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Biomedical subjects

J L Selam

Publications and source records attributed to J L Selam.

At least 19 recordsLinked to original sources
PubMed1997

Long-term therapy of IDDM with an implantable insulin pump. The Implantable Insulin Pump Trial Study Group.

OBJECTIVE: To examine the long-term benefits and risks of treatment of IDDM with an implantable programmable insulin pump. RESEARCH DESIGN AND METHODS: Seventy-six patients with IDDM were studied at nine clinical centers. After 3-4 months of intensive subcutaneous therapy, the Infusaid Model 1000 pump was implanted, and insulin was delivered either intraperitoneally or intravenously for an average of 39.6 +/- 10 months (251 patient-years). Data was collected for glycemic control, lipid levels, weight gain, insulin requirements, adverse events, and quality of life. Sixty-three patients were also followed for 8.5 +/- 6.3 months (45 patient-years) after pump therapy was discontinued. RESULTS: Mean quarterly HbA1c fell with subcutaneous intensive therapy and remained stable on implantable pump therapy between 6.9 and 7.5%. Severe hypoglycemia was relatively rare, with only 4 episodes/100 patient-years of implantable pump therapy. This rate was significantly less than with subcutaneous intensive therapy before implantable pump initiation (33 episodes/100 patient-years) or after discontinuation of implantable pump therapy (36/100 patient-years) (P < 0.003). Weight did not increase significantly in the 1st year of therapy, but increased by 2.0 +/- 4.3 kg after 3 years of therapy. There were no significant differences in metabolic control or adverse events between intraperitoneal and intravenous insulin therapy except for minor differences in lipid levels and the more frequent development of catheter obstruction with intravenous delivery. Most pump slow-downs and catheter occlusions were corrected noninvasively. Quality of life, as measured by the Diabetes Control and Complications Trial instrument, showed high satisfaction and improved impact scores. CONCLUSIONS: Long-term implantable pump therapy maintained HbA1c in a range similar to intensive subcutaneous therapy, but with fewer episodes of severe hypoglycemia. Although pump and catheter occlusions remain a limitation, patient satisfaction with implantable pump therapy remains high.

Adult↗
PubMed1997

[From the concept of fast acting analogs to the properties of the insulin Lispro].

The difficulties of achieving good glycaemic control in insulin-dependent diabetes are due in large part to the inadequacies of subcutaneously administered insulin. In particular, resorption with the long acting form is variable from one subject to another and from one day to another and irregular over time, whereas the action of the rapid acting form is too late and prolonged. The slowness of absorption of the rapid acting form is attributable to the need for hexamer dissociation. The Lilly Laboratories, by inverting the amino acids lysine and proline in positions 28 and 29 in the B chain, have created an insulin (Lispro) which more rapidly dissociates into monomers after injection. The stability of Lispro is good, probably because of its phosphate buffer. In our experience, in conditions simulating use in portable insulin pumps, Lispro proved to be more stable than insulins specially intended for this use. The affinity in vitro was identical to that of insulin for its receptor. The affinity for insulin-like growth factor-I (IGF-I) receptor has been found to be 1.5 times as high as that of fast insulin in some models and comparable in others, and nearly 1,000 times less than that of IGF-1. Studies on in vivo potency and ex vivo cell growth, as well as of tolerance in the animal (mutagenicity, toxicity and carcinogenicity), have not shown a different effect from regular insulin (contrary to results for analogue Asp B10). The pharmacokinetics has shown an earlier and higher insulinaemic peak and a more rapid return to baseline values than regular insulin. On the basis of pharmacokinetic studies in normal subjects and diabetic patients, the characteristics retained by the licensing authorities are onset of action at 15 min, insulinemic peak between 30 and 70 min, and duration of action 2 to 5 h. Some clinical studies have shown a shortened action period of 1 to 3 h as compared to regular insulin and less influence of dose and injection site, notably with a return to normal insulin levels. The time required for normalisation is increased by 1 h if the injection is made in the thigh rather than the abdomen, as compared to 2 to 3 h for conventional insulin. This suggests that Lispro should be administered just before the meal (0 to 15 min). In some patients, an insulin with prolonged action can be added if the interval between injections is prolonged, i.e. always at the evening meal but possibly also at the noon meal. Lispro can be mixed with Umuline NPH or Umuline zinc without any alteration in its pharmacokinetics and potency if the injection is performed immediately. The few studies that have considered glycaemic stability and reproducibility have shown a tendency toward improvement in glycaemic excursions during the day, as measured by MAGE, and in insulinaemia variability expressed in area under the curve, which was reduced by half in the same individual or from one individual to another, with less marked impact on the variability from one day to another of glycaemic excursions. On the whole, Lispro provides faster kinetics, greater stability and possibly better reproducibility than fast insulin. These advantages, if confirmed by clinical experience, should allow an improvement in the comfort and glycaemic stability of diabetic patients.

Humans↗
PubMed1997

[Pharmacokinetics of hypoglycemic sulfonamides: Ozidia, a new concept].

Hypoglycaemic sulfonamides differ in their properties, which vary in clinical importance. The potency of sulfonamide has increased with the generations. However, this potency is compensated in practice by the dose prescribed, which is much smaller for recent generations. The half-life is a far more important property. The effective action period is correlated with half-life but is much longer. The action period for "short-term" sulfonamides is < or = 24 h (tolbutamide, glipizide) and can exceed 24 h for "long-term" sulfonamides (e.g. glibenclamide). Metabolism and elimination reduce the risk of accumulation. All sulfonamides are metabolised more than 95% by the liver. The metabolites are inactive except for one from glibenclamide. As a function of their action period and possibly of intrinsic properties, some sulfonamides more than others (e.g. glibenclamide) affect fasting hepatic glucose production, which is particularly increased early in the day in non-insulin-dependent diabetic patients because of a circadian drop in insulin sensitivity (dawn phenomenon). Finally, in chronic administration, all sulfonamides cause a progressive desensitisation of the beta cell, which responds by an insulin secretion peak only during food intake. This condition indicates the unuselessness of sulfonamide fractionation and, contrary to the classic notion, the low risk of hypoglycaemia after a meal is skipped. The ideal product would be a sulfonamide with high potency and an ultra-short half-life, but capable of maintaining plasma concentrations for 24 h (which might seem incompatible except in continuous administration). Moreover, it would exert its action at relatively low levels of insulinaemia and be completely metabolisable. Glipizide in its osmotic oral form (Ozidia) satisfies all these conditions since it is a very potent sulfonamide with a quite short half-life but with intestinal delivery up to 16 h after administration because of its osmotic principle. It controls fasting glycaema better than ordinary glipizide and at least as well as glibenclamide by acting on hepatic glucose production. Compared to glibenclamide, it has the advantage of generation this effect at lower levels of insulinaemia. In comparison with normal glipizide, it allows identical control for lower postprandial inslinaemias, which is proof of its powerful inductive effect on insulin sensitivity.

Administration, Oral↗
PubMed1997

Extreme insulin resistance: clinical management by external subcutaneous insulin infusion.

Management of very high insulin requirements in rare extreme insulin resistance syndromes is difficult and poorly documented. We report a case of a type B insulin-resistant patient requiring approximately 10,000 units of insulin per day, i.e. beyond the possibilities of current insulin formulations and delivery devices. Only the Panomat C10 portable pump model (Disetronic) and U500 Humulin (Lilly) allowed the required rate of 400 units per hour to be attained only when the reservoir was changed twice daily and the site and catheter were changed once daily. Three months after discharge, the patient was in good general and local condition, but with only fair diabetes control (glycated haemoglobin 9.5%).

Adult↗
PubMed1996

Comparison between a rapid glycohaemoglobin (HbA1c) immunoassay and other indices of glycaemic control.

The aims of the study were to compare glycohaemoglobin (HbA1c) values measured by DCA (a benchtop analyzer primarily designed for within-clinic rapid HbA1c determination) to a reference HbA1c method and home blood glucose monitoring, and to explore the possibility of an uniform expression of data. A total of 103 blood samples and the corresponding mean capillary glucose values (4.4 +/- 1.2 tests/day) of the preceding 2 months were collected from 34 insulin-dependent diabetic adults. We measured the correlations and agreements using the residual plots method and regression equations between HbA1c measured by DCA and high-pressure liquid chromatography (HPLC), and between DCA and capillary glucose values. A highly significant correlation (r2 = 0.85, P < 0.001) and an acceptable agreement (97% of values within 2 SD of the mean difference of 0.9% +/- 0.4%) was found between DCA and HPLC values. The regression equation calculated on the first half of the cases was: DCA (%) = 0.72 HPLC (%) +1.38. Of DCA values expressed in HPLC terms using this equation 87% fell within a clinically acceptable confidence interval when compared with measured HPLC data. A significant correlation (r2 = 0.40, P < 0.01) was found between DCA and capillary glucose values, and the regression equation was: DCA (%) = 0.34 capillary glucose (mM) +4.44. Of glycaemic levels calculated from DCA values using this formula 82% fell within a clinically acceptable error range when compared with measured glycaemic values. We conclude that the three methods of assessment of diabetes control are well correlated and that it is possible, with a degree of precision acceptable for the clinical setting, to express all data in uniform units, e.g. mM of capillary glucose or percentage of HPLC-HbA1c, though a simple correspondence table based on our transfer equations may be clinically sufficient and more handy.

Adult↗
PubMed1996

Implantable insulin pumps: diagnosis and management of decreased flow rates using radionuclide investigation.

The aim of this study was to develop a diagnostic procedure for pumping unit malfunction by radionuclide imaging (RI) and to validate the method by comparing the results with those obtained using more conventional methods. Fifteen radionuclide investigations were performed in 11 patients with intraperitoneal implantable insulin pumps. One mCi of 99 mTc in 1 ml isotonic sodium chloride was injected into the reservoir. The results based on catheter visualization and peritoneal accumulation were compared blindly to the efficacy of alkaline rinses and laparoscopic findings. In all RI stoppage cases except one alkaline rinses failed to restore flow. Where laparoscopy was performed, comparisons were concordant i.e. no outflow from the tip of the catheter. The RI images obtained were reproduced in vitro using a pump under normal flow conditions and complete proximal and distal catheter obstruction. RI is a safe, quick non invasive method which allows the location of the site of pump/catheter malfunction within a one step procedure and the prediction of the efficacy of sodium hydroxide rinses.

Adult↗
PubMed1995

Symptoms, hormones, and glucose fluxes during a gradual hypoglycaemia induced by intraperitoneal vs venous insulin infusion in Type I diabetes.

Intraperitoneal (IP) insulin infusion with programmable implantable pumps is associated with a reduction in hypoglycaemic events when compared to intensive diabetes management with subcutaneous insulin in patients with Type 1 diabetes mellitus. The mechanism may involve more physiological insulin kinetics, lower peripheral insulin levels or a specific hepatic action of portal insulin on hypoglycaemic counter regulation. To investigate the latter two hypotheses, we performed two hypoglycaemic clamps (controlled blood glucose decrement to 2.2 mmol l-1) in random order in 12 Type 1 diabetic patients. Insulin was infused either IP or IV for 150 min, at rates chosen to generate similar peripheral insulin levels (1 mU/kg-1 min-1 IV or 2 mU/kg-1 min-1 IP, n = 6) to evaluate direct hepatic action, or at similar rates (1 mU/kg-1 min-1 IV and IP, n = 6) to evaluate IP indirect effects via lower peripheral insulinaemia. Hepatic glucose production and glucose utilization were measured by [6.6 2H] glucose dilution technique. Glucose production was lower (1.7 +/- 0.4 vs 0.5 +/- 0.4 mg kg-1 min-1, p < 0.05), and utilization was similar at the end of the matched-insulinaemia IV and IP clamps, respectively. By contrast, glucose production was higher (1.7 +/- 0.5 IV vs 2.7 +/- 0.3 IP mg kg-1 min-1, p < 0.01) and glucose utilization lower (4.4 +/- 1.0 IV vs 3.3 +/- 0.2 IP mg kg-1 min-1, p < 0.05) with IP delivery at the end of the matched-dose clamps. Counterregulatory hormones and hypoglycaemic symptoms increased similarly in all clamps. In summary, IP insulin, when compared to IV insulin at similar delivery rates, but not at similar insulinaemia, is associated with a less negative glucose balance (glucose production-glucose utilization) during hypoglycaemia. Such a mechanism may play a role in the reduced hypoglycaemic risk seen with IP implantable pumps.

Adult↗