title: Sensitivity of Traditional and Risk-Based Glycemic Variability Measures to the Effect of Glucose-Lowering Treatment in Type 2 Diabetes Mellitus.
abstract: BACKGROUND
  Here we assess associations between glycemic variability (GV) measures and outcomes from glucose-lowering therapy in patients with type 2 diabetes (T2DM) to identify the metrics most sensitive to treatment response.
  
  
  METHODS
  Data from 1699 patients in 6 previously reported studies in adults with T2DM treated with basal insulin and/or oral glucose-lowering drugs were included in a post hoc meta-analysis. Using 7-point blood glucose (BG) profiles we compared the GV metrics standard deviation (SD), mean amplitude of glycemic excursion (MAGE), mean absolute glucose (MAG), low and high BG risk indices (LBGI, HBGI), and average daily risk range (ADRR). Treatment-related changes in GV and risk status and associations between end-of-trial GV/risk metrics with treatment outcomes (end-of-trial glycated hemoglobin A1c[A1C] level ≥7.0%, hypoglycemia, and composite outcome of A1C <7.0% and no hypoglycemia), were evaluated.
  
  
  RESULTS
  Significant changes from baseline to end of treatment were observed in all measures (all P < .0001), with the largest reduction following treatment for HBGI (-65.5%) and ADRR (-43.3%). The baseline risk classification for hyperglycemia based on the risk categories of HBGI improved for 66.8%, remained unchanged for 29.8%, and deteriorated for 3.3% of patients (chi-square P < .0001), while the risk for hypoglycemia did not change. HBGI showed the strongest association with A1C ≥7.0% at the end of treatment, and LBGI showed the strongest association with symptomatic hypoglycemia.
  
  
  CONCLUSIONS
  During glucose-lowering therapy in T2DM, HBGI and LBGI offer insights into hyperglycemia and trends toward hypoglycemia, respectively; ADRR may be the optimal GV measure responsive to hypo- and hyperglycemic treatment effects.
authors.affiliation: University of Virginia Health System, Charlottesville, VA, USA boris@virginia.edu.
authors.forename: Boris
authors.initials: B
authors.lastname: Kovatchev
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Umpierrez
authors.affiliation: Isis Pharmaceuticals, Inc, Carlsbad, CA, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: DiGenio
authors.affiliation: Medpace Inc, Cincinnati, OH, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Yale School of Medicine, New Haven, CT, USA.
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Inzucchi
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007267:Injections; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human
keywords: glycemic variability; measure; treatment response; type 2 diabetes mellitus