title: Effect of Short-term Intensive Insulin Therapy on Post-challenge Hyperglucagonemia in Early Type 2 Diabetes.
abstract: BACKGROUND
  Hyperglucagonemia is a characteristic feature of type 2 diabetes (T2DM) that has been postulated to be due to β-cell dysfunction and the resultant loss of insulin-mediated α-cell suppression. When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve β-cell function, resulting in reduced glycemic variability.
  
  
  OBJECTIVE
  To evaluate the impact of IIT on hyperglucagonemia and its associations with β-cell function and glycemic variability. Design/Setting/Participants/Intervention: Sixty-two patients with T2DM of mean 3.0 ± 2.1 years duration and glycated hemoglobin of 6.8 ± 0.7% underwent 4 weeks of IIT, consisting of basal detemir and premeal insulin aspart.
  
  
  METHODS
  Glucagon response was measured by area under the glucagon curve (AUCglucagon) on oral glucose tolerance test at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index (where ISR is the prehepatic insulin secretion rate determined by C-peptide deconvolution). Glucose variability was assessed in both the first and last weeks by the coefficient of variation of capillary glucose on daily six-point self-monitoring profiles.
  
  
  RESULTS
  Both Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index demonstrated improvement in β-cell function after IIT (both P ≤ .02), accompanied by reduced glycemic variability (P = .05). There was a marked reduction in AUCglucagon after IIT, as compared to baseline (P < .001). However, the decrease in AUCglucagon was not associated with the change in either β-cell measure (both P ≥ .34) or glucose variability (P = .37).
  
  
  CONCLUSIONS
  Short-term IIT can reduce post-challenge hyperglucagonemia in early T2DM, but this effect does not appear to be due to improved β-cell function.
authors.affiliation: Leadership Sinai Centre for Diabetes (C.K.K., B.Z., H.C., R.R.), Mt Sinai Hospital, Toronto, ON M5T 3L9, Canada; Division of Endocrinology (C.K.K., B.Z., R.R.), University of Toronto, Toronto, ON M5G 2C4, Canada; and Lunenfeld-Tanenbaum Research Institute (B.Z., R.R.), Mt Sinai Hospital, Toronto, ON M5G 1X5, Canada.
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Kramer
authors.affiliation: Leadership Sinai Centre for Diabetes (C.K.K., B.Z., H.C., R.R.), Mt Sinai Hospital, Toronto, ON M5T 3L9, Canada; Division of Endocrinology (C.K.K., B.Z., R.R.), University of Toronto, Toronto, ON M5G 2C4, Canada; and Lunenfeld-Tanenbaum Research Institute (B.Z., R.R.), Mt Sinai Hospital, Toronto, ON M5G 1X5, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Leadership Sinai Centre for Diabetes (C.K.K., B.Z., H.C., R.R.), Mt Sinai Hospital, Toronto, ON M5T 3L9, Canada; Division of Endocrinology (C.K.K., B.Z., R.R.), University of Toronto, Toronto, ON M5G 2C4, Canada; and Lunenfeld-Tanenbaum Research Institute (B.Z., R.R.), Mt Sinai Hospital, Toronto, ON M5G 1X5, Canada.
authors.forename: Haysook
authors.initials: H
authors.lastname: Choi
authors.affiliation: Leadership Sinai Centre for Diabetes (C.K.K., B.Z., H.C., R.R.), Mt Sinai Hospital, Toronto, ON M5T 3L9, Canada; Division of Endocrinology (C.K.K., B.Z., R.R.), University of Toronto, Toronto, ON M5G 2C4, Canada; and Lunenfeld-Tanenbaum Research Institute (B.Z., R.R.), Mt Sinai Hospital, Toronto, ON M5G 1X5, Canada.
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005934:Glucagon / Q000097:blood*; D005951:Glucose Tolerance Test / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D061386:Insulin, Regular, Human / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010182:Pancreatic Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; D061386:Insulin, Regular, Human