title: The Effects of Transition from Bedtime to Morning Glargine Administration in Patients with Poorly Regulated Type 1 Diabetes Mellitus: Croatian Pilot Study.
abstract: BACKGROUND
  The objective of this study was to compare differences in glucoregulation, frequency of hypoglycemic episodes, glucose variability and lipid profiles of inpatients with poorly regulated type 1 diabetes mellitus (T1DM) after evening versus morning glargine application.
  
  
  METHODS
  Eighteen patients with poorly regulated T1DM, glycated hemoglobin (Hba1c) levels ≥7% and frequent nocturnal and/or morning hypoglycemic episodes were included in this study. There was a 12-week screening phase where patients continued their usual insulin regimen and were encouraged to achieve optimal glycemic control; however, all patients maintained HbA1c values ≥7% and continued to have frequent nocturnal and/or morning hypoglycemic events and were therefore transitioned to morning application of insulin glargine for 12 weeks. The primary outcome was to investigate changes in HbA1c values 12 weeks after the transition. The secondary outcome was to evaluate the effect of transition on glucose variability, incidence of hypoglycemic episodes, insulin doses, lipid profile and weight. Data were analyzed using paired Student's t test and Pearson correlation.
  
  
  RESULTS
  After the transition, there was no significant change in total daily dose of basal insulin (p 0.114) and the average body weight remained unchanged, while significant reduction of HbA1c was present (8.02 ± 0.5 vs. 7.4 ± 0.3%) (p < 0.01) resulting in a decrease in nocturnal and daytime hypoglycemic episodes per month per person (p < 0.01). Parameters of glucose variability (glycemic standard deviations and J-index) were also improved after transition period (p < 0.01). As for the lipid profile, increase of high-density lipoprotein cholesterol and decrease of triglycerides (p < 0.01) were noticed, while other lipid parameters remained unaffected. Furthermore, insignificant association of basal insulin dose with HbA1c values regardless of the time of administration was observed.
  
  
  CONCLUSIONS
  In patients with poorly regulated T1DM, transition to morning application of glargine improved glucoregulation (including a decrease in HbA1c, glucose variability and number of nocturnal hypoglycemic episodes), followed by favorable changes in lipid profile without affecting body weight. These effects were associated with the time of application, but not with the insulin dose.
authors.affiliation: Department of Internal Medicine, General Hospital Čakovec, 40000, Čakovec, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Gradiser
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Osijek, University Hospital Center Osijek, 31000, Osijek, Croatia. ibcurcic@mefos.hr.
authors.forename: Ines
authors.initials: I
authors.lastname: Bilic-Curcic
authors.affiliation: Institute of Pathophysiology, School of Medicine, University in Nis, 18000, Nis, Serbia.
authors.forename: Boris
authors.initials: B
authors.lastname: Djindjic
authors.affiliation: Clinical Department of Diabetes, Endocrinology and Metabolism Disorders, University Hospital Centre "Sestre Milosrdnice", 1000, Zagreb, Croatia.
authors.forename: Maja Cigrovski
authors.initials: MC
authors.lastname: Berkovic
keywords: Basal insulin; Diabetes type 1; Glucoregulation; Hypoglycemia; Lipid profile; Morning administration