Based on basic research it might be intuitive that the relationship between hypoglycemia requiring assistance (SH) and clinical cardiovascular events (CVE) differs in cohorts with no vs. early microvascular complications (PRIM vs. SEC) in type 1 diabetes (T1DM). We analyze Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) data to examine whether PRIM vs. SEC differences exist in effect of cumulative SH on CVE. At DCCT baseline, 726 PRIM and 715 SEC (with minimal to moderate nonproliferative retinopathy and < 200 mg / 24 h of albuminuria) volunteers were enrolled. Otherwise, subjects (ages 13-39) were in overall good health. Mean follow-up was 27 years. Cox proportional hazard models assessed the effects of time-dependent updated mean SH rate per 100 years on CVE risk. Two outcomes were analyzed: MAJOR (fatal or nonfatal myocardial infarction (MI) or stroke) and ANYCVE (MAJOR, subclinical MI, angina, revascularization, or congestive heart failure). All models were adjusted for clinical covariates. Due to skewness, SH rate was log transformed: ln(SH rate+1). Interaction between mean updated SH rate and ANYCVE (or MAJOR) was significant with p<0.001 (p<0.01). In further analyses by cohort, SH emerged as an independent CVE factor in SEC with hazard ratios of 1.19 (CI95% 1.08-1.31), p<0.001, for ANYCVE and 1.32 (CI95% 1.14-1.53), p<0.001, for MAJOR. No associations were found for PRIM. To get additional insight, DCCT-SH and updated mean EDIC-SH effects on CVE were analyzed during EDIC period (1994-2013). In SEC, DCCT-SH emerged as a significant ANYCVE and MAJOR factor; EDIC-SH was associated with MAJOR but did not reach significance with ANYCVE (p∼0.09). To our best knowledge, this is the first T1DM analysis demonstrating an association of cumulative SH with clinical CVE for SEC patients. In addition to HbA1c, SH in T1DM should be considered as a non-traditional chronic CVE risk factor in SEC and managed accordingly.


E.R. Fahrmann: None. L.J. Adkins: None. H. Driscoll: None.

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