We conducted a prospective multicenter randomized trial to determine both the feasibility of maintaining blood glucose control at differing levels and the effect of improved control on diabetic microangiopathy and albuminuria. Seventy patients with diabetes (low C-peptide level) with nonproliferative retinopathy were randomly assigned to continuous subcutaneous insulin infusion or unchanged conventional injection treatment. At entry, both groups had similar demographic, clinical, and glycemic characteristics. Over the succeeding eight months, mean 24-hour glucose concentrations (175 +/- 9 mg per deciliter) and glycosylated hemoglobin levels (10.0 +/- 0.3 per cent) remained elevated during conventional treatment but fell to nearly normal levels (117 +/- 6 mg per deciliter and 8.1 +/- 0.2 per cent, respectively) with continuous insulin infusion. The frequency of biochemical hypoglycemia (less than 40 mg of blood glucose per deciliter) was similar in both groups, but ketoacidosis occurred only during continuous infusion. The level of retinopathy, assessed from photographs, progressed in both groups. Continuous infusion was associated with slightly more deterioration, mainly because of the appearance of soft exudates and intraretinal microvascular abnormalities. In contrast, elevated albumin-excretion rates fell during continuous infusion but not during conventional treatment. We conclude that maintenance of differing levels of blood glucose is feasible in a multicenter trial and that a nearly normal blood glucose level for eight months does not retard progression of, and may initially worsen, established retinopathy. These preliminary observations indicate the need for longer trials (particularly of primary prevention).
This article has been cited by other articles:
Kilpatrick, E. S., Rigby, A. S., Atkin, S. L.
(2008). A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes: Data from the Diabetes Control and Complications Trial. Diabetes Care
31: 2198-2202
[Abstract][Full Text]
Sherwin, R. S.
(2008). Bringing Light to the Dark Side of Insulin: A Journey Across the Blood-Brain Barrier. Diabetes
57: 2259-2268
[Full Text]
Wu, M., Chen, Y., Wilson, K., Chirindel, A., Ihnat, M. A., Yu, Y., Boulton, M. E., Szweda, L. I., Ma, J.-X., Lyons, T. J.
(2008). Intraretinal Leakage and Oxidation of LDL in Diabetic Retinopathy. IOVS
49: 2679-2685
[Abstract][Full Text]
Bavbek, N., Kargili, A., Kaftan, O., Karakurt, F., Kosar, A., Akcay, A.
(2007). Elevated Concentrations of Soluble Adhesion Molecules and Large Platelets in Diabetic Patients: Are They Markers of Vascular Disease and Diabetic Nephropathy?. CLIN APPL THROMB HEMOST
13: 391-397
[Abstract]
Mohamed, Q., Gillies, M. C., Wong, T. Y.
(2007). Management of Diabetic Retinopathy: A Systematic Review. JAMA
298: 902-916
[Abstract][Full Text]
Casson, R J, Wood, J P M, Osborne, N N
(2004). Hypoglycaemia exacerbates ischaemic retinal injury in rats. Br. J. Ophthalmol.
88: 816-820
[Abstract][Full Text]
Klein, R.
(2003). Has the Frequency of Proliferative Diabetic Retinopathy Declined in the U.S.?. Diabetes Care
26: 2691-2692
[Full Text]
Cameron, J S.
(2003). Fifty years of established diabetic nephropathy -- a personal perspective. British Journal of Diabetes & Vascular Disease
3: 8-16
Kohner, E. M
(2002). Review: Thirty-seven years with diabetic retinopathy. British Journal of Diabetes & Vascular Disease
2: 452-456
[Abstract]
Pickup, J., Mattock, M., Kerry, S.
(2002). Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ
324: 705-705
[Abstract][Full Text]
Lenhard, M. J., Reeves, G. D.
(2001). Continuous Subcutaneous Insulin Infusion: A Comprehensive Review of Insulin Pump Therapy. Arch Intern Med
161: 2293-2300
[Abstract][Full Text]
Zhang, L., Krzentowski, G., Albert, A., Lefebvre, P. J.
(2001). Risk of Developing Retinopathy in Diabetes Control and Complications Trial Type 1 Diabetic Patients With Good or Poor Metabolic Control. Diabetes Care
24: 1275-1279
[Abstract][Full Text]
The European Study for the Prevention of Renal Dis,
(2001). Effect of 3 Years of Antihypertensive Therapy on Renal Structure in Type 1 Diabetic Patients With Albuminuria: The European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT). Diabetes
50: 843-850
[Abstract][Full Text]
Lu, M., Amano, S., Miyamoto, K., Garland, R., Keough, K., Qin, W., Adamis, A. P.
(1999). Insulin-Induced Vascular Endothelial Growth Factor Expression in Retina. IOVS
40: 3281-3286
[Abstract][Full Text]
Ferris, F. L., Davis, M. D., Aiello, L. M.
(1999). Treatment of Diabetic Retinopathy. NEJM
341: 667-678
[Full Text]
The Diabetes Control and Complications Trial Resea,
(1998). Early Worsening of Diabetic Retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol
116: 874-886
[Abstract][Full Text]
Fulcher, T., Griffin, M., Crowley, S., Firth, R., Acheson, R., O'Meara, N.
(1998). Diabetic retinopathy in Down's syndrome. Br. J. Ophthalmol.
82: 407-409
[Abstract][Full Text]
Stern, M. P.
(1998). The Effect of Glycemic Control on the Incidence of Macrovascular Complications of Type 2 Diabetes. Arch Fam Med
7: 155-162
[Abstract][Full Text]
BEST, R M, CHAKRAVARTHY, U
(1997). Diabetic retinopathy in pregnancy. Br. J. Ophthalmol.
81: 249-251
[Full Text]
Konen, J. C., Curtis, L. G., Summerson, J. H.
(1996). Symptoms and Complications of Adult Diabetic Patients in a Family Practice. Arch Fam Med
5: 135-145
[Abstract]
Microalbuminuria Collaborative Study Group,
(1995). Intensive therapy and progression to clinical albuminuria in patients with insulin dependent diabetes mellitus and microalbuminuria. BMJ
311: 973-977
[Abstract][Full Text]
Clark, C. M., Lee, D. A.
(1995). Prevention and Treatment of the Complications of Diabetes Mellitus. NEJM
332: 1210-1217
[Full Text]
The Diabetes Control and Complications Trial Resea,
(1993). The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. NEJM
329: 977-986
[Abstract][Full Text]
Reichard, P., Nilsson, B.-Y., Rosenqvist, U.
(1993). The Effect of Long-Term Intensified Insulin Treatment on the Development of Microvascular Complications of Diabetes Mellitus. NEJM
329: 304-309
[Abstract][Full Text]
Nathan, D. M.
(1993). Long-Term Complications of Diabetes Mellitus. NEJM
328: 1676-1685
[Full Text]
Konen, J. C., Summerson, J. H., Dignan, M. B.
(1993). Family Function, Stress, and Locus of Control: Relationships to Glycemia in Adults With Diabetes Mellitus. Arch Fam Med
2: 393-402
[Abstract]
Skyler, J. S.
(1989). Intensive Insulin Therapy: A Personal and Historical Perspective. The Diabetes Educator
15: 33-39
Mecklenburg, R. S.
(1989). Acute Complications Associated With the Use of Insulin Infusion Pumps. The Diabetes Educator
15: 40-43
Annahern, J., Kruger, D. F., Gatcomb, P. M., Petit, W. A., Tamborlane, W. V.
(1989). The Diabetes Control and Complications Trial (DCCT): The Trial Coordinator Perspective: Report by the DCCT Research Group. The Diabetes Educator
15: 236-241
Cosimi, A. B., Auchincloss, H. Jr, Delmonico, F. L., Fang, L., Nathan, D. M., Tolkoff-Rubin, N., Rubin, R. H., Yang, H. C., Russell, P. S.
(1988). Combined Kidney and Pancreas Transplantation in Diabetics. Arch Surg
123: 621-625
[Abstract]
Bernbaum, M., Albert, S. G., Brusca, S. R., Drimmer, A., Duckro, P. N.
(1988). A Team Approach: Promoting Diabetes Self-Management and Independence in the Visually Impaired: A Model Clinical Program. The Diabetes Educator
14: 51-54
Dunn, S. M.
(1988). "Speaking of Complications" : Talking With Patients About Diabetic Complications. The Diabetes Educator
14: 424-424
Previous
