title: Determinants of reversibility of β-cell dysfunction in response to short-term intensive insulin therapy in patients with early type 2 diabetes.
abstract: Short-term intensive insulin therapy (IIT) can improve pancreatic β-cell function when administered early in the course of type 2 diabetes mellitus (T2DM). However, the degree of improvement in response to this therapy varies between patients. Thus, we sought to characterize the determinants of improvement in β-cell function in response to short-term IIT in early T2DM. Sixty-three patients with mean 3.0 ± 2.1 yr duration of T2DM and Hb A1c of 6.8 ± 0.8% underwent 4 wk of IIT consisting of basal insulin detemir and premeal insulin aspart, with oral glucose tolerance test administered at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion Sensitivity Index-2 (ISSI-2). Reversibility of β-cell dysfunction was defined as percentage change in ISSI-2 of ≥25%. Overall, the study population experienced an increase in ISSI-2 from baseline to post-IIT (P = 0.01), with one-third of participants achieving ≥25% improvement in ISSI-2. Compared with their peers, those with increases in ISSI-2 of ≥25% had greater decrements in fasting glucose (P < 0.0001), Hb A1c (P = 0.001), ALT (P = 0.04), AST (P = 0.02), and HOMA-IR (P < 0.0001). On logistical regression analysis, baseline Hb A1c (OR = 2.83, 95% CI 1.16-6.88, P = 0.02) and change in HOMA-IR (OR = 0.008, 95%CI 0.0004-0.16, P = 0.001) emerged as independent predictors of reversibility of β-cell dysfunction. Indeed, reversibility of β-cell dysfunction was achieved in only those participants in whom IIT yielded an improvement in HOMA-IR. In conclusion, decline in HOMA-IR may be a key determinant of improvement of β-cell function in response to short-term IIT, suggesting a fundamental contribution of insulin resistance to the reversible component of β-cell dysfunction in early T2DM.
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Caroline Kaercher
authors.initials: CK
authors.lastname: Kramer
authors.forename: Haysook
authors.initials: H
authors.lastname: Choi
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D061386:Insulin, Regular, Human / Q000008:administration & dosage*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D061386:Insulin, Regular, Human; D000069057:Insulin Detemir
keywords: insulin resistance; intensive insulin therapy; remission; type 2 diabetes; β-cell function