Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus

J Clin Endocrinol Metab. 2008 Jun;93(6):2115-21. doi: 10.1210/jc.2007-2267. Epub 2008 Apr 8.


Objective: We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve beta-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults.

Methods: This multicenter, randomized, nonblinded clinical study screened 4089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin-requiring diabetic patients with a 5-yr duration or shorter of diabetes were assigned to either the SU group (n = 30) or the insulin group (n = 30). Serum C-peptide responses to annual oral glucose tolerance tests were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during the oral glucose tolerance test (SigmaC-peptide) less than 4 ng/ml (1.32 nmol/liter).

Results: The progression rate to an insulin-dependent state in the insulin group (three of 30, 10%) was lower than that in the SU group (13 of 30, 43%; P = 0.003, log-rank). Longitudinal analysis demonstrated that SigmaC-peptide values were better preserved in the insulin group than in the SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers [> or =10 U/ml (180 World Health Organization U/ml)] and preserved beta-cell function [SigmaC-peptide > or = 10 ng/ml (3.31 nmol/liter)] at entry. No severe hypoglycemic episodes occurred during the study.

Conclusions: Insulin intervention to preserve beta-cell function is effective and safe for patients with SPIDDM or latent autoimmune diabetes in adults.

Trial registration: NCT00232375.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / analysis
  • Autoantibodies / blood
  • Blood Glucose / drug effects
  • Body Mass Index
  • C-Peptide / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Glucose Tolerance Test
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / therapeutic use*
  • Male
  • Middle Aged
  • Sulfonylurea Compounds / therapeutic use
  • Time Factors


  • Autoantibodies
  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • Glutamate Decarboxylase

Associated data