Strategies for extended lifetime of implantable intraperitoneal insulin catheters

IntroductionThe effect of intraperitoneal insulin infusion has limited evidence in the literature. Therefore, the aim of the study was to investigate the pharmacokinetics and pharmacodynamics of different intraperitoneal insulin boluses. There is a lack of studies comparing the insulin appearance in the systemic circulation after intraperitoneal compared with subcutaneous insulin delivery. Thus, we also aimed for a comparison with the subcutaneous route.Research design and methodsEight anesthetized, non-diabetic pigs were given three different intraperitoneal insulin boluses (2, 5 and 10 U). The order of boluses for the last six pigs was randomized. Endogenous insulin and glucagon release were suppressed by repeated somatostatin analog injections. The first pig was used to identify the infusion rate of glucose to maintain stable glucose values throughout the experiment. The estimated difference between insulin boluses was compared using two-way analysis of variance (GraphPad Prism V.8).In addition, a trial of three pigs which received subcutaneous insulin boluses was included for comparison with intraperitoneal insulin boluses.ResultsDecreased mean blood glucose levels were observed after 5 and 10 U intraperitoneal insulin boluses compared with the 2 U boluses. No changes in circulating insulin levels were observed after the 2 and 5 U intraperitoneal boluses, while increased circulating insulin levels were observed after the 10 U intraperitoneal boluses. Subcutaneously injected insulin resulted in higher values of circulating insulin compared with the corresponding intraperitoneal boluses.ConclusionsSmaller intraperitoneal boluses of insulin have an effect on circulating glucose levels without increasing insulin levels in the systemic circulation. By increasing the insulin bolus, a major increase in circulating insulin was observed, with a minor additive effect on circulating glucose levels. This is compatible with a close to 100% first-pass effect in the liver after smaller intraperitoneal boluses. Subcutaneous insulin boluses markedly increased circulating insulin levels.

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Continuous intraperitoneal insulin infusion in type 1 diabetes: a 6-year post-trial follow-up

BMC Endocrine Disorders ◽

10.1186/1472-6823-14-30 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 11

Author(s):

Peter R van Dijk ◽

Susan JJ Logtenberg ◽

Klaas H Groenier ◽

Rijk OB Gans ◽

Nanne Kleefstra ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Infusion ◽

Intraperitoneal Insulin ◽

Post Trial

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Comparison of intraperitoneal, intraportal and intravenous insulin infusion

Acta Endocrinologica ◽

10.1530/acta.0.0950500 ◽

1980 ◽

Vol 95 (4) ◽

pp. 500-504 ◽

Cited By ~ 6

Author(s):

J. S. Dirch Poulsen ◽

Mogens Smith ◽

Marja Deckert ◽

Torsten Deckert

Keyword(s):

Portal Vein ◽

Peritoneal Cavity ◽

Plasma Insulin ◽

Insulin Infusion ◽

Peripheral Vein ◽

Intravenous Insulin ◽

Intraperitoneal Insulin ◽

Arterial Plasma ◽

Mini Pump

Abstract. In order to avoid complications induced by long-term infusions of insulin into the portal vein, we examined the effect of intraperitoneal (ip) insulin infusion on arterial plasma insulin and glucose concentrations in 6 pigs, made diabetic by a constant intravenous (iv) infusion of glucose, epinephrine and propranolol. Insulin was infused by an electromechanical programmable mini-pump (Pharmaject Micro Infusion System®, Pharmacia Electronics) as a booster injection of 46 mU highly purified porcine insulin Leo®/kg body weight, followed by 3 infusion periods of 30 min each with stepwise decreasing infusion rates of 1.6–0.8 and 0.2 mU/kg/min in a total volume of 192 μ1. Insulin was infused in a peripheral vein, a portal vein and into the peritoneal cavity. A steep rise of arterial plasma insulin was demonstrated followed by a slow and identical decline in the peripheral and portal experiments, whereas only a small increase of plasma insulin was seen in the ip experiment, indicating insufficient absorption of insulin from the peritoneal cavity. The decrease of plasma glucose was identical in the peripheral and portal vein experiments, indicating that insulin infused in the portal vein does not seem to have a higher hypoglycaemic effect, than insulin infused in a peripheral vein. Intraperitoneal insulin infusion seems not to be a practical substitute for iv insulin infusion.

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The effect of intraperitoneal insulin delivery on carbohydrate metabolism in type 1 (insulin-dependent) diabetic patients

Diabetes Research and Clinical Practice ◽

10.1016/0168-8227(92)90030-u ◽

1992 ◽

Vol 15 (3) ◽

pp. 237-244 ◽

Cited By ~ 6

Author(s):

L.D. Monti ◽

P.M. Piatti ◽

P.D. Home ◽

C. Tomson ◽

K.G.M.M. Alberti

Keyword(s):

Carbohydrate Metabolism ◽

Insulin Delivery ◽

Diabetic Patients ◽

Insulin Dependent ◽

Intraperitoneal Insulin ◽

Insulin Dependent Diabetic

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Splanchnic and systemic absorption of intraperitoneal insulin using a new double-tracer method

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.266.5.e750 ◽

1994 ◽

Vol 266 (5) ◽

pp. E750-E759 ◽

Cited By ~ 2

Author(s):

J. Radziuk ◽

S. Pye ◽

D. E. Seigler ◽

J. S. Skyler ◽

R. Offord ◽

...

Keyword(s):

Inferior Vena Cava ◽

Portal Vein ◽

Inferior Vena ◽

Vena Cava ◽

Systemic Absorption ◽

Tracer Method ◽

Total Recovery ◽

Before And After ◽

Intraperitoneal Insulin ◽

Serial Samples

The absorption of a bolus of intraperitoneal insulin into the splanchnic and peripheral circulations was separately assessed in dogs using an infusion of two insulin tracers (A1-[3H]insulin and B1-[3H]insulin). One tracer was infused into the superior mesenteric artery and the second into the jugular vein. Serial samples were taken before and after an injection of insulin (1 U/kg ip). Sampling was from the portal vein and the inferior vena cava. By using the principle of equivalent entry of tracer and unlabeled material, we developed two simultaneous equations for the rate of splanchnic and peripheral insulin absorption at each time point. These were solved to yield the two rates. Mean concentrations in the portal vein were approximately 25% higher than in the inferior vena cava, reflecting the splanchnic absorption. This rate accounted for almost half (51 +/- 9%) of the insulin absorbed. The remainder of the absorption was peripheral. The total recovery of intraperitoneal insulin, absorbed by either route, was 88 +/- 11%. Portal absorption peaked earlier than peripheral. Absorption by both routes was 90% complete within approximately 2 h (131 +/- 16 min). In summary, therefore, intraperitoneal insulin is rapidly and almost completely absorbed, with absorption split between the splanchnic and peripheral routes of entry.

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The Diabetic Patient on Continuous Ambulatory Peritoneal Dialysis

Peritoneal Dialysis International ◽

10.1177/089686088300301s06 ◽

1983 ◽

Vol 3 (1_suppl) ◽

pp. 16-20 ◽

Cited By ~ 5

Author(s):

C.T. Flynn

Keyword(s):

Peritoneal Dialysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Diabetic Patients ◽

Term Survival ◽

Basic Issue ◽

Insulin Dependent ◽

Intraperitoneal Insulin ◽

Insulin Dependent Diabetic

Insulin-dependent diabetics with renal failure have a relatively poor long-term survival. The basic issue, therefore, is quality of life. CAPD allows the patient to be independent. The procedure can be performed as well by the blind as by a sighted patient and thus is available to blind diabetics. Intraperitoneal insulin offers a safe, consistent and convenient control of the blood sugar. Our experience suggests that continuous ambulatory peritoneal dialysis is the dialytic treatment of choice for the majority of insulin-dependent diabetic patients.

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Intraperitoneal Insulin Reduces Plasma Leptin Concentration in Diabetic Patients on CAPD

Peritoneal Dialysis International ◽

10.1177/089686080002000106 ◽

2000 ◽

Vol 20 (1) ◽

pp. 27-32 ◽

Cited By ~ 4

Author(s):

Pasi I. Nevalainen ◽

Jorma T. Lahtela ◽

Jukka Mustonen ◽

Amos Pasternack

Keyword(s):

Insulin Therapy ◽

Tertiary Care ◽

University Hospital ◽

Glucose Disposal ◽

Diabetic Patients ◽

Type I ◽

Intraperitoneal Insulin ◽

End Stage ◽

Plasma Leptin ◽

Glucose Disposal Rate

Objective To determine the effects of subcutaneous (SC) and intraperitoneal (IP) insulin on serum leptin concentration in type I diabetic patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD). Design Prospective, open, before–after study. Setting Tertiary-care university hospital. Participants Twelve type I diabetic patients with stabilized CAPD, age 43.9 ± 2.8 years, and duration of diabetes 30.4 ± 3.5 years. Intervention After stabilized CAPD therapy, all patients were treated first with SC insulin for a median of 3 months, and thereafter with IP insulin for another 3 months. Main Outcome Measures Plasma leptin, insulin sensitivity with euglycemic clamp, and glycemic and uremic status after both treatment periods. Results During SC insulin therapy, plasma leptin concentration was significantly higher than during IP insulin (19.8 ± 5.9 ng/mL and 12.8 ± 6.2 ng/mL, respectively; p < 0.001). Leptin concentration was higher in CAPD patients and was related to body mass index in both genders. No correlation was detected between plasma leptin and fasting insulin, glycemic control, glucose disposal rate, or serum lipids. Conclusion Plasma leptin concentration is lower during IP insulin therapy compared to SC insulin. Insulin has probably a direct effect on both peritoneal leptin clearance and adipose tissue leptin production. The significance of leptin in regulating appetite and anorexia in uremia remains unclear.

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