title: Optimized basal-bolus therapy using a fixed mixture of 75% lispro and 25% NPL insulin in type 1 diabetes patients: no favorable effects on glycemic control, physiological responses to hypoglycemia, well-being, or treatment satisfaction.
abstract: OBJECTIVE
  To investigate the effects of a multiple injection regimen with a mixture of 75% lispro and 25% intermediate-acting insulin (lispro high mixture [HM]) before meals on glycemic control, physiological responses to hypoglycemia, well-being, and treatment satisfaction.
  
  
  METHODS
  We studied 35 type 1 diabetes patients. After an 8- to 10-week lead-in period, patients were randomized to HM or human regular insulin therapy for 12-14 weeks. During the lead-in and treatment periods, HbA1c levels and hypoglycemic frequencies were measured, and patients completed the Well-Being Questionnaire and the Diabetes Treatment Satisfaction Questionnaire. In 19 patients, responses to hypoglycemia were tested during stepped euglycemic-hypoglycemic clamps.
  
  
  RESULTS
  HM treatment improved postprandial glycemia but had no effect on HbA1c, frequency of hypoglycemia, well-being, or treatment satisfaction. During experimental hypoglycemia, HM therapy was associated with a slightly lower total adrenaline response and a higher autonomic symptom threshold (i.e., the autonomic symptom response occurred at a lower blood glucose level) than human regular insulin therapy. We speculate that this effect resulted from an accumulation of insulin during the night.
  
  
  CONCLUSIONS
  Multiple injection therapy with HM rather than human regular insulin before meals does not offer advantages regarding glycemic control, frequency of hypoglycemia, well-being, or treatment satisfaction. In addition, this regimen causes an attenuation of the adrenaline and autonomic symptom responses to hypoglycemia.
authors.affiliation: Research Institute for Endocrinology, Reproduction and Metabolism and the Department of Epidemiology and Biostatistics, Faculty of Medicine, Vrije Universiteit Amsterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Janssen
authors.forename: F J
authors.initials: FJ
authors.lastname: Snoek
authors.forename: N
authors.initials: N
authors.lastname: Masurel
authors.forename: R P
authors.initials: RP
authors.lastname: Hoogma
authors.forename: W L
authors.initials: WL
authors.lastname: Devillé
authors.forename: C
authors.initials: C
authors.lastname: Popp-Snijders
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004837:Epinephrine / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D061268:Insulin Lispro; D008297:Male; D017060:Patient Satisfaction; D011479:Protamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D004837:Epinephrine; D006442:Glycated Hemoglobin; D007328:Insulin; D061268:Insulin Lispro; D011479:Protamines; C110077:neutral protamine lispro insulin