PubMed Health⌕ Search

Biomedical subjects

J L Selam

Publications and source records attributed to J L Selam.

At least 73 records · Page 4Linked to original sources
PubMed1990

Determination of portal insulin absorption from peritoneum via novel nonisotopic method.

The absorption mechanism of insulin administered in the peritoneal cavity (IP) is of current interest because of the near availability of implantable insulin-infusion devices for the treatment of diabetes. To determine the fraction of insulin absorbed by the portal circulation after IP administration, a novel nonisotopic method is described. Conscious fasting diabetic dogs were studied at normoglycemia via the euglycemic insulin-clamp method. Posthepatic appearance of insulin and C-peptide were measured in peripheral blood during IP or intravenous (IV) equimolar infusion of insulin and C-peptide at two sequential 3-h infusion rates of 3.2 and 12.8 pmol.kg-1.min-1. Prior studies have shown that 40-60% of portal insulin is extracted at first pass by the liver, whereas C-peptide is not extracted. Thus, the fraction (F) of IP insulin not taken up by liver at first pass and consequently the fraction absorbed by the portal circulation can be derived from insulin (I) and C-peptide (C) plasma concentration values at steady state with a monocompartmental model where F = (IIP/IIV)(CIV/CIP). The mean +/- SE value of F was 49.7 +/- 8.8%. Glucose disappearance rates were lower with IP than IV infusion but similar when peripheral insulin levels were matched. We conclude that IP insulin is almost entirely absorbed by the portal circulation and induces lower glucose disappearance rates than IV insulin because of lower peripheral circulating insulin levels. Whether these properties make the IP route a more appropriate route for insulin therapy than the subcutaneous or IV routes remains to be established.

Absorption↗
PubMed1990

Devices for insulin administration.

There is a significant need for revised, safe, and more effective insulin-delivery methods than subcutaneous injections in the treatment of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. The aim of this review is to describe the rationale and methods for better use of injection and infusion devices for intensive insulin therapy and to describe results of animal and human research that will lead to an implantable artificial pancreas. Injection devices, e.g., jet injectors, insulin pens, and access ports, cannot be considered as a major breakthrough in the quest for improved control, although they may improve the patient's comfort. External pumps have benefits over multiple injections and conventional insulin therapy only in specific subgroups of patients, e.g., those with recurrent severe hypoglycemia, but only when used by experienced personnel. The external artificial pancreas (Biostator) is also to be used by experienced personnel for limited clinical and research applications, e.g., surgery of the diabetic patient. The development of an implantable version of the artificial pancreas is linked to progress in the field of reliable long-duration glucose sensors. Finally, programmable implantable insulin pumps, used as an open-loop delivery system, are the most promising alternative to intensive subcutaneous insulin strategies in the short term, although clear evidence of improved safety and efficacy remains to be documented.

Diabetes Mellitus, Type 1↗
PubMed1990

Blood glucose levels stimulating hypoglycemic counterregulation are related to chronic diabetes control.

Intensive insulin therapy is associated with an increased risk of hypoglycemia. To assess the effects of chronic glycemic control on hypoglycemic counterregulation, 21 type I diabetic patients underwent an intravenous insulin infusion of 40 mU/kg/hr for up to 180 min. Five patients had blood glucose levels which fell below 25 mg/dl or significant neurological symptoms ensured. These patients were considered to have inadequate hypoglycemic counterregulation. Of the 16 patients having successfully completed the test, blood glucose levels stabilized at 40 +/- 2 mg/dl after 109 +/- 8 min of insulin infusion, indicating adequate hypoglycemic counterregulation. The levels at which blood glucose stabilized were compared with previous metabolic control as assessed by hemoglobin Alc. A positive correlation (r = 0.57, p = 0.02) was found between the two parameters. It is concluded that (a) long term metabolic diabetes control may affect hypoglycemic counterregulatory mechanisms and (b) intensive insulin therapy may make diabetic patients more vulnerable to hypoglycemia by lowering the effective blood glucose concentration associated with hypoglycemic counterregulation.

Adult↗
PubMed1990

Implantable insulin pumps: a major piece of computerized diabetes therapy.

There is a significant need for revised, safe and more effective insulin delivery methods than subcutaneous insulin therapy, including CSII, in the treatment of type 1 diabetes. The aim of the review is to describe the current status, issues and prospects of insulin therapy with implantable insulin pumps. The International Registry of Human Implantation reports that, as of May 1988, 249 pumps have been implanted, using the intravenous or intraperitoneal route for insulin infusion. The data suggest a reasonable safety of the method, no pump run-away having been reported and only one patient having died of severe hypoglycemia possibly related to the pump. The more recent European (POINT) and U.S. (PIMS) trials with programmable pumps have confirmed the safety and suggested a better efficacy of the method over subcutaneous insulin administration. They also have pointed out that in order to represent an acceptable alternative to existing methods, implantable pumps still have to a) cope with or increase catheter longevity, presently of 2-3 years only, namely by improving catheter biocompatibility and b) clearly prove its superiority over subcutaneous methods at controlling diabetes, using large-scale, randomized, prospective controlled studies.

Diabetes Mellitus, Type 1↗
PubMed1989

A preliminary trial of the programmable implantable medication system for insulin delivery.

We undertook a trial to determine whether an implanted insulin-delivery system, the programmable implantable medication system (PIMS), could be used to treat patients with insulin-dependent diabetes. PIMS is a pulsatile, programmable pump with a battery life expectancy of five years. The reservoir is refilled transcutaneously every two months with a surfactant-stabilized human insulin preparation containing 400 U of insulin per milliliter. Eighteen patients received PIMS-delivered insulin for 4 to 25 months (mean, 18). The total PIMS-implantation experience comprised 28 patient-years. Good glycemic control was established and sustained during treatment (mean plasma glucose level, 7.3 mmol per liter; mean glycohemoglobin level, 8 percent [upper limit of normal, 7.5 percent]), with significantly reduced glycemic fluctuations. The total mean daily insulin dose did not change. Insulin solutions withdrawn from the pump reservoirs contained 92 percent native insulin and preserved biologic activity. There were no surgical or skin complications, severe hypoglycemic episodes, or instances of diabetic ketoacidosis. One pump was replaced because of a manufacturing defect, and four patients had catheter blockages due to omental-tissue encapsulation; two withdrew from the study and two had devices that were repaired successfully. The actuarial rate of survival of catheter function was 78 percent at 1.5 years. We conclude from this pilot study that insulin treatment with an implanted, variable-rate, programmable pump is feasible for periods up to two years.

Adult↗
PubMed1989

Failure to achieve tight control of plasma cholesterol and apolipoprotein B with intraperitoneal insulin infusion in type 1 diabetes.

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.

Adult↗
PubMed1989

Comparison of intraperitoneal and subcutaneous insulin administration on lipids, apolipoproteins, fuel metabolites, and hormones in type I diabetes mellitus.

The relative biologic efficacy of intraperitoneal (IP) insulin administration over peripheral routes of insulin infusion for artificial delivery devices is still poorly documented. Thus, the effects of IP insulin administration have been compared with the effects of subcutaneous (SC) insulin administration upon circulating fuel metabolites, hormones and lipoproteins. In a longitudinal study, seven type I diabetic patients, aged 33 +/- 3 years, duration 16 +/- 4 years, were studied. SC intensive insulin therapy was used for 3 months, then insulin was infused IP via an implantable pump for 6 months with a similar good blood glucose control. Lipids including high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol, apolipoproteins A-I, A-II, and B were measured every 3 months. Although all values remained in the normal range, significant changes occurred in plasma triglycerides (63 +/- 9 SC v 88 +/- 12 mg/dL IP, P less than .05) and HDL-cholesterol (57 +/- 4 SC v 42 +/- 4 mg/dL IP, P less than .05) without concomitant changes in apolipoprotein levels. In another cross-sectional study, six of the patients consumed a standardized 400 kcal breakfast after 0.15 U/kg insulin. Eight SC insulin infused age-, glucose control- and weight-matched diabetic patients also underwent the same test using SC insulin. Six normal subjects consumed the same breakfast and served as controls. Plasma glucose, B-hydroxybutyrate, lactate, alanine, free fatty acids, free insulin and glucagon were measured for five hours after the meal. All measured parameters were comparable in both groups except free insulin and lactate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effect of different insulin administration modalities on vitamin D metabolism of insulin-dependent diabetic patients.

The vitamin D status of IDDs was studied in 3 groups of patients who were treated for several months with (i) conventional insulin therapy (group I, n = 17, HbA1 = 10.1 +/- 0.5%); (ii) continuous subcutaneous insulin infusion (CSII, group II, n = 11, HbA1 = 8.9 +/- 0.6%); and (iii) continuous intraperitoneal insulin infusion (CPII, group III, n = 13, HbA1 = 8.0 +/- 0.4%). In all patient groups the plasma concentration of vitamin D metabolites were within normal range. However plasma 25 OH D (ng/ml) was significantly lower in groups I (13.0 +/- 0.8, P less than 0.01) and II (12.5 +/- 1.5, P less than 0.02) than in group III: 22.1 +/- 2.3 (normal range 7-27). Plasma 24,25-(OH)2D (ng/ml) was positively correlated to plasma 25 OH D and was significantly decreased in groups I (1.5 +/- 0.2, P less than 0.05) and II (1.4 +/- 0.2, P less than 0.05) compared with group III: 2.3 +/- 0.3. No significant differences were found in plasma 1,25-(OH)2D between the three groups of diabetics. Plasma PTH was similar in the three groups. The same differences in plasma 25 OH D were observed between the patients treated with CPII and 15 subcutaneously treated patients matched for diabetic control (HbA1 less than 10 per cent). The present results seem to indicate that insulin might have a stimulatory effect on the hepatic 25 hydroxylase activity.

Adult↗
PubMed1989

Comparison of the safety and effectiveness of human and bovine long-acting insulins.

Since ultralente insulin pharmacokinetics suggest faster absorption by human insulin when compared with bovine insulin using the subcutaneous route, the safety and efficacy of human ultralente in the outpatient setting was evaluated. Twenty type I patients participated in a randomized study using a crossover design of four six-week phases: (a) one daily injection of human ultralente; (b) two daily injections of human ultralente; (c) one daily injection of bovine ultralente and (d) two daily injections of bovine ultralente. Pre-meal human regular insulin was used with ultralente insulins and comprised 39 +/- 2% of the total daily insulin dose. Total and ultralente daily insulin doses were lower with human ultralente insulin (51.3 +/- 3.0 total and 30.9 +/- 3.4 ultra lente u/day) when compared to bovine ultralente insulin (57.8 +/- 4.4 and 36.1 +/- 4.4 u/day, p less than 0.01), yet the metabolic control achieved was virtually identical during both phases: (hemoglobin Alc 8.6 +/- 0.2% human vs. 8.4 +/- 0.4 bovine, p = NS). The frequency of mild hypoglycemia was 3.0 +/- 0.5 events per week vs 2.0 +/- 0.3 (p = NS). No severe hypoglycemia occurred. There were no differences between blood glucose daily profiles, insulin doses, hemoglobin Alc (8.6 +/- 0.4% BID vs. 8.4 +/- 0.3% QD injections) and occurrence of hypoglycemia between the single and two-dose long-acting regimens. These data indicate that long-acting semi-synthetic human insulin (a) can be effectively used as a once daily injection, (b) may be more biologically active than bovine, and (c) can be associated with safe and effective diabetes control.

Adult↗
PubMed1988

Cellular immune alterations associated with human insulin therapy.

To evaluate the immunogenicity of human insulin preparations, the treatment of 10 insulin-dependent diabetic patients was changed from purified porcine insulins to lente and regular semisynthetic human insulin (SSHI, N = 5) or NPH and regular biosynthetic human insulin (BHI, N = 5). Circulating levels of T lymphocyte subsets, in vitro responses of enriched mononuclear cells to mitogens and circulating insulin antibody measurements were performed before and during the 24 weeks of treatment. Insulin antibody levels did not change significantly in either human insulin treatment group. Circulating levels of Leu 1 and Leu 3 positive cells, identifying total and helper/inducer T lymphocyte populations respectively, and the Leu 3:Leu 2 (helper/inducer: suppressor/cytotoxic) T cell ration were all reduced (p less than 0.025) at eight weeks in the BHI treatment group. Cells identified with murine monoclonal antibody, Leu 7 defining a natural killer cell phenotype, were increased in the SSHI group at four weeks of study (p less than 0.05). There was a decreased pokeweed mitogen-induced proliferation of mononuclear cells in SSHI treated patients (p less than 0.01) at 12 weeks and both insulin treatment groups had increased responses to phytohemagglutinin (p less than 0.05) but not concanavalin A at 24 weeks. These data indicate that changes in the cellular immune system without associated changes in circulating anti-insulin antibody levels can be observed in patients whose treatment was changed from purified porcine to human insulin preparations. Thus, cellular immune responses may be more sensitive than humoral immune responses as indicators of immunological alterations to insulin preparations.

Adult↗
PubMed1988

Reduction of severe hypoglycemic events in type I (insulin dependent) diabetic patients using continuous subcutaneous insulin infusion.

In order to evaluate the safety and effectiveness of insulin pump treatment and to establish criteria for its use, we retrospectively studied 45 patients from a referral university diabetes clinic who were treated with either intensive subcutaneous insulin injections or continuous subcutaneous insulin infusion. Hemoglobin A1C was 8.5 +/- 0.3% (SEM) before and 8.1 +/- 0.1% during continuous subcutaneous insulin infusion (p = NS), but rose to 10.0 +/- 0.2% at a 16-month post-study follow-up. The frequency of ketoacidosis was 0.17 events/year before and 0.20 during infusion pump use (p = NS) and declined to 0.10 at the follow-up (p = NS). Severe hypoglycemia was reduced from 2.73 events/year to 0.22 during continuous subcutaneous infusion treatment (p less than 0.001), and from 3.72-0.32 (p less than 0.001) in a subgroup of 23 patients who initiated insulin pump treatment because of frequent and severe hypoglycemic events during intensive insulin injection treatment. Insulin pump use, compared to intensive insulin injections in a non-research setting, (a) is equally effective for maintenance of near normal glycosylated hemoglobin levels, (b) need not result in increased ketoacidosis, and (c) is effective for reducing hypoglycemic events. Thus, insulin pump treatment can benefit larger and randomized studies are needed to confirm these results.

Adult↗