title: Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes.
abstract: OBJECTIVE
  In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2-4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to 1 year in some patients. However, little is known about the predictors of such a sustained remission.
  
  
  METHODS
  We evaluated data from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM.
  
  
  RESULTS
  At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function (Insulin Secretion-Sensitivity Index-2) (p=0.01) that was then sustained across 48 weeks post-IIT (p=0.006). On logistic regression analyses, however, shorter duration of diabetes supplanted baseline A1c (p=0.24) and β-cell function (p=0.19) as an independent predictor of remission (p=0.04). In particular, diabetes duration <2 years predicted persistence of remission (p=0.006).
  
  
  CONCLUSIONS
  The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis.
  
  
  BACKGROUND
  ClinicalTrials.Gov NCT01270789; Post-results.
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Kramer
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital , Toronto, Ontario , Canada.
authors.forename: Haysook
authors.initials: H
authors.lastname: Choi
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
keywords: Beta Cell Function; Intensive Insulin Therapy; Type 2 Diabetes