Correspondence

Therapy to Prevent Type 1 Diabetes Mellitus

N Engl J Med 2002; 347:1115-1116October 3, 2002

Article

To the Editor:

The results of the Diabetes Prevention Trial–Type 1 Diabetes Study (DPT-1) (May 30 issue)1 show that parenteral insulin therapy does not prevent type 1 diabetes in the relatives of patients with the disease. We made a similar observation in a smaller population of young, nondiabetic first-degree relatives of patients with diabetes. A total of 29 children and adolescents (median age, 10.3 years; interquartile range, 7.5 to 13.8; range, 3.4 to 18.0) were identified through screening of a population of 4000 relatives of patients with type 1 diabetes for diabetes-related autoantibodies. These children and adolescents participated in a double-blind trial (the European Prediabetes Prevention–Subcutaneous Insulin Trial), in which they received either an injectable placebo preparation2 or ultralente insulin (0.2 U per kilogram of body weight before breakfast [Ultratard, Novo Nordisk]). Subjects were followed for a median of 3.3 years (interquartile range, 1.6 to 4.5). Diabetes developed in 6 of the 14 subjects in the insulin group and 8 of the 15 subjects in the placebo group. The cumulative incidence of diabetes was similar in the two groups and similar to that observed in the DPT-1 (Figure 1Figure 1Kaplan–Meier Curve Showing the Proportion of Subjects without Diabetes, According to Treatment-Group Assignment.). These results strengthen the conclusions of the DPT-1, because our trial was double-blind and placebo-controlled and used a different insulin regimen. The use of parenteral insulin to prevent type 1 diabetes through the modulation of the anti-islet immune response (“beta-cell rest”) did not prove efficacious in two independent controlled trials. Moreover, the concept of beta-cell rest appears to have little basis in reality, at least for humans under the conditions used in these studies.3

Jean-Claude Carel, M.D.
Hôpital Cochin–Saint Vincent de Paul, 75014 Paris, France
carel@cochin.inserm.fr

Paul Landais, M.D.
Faculté Necker–Enfants Malades, 75014 Paris, France

Pierre Bougnères, M.D.
Hôpital Cochin–Saint Vincent de Paul, 75014 Paris, France

3 References

1. 1

   Diabetes Prevention Trial-Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 2002;346:1685-1691
   Full Text | Web of Science | Medline

2. 2

   Johnson RG, Godine JE, Hurxthal K, Nathan DM. The preparation of an acceptable placebo for NPH insulin. Diabetes Care 1985;8:601-602
   CrossRef | Web of Science | Medline

3. 3

   Coutant R, Carel JC, Aubry V, et al. Effects of prolonged administration of ultralente insulin on fasting and postbreakfast beta-cell function in normal adults. Metabolism 2000;49:1243-1246
   CrossRef | Web of Science | Medline

To the Editor:

We conducted a pilot trial of isophane insulin suspension in a group of high-risk, nondiabetic, first-degree relatives of patients with type 1 diabetes1,2 and found that this approach had only minor effects on some immunological markers and did not prevent overt diabetes.2 Considering the scarcity of information concerning the use of insulin in humans to prevent or delay the onset of type 1 diabetes,3,4 we believe that our results, which confirm the results of the DPT-1, are of interest.

Camino Rodriguez-Villar, M.D.
Roser Casamitjana, M.D.
Ignacio Conget, M.D.
Hospital Clinic i Universitari, 08036 Barcelona, Spain

4 References

1. 1

   Rodriguez-Villar C, Conget I, Gonzalez-Clemente JM, et al. Effects of insulin administration on beta-cell function in subjects at high risk for type I diabetes mellitus. Metabolism 1996;45:873-875
   CrossRef | Web of Science | Medline

2. 2

   Rodriguez-Villar C, Conget I, Casamitjana R, Ercilla G, Gomis R. Effects of insulin administration in a group of high-risk, non-diabetic, first-degree relatives of type 1 diabetic patients: an open pilot trial. Diabet Med 1999;16:160-163
   CrossRef | Web of Science | Medline

3. 3

   Fuchtenbusch M, Rabl W, Grassl B, Bachmann W, Standl E, Ziegler AG. Delay of type I diabetes in high risk, first degree relatives by parenteral antigen administration: the Schwabing Insulin Prophylaxis Pilot Trial. Diabetologia 1998;41:536-541
   CrossRef | Web of Science | Medline

4. 4

   Keller RJ, Eisenbarth GS, Jackson RA. Insulin prophylaxis in individuals at high risk of type I diabetes. Lancet 1993;341:927-928
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Slobodan Culina, Christian Boitard, Roberto Mallone. (2011) Antigen-Based Immune Therapeutics for Type 1 Diabetes: Magic Bullets or Ordinary Blanks?. Clinical and Developmental Immunology 2011, 1-15
   CrossRef

2. 2

   Dirk Homann, Matthias von Herrath. (2004) Regulatory T cells and type 1 diabetes. Clinical Immunology 112:3, 202-209
   CrossRef

3. 3

   Michael R. Pinsky. (2003) Genetic testing: Costs and access to intensive care unit care. Critical Care Medicine 31:Supplement, S411-S415
   CrossRef