title: A Large Difference in Dose Timing of Basal Insulin Introduces Risk of Hypoglycemia and Overweight: A Cross-Sectional Study.
abstract: BACKGROUND
  Basal insulin should be injected at the same time each day, but people with diabetes sometimes mistime their injections. It is not known whether irregular daily dose timing affects diabetes-related factors. We report here our evaluation of the effects of deviations from a regular dosing schedule on glycemic control and hypoglycemia on patients treated with long-acting insulin (insulin glargine U100). We also consider the effects of ultra-long-acting insulin (insulin degludec) in this context.
  
  
  METHODS
  Nineteen individuals with type 1 diabetes and 58 with type 2 diabetes were enrolled. Demographic data on all participants were retrieved from their medical records. Variation in dose timing was determined as the difference between the time of the earliest mistimed dose and the time of the latest mistimed dose, for each participant, over a 2-week period. All participants completed the Summary of Diabetes Self-Care Activities questionnaire, Problem Areas in Diabetes scale and 5-Item World Health Organization Well-being Index. Glargine U100 was switched to degludec in those individuals with type 2 diabetes who achieved inadequate glycemic control or suffered from frequent hypoglycemic episodes or who required two injections per day, and changes in hemoglobin A1c level and frequency of hypoglycemic episodes during the 12-week period were compared.
  
  
  RESULTS
  A greater difference in dose timing was related to a higher frequency of hypoglycemic episodes and overweight in persons with type 2 diabetes. Smoking, drinking and living alone were independently associated with a greater difference in dose timing. Insulin degludec decreased the frequency of hypoglycemia and improved glycemic control in participants whose dose mistiming was >120 min.
  
  
  CONCLUSIONS
  Fixed dose timing should be employed for basal insulin, as a larger difference in dose timing worsens diabetes-related factors. Insulin degludec improved glycemic control and lowered the hypoglycemia rate in persons with more irregular dose timing.
authors.affiliation: Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan. harasima@kuhp.kyoto-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Harashima
authors.affiliation: Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Department of Foundation of Nursing, Kobe City College of Nursing, Kobe, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Fukushige
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Division of Endocrinology and Metabolism, Department of Lifestyle-Related Diseases, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
keywords: Basal insulin; Dose timing; Insulin therapy; Insulin-induced hypoglycemia; Overweight; Treatment adherence; Type 1 diabetes; Type 2 diabetes