title: Additional lunchtime basal insulin during insulin lispro intensive therapy in a randomized, multicenter, crossover study in adults : a real-life design.
abstract: OBJECTIVE
  This study was performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night.
  
  
  METHODS
  The study was a 10-month multicenter, randomized, crossover trial. After a 2-month run-in period, subjects injected NPH insulin once (1 x NPH) or twice (2 x NPH) daily for 4 months in a randomized order. Adult patients were included if they had HbA(1c) levels <8.5%. Efficacy measures were HbA(1c) levels, 8-point glucose profiles, and the frequency of hypoglycemia. The statistical analysis included a within-patient comparison for crossover trials.
  
  
  RESULTS
  In all, 104 patients completed the trial. The mean HbA(1c) level before randomization was 7.1 +/- 0.85%. The HbA(1c) levels did not change significantly within patients (t test, mean difference = 0.06%; 95% confidence interval [CI] -0.073 to 0.20). The pre-dinner blood glucose values were significantly lower during the 2 x NPH daily protocol, with a mean difference of 0.76 mmol/l (t test, P = 0.004; CI 0.25 to 1.3). In the evening, the frequency of hypoglycemia increased significantly during the 2 x NPH daily protocol with a median difference of 0.56 mild episodes/30 days (P = 0.001) and 6.9 severe episodes/patient year (P = 0.007), respectively.
  
  
  CONCLUSIONS
  Equal HbA(1c) levels and increasing frequencies of hypoglycemia in the evening overshadow the slight improvement of the evening glucose profiles during a regimen with 2 x NPH daily insulin. Therefore, generalized use of a second injection of NPH insulin at lunchtime cannot be recommended to all adult patients with type 1 diabetes using intensive insulin lispro therapy.
authors.affiliation: Department of Internal Medicine, Diakonessenhuis Utrecht, Utrecht, The Netherlands. astades@diakhuis.nl
authors.forename: Aline M E
authors.initials: AM
authors.lastname: Stades
authors.forename: Joost B L
authors.initials: JB
authors.lastname: Hoekstra
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van den Tweel
authors.forename: D Willem
authors.initials: DW
authors.lastname: Erkelens
authors.forename: Frits
authors.initials: F
authors.lastname: Holleman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004435:Eating; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D061268:Insulin Lispro; D007336:Insulin, Isophane / Q000627:therapeutic use*; D008297:Male
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D007336:Insulin, Isophane