title: Clinical predictors and time course of the improvement in β-cell function with short-term intensive insulin therapy in patients with Type 2 diabetes.
abstract: OBJECTIVE
  In patients with Type 2 diabetes, a short course of intensive insulin therapy can improve β-cell function and even induce transient remission of diabetes. However, not all patients respond to this therapy. Although the achievement of fasting glucose  < 7.0 mmol/l one day after stopping intensive insulin therapy can identify patients in whom β-cell function has improved, we sought to determine clinical predictors for the early identification of such responders and the time course of response.
  
  
  METHODS
  We pooled data from two studies in which 97 patients with Type 2 diabetes mellitus (median 3 years duration) and HbA1c 51 ± 8.7 mmol/mol (6.8 ± 0.8%) underwent 4-8 weeks of intensive insulin therapy, consisting of basal detemir and pre-meal insulin aspart. They were classified as responders (n = 74) or non-responders (n = 23), defined by the achievement of fasting glucose  < 7.0 mmol/l after stopping intensive insulin therapy.
  
  
  RESULTS
  On logistic regression analyses, duration of diabetes (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.56-0.92, P = 0.009) and baseline fasting glucose (OR = 0.40, 95% CI 0.24-0.68, P = 0.001) emerged as predictors of the likelihood of responding. Ninety per cent of patients with duration ≤ 4 years and fasting glucose ≤ 8.0 mmol/l responded to intensive insulin therapy. Despite having lower glucose levels during intensive insulin therapy, responders had less hypoglycaemia than non-responders (median 0.3 vs. 1.6 episodes/week, P < 0.0001), with rates of hypoglycaemia diverging sharply from the third week onwards.
  
  
  CONCLUSIONS
  At baseline, shorter duration of diabetes and lower fasting glucose can identify patients most likely to benefit from short-term intensive insulin therapy. Most importantly, during therapy, responders had less hypoglycaemia from the third week onwards, despite lower glycaemia, suggesting that 2 weeks of intensive insulin therapy may be needed to improve endogenous islet function.
authors.affiliation: Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Stein
authors.forename: C K
authors.initials: CK
authors.lastname: Kramer
authors.forename: B
authors.initials: B
authors.lastname: Zinman
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.forename: C
authors.initials: C
authors.lastname: Opsteen
authors.forename: R
authors.initials: R
authors.lastname: Retnakaran
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin