title: Effect of pioglitazone on the course of new-onset type 1 diabetes mellitus.
abstract: OBJECTIVE
  Type 1 diabetes mellitus (T1DM) is caused by insulin deficiency resulting from progressive destruction of β cells. The histological hallmark of the diabetic islet is mononuclear cell infiltration. Thiazolidinediones (TZDs) activate PPARg and enhance the actions of insulin. Studies in non-obese diabetic and streptocotozin-treated mouse models demonstrated that pretreatment with TZDs prevented the development of T1DM. The purpose of this study was to examine whether pioglitazone, given with insulin, preserved β cell function in patients with new-onset T1DM.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled 24-week study. Subjects received pioglitazone or placebo. Blood sugar, glycated hemoglobin (HbA1c), C-peptide, and liver enzymes were measured at baseline. Boost© stimulated C-peptide responses were measured at baseline and at 24 weeks. Blood sugar, insulin dose, height, weight, and liver enzymes were monitored at each visit. HbA1c was performed every 12 weeks.
  
  
  RESULTS
  Of the 15 patients, 8 received pioglitazone, and 7 - placebo. There was no clinical improvement in HbA1c between or within groups at the completion of the study. Mean peak C-peptide values were similar between groups at baseline. Mean peak C-peptide level was slightly higher at 24 weeks in the pioglitazone group compared to the placebo (1.8 vs. 1.5 ng/mL) which was considered as clinically insignificant. The interaction of HbA1c and insulin dose (HbA1c* insulin/kg/day), which combines degree of diabetic control and dose of insulin required to achieve this control, showed transient improvement in the pioglitazone group at 12 weeks but was not sustained at 24 weeks.
  
  
  CONCLUSIONS
  In this pilot study, pioglitazone did not preserve β cell function when compared to placebo.
authors.affiliation: Division of Pediatric Endocrinology, Stony Brook Children's Hospital, Stony Brook, United States. E-mail: Kimberly.Tafuri@stonybrookmedicine.edu.
authors.forename: Kimberly Sue
authors.initials: KS
authors.lastname: Tafuri
authors.forename: Mushtaq Ahmed
authors.initials: MA
authors.lastname: Godil
authors.forename: Andrew Harry
authors.initials: AH
authors.lastname: Lane
authors.forename: Thomas Allen
authors.initials: TA
authors.lastname: Wilson
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D008297:Male; D010865:Pilot Projects; D000077205:Pioglitazone; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077205:Pioglitazone; D045162:Thiazolidinediones