Phenotyping the Prediabetic Population-A Closer Look at Intermediate Glucose Status and Cardiovascular Disease

Abstract

Even though the new thresholds for defining prediabetes have been around for more than ten years, there is still controversy surrounding the precise characterization of this intermediate glucose metabolism status. The risk of developing diabetes and macro and microvascular disease linked to prediabetes is well known. Still, the prediabetic population is far from being homogenous, and phenotyping it into less heterogeneous groups might prove useful for long-term risk assessment, follow-up, and primary prevention. Unfortunately, the current definition of prediabetes is quite rigid and disregards the underlying pathophysiologic mechanisms and their potential metabolic progression towards overt disease. In addition, prediabetes is commonly associated with a cluster of risk factors that worsen the prognosis. These risk factors all revolve around a common denominator: inflammation. This review focuses on identifying the population that needs to be screened for prediabetes and the already declared prediabetic patients who are at a higher risk of cardiovascular disease and require closer monitoring.

Keywords: ASCVD; atherosclerosis; insulin resistance; macrovascular disease; prediabetes cluster; prognosis.

Figure 1

Risk factors associated with prediabetes.

Figure 2

A stratified screening process for prediabetes. ASCVD, atherosclerotic cardiovascular disease; cluster 3, high-risk prediabetic phenotype with low insulin secretion and high genetic risk; cluster 5, high-risk prediabetic phenotype, high liver fat content, and high IR [31]; CVD, cardiovascular disease; DM, diabetes mellitus; PDM, prediabetes.

Figure 3

Possible interventions in intermediate glucose states. DPP4—Dipeptidyl peptidase-4, GLP—1RA-Glucagon-like peptide-1 receptor agonist, TZD—thiazolidinediones.