title: Association of the average rate of change in HbA1c with severe adverse events: a longitudinal evaluation of audit data from the Bavarian Disease Management Program for patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  In patients with type 2 diabetes mellitus, the effects of HbA1c variability on macrovascular events remain uncertain. The present investigation evaluates the association of HbA1c variability with non-fatal cardiovascular events, emergency admissions and episodes of severe hypoglycaemia in a cohort of patients newly started on insulin therapy.
  
  
  METHODS
  HbA1c variability was defined as the rate of change in values between observations. The medical records of 406,356 patients enrolled in a disease management programme for type 2 diabetes mellitus were analysed to identify a cohort of 13,777 patients with observed transition to insulin therapy. The cohort was observed for a period of at least 5 years. Cox regression models were applied to quantify the association of HbA1c variability with the events of interest.
  
  
  RESULTS
  The models reveal a significant non-linear association between HbA1c variability and the risk of experiencing myocardial infarction, stroke and hypoglycaemia. The lowest risk is seen with a variability of approximately 0.5% (5.5 mmol/mol) per quarter. Using Cox models to predict survival curves for the cohort with hypothetical HbA1c variability of 0.5% (5.5 mmol/mol) and 1.5% (16.4 mmol/mol) per quarter, the proportion experiencing myocardial infarction within 2 years increases significantly from 1% to 10%. The proportion experiencing stroke increases from 1% to 29%, hypoglycaemia from 2% to 24% and the risk of emergency admission from 2% to 21%.
  
  
  CONCLUSIONS
  In patients newly started on insulin therapy, rapid and higher HbA1c variability is associated with an increased risk of myocardial infarction, stroke, severe hypoglycaemia and emergency admission.
authors.affiliation: Institute of General Practice, University Hospital Klinikum rechts der Isar, Technische Universität München, Orleansstr. 47, 81667, München, Germany.
authors.forename: Florian C
authors.initials: FC
authors.lastname: Bonke
authors.affiliation: Association of Statutory Health Insurance Physicians of Bavaria, Munich, Germany.
authors.forename: Ewan
authors.initials: E
authors.lastname: Donnachie
authors.affiliation: Institute of General Practice, University Hospital Klinikum rechts der Isar, Technische Universität München, Orleansstr. 47, 81667, München, Germany.
authors.forename: Antonius
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Institute of General Practice, University Hospital Klinikum rechts der Isar, Technische Universität München, Orleansstr. 47, 81667, München, Germany. michael.mehring@tum.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Mehring
mesh_terms: D000368:Aged; D054869:Clinical Audit; D048909:Diabetes Complications / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005858:Germany / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis* / Q000453:epidemiology; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011787:Quality of Health Care; D012720:Severity of Illness Index
chemical_list: D006442:Glycated Hemoglobin; D007328:Insulin
keywords: Disease management programme; HbA1c variability; Health services research; Severe adverse events; Type 2 diabetes mellitus