Biomedical subjects

J L Selam

Publications and source records attributed to J L Selam.

At least 19 recordsLinked to original sources

PubMed2006

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

Adult↗

PubMed2003

Effects of dipeptide administration on hypoglycaemic counterregulation in type 1 diabetes.

OBJECTIVES: To investigate if a dipeptide made of glutamine and alanine is able to contribute to the recovery from insulin-induced hypoglycaemia in type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifteen adult type 1 patients were randomly assigned to study group (n=7): intravenous infusion of 20 g Dipeptiven in normal saline (i.e., 8 g alanine and 13 g glutamine), or control group (n=8): same infusion, normal saline only. A 150 min gradual hypoglycaemic hyperinsulinemic clamp was administered after 2 h of infusion. Counterregularory hormones, symptoms, and cognitive function (4 choice reaction test) were regularly measured during the study. RESULTS: Blood glucose and glucose infusion rates were similar in the 2 groups. Circulating levels of alanine and glutamine peaked at 90 min and remained elevated throughout the test. This was associated with significant differences in: glucagonemia 107 +/- 20 vs 58 +/- 8 pg/ml, and neuroglycopenic symptoms scores: 7 +/- 3 vs 18 +/- 13, at t 150 min, in study and control group, p<0.05. Dysautonomic symptoms, cognitive tests as well as epinephrine, norepinephrine, cortisol and growth hormone were similar between groups. CONCLUSION: Intravenous infusion of a dipeptide made of alanine and glutamine is capable to reactivate glucagon secretion during insulin-induced hypoglycaemia and to reduce hypoglycaemic symptoms.

Adult↗

PubMed2003

Combined improvements in implantable pump technology and insulin stability allow safe and effective long term intraperitoneal insulin delivery in type 1 diabetic patients: the EVADIAC experience.

OBJECTIVE: To report a long-term multicentre experience with implantable insulin pumps in type 1 diabetic patients, and to test safety and accuracy of the systems following improvements in infused insulin solutions and peritoneal catheter. RESEARCH DESIGN AND METHODS: Forty MiniMed Implantable Pumps model 2001 were consecutively implanted over a two-month period in type 1 diabetic volunteers. The systems were equipped by a new compliant sideport catheter and were refilled at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical stability in vitro. Safety was assessed from the incidence of acute adverse events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was measured at each pump refill by comparing residual insulin in the pump reservoir with expected amount according to programmed infusion. The study lasted until pump battery depletion or premature pump explantation. RESULTS: Cumulated experience was 106 patient-years. Premature explantations occurred in 3 cases, due to one electronic pump failure and two "pump-pocket" infections. Near-normal insulin delivery was sustained until expected battery depletion in 13 cases. Forty underdelivery events occurred in 24 pumps, but 36 among them were related to pump slowdowns due to insulin aggregation in pumps that were promptly solved by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by catheter obstructions that required laparoscopy to remove peritoneal tissue overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only one severe hypoglycemia and one ketoacidosis occurred during the whole study. CONCLUSION: Our current experience with improved implantable pumps and insulin solutions shows both long-term safety and effectiveness of this treatment in type 1 diabetic patients following improvement in infused insulin solutions and catheter. This therapy may be a good alternative for patients that experience frequent severe hypoglycemia with intensive subcutaneous insulin therapy.

Adult↗

PubMed2001

Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus.

AIMS/HYPOTHESIS: Ninety percent of all men with diabetes have Type II (non-insulin-dependent) diabetes mellitus, and erectile dysfunction (ED) is common in this patient group. This study evaluated the effects of sildenafil on men with erectile dysfunction and Type II diabetes and compared the results with glycated haemoglobin concentrations and chronic diabetic complications. METHODS: Patients (mean age, 59 years) in this double-blind, placebo-controlled trial were randomised to sildenafil (25-100 mg; n = 110) or matching placebo (n = 109) for 12 weeks. Primary criteria for efficacy included questions 3 (achieving an erection) and 4 (maintaining an erection) from the International Index of Erectile Function (IIEF, score range, 0-5). Secondary outcome measures included a global efficacy question (GEQ), patient event logs, a life satisfaction checklist, and the remaining IIEF questions. RESULTS: After 12 weeks, the mean scores for questions 3 and 4 had improved significantly in patients receiving sildenafil (3.42 +/- 0.23 and 3.35 +/- 0.24) compared with placebo (1.86 +/- 0.22 and 1.84 +/- 0.23; p < 0.0001). Similarly, the GEQ score was higher in the sildenafil (64.6 %) than the placebo group (10.5 %). Even when correlating efficacy with glycated haemoglobin concentrations ( < or = 8.3 % or > 8.3 %, the median concentration found in this study) or the number of diabetic complications (0 or > or = 1), the mean scores for the GEQ and questions 3 and 4 from the IIEF remained higher for all the sildenafil groups compared with the placebo groups (p < 0.0001). CONCLUSION/INTERPRETATION: Sildenafil was well-tolerated and effective in improving erectile dysfunction in men with Type II diabetes, even in patients with poor glycaemic control and chronic complications.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

Efficacy and tolerance of intranasal insulin administered during 4 months in severely hyperglycaemic Type 2 diabetic patients with oral drug failure: a cross-over study.

AIMS: We have evaluated the local tolerance and the metabolic efficacy of a lyophilized nasal insulin preparation in 10 severely hyperglycaemic Type 2 diabetic patients. METHODS: The study included two 4-month randomized periods: (A) three preprandial doses of nasal insulin secondarily combined with one evening subcutaneous NPH if the desired glycaemic control was not achieved; (B) two NPH injections daily. We assessed: (i) diabetes control on monthly HbA1c levels and occurrence of hypoglycaemic events; (ii) local tolerance on clinical symptoms, rhinoscopy, nasal muco-ciliary clearance and nasal biopsies; (iii) insulin absorption at months 0 and 4. RESULTS: One patient was withdrawn because of cough and dizziness after each nasal application. HbA1c was not significantly different at month 4 (9.4 +/- 0.5% vs. 8.8 +/- 0.2%, A vs. B). Blood glucose control remained only fair in the majority of our patients. Nasal insulin was able to replace the daytime fraction of the subcutaneous insulin with a 18% efficacy. Side-effects included transient nasal hyperactivity (pruritus, sneezing and rhinorrhoea) and chronic persistence of nasal crusts. Plasma insulin profiles were not significantly different between months 0 and 4. CONCLUSIONS: The utilization of nasal insulin (with or without NPH) was associated with similar diabetes control compared with NPH twice daily. Nasal insulin alone was able to achieve an adequate glycaemic control in three of the 10 patients.

Administration, Intranasal↗

PubMed2001

Beta-cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetes.

BACKGROUND AND AIMS: Secondary failure to oral hypoglycaemic agents, a common evolution of long-standing Type 2 diabetes, is usually assessed by non-standardized indices requiring fine clinical assessment, including hyperglycaemia resistant to maximum doses of sulphonylureas despite appropriate diet and follow-up. The goal of this study was to evaluate if HOMA, a modelized plasma insulin/glucose ratio allowing simple evaluation of residual insulin secretion and sensitivity, is a better predictor of the insulin requiring stage than clinical indices. MATERIALS AND METHODS: HOMA was measured in 84 Type 2 diabetic patients aged 58 +/- SD 6 years, with diabetes duration 11 +/- 4 years, hospitalized because of hyperglycaemia resistant to maximal doses of sulphonylureas (e.g. glibenclamide > or = 15 mg/day), with no apparent external reason for hyperglycaemia. Despite reinforced appropriate diet recommendations, 62 of these patients remained hyperglycaemic (insulin-requiring group). RESULTS: Age, duration of diabetes, body mass index (BMI) and HOMA value for insulin sensitivity (71 +/- 6% vs. 76 +/- 7%, normal values 59-161%) were comparable in the two groups. HbA(1c) was higher (10.0 +/- 0.2% vs. 8.3 +/- 0.3%, P < 0.001) and HOMA insulin secretion values lower (25 +/- 2% vs. 43 +/- 6%, normal values 70-150%, P < 0.01) in the insulin-requiring group. Of the following potential predictors: HbA(1c) > 8%, duration of diabetes > or = 10 years, HbA(1c) combined with diabetes duration, insulin sensitivity < or = 40%, insulin secretion < or = 20%, the latter showed the best positive predictivity (86% patients with low insulin secretion were insulin-requiring). CONCLUSIONS: (i) HOMA is a simple and good predictor of the insulin-requiring stage in Type 2 diabetes mellitus; (ii) this stage of diabetes is characterized by a further decline of insulin secretion rather than of insulin sensitivity. Diabet. Med. 18, 584-588 (2001)

Biomarkers↗

PubMed2001

External and implantable insulin pumps: current place in the treatment of diabetes.

External insulin infusion (CSII) pumps have regained interest since DCCT, the number of patients approaching 100,000 in the USA. Only 2 manufacturers (Minimed, Disetronic) and 2 insulins (lispro, insuman) are sharing the market. The major advantages over multiple s.c. injections (MDI) are a reduction of nightly instability and hypoglycemia, and time flexibility. Patients poorly controlled under MDI and/or with recurrent hypoglycemias thus represent the best indications. Pumps are predicted to expand in some european countries e.g. France with changes in reimbursement regulations. Implantable insulin pumps are still not commercialized except in few countries e.g. France. Therefore only 1065 pumps have been implanted worldwide so far. The only material available is the Minimed 2007 pump, with the Aventis Genapol insulin. The catheter is intraperitoneal for portal insulin absorption. Metabolic results are better than CSII in terms of glycemic fluctuations and hypoglycemias. Adverse events are limited to catheter obstructions (15% per patient-year). Ideally, indications should be restricted only to patients with recurrent severe hypoglycemias and/or poor control with CSII because of high cost of the pump ($ 15,000).

Diabetes Mellitus↗

PubMed2001

Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: efficacy vs subcutaneous injections and local tolerance.

OBJECTIVE: Nasal insulin administration is a potential route for intensive insulin management, less invasive and more rapid than subcutaneous injections. Previous studies have shown poor bioavailability (less than 15%) with nasal insulin administration with various absorption enhancers. The aim of the study was to evaluate in type 1 diabetic patients, the metabolic efficacy and local tolerance of a new gelified sprayed nasal insulin containing glychocolate and methylcellulose as absorption promoters. MATERIAL AND METHODS: The study was conducted in 16 type 1 diabetic patients (HbA1c 8.6+/-0.2%) in a cross-over trial including 2 six month randomized periods: a) NPH twice daily + 3 pre-prandial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia; b) NPH twice daily + 3 pre-prandial regular insulin injections. End points were HbA1c levels, hypoglycaemic episodes and tolerance evaluated at month 0, 2, 6 and 8 on clinical symptoms and objective nasal assessments. RESULTS: Four patients were withdrawn because of nasal burning (3 cases) and persistent sinusitis (1 case), and one patient had purulent sinusitis at the month 6 examination. At month 6, HbA1c levels were comparable (8.3 +/- 0.1 vs 8.6 +/- 0.1%, m +/- SEM, NS) for nasal and subcutaneous period respectively. The number of hypoglycaemic events was identical during the 2 periods (88 episodes). Nasal tolerance with the gelified form was better than with the already reported lyophilized form but, when present, symptoms were more marked, suggesting a potentiating additional role of methylcellulose excipient on nasal intolerance. CONCLUSIONS: 1) Gelified nasal insulin is as efficient as subcutaneous regular insulin in type 1 diabetic patients. 2) Other galenic forms should be investigated to improve nasal tolerance and bioavailability.

Administration, Intranasal↗

PubMed2001

[Inhaled insulin: clinical results in type 2 diabetic patients].

French type 2 diabetic patients are underinsulinised mainly because of fear of injections. Among all alternatives to the subcutaneous route, only the lung has a sufficient bioavailability of 10% without addition of promoters. This is made possible by the large surface and thinness of the alveolo-capillary barrier, and only if insulin particles have an ideal size (2-3 microns). The Pfizer-Aventis-Inhale project utilises powder aerosolisation, whether the Novo-Aradigm project utilises liquid nebulization. In the former project, phase 1 studies have shown plasma kinetics similar to subcutaneous lispro, and intrasubject reproducibility non significantly different from rapid and lispro insulins. Phase 2 studies, performed on more than 200 insulin-treated and non insulin-treated subjects have shown an efficacy similar to subcutaneous insulin, with no difference in terms of side-effects (hypoglycaemia, weight gain) and a satisfactory 1-year local tolerance, as evaluated by functional tests. Phase 3 studies, performed on 1400 subjects have just been completed and are not published yet. Though results are promising, some important questions remain to be clarified: long term tolerance, miniaturisation of the inhaler, overcost, and long-term acceptability, especially in type 2 patients. It already appears that the major potential indications may be "functional" (flexible) insulin therapy of type 1 diabetes and early insulinisation of type 2 patients with oral drugs failure.

Administration, Inhalation↗

PubMed2000

Insufficient adaptation of hypoglycaemic threshold for cognitive impairment in tightly controlled type 1 diabetes.

UNLABELLED: It is well known that hypoglycaemic thresholds for hormones and symptoms occur at lower plasma glucose levels in patients with strict glycaemic control. However, whether the threshold for cognitive impairment also shifts is still an unresolved question. We studied 19 type 1 diabetic patients, including 8 with hypoglycaemia unawareness, aged 37.0 +/- 7.4 y.r., with diabetes duration 15.2 +/- 10.7 yr, and HbA1c 7.6 +/- 1.1%. Hypoglycaemic thresholds for hormones, symptoms, awareness and cognitive function using the 4-choice reaction time test (4RT), were measured every 30 min during a 150 min stepped 4.4 to 2.2 mM hypoglycaemic hyperinsulinemic clamp. We found that 4RT- accuracy deteriorated earlier than 4RT-time (3.2 and 2.7 mM, respectively, p<0.01), and that both correlated poorly with HbA1C before and after adjustment for age and diabetes duration (r=0.11, and 0.18, respectively). On the opposite, adrenaline, autonomic and neuroglycopenic symptoms, and awareness significantly correlated with HbA1c values (r=0.56, 0.70, 0.61, and 0.63, after adjustment, respectively). Furthermore, after allocating the patients into two subgroups according to HbA1c values (<8% n=12, and >=8% n=7), we found that, as opposed to other thresholds, accuracy and 4RT-time were minimally and not significantly influenced by glycaemic control, therefore exhibiting the smaller glucose thresholds shifts (- 0.2 and - 0.5 mM for accuracy and time, respectively, vs. 0.6 -0.8 for other thresholds). IN CONCLUSION: 1) the hypoglycaemic thresholds for cognitive dysfunction shift with strict glycaemic control, but not significantly and less than other thresholds, 2) as opposed to other reports, accuracy deteriorates earlier than speed during the 4RT test, and 3) these "maladapted" reactions may contribute to the higher risk for severe hypoglycaemia in subjects with tight glycaemic control.

Adult↗

PubMed2000

[How to measure glycemic instability?].

Instability of glycemic levels is "normal" in type 1 diabetes, with different levels of severity, up to the restrictive definition of brittle diabetes (repeated ketoacidosis and/or severe hypoglycemias). Quantification of glycemic instability, in terms of intraday variability and day-to-day reproducibility, is advisable. Standard deviation of blood glucose, though a simple index does not discriminate between slow and brutal variations. Repartition of blood glucose values also only indicates dispersion. M values compares the patient values to an ideal blood glucose level, emphasizing the role of low values. The MAGE index measures the amplitude of the largest glucose excursions, thus evaluating appropriately glycemic variability. The Low Blood Glucose Index (LBGI) is a new index of variability emphasising (as the M value) the low glycemias. Each glycemia is given a value from O (if >=110 mg/dl) to 100 (if 20 mg/dl). It thus integrates the frequency and severity of hypoglycemias. According to its authors the LBGI would be the best indicator of severe hypoglycemias. The Mean of Daily Differences (MODD) evaluates the day-to-day reproducibility of blood glucose values. All the above indexes could easily be incorporated in the programmes of large memory glucose meters.

Blood Glucose↗

PubMed2000

[How to prescribing Viagra in practice...].

Diabetes can induce sexual disorders by different mechanisms. These troubles are more frequent in diabetics subjects. Thus, management of sexual impotence is an important aspect of diabetes care. However, most diabetologists are not trained to treat sexual disorders. The recent availability of oral drugs, i. e. Sildenafil (Viagra), has partly simplified the treatment of sexual impotence, particularly in diabetic patients. However, Viagra is efficient in only 60% cases in diabetic subjects. In the remaining cases, intracavernosal injections or vacuum can be used. Since Viagra has been available, more diabetic patients complained with sexual disorders, and ask for treatment of impotence. Cardio-vascular diseases must retain more attention in diabetic patients who are exposed to silencious myocardial ischemia. In such subjects, Viagra is not contra-indicated, but must be used after myocardial explorations, especially if the patients have cardio-vascular risk factors. However, patients and their doctors have been threatened by death cases reported with Viagra in United States. The lack of detailed informations has restrained Viagra's prescription. The following explains how to manage sexual disorders as part of diabetes care, and suggests rules for Viagra's prescription in diabetic patients.

Cardiovascular Diseases↗

PubMed1999