American Diabetes Association
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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

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posted on 2021-07-07, 20:41 authored by Elke R. Fahrmann, Laura Adkins, Henry K. Driscoll

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.


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.