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…

Florian C. Bonke, Ewan Donnachie, Antonius Schneider, Michael Mehring

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. 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. 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%. 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.