8.7 +/- 1.5 vs. 7.8 +/- 1.0 mmol/l, P < 0.001), and blood glucose SDs (3.8 +/- 0.8 vs. 3.3 +/- 0.8 mol/l, P < 0.001) decreased significantly after 6 months and remained lower than baseline thereafter. CONCLUSIONS: Intraperitoneal insulin infusion using an implantable programmable pump is a feasible and relatively safe technique that may improve metabolic control and glycemic stability. Long-term studies, however, are needed to demonstrate whether or not the improvement in glycemic control could be sustained for several years.
Adult↗
Cecum erosion: unusual but serious complication of an implanted catheter for peritoneal insulin delivery.
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Appendicitis↗
[Insulin pumps (portable pump for subcutaneous perfusion of insulin].
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Contraindications↗
Insulin and IGF-1 signaling in oocyte maturation.
Xenopus laevis oocytes possess insulin and/or insulin-like growth factor-1 (IGF-1) receptors and respond to respective hormones by increasing glucose transport and progressing from the G2 to M phase of the cell cycle (maturation). While molecular transduction mechanisms involving mitogen-activating kinases and cyclin-dependent kinases begin to be elucidated, missing links remain between the initial receptor tyrosine phosphorylation events and downstream signaling. The discovery that phosphotyrosines produced by receptor autophosphorylation or during substrate phosphorylation serve as an anchor for src homology 2 domains of several signaling proteins had a major impact on understanding how cytoplasmic enzymes are recruited at the level of the plasma membrane for subsequent activation.
Animals↗
Complications of the pump pocket may represent a significant cause of incidents with implanted systems for intraperitoneal insulin delivery.
OBJECTIVE: To increase awareness of adverse events associated with the use of programmable implantable pumps (PIPs). CASES: There were 7 cases of complications associated with the pump-pocket among 40 patients treated by PIP, and we searched for risk factors. RESULTS: Seven of 40 type I diabetic patients treated by PIP presented severe complications of the pump-pocket, resulting in five definitive explanations and nine other surgical interventions. The lesions included an exudative reaction in the pump-pocket and a skin retraction or atrophy, which were complicated by skin erosion in five patients. Coagulase-negative staphylococcus was identified in the pump-pocket in four patients, including three cases of skin erosion. No specific risk of local complications could be attributed to age, sex, duration of diabetes, body mass index, presence of retinopathy or peripheral neuropathy, HbA1c level since implantation, depth of implantation in the abdominal wall, or duration of experience with PIP. Usual physical activity corresponding to > 2,000 kcal energy expenditure per week, estimated by a questionnaire, appeared to be the only identified significant risk factor. CONCLUSIONS: From these results, we suggest that physical activity should be limited to moderate exercise and exclude vigorous efforts in diabetic patients treated by PIP to avoid an increased risk of complications at the implantation site.
Adolescent↗
Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system.
Insulin receptor substrate 1 (IRS-1) is the primary cytosolic substrate of the insulin and insulin-like growth factor-I (IGF-I) receptors. Following tyrosine phosphorylation IRS-1 binds to and activates specific proteins containing SH2 domains. Using biochemical and immunocytochemical techniques, we have mapped the distribution of IRS-1 in the CNS of the adult rat and compared it with that of insulin and IGF-I receptors and phosphatidylinositol 3-kinase (PI-3 kinase), a signaling molecule functionally related to IRS-1. Immunoprecipitation and Western blotting experiments demonstrate the presence of substantial amounts of IRS-1, insulin receptor, and PI-3 kinase in the brain. IRS-1 immunoreactivity is widely distributed in neurons from several areas of the brain and spinal cord. The cerebral cortex, the hippocampus, many hypothalamic and thalamic nuclei, the basal ganglia, the cerebellar cortex, the brainstem nuclei, and the lamina X of the spinal cord are particularly rich of immunopositive nerve cells. In these areas most of the neurons immunoreactive for IRS-1 are also stained by either anti-insulin receptor or anti-IGF-I receptor antibodies as well as PI-3 kinase antiserum. IRS-1 immunostaining was very weak or totally absent in neurons of the olfactory bulb, the supraoptic and paraventricular nuclei, the mesencephalic trigeminal nucleus, and the granule cell layer of the cerebellum, despite the fact that these areas were immunolabeled with antibodies against insulin or IGF-I receptors and/or PI-3 kinase. These results show that neurons in the adult rat CNS are endowed with some of the components of the early signaling pathway for growth factors of the insulin/IGF-I family, although IRS-1 has a distribution distinct from that of the two receptors.
Animals↗
[Perspectives in the treatment of type 2 diabetes. Role of insulin therapy?].
Independently of its initial mechanism, Type 2 diabetes associates in various degrees disorders in insulin sensibility and secretion. The dissociated insulin resistance among tissues explains the predictable imperfection of insulin therapy in this disease due to frequent weight increase and the potential risks of insulin on atherogenesis raised on the basis of experimental studies. All diabetic subjects are not equally insulin resistant and do not have the same insulin secretory capacity evaluated in practice by means of the response of insulin or C peptide plasma levels to various secreting agents. Intensity and duration of hyperglycaemia, muscular mass, physical activity and way of life, age, weight and fat patterning, the presence of complications, acceptance, education feasibility and compliance are essential in selecting towards insulin therapy. Meanwhile, as the results of the prospective studies in progress become available, it seems that insulin should be restricted to the smallest useful dosage possible and that weight change should be carefully checked within the weeks following initiation of insulin. The future of insulin therapy in Type 2 diabetes requires (1) better selection of patients showing a demonstrated beneficial effect of insulin, (2) the association of insulin with new molecules capable of reducing its dosage and preventing its deleterious effects, (3) a change in the mode of insulin administration, with an appropriate balance between comfort and efficacy, (4) change in the insulin structure towards analogues or compounds related to insulin but with less perverted effects.
Clinical Trials as Topic↗
Body composition and regional fat distribution in polycystic ovarian syndrome. Relationship to hormonal and metabolic profiles.
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Acanthosis Nigricans↗
[Sex steroids. Effects on the carbohydrate metabolism before and after menopause].
The action of female sex steroids on carbohydrate metabolism has clearly been demonstrated by numerous clinical and experimental studies. A beneficial effect of 17 beta oestradiol has been reported on insulin secretion and insulin sensitivity, inducing an improvement of glucose tolerance through an increase of glucose clearance by liver, muscle and adipose tissues. Progesterone has, to a lesser degree, the same stimulant effect on insulin secretion and improves glucose assimilation by the liver, although a relative insulin resistance is observed in the other two tissues. Menopausal hormonal privation does not significantly alter glucose tolerance in the absence of such predisposition factors as overweight or history of gestational or familial diabetes mellitus. The first trials of menopausal substitution with oral synthetic oestrogens, especially in doses of more than 50 micrograms per day, were responsible for the bad reputation of oestroprogestins due to their effects on metabolic parameters. As shown by prescription for contraceptive use, replacement therapy with oral synthetic oestrogens induces a diabetogenic tendency as well as hypertensive, dyslipidaemic and thrombogenic risks, especially when associated with progestins issued from nortestosterone. Reducing the oestrogen doses, using equine sulfoconjugates and selecting non-androgenic progestins has already minimized these deleterious effects. The present availability of oral or percutaneous natural 17 beta oestradiol and of norpregnanes calls for reconsideration of the glucidic risk due to oestroprogestin prescription. A few studies have already shown that in fact they can improve glucose tolerance. The recommended substitution of menopause to prevent atherosclerosis must lead to a better characterization of its glycaemic and insulinaemic effects.
Aged↗
[Thyroid nodules and non-functional goiters. Diagnostic contribution of nuclear resonance imaging].
The finding of a "cold" thyroid nodular or goiter raises the problem of its potential malignancy, usually resulting in systematic surgery. Ultrasonography and computerized tomography provide accurate information concerning the size, structure and connections of these abnormalities, but they have very little to say about their histological nature. We evaluated the contribution of magnetic resonance imaging (MRI) to the histological diagnosis by attempting tissue characterization before surgery in 97 patients with nonfunctional thyroid nodule or goiter. Comparisons with the pathological study of operative specimens showed a very small percentage (1.05 percent) of false negative results in terms of malignancy, and this was due to reliable arguments for benignity which we were able to collect from MRI signal intensity and structural analysis. Without these criteria, a decisive answer would have been very difficult, as shown by the significant rate of false positive results (14.73 percent) and a specificity of only 81.8 percent if every lesion interpreted as doubtful is considered malignant. Attention is drawn to the difficulties encountered in characterizing lesion with intracystic vegetations and in distinguishing between thyroiditis and lymphoma. The possibility of obtaining frontal and sagittal sections increases the usefulness of MRI. The operator's experience is essential in interpreting the signals and deciding on the therapeutic approach.
Adult↗