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October 23, 1996, Vol 276, No. 16 >
ARTICLE | October 23, 1996

Implantable Insulin Pump vs Multiple-Dose Insulin for Non—Insulin-Dependent Diabetes Mellitus: Title and subTitle BreakA Randomized Clinical Trial FREE

Christopher D. Saudek, MD; William C. Duckworth, MD; Anita Giobbie-Hurder, MS; William G. Henderson, PhD; Robert R. Henry, MD; David E. Kelley, MD; Steven V. Edelman, MD; Franklin J. Zieve, MD, PhD; Robert A. Adler, MD; James W. Anderson, MD; Robert J. Anderson, MD; Bruce P. Hamilton, MD; Thomas W. Donner, MD; M. Sue Kirkman, MD; Nancy A. Morgan, RPh, MBA
[+] Author Affiliations

Dr Saudek receives research support from Mini-Med Technologies, Inc (MMT), manufacturers of the Mini-Med Implantable Pump used in this study. Dr Saudek is also a member of MMT's medical advisory board. Dr Edelman has received honoraria for public speaking from MMT.

A complete list of the members of the Department of Veterans Affairs Implantable Insulin Pump Study Group appears at the end of this article.

Reprints: Christopher D. Saudek, MD, Osier Bldg, Room 576, Johns Hopkins Hospital, Baltimore, MD 21205.


JAMA. 1996;276(16):1322-1327. doi:10.1001/jama.1996.03540160044031
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References

Objective.  —To determine whether implantable insulin pump (IIP) therapy and multiple daily insulin (MDI) injections could equally attain improved blood glucose control, and to compare the 2 treatments with respect to reducing daily blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and improving patients' quality of life.

Design.  —Randomized clinical trial.

Setting.  —Seven Veterans Affairs medical centers.

Patients.  —One hundred twenty-one male type II diabetic patients between the ages of 40 and 69 years, receiving at least 1 injection of insulin per day and having hemoglobin A1c (HbA1c) levels of 8% or above.

Intervention.  —Intensive therapy (IIP or MDI) for 1 year.

Main Outcome Measures.  —Hemoglobin A1c and blood glucose levels.

Results.  —Blood glucose levels declined to 7.96±1.08 mmol/L (143.4±19.5 mg/dL) and 8.30±1.52 mmol/L (149.6±27.4 mg/dL) (mean ± SD) for IIP and MDI, respectively (P=.57). Hemoglobin A1c levels improved in both groups (time effect P<.001), to means of 7.54%±0.83% (MDI) vs 7.34%±0.79% (IIP). IIP reduced blood glucose fluctuations compared with MDI (P<.001), and reduced the incidence of mild clinical hypoglycemia by 68% (P<.001); IIP also eliminated the weight gain associated with MDI therapy and yielded better overall quality-of-life (P=.03) and impact-of-disease subscale scores (P=.05). Adverse events included 25% of subjects with episodes of insulin underdelivery due to microprecipitates of insulin within the pump.

Conclusions.  —Intensive insulin therapy with IIP and MDI is effective in controlling non—insulin-dependent diabetes mellitus. IIP has significant advantages in reducing glycemic variability, clinical hypoglycemia, and weight gain, while improving aspects of quality of life.

REFERENCES

1 +
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 . N Engl J Med . 1993;;329:977-986.
2 +
Blackshear PJ, Rohde TD, Prosl F, Buchwald J.  The implantable infusion pump: a new concept in drug delivery . Med Prog Technol . 1979;;6:149.
3 +
Irsigler K, Kritz H, Hagmuller G, et al.  Long-term continuous intraperitoneal insulin infusion with an implantable remote-controlled insulin infusion device . Diabetes . 1981;;30:1072-1075.
4 +
Point Study Group.  One year trial of a remotecontrolled implantable insulin infusion system in type 1 diabetic patients . Lancet . 1988;;2:866-869.
5 +
Saudek CD, Selam J-L, Pitt HA, et al.  A preliminary trial of the programmable implantable medication system for insulin delivery . N Engl J Med . 1989;;321:574-579.
6 +
Saudek CD.  Implantable insulin infusion pumps . Endocrinologist . 1993;;3:15-20.
7 +
American Diabetes Association. Diabetes 1993 Vital Statistics . Alexandria, Va: American Diabetes Association; 1993;:13-19.
8 +
Henry RR, Gumbiner B, Ditzler T, Wallace P, Lyon R, Glauber HS.  Intensive conventional insulin therapy for type 1 diabetes: metabolic effects during a 6-month outpatient trial . Diabetes Care . 1993;;16:21-31.
9 +
Saudek CD, Duckworth WC.  The Department of Veterans Affairs Implantable Insulin Pump Study . Diabetes Care . 1992;;15:567-570.
10 +
Saudek CD.  Insulin infusion devices . In: Al-berti KGMM, Krall LP, eds. The Diabetes Annual/ 6 . New York, NY: Elsevier Science Inc; 1991;:524-539.
11 +
Grau U, Saudek CD.  Stable insulin preparation for implanted insulin pumps: laboratory and animal trials . Diabetes . 1987;;36:1453-1459.
12 +
DCCT Research Group.  Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial . Am J Med . 1991;;90:450-459.
13 +
DCCT Research Group.  Reliability and validity of a diabetes quality of life measure for the Diabetes Control and Complications Trial (DCCT) . Diabetes Care . 1988;;11:725-732.
14 +
Blackshear PJ, Shulman GI, Roussell AM, et al.  Metabolic response to three years of continuous, basal rate intravenous insulin infusion in type II diabetic patients . J Clin Endocrinol Metab . 1985;;61:753-780.
15 +
Duckworth WC, Saudek CD, Henry RR.  Why intraperitoneal delivery of insulin with implantable pumps in NIDDM? Diabetes . 1992;;41:667-671.
16 +
Laakso M, Ronnemaa T, Sarlund H, Pyorala K, Kallio V.  Factors associated with fasting and postglucagon plasma c-peptide levels in middle-aged insulin-treated diabetic patients . Diabetes Care . 1989;;12:83-88.
17 +
Brunzell JD, Robertson RP, Lerner RL, et al.  Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance test . J Clin Endocrinol Metab . 1976;;42:222-229.
18 +
Klein R, Klein BEK, Moss SE, et al.  The Wisconsin Epidemiologic Study of Diabetic Retinopathy, III: prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years . Arch Ophthalmol . 1984;;102:527-532.
19 +
Ballard DJ, Humphrey LL, Melton LJ III, et al.  Epidemiology of persistent proteinuria in type II diabetes mellitus: population-based study in Rochester, Minnesota . Diabetes . 1988;;37:405-412.
20 +
Reaven GM.  Banting Lecture 1988: role of insulin resistance in human disease . Diabetes . 1988;;37:1595-1607.
21 +
Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP.  Prospective analysis of the insulin-resistance syndrome (syndrome X) . Diabetes . 1992;;41:715-722.
22 +
Schade DS, Eaton RP, Davis T, et al.  The kinetics of peritoneal insulin absorption . Metabolism . 1981;;30:149-155.
23 +
Micossi P, Cristallo M, Librenti MC, et al.  Freeinsulin profiles after intraperitoneal, intramuscular, and subcutaneous insulin administration . Diabetes Care . 1986;;9:575-578.
24 +
Yki-Jarvinen H, Kauppila M, Kujansuu E, et al.  Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus . N Engl J Med . 1992;;327:1426-1433.
25 +
Hepburn DA, MacLeod KM, Pell ACH, Scougel IJ, Frier BM.  Frequency and symptoms of hypoglycemia experienced by patients with type 2 diabetes treated with insulin . Diabet Med . 1993;;10:231-237.
26 +
Cox DJ, Kovatchev BP, Julian DM, et al.  Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from selfmonitoring blood glucose data . J Clin Endocrinol Metab . 1994;;79:1659-1662.
27 +
Wing RR, Klein R, Moss SE.  Weight gain associated with improved glycemic control in population-based sample of subjects with type 1 diabetes . Diabetes Care . 1990;;13:1106-1109.
28 +
DCCT Research Group.  Weight gain associated with intensive therapy in the Diabetes Control and Complications Trial . Diabetes Care . 1988;;11:567-573.
29 +
Carlson MG, Campbell PJ.  Intensive insulin therapy and weight gain in IDDM . Diabetes . 1993;;42:1700-1707.
30 +
Haardt M-J, Dorange C, Selam J-L, et al.  A cost-benefit comparison of intensive diabetes management with implantable pumps versus multiple subcutaneous injections in patients with type 1 diabetes . Diabetes Care . 1994;;17:847-851.
31 +
DCCT Research Group.  Resource utilization and costs of care in the Diabetes Control and Complications Trial . Diabetes Care . 1995;;18:1468-1478.

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1 +
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 . N Engl J Med . 1993;;329:977-986.
2 +
Blackshear PJ, Rohde TD, Prosl F, Buchwald J.  The implantable infusion pump: a new concept in drug delivery . Med Prog Technol . 1979;;6:149.
3 +
Irsigler K, Kritz H, Hagmuller G, et al.  Long-term continuous intraperitoneal insulin infusion with an implantable remote-controlled insulin infusion device . Diabetes . 1981;;30:1072-1075.
4 +
Point Study Group.  One year trial of a remotecontrolled implantable insulin infusion system in type 1 diabetic patients . Lancet . 1988;;2:866-869.
5 +
Saudek CD, Selam J-L, Pitt HA, et al.  A preliminary trial of the programmable implantable medication system for insulin delivery . N Engl J Med . 1989;;321:574-579.
6 +
Saudek CD.  Implantable insulin infusion pumps . Endocrinologist . 1993;;3:15-20.
7 +
American Diabetes Association. Diabetes 1993 Vital Statistics . Alexandria, Va: American Diabetes Association; 1993;:13-19.
8 +
Henry RR, Gumbiner B, Ditzler T, Wallace P, Lyon R, Glauber HS.  Intensive conventional insulin therapy for type 1 diabetes: metabolic effects during a 6-month outpatient trial . Diabetes Care . 1993;;16:21-31.
9 +
Saudek CD, Duckworth WC.  The Department of Veterans Affairs Implantable Insulin Pump Study . Diabetes Care . 1992;;15:567-570.
10 +
Saudek CD.  Insulin infusion devices . In: Al-berti KGMM, Krall LP, eds. The Diabetes Annual/ 6 . New York, NY: Elsevier Science Inc; 1991;:524-539.
11 +
Grau U, Saudek CD.  Stable insulin preparation for implanted insulin pumps: laboratory and animal trials . Diabetes . 1987;;36:1453-1459.
12 +
DCCT Research Group.  Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial . Am J Med . 1991;;90:450-459.
13 +
DCCT Research Group.  Reliability and validity of a diabetes quality of life measure for the Diabetes Control and Complications Trial (DCCT) . Diabetes Care . 1988;;11:725-732.
14 +
Blackshear PJ, Shulman GI, Roussell AM, et al.  Metabolic response to three years of continuous, basal rate intravenous insulin infusion in type II diabetic patients . J Clin Endocrinol Metab . 1985;;61:753-780.
15 +
Duckworth WC, Saudek CD, Henry RR.  Why intraperitoneal delivery of insulin with implantable pumps in NIDDM? Diabetes . 1992;;41:667-671.
16 +
Laakso M, Ronnemaa T, Sarlund H, Pyorala K, Kallio V.  Factors associated with fasting and postglucagon plasma c-peptide levels in middle-aged insulin-treated diabetic patients . Diabetes Care . 1989;;12:83-88.
17 +
Brunzell JD, Robertson RP, Lerner RL, et al.  Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance test . J Clin Endocrinol Metab . 1976;;42:222-229.
18 +
Klein R, Klein BEK, Moss SE, et al.  The Wisconsin Epidemiologic Study of Diabetic Retinopathy, III: prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years . Arch Ophthalmol . 1984;;102:527-532.
19 +
Ballard DJ, Humphrey LL, Melton LJ III, et al.  Epidemiology of persistent proteinuria in type II diabetes mellitus: population-based study in Rochester, Minnesota . Diabetes . 1988;;37:405-412.
20 +
Reaven GM.  Banting Lecture 1988: role of insulin resistance in human disease . Diabetes . 1988;;37:1595-1607.
21 +
Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP.  Prospective analysis of the insulin-resistance syndrome (syndrome X) . Diabetes . 1992;;41:715-722.
22 +
Schade DS, Eaton RP, Davis T, et al.  The kinetics of peritoneal insulin absorption . Metabolism . 1981;;30:149-155.
23 +
Micossi P, Cristallo M, Librenti MC, et al.  Freeinsulin profiles after intraperitoneal, intramuscular, and subcutaneous insulin administration . Diabetes Care . 1986;;9:575-578.
24 +
Yki-Jarvinen H, Kauppila M, Kujansuu E, et al.  Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus . N Engl J Med . 1992;;327:1426-1433.
25 +
Hepburn DA, MacLeod KM, Pell ACH, Scougel IJ, Frier BM.  Frequency and symptoms of hypoglycemia experienced by patients with type 2 diabetes treated with insulin . Diabet Med . 1993;;10:231-237.
26 +
Cox DJ, Kovatchev BP, Julian DM, et al.  Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from selfmonitoring blood glucose data . J Clin Endocrinol Metab . 1994;;79:1659-1662.
27 +
Wing RR, Klein R, Moss SE.  Weight gain associated with improved glycemic control in population-based sample of subjects with type 1 diabetes . Diabetes Care . 1990;;13:1106-1109.
28 +
DCCT Research Group.  Weight gain associated with intensive therapy in the Diabetes Control and Complications Trial . Diabetes Care . 1988;;11:567-573.
29 +
Carlson MG, Campbell PJ.  Intensive insulin therapy and weight gain in IDDM . Diabetes . 1993;;42:1700-1707.
30 +
Haardt M-J, Dorange C, Selam J-L, et al.  A cost-benefit comparison of intensive diabetes management with implantable pumps versus multiple subcutaneous injections in patients with type 1 diabetes . Diabetes Care . 1994;;17:847-851.
31 +
DCCT Research Group.  Resource utilization and costs of care in the Diabetes Control and Complications Trial . Diabetes Care . 1995;;18:1468-1478.

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