Relationships between the Cumulative Incidences of Long-Term Complications in Type 1 Diabetes Mellitus: the DCCT/EDIC Study

Objective To describe the relationships between the cumulative incidences of long-term complications in individuals with type 1 diabetes (T1D), and assess whether observed associations are independent of age, duration of diabetes, and glycemic levels. 

Methods Proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), reduced eGFR, amputations, cardiovascular disease (CVD) and mortality were assessed in DCCT/EDIC over ~30 years. 

Results The cumulative incidence of complications ranged from 3% (amputations) to 37% (CSME). There were large differences in the cumulative incidence of: PDR between participants with versus without prior CSME (66% vs. 15%), reduced eGFR (59% vs. 29%) and amputation (68% vs. 32%); reduced eGFR with/without prior PDR (25% vs. 9%), amputation (48% vs. 13%), and CVD (30% vs. 11%); CVD with/without prior reduced eGFR (37% vs. 14%) and amputation (50% vs. 16%); and mortality with/without prior reduced eGFR (22% vs. 9%), amputation (35% vs. 8%) and CVD (25% vs. 8%).  Adjusted for age, duration of T1D, and mean updated HbA1c, the complications and associations with higher risk included: PDR with CSME (HR=1.88, 95%CI:[1.42,2.50]), reduced eGFR (HR=1.41, [1.01,1.97]), and CVD (HR=1.43, [1.06,1.92]); CSME with higher risk of PDR (HR=3.94, [3.18,4.89]), reduced eGFR (HR=1.49, [1.10,2.01]), and CVD (HR=1.35, [1.03,1.78]); reduced eGFR with higher risk of CVD (HR=2.09, [1.44,3.03]) and death (HR=3.40, [2.35,4.92]); amputation(s) with death (HR=2.97, [1.70,2.90]); and CVD with reduced eGFR (HR=1.59, [1.08,2.34]) and death (HR=1.95, [1.32,2.90]).

Conclusions Long term micro- and macrovascular complications and mortality are highly correlated. Age, diabetes duration, and glycemic levels do not completely explain these associations.