History of Insulin Pump Therapy

The notion that it would be beneficial to provide insulin in a more physiologic manner by continuous infusion began to receive serious attention in the 1970s. Early studies used intravenous delivery of insulin to achieve near-normal plasma glucose levels (1-3). Promising reports of subcutaneous delivery of insulin using portable pumps soon followed (4,5) and the concept of continuous subcutaneous insulin infusion (CSII) or ‘insulin pump therapy’ was born.

The early portable pumps were large and quite complicated to use. They offered a single basal rate, plus a stepped up rate of infusion to cover increased insulin requirement after meals. Insulin (diluted with saline) was delivered through a nylon cannula implanted in the abdominal wall (4).

It was soon demonstrated that CSII could offer an alternative means of improving glycaemic control (6,7) and the feasibility of using insulin pump therapy to obtain near-normoglycaemia during pregnancy was also recognised (8,9).

Whilst it was acknowledged that near-normoglycaemia could be achieved with the use of an insulin pump, there remained the possibility that the same improvement in glycaemic control could be achieved by using multiple daily injection regimens (10-12).

In one crossover study, it was reported that pump therapy and multiple injection regimens were both equally effective during the initial 2 – 4 day period of inpatient management. However, pump therapy was found to be more effective in achieving blood glucose control in the outpatient setting. Importantly, patients also found pump therapy preferable to multiple daily injections (13).

Longer studies were conducted in order to evaluate the long-term efficacy of insulin pump therapy. Mecklenburg and co-workers demonstrated significantly improved glycaemic control over a three year period in patients using CSII (14).

Early reports of patient satisfaction with insulin pump therapy confirmed that greater flexibility in diet and insulin delivery were appreciated (15) and many patients reported an improved quality of life associated with using an insulin pump (16).

The success of insulin pump therapy is highly dependent upon motivation of patients (15) and confidence in their own ability to self-manage diabetes (17). These factors are of importance in selecting suitable candidates for insulin pump therapy.

During the 1980s much attention was focussed on the importance of glycaemic control in relation to the development of the late complications of diabetes. CSII was widely used as a means of achieving near-normoglycaemia in such studies. The results of the Diabetes Control and Complications Trial (DCCT) (18) subsequently provided the most compelling proof that intensive treatment, aimed at achieving near-normal blood glucose levels, could prevent or delay the onset of microvascular complications. Such as retinopathy (eye disease), nephropathy (kidnbey disease) and neuropathy (damage to nerves). By the end of the study, 42 % of participants in the intensive treatment group were using insulin pump therapy (19).

Enthusiasm for CSII was tempered as potential complications specific to insulin pump therapy were realised. In particular, reports of infusion site infection (20) and accelerated ketoacidosis (21) caused concern. However, the risk of these problems is considerably reduced if patients are properly supervised, and perform frequent self-monitoring of blood glucose (SMBG) (22). Indeed, it was noted that factors such as insufficient blood glucose monitoring, failure to detect mechanical problems, failure to adhere to sick day management guidelines and delay in seeking medical assistance contribute to the risk of ketoacidosis (23). All of these factors can be minimised with careful patient selection, and thorough education and training.

The recently introduced insulin analogue insulin lispro is stable in subcutaneous insulin infusion systems (24) and has been reported to improve glycaemic control without increasing the risk of hypoglycaemia (25). Whilst there remains the possibility that metabolic deterioration may be accelerated on interruption of insulin delivery when using insulin lispro, its rapid action more effectively help correct this state (26).

 

Insulin pump therapy today

In recent years, insulin pump technology has improved considerably. Today’s pumps such as the DANA R from Sooil are smaller and less complicated to use and have advanced safety features and alarms. In addition developments in infusion technology have reduced the potential for blockage of the tube and hence the risk of ketoacidosis. The potential complications of ketoacidosis and infusion site problems can be minimized through careful selection of patients, proper education, adequate self-care skills and appropriate hygiene precautions. The American Diabetes Association recognize that CSII is as safe as multiple injection therapy, when recommended procedures are followed (27).

 

References

1. Albisser AM, Leibel BS, Ewart TG, et al. Clinical control of diabetes by the artificial pancreas. Diabetes 1974;23(5):397-404.

2. Slama G, Hautecouverture M, Assan R, Tchobroutsky G. One to five days of continuous intravenous insulin infusion on seven diabetic patients. Diabetes 1974;23(9):732-8.

3. Genuth S, Martin P. Control of hyperglycemia in adult diabetics by pulsed insulin delivery. Diabetes 1977;26(6):571-81.

4. Pickup JC, Keen H, Parsons JA, Alberti KG. Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. British Medical Journal 1978;1(6107):204-7.

5. 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. New England Journal of Medicine 1979;300(11):573-8.

6. Champion MC, Shepherd GA, Rodger NW, Dupre J. Continuous subcutaneous infusion of insulin in the management of diabetes mellitus. Diabetes 1980;29(3):206-12.

7. Home PD, Capaldo B, Burrin JM, Worth R, Alberti KG. A crossover comparison of continuous subcutaneous insulin infusion (CSII) against multiple insulin injections in insulin-dependent diabetic subjects: improved control with CSII. Diabetes Care 1982;5(5):466-71.

8. Potter JM, Reckless JP, Cullen DR. The effect of continuous subcutaneous insulin infusion and conventional insulin regimes on 24-hour variations of blood glucose and intermediary metabolites in the third trimester of diabetic pregnancy. Diabetologia 1981;21(6):534-9.

9. Rudolf MC, Coustan DR, Sherwin RS, et al. Efficacy of the insulin pump in the home treatment of pregnant diabetics. Diabetes 1981;30(11):891-5.

10. Rizza RA, Gerich JE, Haymond MW, et al. Control of blood sugar in insulin-dependent diabetes: comparison of an artificial endocrine pancreas, continuous subcutaneous insulin infusion, and intensified conventional insulin therapy. New England Journal of Medicine 1980;303(23):1313-8.

11. Schiffrin A, Belmonte MM. Comparison between continuous subcutaneous insulin infusion and multiple injections of insulin. A one-year prospective study. Diabetes 1982;31(3):255-64.

12. Reeves ML, Seigler DE, Ryan EA, Skyler JS. Glycemic control in insulin-dependent diabetes mellitus. Comparison of outpatient intensified conventional therapy with continuous subcutaneous insulin infusion. American Journal of Medicine 1982;72(4):673-80.

13. Nathan DM, Lou P, Avruch J. Intensive conventional and insulin pump therapies in adult type I diabetes. A crossover study. Annals of Internal Medicine 1982;97(1):31-6.

14. Mecklenburg RS, Benson EA, Benson JWJ, et al. Long-term metabolic control with insulin pump therapy. Report of experience with 127 patients. New England Journal of Medicine 1985;313(8):465-8.

15. Pickup JC, Keen H, Viberti GC, Bilous RW. Patient reactions to long-term outpatient treatment with continuous subcutaneous insulin infusion. British Medical Journal (Clinical Research ed.) 1981;282(6266):766-8.

16. Beck-Nielsen H, Richelsen B, Schwartz Sorensen N, Hother Nielsen O. Insulin pump treatment: effect on glucose homeostasis, metabolites, hormones, insulin antibodies and quality of life. Diabetes Research 1985;2(1):37-43.

17. Floyd JCJ, Cornell RG, Jacober SJ, et al. A prospective study identifying risk factors for discontinuance of insulin pump therapy. Diabetes Care 1993;16(11):1470-8.

18. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine 1993;329:977-986.

19. The Diabetes Control and Complications Trial Research Group. Implementation of treatment protocols in the Diabetes Control and Complications Trial. Diabetes Care 1995;18(3):361-76.

20. Pietri A, Raskin P. Cutaneous complications of chronic continuous subcutaneous insulin infusion therapy. Diabetes Care 1981;4(6):624-6.

21. Pickup JC, Viberti GC, Bilous RW, et al. Safety of continuous subcutaneous insulin infusion: metabolic deterioration and glycaemic autoregulation after deliberate cessation of infusion. Diabetologia 1982;22(3):175-9.

22. Teutsch SM, Herman WH, Dwyer DM, Lane JM. Mortality among diabetic patients using continuous subcutaneous insulin-infusion pumps. New England Journal of Medicine 1984;310(6):361-8.

23. Peden NR, Braaten JT, McKendry JB. Diabetic ketoacidosis during long-term treatment with continuous subcutaneous insulin infusion. Diabetes Care 1984;7(1):1-5.

24. Lougheed WD, Zinman B, Strack TR, et al. Stability of insulin lispro in insulin infusion systems. Diabetes Care 1997;20(7):1061-5.

25. Zinman B, Tildesley H, Chiasson JL, Tsui E, Strack T. Insulin lispro in CSII: results of a double-blind crossover study [published erratum appears in Diabetes 1997 Jul;46(7):1239]. Diabetes 1997;46(3):440-3.

26. Guerci B, Meyer L, Salle A, et al. Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients. Journal of Clinical Endocrinology and Metabolism 1999;84(8):2673-8.

27. American Diabetes Association. Continuous Subcutaneous Insulin Infusion. Position Statement. Diabetes Care 2000;23(Suppl 1):S90.