Intraperitoneal insulin infusion: on the way to the artificial pancreas

Creating an "artificial pancreas" (a "closed loop" insulin pump, with self-adjusting insulin abilities, based on real time continuous glucose monitoring data) – is one of the most actual medical challenges of modern engineering and cybernetics.

Artificial pancreas (AP) prototypes based on wearable insulin pump with subcutaneous insulin delivery are still problematic, mainly because of slow insulin pharmacokinetics. Intravenous insulin infusion via AP allows effectively maintain euglycaemia for inpatients, due to insulin pharmacokinetics and pharmacodynamics advantages. Unfortunately, it can’t be used for outpatients. Intraperitoneal insulin infusion is still relatively infrequently used in the world, but it is a promising alternative, compared to both previous methods due to a physiological action profile, fast insulin pharmacokinetics, relatively better safety and availability for outpatient usage.

The purpose of this review is to describe the intraperitoneal insulin infusion features for diabetes patients at a point of AP creation perspectives.

1. Renard E. Implantable closed-loop glucose-sensing and insulin delivery: the future for insulin pump therapy. Curr. Opin. Pharmacol. 2002;2(6):708-716. doi: 10.1016/S1471-4892(02)00216-3

2. Cobelli C, Renard E, Kovatchev B. Artificial pancreas: past, present, future. Diabetes. 2011;60(11):2672-2682. doi: 10.2337/db11-0654.

3. Klonoff DC. The artificial pancreas: how sweet engineering will solve bitter problems. J Diabetes Sci Technol. 2007;1:72-81. doi: 10.1177/193229680700100112

4. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. 2003;289(17):2254-2264. doi: 10.1001/jama.289.17.2254

5. Schaepelynck P, Renard E, Jeandidier N, et al. A recent survey confirms the efficacy and the safety of implanted insulin pumps during long-term use in poorly controlled type 1 diabetes patients. Diabetes Technol. Ther. 2011;13(6):657-660. doi: 10.1089/dia.2010.0209.

6. Bryant W, Greenfield JR, Chisholm DJ, Campbell LV. Diabetes guidelines: easier to preach than to practise? Med. J. Aust. 2006;185(6):305-309.

7. Govan L, Wu O, Briggs A, et al. Achieved levels of HbA1c and likelihood of hospital admission in people with type 1 diabetes in the Scottish population: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetes Care.2011;34(9):1992-1997. doi: 10.2337/dc10-2099.

8. Renard E. Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons. J Diabetes Sci Technol. 2008;2(4):735-738. 2769765.

9. Pickup JC, Keen H, Parsons JA, Alberti KG. Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. Br. Med. J. 1978;1(6107):204-207. 1602534.

10. Tamborlane WV, Sherwin RS, Genel M, Felig P. Reduction to normal of plasma glucose in juvenile diabetes by subcutaneous administration of insulin with a portable infusion pump. N. Engl. J. Med. 1979;300(11):573-578. doi: 10.1056/NEJM197903153001101.

11. Shichiri M, Kawamori R, Yamasaki Y, et al. Wearable artificial endocrine pancrease with needle-type glucose sensor. Lancet. 1982;2(8308):1129-1131. doi: 10.1016/S0140-6736(82)92788-X

12. Shichiri M, Sakakida M, Nishida K, Shimoda S. Enhanced, simplified glucose sensors: long-term clinical application of wearable artificial endocrine pancreas. Artif. Organs. 1998;22(1):32-42. doi: 10.1046/j.1525-1594.1998.06043.x

13. Hashiguchi Y, Sakakida M, Nishida K, et al. Development of a miniaturized glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method. Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients. Diabetes Care. 1994;17(5):387-396. doi: 10.2337/diacare.17.5.387

14. Kadish AH. Automation Control of Blood Sugar. I. A Servomechanism for Glucose Monitoring and Control. Am. J. Med. Electron. 1964;3:82-86.

15. Clemens AH, Chang PH, Myers RW. The development of Biostator, a Glucose Controlled Insulin Infusion System (GCIIS). Horm. Metab. Res. 1977;Suppl 7:23-33.

16. Yatabe T, Yamazaki R, Kitagawa H, et al. The evaluation of the ability of closed-loop glycemic control device to maintain the blood glucose concentration in intensive care unit patients. Crit. Care Med. 2011;39(3):575-578. doi: 10.1097/CCM.0b013e318206b9ad.

17. Kambe N, Kawahito S, Mita N, et al. Impact of newly developed, next-generation artificial endocrine pancreas. J. Med. Invest. 2015;62(1-2):41-44. doi: 10.2152/jmi.62.41.

18. Gin H, Melki V, Guerci B, et al. Clinical evaluation of a newly designed compliant side port catheter for an insulin implantable pump: the EVADIAC experience. Evaluation dans le Diabete du Traitement par Implants Actifs. Diabetes Care.2001;24(1):175. doi: 10.2337/diacare.24.1.175

19. Haveman JW, Logtenberg SJ, Kleefstra N, et al. Surgical aspects and complications of continuous intraperitoneal insulin infusion with an implantable pump. Langenbecks Arch. Surg. 2010;395(1):65-71. doi: 10.1007/s00423-008-0437-9.

20. LeBlanc H, Chauvet D, Lombrail P, Robert JJ. Glycemic control with closed-loop intraperitoneal insulin in type I diabetes. Diabetes Care. 1986;9(2):124-128. doi: 10.2337/diacare.9.2.124

21. van Dijk PR, Logtenberg SJ, Groenier KH, et al. Report of a 7 year case-control study of continuous intraperitoneal insulin infusion and subcutaneous insulin therapy among patients with poorly controlled type 1 diabetes mellitus: favourable effects on hypoglycaemic episodes. Diabetes Res. Clin. Pract. 2014;106(2):256-263. doi: 10.1016/j.diabres.2014.08.018.

22. Renard E, Place J, Cantwell M, et al. Closed-loop insulin delivery using a subcutaneous glucose sensor and intraperitoneal insulin delivery: feasibility study testing a new model for the artificial pancreas. Diabetes Care. 2010;33(1):121-127. doi: 10.2337/dc09-1080.

23. Renard. Implantable insulin delivery pumps. Minim. Invasive Ther. Allied Technol. 2004;13(5):328-335. doi: 10.1080/13645700410004582.

24. Logtenberg SJ, Kleefstra N, Houweling ST, et al. Health-related quality of life, treatment satisfaction, and costs associated with intraperitoneal versus subcutaneous insulin administration in type 1 diabetes: a randomized controlled trial. Diabetes Care.2010;33(6):1169-1172. doi: 10.2337/dc09-1758.

25. Lee JJ, Dassau E, Zisser H, Doyle FJ, 3rd. Design and in silico evaluation of an intraperitoneal-subcutaneous (IP-SC) artificial pancreas. Comput. Chem. Eng. 2014;70:180-188. doi: 10.1016/j.compchemeng.2014.02.024.

26. Shishko PI, Kovalev PA, Goncharov VG, Zajarny IU. Comparison of peripheral and portal (via the umbilical vein) routes of insulin infusion in IDDM patients. Diabetes. 1992;41(9):1042-1049. doi: 10.2337/diab.41.9.1042

27. Logtenberg SJ, Kleefstra N, Houweling ST, et al. Improved glycemic control with intraperitoneal versus subcutaneous insulin in type 1 diabetes: a randomized controlled trial. Diabetes Care. 2009;32(8):1372-1377. doi: 10.2337/dc08-2340.

28. Oskarsson PR, Lins PE, Backman L, Adamson UC. Continuous intraperitoneal insulin infusion partly restores the glucagon response to hypoglycaemia in type 1 diabetic patients. Diabetes Metab. 2000;26(2):118-124.

29. Selam JL, Medlej R, M’Bemba J, et al. Symptoms, hormones, and glucose fluxes during a gradual hypoglycaemia induced by intraperitoneal vs venous insulin infusion in Type I diabetes. Diabet. Med. 1995;12(12):1102-1109. doi: 10.1111/j.1464-5491.1995.tb00428.x.

30. Liebl A, Hoogma R, Renard E, et al. A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion. Diabetes Obes Metab. 2009;11(11):1001-1008. doi: 10.1111/j.1463-1326.2009.01059.x.

31. van Dijk PR, Logtenberg SJ, Gans RO, et al. Intraperitoneal insulin infusion: treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia. Clin. Endocrinol. (Oxf.). 2014;81(4):488-497. doi: 10.1111/cen.12546.

32. Spaan N, Teplova A, Stam G, et al. Systematic review: continuous intraperitoneal insulin infusion with implantable insulin pumps for diabetes mellitus. Acta Diabetol. 2014;51(3):339-351. doi: 10.1007/s00592-014-0557-3.

33. Renard E. Quality of life in diabetic patients treated by insulin pumps. Quality of Life Newsletter. 2002:11-12.

34. Yki-Jarvinen H, Makimattila S, Utriainen T, Rutanen EM. Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone-binding globulin and insulin-like growth factor binding protein 1 in vivo. J. Clin. Endocrinol. Metab.1995;80(11):3227-3232. doi: 10.1210/jcem.80.11.7593430.

35. Lassmann-Vague V, Raccah D, Pugeat M, et al. SHBG (sex hormone binding globulin) levels in insulin dependent diabetic patients according to the route of insulin administration. Horm. Metab. Res. 1994;26(9):436-437. doi: 10.1055/s-2007-1001725.

36. Verges B. Lipid disorders in type 1 diabetes. Diabetes Metab. 2009;35(5):353-360. doi: 10.1016/j.diabet.2009.04.004.

37. Dullaart RP. Plasma lipoprotein abnormalities in type 1 (insulin-dependent) diabetes mellitus. Neth. J. Med. 1995;46(1):44-54. doi: 10.1016/0300-2977(94)00048-E

38. Bagdade JD, Dunn FL, Eckel RH, Ritter MC. Intraperitoneal insulin therapy corrects abnormalities in cholesteryl ester transfer and lipoprotein lipase activities in insulin-dependent diabetes mellitus. Arterioscler. Thromb. 1994;14(12):1933-1939. doi: 10.1161/01.ATV.14.12.1933

39. Ruotolo G, Parlavecchia M, Taskinen MR, et al. Normalization of lipoprotein composition by intraperitoneal insulin in IDDM. Role of increased hepatic lipase activity. Diabetes Care. 1994;17(1):6-12. doi: 10.2337/diacare.17.1.6

40. Duvillard L, Florentin E, Baillot-Rudoni S, et al. Comparison of apolipoprotein B100 metabolism between continuous subcutaneous and intraperitoneal insulin therapy in type 1 diabetes. J. Clin. Endocrinol. Metab. 2005;90(10):5761-5764. doi: 10.1210/jc.2005-0989.

41. Meyer L, Jeantroux J, Riveline JP, et al. Reversible focal hepatic steatosis in type 1 diabetic patients treated with intraperitoneal insulin implantable pump therapy. Diabetes Care. 2008;31(6):e49. doi: 10.2337/dc07-2393.

42. Pereira RI, Snell-Bergeon JK, Erickson C, et al. Adiponectin dysregulation and insulin resistance in type 1 diabetes. J. Clin. Endocrinol. Metab. 2012;97(4):E642-647. doi: 10.1210/jc.2011-2542.

43. Forsblom C, Thomas MC, Moran J, et al. Serum adiponectin concentration is a positive predictor of all-cause and cardiovascular mortality in type 1 diabetes. J. Intern. Med. 2011;270(4):346-355. doi: 10.1111/j.1365-2796.2011.02406.x.

44. Hadjadj S, Aubert R, Fumeron F, et al. Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects. Diabetologia. 2005;48(6):1088-1092. doi: 10.1007/s00125-005-1747-x.

45. Schneider JG, von Eynatten M, Schiekofer S, et al. Low plasma adiponectin levels are associated with increased hepatic lipase activity in vivo. Diabetes Care. 2005;28(9):2181-2186. doi: 10.2337/diacare.28.9.2181

46. von Eynatten M, Schneider JG, Humpert PM, et al. Decreased plasma lipoprotein lipase in hypoadiponectinemia: an association independent of systemic inflammation and insulin resistance. Diabetes Care. 2004;27(12):2925-2929. doi: 10.2337/diacare.27.12.2925

47. Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest. 2006;116(7):1784-1792. doi: 10.1172/JCI29126.

48. Colette C, Pares-Herbute N, Monnier L, et al. Effect of different insulin administration modalities on vitamin D metabolism of insulin-dependent diabetic patients. Horm. Metab. Res. 1989;21(1):37-41. doi: 10.1055/s-2007-1009144.

49. Olsen CL, Chan E, Turner DS, et al. Insulin antibody responses after long-term intraperitoneal insulin administration via implantable programmable insulin delivery systems. Diabetes Care. 1994;17(3):169-176. doi: 10.2337/diacare.17.3.169

50. van Dijk PR, Logtenberg SJ, Groenier KH, et al. Complications of continuous intraperitoneal insulin infusion with an implantable pump. World J Diabetes. 2012;3(8):142-148. doi: 10.4239/wjd.v3.i8.142.

51. Jeandidier N, Boullu S, Delatte E, et al. High antigenicity of intraperitoneal insulin infusion via implantable devices: preliminary rat studies. Horm. Metab. Res. 2001;33(1):34-38. doi: 10.1055/s-2001-12624.

52. Dufaitre-Patouraux L, Riveline JP, Renard E, et al. 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. Diabetes Metab.2006;32(5 Pt 1):427-432. doi: 10.1016/S1262-3636(07)70300-2

53. Lassmann-Vague V, Belicar P, Raccah D, et al. Immunogenicity of long-term intraperitoneal insulin administration with implantable programmable pumps. Metabolic consequences. Diabetes Care. 1995;18(4):498-503. doi: 10.2337/diacare.18.4.498

54. Schade DS, Eaton RP, Davis T, et al. The kinetics of peritoneal insulin absorption. Metabolism. 1981;30(2):149-155. doi: 10.1016/0026-0495(81)90164-5

55. Radziuk J, Pye S, Seigler DE, et al. Splanchnic and systemic absorption of intraperitoneal insulin using a new double-tracer method. Am. J. Physiol. 1994;266(5 Pt 1):E750-759.

56. Botz CK, Leibel BS, Zingg W, et al. Comparison of peripheral and portal routes of insulin infusion by a computer-controlled insulin infusion system (artificial endocrine pancreas). Diabetes. 1976;25(8):691-700. doi: 10.2337/diab.25.8.691

57. Steil GM, Panteleon AE, Rebrin K. Closed-loop insulin delivery-the path to physiological glucose control. Adv Drug Deliv Rev. 2004;56(2):125-144. doi: 10.1016/j.addr.2003.08.011

58. Selam JL, Bergman RN, Raccah D, et al. Determination of portal insulin absorption from peritoneum via novel nonisotopic method. Diabetes. 1990;39(11):1361-1365. doi: 10.2337/diab.39.11.1361

59. Nathan DM, Dunn FL, Bruch J, et al. Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients. Am. J. Med. 1996;100(4):412-417. doi: 10.1016/s0002-9343(97)89516-2.

60. Schaepelynck Belicar P, Vague P, Lassmann-Vague V. Reproducibility of plasma insulin kinetics during intraperitoneal insulin treatment by programmable pumps. Diabetes Metab. 2003;29(4 Pt 1):344-348. doi: 10.1016/S1262-3636(07)70045-9

61. Nathan DM, Dunn FL, Bruch J, et al. Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients. The American Journal of Medicine.100(4):412-417. doi: 10.1016/S0002-9343(97)89516-2.

62. Schade DS, Eaton RP, Friedman N, Spencer W. The intravenous, intraperitoneal, and subcutaneous routes of insulin delivery in diabetic man. Diabetes. 1979;28(12):1069-1072. doi: 10.1016/S1262-3636(07)70045-9

63. Giacca A, Caumo A, Galimberti G, et al. Peritoneal and subcutaneous absorption of insulin in type I diabetic subjects. J. Clin. Endocrinol. Metab. 1993;77(3):738-742. doi: 10.1210/jcem.77.3.8370695.

64. Nathan DM, Dunn FL, Bruch J, et al. Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients. The American Journal of Medicine. 1996;100(4):412-417. doi: 10.1016/s0002-9343(97)89516-2.

65. Palerm CC. Physiologic insulin delivery with insulin feedback: a control systems perspective. Comput. Methods Programs Biomed. 2011;102(2):130-137. doi: 10.1016/j.cmpb.2010.06.007.

66. Parker RS, Doyle FJ, 3rd, Peppas NA. A model-based algorithm for blood glucose control in type I diabetic patients. IEEE Trans. Biomed. Eng. 1999;46(2):148-157. doi: 10.1109/10.740877

67. Grosman B, Dassau E, Zisser HC, et al. Zone model predictive control: a strategy to minimize hyper- and hypoglycemic events. J Diabetes Sci Technol. 2010;4(4):961-975. doi: 10.1177/193229681000400428

68. Kovatchev BP, Breton M, Man CD, Cobelli C. In silico preclinical trials: a proof of concept in closed-loop control of type 1 diabetes. J. Diabetes Sci. Technol. 2009;3(1):44-55. doi: 10.1177/193229680900300106