A period of early, intensive insulin treatment is thought to improve subsequent beta-cell function in insulin-dependent diabetes mellitus (IDDM). To study this hypothesis, we randomly assigned adolescents with newly diagnosed IDDM to receive either conventional treatment (n = 14) (NPH insulin, 1 U per kilogram of body weight per day, in two divided doses) or an experimental treatment (n = 12) (a two-week hospitalization with maintenance of blood glucose levels between 3.3 and 4.4 mmol per liter by continuous insulin infusion delivered by an external artificial pancreas [Biostator]). During the two-week intervention, the experimental-therapy group received four times more insulin than the conventionally treated group, and their endogenous insulin secretion was more completely suppressed, as evidenced by a urinary C-peptide excretion rate one seventh that of the conventionally treated group. After the first two weeks, both groups were treated similarly and received similar amounts of insulin. At one year, the mean (+/- SEM) plasma level of C peptide was significantly higher after mixed-meal stimulation in the experimental-therapy group than in the conventionally treated group (0.51 +/- 0.07 vs. 0.27 +/- 0.06; P less than 0.01). The experimental-therapy group also had better metabolic control, as evidenced by lower glycohemoglobin values (7.2 +/- 0.7 vs. 10.8 +/- 1.2 percent; P less than 0.01). We conclude that suppression of endogenous insulin by intensive, continuous insulin treatment during the first two weeks after the diagnosis of IDDM may improve beta-cell function during the subsequent year.
Source Information
Diabetes Center, University of South Florida Health Sciences Center, Tampa 33612-4799.
This article has been cited by other articles:
Huang, X., Moore, D. J., Ketchum, R. J., Nunemaker, C. S., Kovatchev, B., McCall, A. L., Brayman, K. L.
(2008). Resolving the Conundrum of Islet Transplantation by Linking Metabolic Dysregulation, Inflammation, and Immune Regulation. Endocr. Rev.
29: 603-630
[Abstract][Full Text]
Hinke, S. A.
(2007). Finding GAD: Early Detection of {beta}-Cell Injury. Endocrinology
148: 4568-4571
[Full Text]
Kaizer, E. C., Glaser, C. L., Chaussabel, D., Banchereau, J., Pascual, V., White, P. C.
(2007). Gene Expression in Peripheral Blood Mononuclear Cells from Children with Diabetes. J. Clin. Endocrinol. Metab.
92: 3705-3711
[Abstract][Full Text]
Sosenko, J. M., Palmer, J. P., Greenbaum, C. J., Mahon, J., Cowie, C., Krischer, J. P., Chase, H. P., White, N. H., Buckingham, B., Herold, K. C., Cuthbertson, D., Skyler, J. S., the Diabetes Prevention Trial-Type 1 Study Group,
(2007). Increasing the Accuracy of Oral Glucose Tolerance Testing and Extending Its Application to Individuals With Normal Glucose Tolerance for the Prediction of Type 1 Diabetes: The Diabetes Prevention Trial-Type 1. Diabetes Care
30: 38-42
[Abstract][Full Text]
Haller, M. J., Schatz, D. A., Schwartz, I. D., Keymeulen, B., Pipeleers, D., Chatenoud, L.
(2005). CD3-antibody therapy in new-onset type 1 diabetes mellitus.. NEJM
353: 2086-2087
[Full Text]
Mellado-Gil, J M, Aguilar-Diosdado, M
(2004). High glucose potentiates cytokine- and streptozotocin-induced apoptosis of rat islet cells: effect on apoptosis-related genes. J Endocrinol
183: 155-162
[Abstract][Full Text]
Ortqvist, E., Bjork, E., Wallensteen, M., Ludvigsson, J., Aman, J., Johansson, C., Forsander, G., Lindgren, F., Berglund, L., Bengtsson, M., Berne, C., Persson, B., Karlsson, F. A.
(2004). Temporary Preservation of {beta}-Cell Function by Diazoxide Treatment in Childhood Type 1 Diabetes. Diabetes Care
27: 2191-2197
[Abstract][Full Text]
Bloomgarden, Z. T.
(2003). Diabetes Issues in Women and Children: Polycystic ovary syndrome. Diabetes Care
26: 2457-2463
[Full Text]
Gassner, H. L., Gitelman, S. E.
(2003). Case Study: Type 1 and Type 2, Too?. Clin. Diabetes
21: 140-141
[Full Text]
Greenbaum, C. J., Harrison, L. C.
(2003). Guidelines for Intervention Trials in Subjects With Newly Diagnosed Type 1 Diabetes. Diabetes
52: 1059-1065
[Full Text]
Brod, S. A.
(2002). Ingested Type I Interferon: State of the Art as Treatment for Autoimmunity. Exp. Biol. Med.
227: 981-988
[Abstract][Full Text]
Winter, W. E., Harris, N., Schatz, D.
(2002). Immunological Markers in the Diagnosis and Prediction of Autoimmune Type 1a Diabetes. Clin. Diabetes
20: 183-191
[Abstract][Full Text]
Scottish Study Group for the Care of the Young Dia,
(2001). Factors Influencing Glycemic Control in Young People With Type 1 Diabetes in Scotland: A population-based study (DIABAUD2). Diabetes Care
24: 239-244
[Abstract][Full Text]
Schatz, D., Krischer, J., Skyler, J.
(2000). Now Is the Time to Prevent Type 1 Diabetes. J. Clin. Endocrinol. Metab.
85: 495-498
[Full Text]
Becker, D. J., LaPorte, R. E., Libman, I., Pietropaolo, M., Dosch, H.-M.
(2000). Prevention of Type 1 Diabetes: Is Now the Time?. J. Clin. Endocrinol. Metab.
85: 498-506
[Full Text]
Tamborlane, W. V., Grey, M.
(2000). Is Strict Glycemic Control of Diabetes Necessary and Feasible in Most Children and Adolescents?. J. Clin. Endocrinol. Metab.
85: 515-518
[Full Text]
Mayer, A., Rharbaoui, F., Thivolet, C., Orgiazzi, J., Madec, A. M.
(1999). The Relationship between Peripheral T Cell Reactivity to Insulin, Clinical Remissions and Cytokine Production in Type 1 (Insulin-Dependent) Diabetes Mellitus. J. Clin. Endocrinol. Metab.
84: 2419-2424
[Abstract][Full Text]
Muhammad, B J., Swift, P. G F, Raymond, N. T, Botha, J. L
(1999). Partial remission phase of diabetes in children younger than age 10 years. Arch. Dis. Child.
80: 367-369
[Abstract][Full Text]
Slover, R. H., Eisenbarth, G. S.
(1997). Prevention of Type I Diabetes and Recurrent {beta}-Cell Destruction of Transplanted Islets. Endocr. Rev.
18: 241-258
[Abstract][Full Text]
Atkinson, M. A., Maclaren, N. K.
(1994). The Pathogenesis of Insulin-Dependent Diabetes Mellitus. NEJM
331: 1428-1436
[Full Text]