Low HbA1c and mortality: causation and confounding.

This commentary provides an overview of the clinically important data linking low or lowered HbA(1c) to increased total and CVD mortality in the general population, and in patients with diabetes. This sets the scene for a contribution in this issue of Diabetologia by Andersson et al (DOI: 10.1007/s00125-012-2584-3 ) that suggests that BMI might modify the relationship between HbA(1c) and mortality in patients with type 2 diabetes. The commentary provides a framework for the interpretation of epidemiological data from observational studies and clinical trials, and it addresses the clinical implications of this work. Finally, it highlights new research that is likely to advance this field.