title: The effect of the insulin analog lispro on nighttime blood glucose control in type 1 diabetic patients.
abstract: OBJECTIVE
  Unmodified regular insulin has a long absorption tail, unlike the fast-acting insulin analog lispro, and may contribute to hypoglycemia in the early part of the night. A randomized crossover double-blind study was performed to compare blood glucose concentrations in the early part of the night in type 1 diabetic patients receiving lispro or unmodified regular human insulin, in random order, on 2 separate study days.
  
  
  METHODS
  We studied 23 C-peptide-negative patients; 12 were using a premeal plus basal insulin regimen, and 11 were using twice-daily insulin injections. Patients were admitted to the investigation unit at 5:00 P.M. and received a single dose of lispro or unmodified regular human insulin before the evening meal. In both groups, the NPH insulin dose remained unchanged. Identical meals and snacks were eaten at the same time during both study days.
  
  
  RESULTS
  Average postprandial (6:00-10:00 P.M.) blood glucose concentrations were significantly lower after lispro therapy compared with human insulin (7.1 +/- 0.4 [SE] vs. 8.5 +/- 0.4 mmol/l, P = 0.0002). Nighttime (midnight to 4:00 A.M.) blood glucose concentrations were significantly higher after lispro compared with human insulin (10.3 +/- 0.4 vs. 9.1 +/- 0.4 mmol/l, P = 0.02). This difference was greatest in patients on the premeal plus basal insulin regimen (11.6 +/- 0.5 vs. 8.7 +/- 0.4 mmol/l, P < 0.001). The incidence of nocturnal hypoglycemia (midnight to 4:00 A.M., blood glucose < 3.5 mmol/l) was less with lispro compared with unmodified insulin (1 vs. 6 patients, P = 0.04). Nighttime (midnight to 4:00 A.M.) 3-hydroxybutyrate (102 +/- 13 vs. 51 +/- 7 mumol/l, P = 0.000) and glycerol (52 +/- 3 vs. 42 +/- 2 mumol/l, P < 0.01) were significantly higher after lispro therapy compared with human insulin in patients on the premeal plus bolus insulin regimen.
  
  
  CONCLUSIONS
  Lispro can improve postprandial blood glucose control and reduce the incidence of nocturnal hypoglycemia at the expense of nocturnal hyperglycemia and hyperketonemia in patients using a premeal plus basal insulin regimen.
authors.affiliation: Human Metabolism and Diabetes Research Centre, University of Newcastle upon Tyne, U.K.
authors.forename: A B
authors.initials: AB
authors.lastname: Ahmed
authors.forename: P D
authors.initials: PD
authors.lastname: Home
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004435:Eating; D005215:Fasting; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D061268:Insulin Lispro; D008297:Male; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D019382:Human Growth Hormone