title: The Effect of DPT-1 Intravenous Insulin Infusion and Daily Subcutaneous Insulin on Endogenous Insulin Secretion and Postprandial Glucose Tolerance.
abstract: OBJECTIVE
  To investigate the effect of parenteral insulin therapy on endogenous insulin secretion in the Diabetes Prevention Trial-Type 1 (DPT-1).
  
  
  METHODS
  In the parenteral insulin arm of DPT-1, subjects without diabetes at high risk of future type 1 diabetes randomized to active treatment received a yearly 4-day intravenous insulin infusion (IV-I) and daily subcutaneous insulin (SC-I). To examine the effects of these insulin therapies on endogenous insulin secretion, C-peptide and glucose levels were compared during oral glucose tolerance tests (OGTTs) performed on and off IV-I and SC-I. Forty-six paired OGTTs were performed in 30 subjects from DPT-1 to determine the effect of IV-I. Twenty paired OGTTs were performed in 15 subjects from DPT-1 to determine the effect of SC-I.
  
  
  RESULTS
  IV-I suppressed fasting and OGTT-stimulated C-peptide (62% and 40%, respectively), and it significantly lowered fasting glucose (67.4 ± 4.5 mg/dL during IV-I vs. 90.9 ± 1.8 mg/dL off insulin; P < 0.05). By contrast, post-OGTT glucose levels were significantly higher during IV-I: Glucose during IV-I versus off insulin at 120 min was 203.9 ± 15.1 vs. 151.6 ± 10.2 mg/dL, respectively (P < 0.05); 49% of OGTTs became transiently diabetic (>200 mg/dL at 120 min) when receiving IV-I. Fasting glucose was significantly lower when receiving SC-I versus when off insulin (85 ± 3 vs. 94 ± 2 mg/dL, respectively; P < 0.05), but SC-I did not significantly alter fasting or OGTT-stimulated C-peptide compared with being off insulin.
  
  
  CONCLUSIONS
  These data demonstrate that the IV-I used in the DPT-1 markedly suppressed endogenous insulin secretion, which was frequently associated with postprandial glucose intolerance. SC-I, however, did not.
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA whao@u.washington.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.affiliation: Benaroya Research Institute, Virginia Mason Research Center, Seattle, WA.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.affiliation: Divison of Informatics and Biostatistics, University of South Florida, Tampa, FL.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.affiliation: Pediatric Epidemiology Center, University of South Florida, Tampa, FL.
authors.forename: David
authors.initials: D
authors.lastname: Cuthbertson
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, University of Miami, Miami, FL.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Marks
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA Department of Veterans Affairs, Puget Sound Health Care System, Seattle, WA.
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D018149:Glucose Intolerance / Q000188:drug therapy; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D019518:Postprandial Period; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose