title: Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic variability and patient-centered outcomes during insulin intensification in type 1 and type 2 diabetes: a randomized, controlled, crossover trial.
abstract: BACKGROUND
  In patients with diabetes, intraday glucose variability might predict health outcomes independently from glycosylated hemoglobin (HbA1c).
  
  
  OBJECTIVE
  Our objective was to evaluate patient satisfaction (PS), quality of life (QoL), glycemic control, and variability during insulin intensification to HbA1c below 7.0%.
  
  
  METHODS
  Eighty-two type 1 and 306 insulin-treated type 2 diabetes patients (47% male; age 54±11 yr; HbA1c=7.8±0.7%) participated in this multicenter, randomized, crossover trial at 52 U.S. centers.
  
  
  METHODS
  Interventions included insulin glargine plus premeal glulisine (n=192) vs. twice-daily premix 75/25 or 70/30 analog insulin (n=196) for 12 wk and crossed to the alternate arm for 12 wk.
  
  
  METHODS
  Main outcome measures included PS and QoL questionnaires, 3-d continuous glucose monitoring (CGM), and HbA1c every 4-8 wk.
  
  
  RESULTS
  Mean±se HbA1c change was -0.39±0.09% for glargine-glulisine and -0.05±0.09% for premix (P<0.0001). The PS net benefit scale (0-100) improved from 51.1 to 60.5±1.2 for glargine-glulisine and worsened to 45.4±1.2 for premix (P<0.0001). The PS regimen acceptance scale was comparable (P=0.33). Overall QoL favored glargine-glulisine (P<0.001), as did perceived health (P<0.0001), symptom distress (P<0.0001), general health perceptions (P<0.01), and psychosocial (P<0.02). CGM daily glucose mean, daily glucose sd (glycemic variability), and percent time over 140 mg/dl were lower for glargine-glulisine by 13.1±2.7 mg/dl, 5.9±1.4 mg/dl, and 7.3±1.6%, respectively (all P<0.0001), with no difference in CGM percent time below 70 mg/dl (P=0.09). Symptomatic hypoglycemia rates were comparable. HbA1c, mean CGM daily glucose, and glycemic variability were independent predictors of PS net benefit.
  
  
  CONCLUSIONS
  Patient satisfaction was impacted more positively by improved QoL, reduced glucose variability, and better glycemic control with a basal-bolus regimen than negatively by the burden of additional injections, thereby facilitating insulin intensification and the ability to achieve HbA1c below 7.0%.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Brigham and Women's Hospital, 655 Huntington Avenue, Boston, Massachusetts 02115, USA. testa@hsph.harvard.edu
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Testa
authors.forename: Jasvinder
authors.initials: J
authors.lastname: Gill
authors.forename: Max
authors.initials: M
authors.lastname: Su
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Turner
authors.forename: Lawrence
authors.initials: L
authors.lastname: Blonde
authors.forename: Donald C
authors.initials: DC
authors.lastname: Simonson
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D011788:Quality of Life; D011795:Surveys and Questionnaires
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C479079:insulin glulisine