Increased Risk of Severe Hypoglycemic Events Before and After Cardiovascular Events in Type 2 Diabetes: Validation of a Novel Concept


BACKGROUND: Severe hypoglycemic events (SHEs) in type 2 diabetes (T2D) are associated with an increased risk of subsequent cardiovascular (CV) events. A reverse relationship, however, in which nonfatal CV events are associated with a subsequent increased SHE risk has been demonstrated in TECOS. We sought to validate this novel bidirectional relationship using EXSCEL data.

METHODS: Time-dependent associations were examined between SHEs and subsequent CV events or all-cause mortality (ACM) in a post hoc analysis of 14,752 EXSCEL participants with T2D, and between nonfatal CV events and subsequent SHEs, in both partial and fully adjusted models.

RESULTS: Participants with (versus without) SHEs were on average older, with longer diabetes duration and lower estimated glomerular filtration rate, and were more frequently non-White, insulin treated, and had prior CV or heart failure events. SHEs were not associated with once-weekly exenatide therapy, compared with placebo (hazard ratio 1.13, 95% CI 0.94-1.36, P=0.18). In fully adjusted models, SHEs increased the risk of ACM, CV death and hospitalization for heart failure (hHF), whilst non-fatal MI, non-fatal stroke and hHF all increased subsequent risk of SHEs (Table).

CONCLUSIONS: A robust bidirectional association between SHEs and subsequent risk of CV events, and between nonfatal CV events and subsequent risk of SHEs, was confirmed, suggesting a “frail” T2D sub-phenotype with increased susceptibility to both SHEs and CV events.

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Standl E, Stevens SY, Lokhnygina Y, et al. J Am Coll Cardiol 2019;73(Suppl 1):24.