The influence of long-term therapy with the insulin pump (CSII) in patients with type 1 diabetes mellitus on metabolic compensation and on the incidence of hypoglycaemia. Comparison with intensified conventional insulin therapy (MDI)

Czech version

Authors: J. Olšovský ¹; M. Beránek ²
Authors‘ workplace: II. interní klinika Lékařské fakulty MU a FN u sv. Anny, Brno, přednosta doc. MUDr. Miroslav Souček, CSc. ¹; Ústav patologické fyziologie Lékařské fakulty MU Brno, přednostka prof. MUDr. Anna Vašků, CSc. ²
Published in: Vnitř Lék 2007; 53(6): 637-645
Category: Original Contributions

Overview

The principal objective of this paper is to verify, in clinical practice, the long-term affect (7 to 8 year follow up) and safety of insulin pump treatment in type 1 diabetes mellitus patients and to compare the results for diabetes compensation in patients treated with the insulin pump with a control group of patients treated with intensified insulin therapy using the MDI (multiple daily injection) method.

Patient sample and method:
We followed up 35 patients treated with the insulin pump and 35 patients in the control group. We evaluated the monitored parameters for both patient groups at the beginning and at the end of the follow up period. With respect to glycated haemoglobin, we evaluated the results on a yearly basis, and also on year by year changes. We assessed the incidence of hypoglycaemia in both groups on a yearly basis. The following aspects were considered in order to determine the level of statistical significance of the different parameters: 1. we compared the initial state with that seen at the end of the follow up, 2. we analysed the year by year changes in glycated haemoglobin, 3. we compared the patients treated with the insulin pump with those in the control group. Diabetes compensation was evaluated on the basis of measurement of glycated haemoglobin and calculation of glycaemia. Comparison of the incidence of hypoglycaemia was done for all hypoglycemic events and then separately for severe hypoglycaemia. Also evaluated were changes in weight and in insulin dose in 24 hours.

Results:
The group of patients treated with the insulin pump recorded a dramatic decrease in glycated haemoglobin in the course of the follow up, p < 0.001, and also in average glycaemia, p < 0.001. In the control group only a transitory significant decrease of HbA_1c, p < 0.05, was recorded in the first and second year of follow up, later the result was insignificant, i.e. p > 0.05, as compared with the initial state. In this group of patients, no significant improvement in average glycaemia, p > 0.05, was recorded when compared with the initial state. Comparison of the two groups of patients showed that HbA_1c, p < 0.001, and average glycaemia, p < 0.001, were worse with statistical significance in patients treated with the insulin pump at the beginning of the follow up. At the end of the follow up period, there was no significant difference between the two groups in terms of glycated haemoglobin, p > 0.05, but a statistically significant difference was recorded in average glycaemia, p < 0.001, in favour of the group of patients treated with the insulin pump. The use of the insulin pump resulted in a statistically significant decrease in the incidence of severe hypoglycaemic events as compared with the control group, p = 0.010. This decrease was reflected in the measured parameters from the third year of the study to the end of follow up. However, at the beginning of the study and in the first and second years of follow up there was no statistically significant difference between the two groups in terms of incidence of severe hypoglycaemic episodes, p > 0.05. No statistically significant difference between the two groups was recorded in the incidence of all hypoglycaemic episodes from the beginning of the follow up to its end, p > 0.05. In both groups of patients, a statistically significant gain in weight was seen from the beginning of the study to the end of the follow up period, however, its statistical significance was lower (p < 0.05) in the group of patients treated with insulin pump than in the control group (p < 0.001). We proved a statistically significant decrease in daily insulin dose (p < 0.001)was required in the group of patients treated with insulin pump, whilst no statistically significant change in the dose was recorded in the control group (p > 0.05).

Conclusion:
In the course of the follow up, we proved that treatment with the insulin pump in type 1 diabetes is more beneficial to patients than MDI treatment. This was reflected by both better compensation of diabetes and a lower incidence of severe hypoglycaemic episodes.

Key words:
type 1 diabetes mellitus – insulin pump – diabetes compensation – glycated haemoglobin – average glycaemia – hypoglycaemia

Sources

1. Brinchmann-Hansen O, Dahl-Jorgensen K, Sandvik L et al. Blood glucose concentrations and progression of diabetic retinopathy: the seven year results of the Oslo study. BMJ 1992; 304: 19-22.

2. Mogensen CE. Management of diabetic renal involvement and disease. Lancet 1988; 1: 867-870.

3 Tattersalll RB The quest for normoglycemia: a historical perspective. Diabetologia 1994; 11: 618-635.

4. The Diabetes Control and Complications Trial research group: The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-986.

5. Kohner EM. The effect of diabetic control on diabetic retinopathy. Eye 1993; 7: 309-311.

6. Reichard P. Are there any glycemic thresholds for the serious microvascular diabetic complications? J Diab Compl 1995; 9: 25-30.

7 Pickup JC, Keen H, Parsons JA et al. Continuous subcutaneous insulin infusion: an aproach to achieving normoglycemia. Br Med J 1978; 1: 204-207.

8. Diabetes control and Complications Trial Research Group: Implementation of treatment protocols in the Diabetes Control and Complications Trial. Diabetes Care 1995; 18: 361-376.

9. Strowig SM. Initiation and management of insulin pump therapy. Diabetes Educ 1993; 19: 50-58.

10. Olšovský J. Inzulínová pumpa. In: Perušičová J. Trendy soudobé diabetologie. Praha: Galén 2004: Vol 9, 49-71.

11 Pickup J, Keen H. Continuous subcutaneous insulin infusion et 25 years. Diabetes Care 2002; 25: 593-598.

12. Jankovec Z, Čechurová D, Krčma M et al. Dlouhodobý efekt léčby inzulínovou pumpou (CSII) - výsledky registru pacientů léčených CSII v České republice DMEV 2006; Suppl 2: 26.

13. Koivisto VA, Yki-Yarvinen H, Helve E et al. Pathogenesis and prevention of the dawn phenomenon in diabetic patients treated with CSII. Diabetes 1986; 35: 78-82.

14. Kane K, Jansenn MMU, Keulen ETP et al. Substitution of nighttime CSII therapy for bedtime NPH insulin in a multiple injection regimen improves contraregulatory hormonal response and warning symptoms of hypoglycemia in IDDM. Diabetologia 1998; 41: 322-329.

15. Carrol MF, Schade DS. The dawn fenomenon revisited: implications for diabetes therapy. Endocr Pract 2005; 11: 55-64.

16. Eichner HL, Selan JL, Hollemann CB et al. Reduction of severe hypoglycemic events in type 1 diabetic patients using continuous subcutaneous insulin infusion. Diabetes Res 1988; 8: 189-193.

17. Brož J, Kožnarová R, Bartášková D et al. Současné možnosti léčby diabetes mellitus pomocí inzulínových pump. DMEV 2006; 4: 179-186.

18. Kožnarová R. Přehled pump dostupných v ČR. Remedia 2006; 2: 188.

19 Retnakaran R, Zinman B. CSII vs. MDI: insights from a Health Technology Assessment review. International Diabetes Monitor 2006; 18: 20-22.

20. Retnakaran R, DeVries JH, Hanaire-Broutin H et al. Continuous subcutaneous insulin infusion versus multiple daily injections: modeling predicted benefits in relationship to baseline A1c. Diabetes Care 2005; 28: 1835-1836.

21. Hirsch IB, Bode BW, Garg S et al. for the Insulin Aspart CSII/MDI Comparison Study Group. Continuous subcutaneous insulin infusion of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII. Diabetes Care 2005; 28: 533-538.

22. Jankovec Z, Krčma M, Lacigová S et al. Registr pacientů léčených inzulínovou pumpou v České republice. DMEV 2004; Suppl 1: 22,

23. Melki V, Renard E, Lassmann-Vague V et al. Improvement of HBA1c and blood glucose stability in IDDM patients with lispro insulin analogue in external pump. Diabetes Care 2001; 24: 69-72.

24. Renner R, Pfurzner A, Traurman M et al. Use of insulin lispro in CSII treatment. Diabetes Care 1999; 22: 784-788.

25. Schmaus S, Konig A, Landgraf R. Human insulin analogue (lispro) the ideal pump insulin? Diabet Med 1998; 15: 247-249.

26. Zinman B, Tildesley H, Chiasson J-L et al. Insulin lispro in CSII: results of a double-blind crossover study. Diabetes 1997; 46: 440-443.

27 Bode B, Weinstein R, Bell D et al. Comparison of insulin aspart with buffered regular insulin and insulin lispro in CSII. Diabetes Care 2002; 25: 439-444.

28. Bode B, Steed D, Davidson P. Long-term pump use and SMBG in 205 patients. Diabetes 1994; 43 (Suppl 1): 220A.

29. Bode B, Strange P. Efficacy, safety and pump compatibility of insulin aspart used in CSII therapy with Type 1 diabetes mellitus. Diabetes Care 2001; 24: 69-72.

30. Hoogma RPLM, Schumicki D. Safety of Insulin Glulisine when Given by Continuous Subcutaneous Infusion Using an External Pump in Patients with Type 1 Diabetes. Horm Metab Res 2006; 38: 429-433.

31. McCarter RJ, Hempe JM, Chalew SA. Mean blood glucose and biological variation have greater influence on HbA1c levels then glucose instability: an analysis of data from the Diabetes Control and Complications Trial. Diabetes Care 2006; 29: 352-355.

32. Ng Tang Pui S, Pickup J, Bending JJ. Hypoglycemia and counterregulation in insulin-dependent patients: a comparison of CSII and conventional insulin therapy. Diabetes Care 1986; 15: 221-227.

33. Ronn B, Mathiesen ER, Vang L et al. Evaluation of insulin pump treatment under routine conditions. Diabetes Res Clin Pract 1989; 3: 191-196.

34. Chantelau E, Spraul M, Muhlhauser I et al. Long term safety, efficacy and side-effects of continuous subcutaneous insulin infusion treatment for type 1 diabetes mellitus: a one centre experience. Diabetologia 1989; 32: 421-426.

35. Bell DSH, Cutter G, Clements RS. The feasibility of long-term treatment of diabetes with continuous subcutaneous insulin infusion. Diab Nutr Metab 1993; 6: 57-60.

36. Hirsch IB, Brownlee M. Should minimal blood glucose variability become the gold standard of glycemic control. J Diabetes Complications 2005; 19: 178-181.

37. Doležal T. Farmakoekonomické aspekty léčby diabetu. Farmakoekonomika 2006; 1: 8-12.