title: Association of Glycemic Variability in Type 1 Diabetes With Progression of Microvascular Outcomes in the Diabetes Control and Complications Trial.
abstract: The Diabetes Control and Complications Trial (DCCT) demonstrated the beneficial effects of intensive versus conventional therapy on the development and progression of microvascular complications of type 1 diabetes. These beneficial effects were almost completely explained by the difference between groups in the levels of HbA1c, which in turn were associated with the risk of these complications. We assessed the association of glucose variability within and between quarterly 7-point glucose profiles with the development and progression of retinopathy, nephropathy, and cardiovascular autonomic neuropathy during the DCCT.
  
  
  
  Measures of variability included the within-day and updated mean (over time) of the SD, mean amplitude of glycemic excursions (MAGE), and M-value, and the longitudinal within-day, between-day, and total variances. Imputation methods filled in the 16.3% of expected glucose values that were missing.
  
  
  
  Cox proportional hazards models assessed the association of each measure of glycemic variation, as a time-dependent covariate, with the risk of retinopathy and nephropathy, and a longitudinal logistic regression model did likewise for cardiovascular autonomic neuropathy. Adjusted for mean blood glucose, no measure of within-day variability was associated with any outcome. Only the longitudinal mean M-value (over time) was significantly associated with microalbuminuria when adjusted for the longitudinal mean blood glucose and corrected for multiple tests using the Holm procedure.
  
  
  
  Overall, within-day glycemic variability, as determined from quarterly glucose profiles, does not play an apparent role in the development of microvascular complications beyond the influence of the mean glucose.
authors.affiliation: The Biostatistics Center, The George Washington University, Rockville, MD jml@bsc.gwu.edu.
authors.forename: John M
authors.identifier: 0000-0001-9838-2841
authors.initials: JM
authors.lastname: Lachin
authors.affiliation: The Biostatistics Center, The George Washington University, Rockville, MD.
authors.forename: Ionut
authors.initials: I
authors.lastname: Bebu
authors.affiliation: International Diabetes Center at Park Nicollet, Minneapolis, MN.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
authors.affiliation: University of Michigan, Ann Arbor, MI.
authors.forename: Rodica
authors.initials: R
authors.lastname: Pop-Busui
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN.
authors.forename: F John
authors.initials: FJ
authors.lastname: Service
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: David M
authors.initials: DM
authors.lastname: Nathan
mesh_terms: D000328:Adult; D000419:Albuminuria; D001786:Blood Glucose / Q000378:metabolism*; D002319:Cardiovascular System / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications; D003929:Diabetic Neuropathies / Q000097:blood / Q000150:complications; D003930:Diabetic Retinopathy / Q000097:blood / Q000150:complications; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin