title: Insulin intervention in slowly progressive insulin-dependent (type 1) diabetes mellitus.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Maruyama
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Osamu
authors.initials: O
authors.lastname: Funae
authors.forename: Akira
authors.initials: A
authors.lastname: Kasuga
authors.forename: Azuma
authors.initials: A
authors.lastname: Kanatsuka
authors.forename: Izumi
authors.initials: I
authors.lastname: Takei
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamada
authors.forename: Norikazu
authors.initials: N
authors.lastname: Harii
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D015992:Body Mass Index; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human