Should we shift from delaying diabetes to pursuing pre-diabetes remission for cardiovascular disease prevention?

Abstract

The global epidemic of dysglycemia, spanning from pre-diabetes to overt type 2 diabetes (T2D), constitutes a primary driver of cardiovascular morbidity and mortality worldwide. While managing established T2D remains crucial, accumulating evidence underscores that the pre-diabetic state itself represents a period of active, subclinical cardiovascular injury. This commentary argues for a fundamental strategic shift: from merely delaying progression to T2D toward actively pursuing remission of pre-diabetes - defined as the sustained return to normoglycemia - as a potent and likely essential target for curbing cardiovascular disease. This approach moves beyond traditional risk factor management by targeting a reversible pathophysiological nexus. The rationale is robust, implicating insulin resistance, hyperinsulinemia, β-cell stress, chronic inflammation, endothelial dysfunction, and a pro-atherogenic lipid profile. Notably, long-term follow-up data from landmark prevention trials now provide compelling evidence that achieving remission is associated with a striking reduction of approximately 50% in the risk of cardiovascular death and heart failure hospitalization. Although intensive lifestyle intervention remains the cornerstone, emerging therapeutic options - including potent glucagon-like peptide-1 (GLP-1) receptor agonists, glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonists, and metabolic surgery - offer new pathways to induce remission. Nevertheless, significant gaps persist, primarily the lack of a consensus definition for pre-diabetes remission and the absence of prospective trials with remission as a primary cardiovascular endpoint. Addressing these gaps through coordinated research, consensus-building, and integration into clinical guidelines is imperative to translate this paradigm from a compelling hypothesis into a standard of care capable of altering the cardiovascular trajectory of hundreds of millions at risk.

Keywords

Pre-diabetes remission / cardiovascular disease / insulin resistance / lifestyle intervention / primary prevention

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