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

Diabetologia. 2016 Feb;59(2):286-93. doi: 10.1007/s00125-015-3797-z. Epub 2015 Oct 30.

Abstract

Aims/hypothesis: 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/interpretation: 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.

Keywords: Disease management programme; HbA1c variability; Health services research; Severe adverse events; Type 2 diabetes mellitus.

MeSH terms

  • Aged
  • Clinical Audit
  • Diabetes Complications / blood
  • Diabetes Complications / diagnosis*
  • Diabetes Complications / epidemiology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Disease Progression
  • Female
  • Germany / epidemiology
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced*
  • Hypoglycemia / diagnosis*
  • Hypoglycemia / epidemiology
  • Insulin / administration & dosage
  • Insulin / adverse effects*
  • Male
  • Middle Aged
  • Prognosis
  • Quality of Health Care
  • Severity of Illness Index

Substances

  • Glycated Hemoglobin A
  • Insulin