Great debate: pre-diabetes is not an evidence-based treatment target for cardiovascular risk reduction

with the increasing burden of diabetes as a cause of macro- and microvascular disease linked to the epidemics of obesity, attention is being paid to dysglycaemic states that predict and precede the development of type 2 diabetes. such conditions, termed pre-diabetes, are characterized by fasting plasma glucose, or plasma glucose levels on an oral glucose tolerance test, or values of glycated haemoglobin intermediate between 'normal' values and those characterizing diabetes. these last are by definition associated, in epidemiological terms, with a higher incidence of microvascular disease-mostly retinopathy. pre-diabetes overlaps with the components of the 'metabolic syndrome'-among which are excess visceral adiposity; hypertension; hypertriglyceridaemia; high levels of small, dense low-density lipoproteins; and metabolic-associated fatty liver disease. there is little doubt that pre-diabetes has important prognostic implications, especially for the occurrence of myocardial infarction, ischaemic stroke, and peripheral arterial disease. It is disputed, however, whether pre-diabetes is itself an actionable disease entity, in addition to the risk factors characterizing it. because of this uncertainty, the latest european society of cardiology guidelines chose not to include pre-diabetes as a treatment target for atherosclerotic cardiovascular disease, at variance from the three previous editions of such guidelines. this is spurring a debate, the pro and contra arguments featured in the present debate article.graphical abstract a schematic representation of the time course of development of type 2 diabetes in the context of excess calorie intake. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) occur years before blood glucose exceeds the so-called diabetic threshold, above which microangiopathy starts to occur and type 2 diabetes is diagnosed. much before the diagnosis of diabetes, however, the progressive decline in insulin sensitivity and initially compensatory insulin hypersecretion lead to the earlier occurrence of macroangiopathy (large vessel atherosclerosis) and the development of atherosclerotic vascular disease (circled in red). the time frame of IFG, higher-than-normal glycated haemoglobin (HbA1c), and, probably more relevant, IGT revealed at the oral glucose tolerance test (OGTT) is termed 'pre-diabetes'. whether pre-diabetes is an actionable target for interventions, independent of risk factors common to all vascular disease, is debated. CV, cardiovascular