Vascular complications in prediabetes

Abstract

Prediabetes (defined as impaired fasting glucose [IFG] between 100 and 125 mg/dL, impaired glucose tolerance [IGT] between 140 and 199 mg/dL, or HbA1c between 5.7% and 6.4%) is a pathological state capable of causing early macrovascular and microvascular damage, rather than merely a transitional phase leading to type 2 diabetes^1,2. Its rising global prevalence represents a significant cardiometabolic burden^4,5.

Insulin resistance and chronic hyperglycemia trigger oxidative stress via reactive oxygen species, low-grade systemic inflammation (elevated TNF-α and IL-6), and the accumulation of advanced glycation end-products (AGEs)^1,3. These processes cause endothelial dysfunction, downregulation of the PI3K/Akt pathway, and reduced nitric oxide bioavailability, manifesting as impaired flow-mediated dilation (FMD)^1,3.

At the microvascular level, hyperglycemia promotes capillary basement membrane thickening and alters vascular reactivity, leading to subclinical retinal neurodegeneration and microalbuminuria^1,2. At the macrovascular level, it accelerates atherogenesis and arterial stiffness, increasing carotid intima-media thickness (CIMT) and pulse wave velocity (PWV)^1,3.

Meta-analyses and prospective studies demonstrate that prediabetes independently increases the risk of cardiovascular disease, myocardial infarction, stroke, and all-cause mortality^2-5. IFG and IGT—particularly when combined—are independent predictors of adverse events^1,3,5. In light of the foregoing, a preventive, intensive, and multifactorial approach—focused on lifestyle changes and, if necessary, the use of medication—is warranted to achieve comprehensive metabolic control that prevents the onset of chronic complications^1,4.