title: Does insulin lispro preserve the physiological defences to hypoglycaemia during intensive insulin therapy with a conventional basal bolus regimen?
abstract: OBJECTIVE
  Insulin lispro used in an intensive basal/bolus regimen produces equivalent glycaemic control to human-soluble insulin but reduces rates of hypoglycaemia. We tested the hypothesis that the use of rapid-acting analogues might prevent the development of defective hypoglycaemic counterregulation during intensive insulin therapy.
  
  
  METHODS
  Ten patients with type 1 diabetes (four female, mean age 33 +/- 3 years, diabetes duration 12 +/- 2 years) participated in an open, randomized cross-over study, with 2 months run-in and 4-month treatment periods using either lispro or human-soluble insulin before meals and human NPH insulin (NPH) at night. The total of reported hypoglycaemic episodes (lispro vs. soluble, 123 vs. 128) and HbA(1c) (6.1 +/- 0.2 vs. 6.6 +/- 0.2%) were similar during both treatments. At the end of each period, we measured symptomatic, counterregulatory and cognitive responses, and glycaemic thresholds during hypoglycaemia, induced with a hyperinsulinaemic clamp (blood glucose of 5, 4.5, 3.5 and 2.5 mmol/l).
  
  
  RESULTS
  We found similar overall responses of adrenaline, cortisol, growth hormone and total symptom score. Glycaemic thresholds for rises in adrenaline (3.1 +/- 0.2 vs. 3.1 +/- 0.2 mmol/l, p = 0.76), cortisol (2.2 +/- 0.1 vs. 2.2 +/- 0.1 mmol/l, p = 0.16), growth hormone (3.3 +/- 0.15 vs. 2.9 +/- 0.2 mmol/l, p = 0.13), symptoms (3.2 +/- 0.2 vs. 3.3 +/- 0.1 mmol/l, p = 0.051) and impaired cognitive function (3.0 +/- 0.2 vs. 3.0 +/-0.2 mmol/l, p = 0.20) were also similar.
  
  
  CONCLUSIONS
  Four months of intensive treatment, with insulin lispro used pre-prandially and isophane at night, produced relatively preserved but equivalent physiological responses to hypoglycaemia as those on soluble insulin. Longer periods of treatment or alternative regimens may be necessary to demonstrate beneficial effects on hypoglycaemic physiological responses.
authors.affiliation: University of Sheffield, Sheffield, UK. s.heller@sheffield.ac.uk
authors.forename: S R
authors.initials: SR
authors.lastname: Heller
authors.forename: S A
authors.initials: SA
authors.lastname: Amiel
authors.forename: M L
authors.initials: ML
authors.lastname: Evans
authors.forename: M-F
authors.initials: MF
authors.lastname: Kong
authors.forename: I A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: S R
authors.initials: SR
authors.lastname: Peacey
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003071:Cognition; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004837:Epinephrine / Q000097:blood; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D061268:Insulin Lispro; D007336:Insulin, Isophane / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011930:Reaction Time
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D019382:Human Growth Hormone; D007336:Insulin, Isophane; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine