title: Time to insulin initiation and long-term effects of initiating insulin in people with type 2 diabetes mellitus: the Hoorn Diabetes Care System Cohort Study.
abstract: OBJECTIVE
  The aim of this study was to assess the time to insulin initiation in type 2 diabetes mellitus (T2DM) patients treated with oral glucose-lowering agents and to determine the baseline characteristics associated with time to insulin initiation. This was evaluated in T2DM patients with HbA1c levels consistently ≥7.0% during total follow up and in those with fluctuating HbA1c levels around 7.0%.
  
  
  METHODS
  Prospective, observational study was performed, comprising 2418 persons with T2DM aged ≥40 years who entered the Diabetes Care System between 1998 and 2012 with a minimum follow up of at least 3 years, following the first HbA1c level ≥7.0%. Cox regression analyses were performed to assess the determinants of time to insulin initiation. Data related to long-term effects of insulin initiation were studied at baseline and at the end of follow up using descriptive summary statistics.
  
  
  RESULTS
  Two-thirds of the patients initiated insulin during follow up. The time to insulin varied from 1.2 years (range 0.3-3.1) in patients with HbA1c levels consistently ≥7.0% to 5.4 years (range 3.0-7.5) in patients with fluctuating HbA1c levels around 7.0%. Longer diabetes duration (hazard ratio (HR) 1.04 95% CI 1.03-1.05) and lower age (HR 1.00 95% CI 0.99-1.00) at baseline were associated with a shorter time to initiation. More insulin initiators had retinopathy compared with patients that remained on oral glucose-lowering agents during follow up.
  
  
  CONCLUSIONS
  The time to insulin initiation was short, and most of the patients with HbA1c levels consistently ≥7.0% were initiating insulin. Longer diabetes duration and younger age shortened the time to insulin.
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA m.mast@vumc.nl.
authors.forename: Ruth
authors.initials: R
authors.lastname: Mast
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Danielle Jansen
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Walraven
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Simone P
authors.initials: SP
authors.lastname: Rauh
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Amber A W A
authors.initials: AA
authors.lastname: van der Heijden
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Petra J M
authors.initials: PJ
authors.lastname: Elders
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.affiliation: EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA EMGO Institute for Health and Care ResearchDepartments of Clinical Pharmacology and PharmacyGeneral Practice and Elderly Care MedicineEpidemiology and BiostatisticsOphthalmologyVU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsEli Lilly and Company893 S Delaware St, Indianapolis, Indiana, USA.
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: Hugtenburg
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013997:Time Factors
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human