title: Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes.
abstract: OBJECTIVE
  The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D).
  
  
  METHODS
  Patients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0-11.0% were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60 mg/dl in two or more consecutive readings from CGM.
  
  
  RESULTS
  A total of 50 patients (mean age 53.5 ± 8.2 years, male 48%, mean baseline HbA1c 8.4 ± 1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5 ± 13.8 to 18.8 ± 35.8 min/day, p=0.041), but not with acarbose (from 2.9 ± 10.9 to 14.7 ± 41.9 min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (β coefficient 0.345, p=0.036) or acarbose (β coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models).
  
  
  CONCLUSIONS
  Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jun-Sing
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: I-Te
authors.initials: IT
authors.lastname: Lee
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wen-Jane
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Hua Christian Hospital, Chang-Hua, Taiwan.
authors.forename: Shi-Dou
authors.initials: SD
authors.lastname: Lin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Hua Christian Hospital, Chang-Hua, Taiwan.
authors.forename: Shih-Li
authors.initials: SL
authors.lastname: Su
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Hua Christian Hospital, Chang-Hua, Taiwan.
authors.forename: Shih-Te
authors.initials: ST
authors.lastname: Tu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yao-Hsien
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Medical Technology, College of Life Science, National Chung-Hsing University, Taichung, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan. Electronic address: whhsheu@vghtc.gov.tw.
authors.forename: Wayne Huey-Herng
authors.initials: WH
authors.lastname: Sheu
mesh_terms: D020909:Acarbose / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D018670:Monitoring, Ambulatory
chemical_list: D020909:Acarbose; D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Acarbose; Continuous glucose monitoring; Glibenclamide.; Glycemic excursions; Hypoglycemia; Type 2 diabetes