Modification of the Association Between Severe Hypoglycemia and Ischemic Heart Disease by Surrogates of Vascular Damage Severity in Type 1 Diabetes During ∼30 Years of Follow-up in the DCCT/EDIC Study
Literature suggests that severe hypoglycemia (SH) may be linked to cardiovascular events only in older individuals with high cardiovascular risk score (CV-score). Whether a potential relationship between any-SH and cardiovascular disease exists and whether it is conditional on vascular damage severity in a young type 1 diabetes (T1D) cohort without apparent macro-vascular and no or mild-to-moderate micro-vascular complications at baseline is unknown.
RESEARCH DESIGN AND METHODS
We evaluated data of 1441 Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) volunteers (diabetes duration 1-15 years) followed for ~30 years. Time-dependent associations between any-SH, interactions of any-SH with surrogates of baseline micro-/macro- vascular damage severity (diabetes duration, Early Treatment Diabetic Retinopathy Study scale (ETDRS), Diabetes Complications Severity Index (DCSI), or CV-scores) and ischemic heart disease (IHD: death, silent/nonfatal myocardial infarct, revascularization, or confirmed angina) were analyzed.
Without interactions, in the minimal adjusted model controlling for confounding bias by age and HbA1c, SH was a significant IHD factor (p~0.003). SH remained a significant factor for IHD in fully adjusted models (p<0.05). In models with interactions, interactions between SH and surrogates of microvascular complications severity, but not between SH and CV-score, were significant. Hazard ratios for IHD based on SH increased 1.19-fold, 1.32-fold, and 2.21-fold for each additional year of diabetes duration, ETDRS-unit, and DCSI-unit, respectively. At time of IHD event, ~15% of 110 participants with SH had high CV-scores.
In a young T1D cohort with no baseline macrovascular complications, surrogates of baseline microvascular damage severity impact the effect of SH on IHD. Older age with high CV-score per se is not mandatory for an association of SH with IHD. However, the association is multifactorial.