Prediabetes and macrovascular disease: Review of the association, influence on outcome and effect of treatment

Prediabetes is an intermediate metabolic state between normal glucose metabolism and diabetes mellitus. Patients with prediabetes have an increased risk (of up to 70%) of developing type 2 diabetes. Prediabetes is highly prevalent in patient with macrovascular disease including coronary artery disease, stroke and peripheral artery disease, persisting in the post-acute phase, which suggests true disturbance of glucose metabolism rather than a temporary reflection of stress. Moreover, the clinical and functional outcome in these patients is worse compared to patients with normal glucose metabolism. As the prevalence of prediabetes is growing rapidly, prediabetes might become an important modifiable therapeutic target in both primary and secondary prevention. Concerning primary prevention, lifestyle modification and to a lesser extend antidiabetic drugs decrease the risk of developing type 2 diabetes in patients with prediabetes. Furthermore, long-term follow-up studies showed that intensive lifestyle intervention, and/or medical treatment of cardiovascular risk factors reduced the incidence of macrovascular mortality and all-cause mortality in these patients as well. As to secondary prevention, there is only little evidence that treatment of prediabetes in patients with macrovascular disease decreases the recurrence of macrovascular complications and improves outcome. This review focuses on the association of prediabetes with outcome in patients with macrovascular disease, and the effect of treatment of prediabetes on the risk of developing macrovascular disease (in primary prevention) as well as on the outcome in patients with established macrovascular disease (secondary prevention).