Microvascular Disease Burden and All-Cause Mortality in Type 1 Diabetes-A 10-Year Follow-Up Study

Type 1 diabetes (T1D) is associated with a sustantially increased risk of cardiovascular (CV) events and premature death. The effect of the microvascular disease (MD) burden, i.e., the cumulative burden of retinopathy, nephropathy and peripheral neuropathy on all-cause mortality was evaluated in 774 T1D (age 40.2±11.7; DD 19.4±12.2 years; HbA1c 7.8±1.2%) in a mean follow-up of 10.6±2.5 years. Distribution of MD was: no-MD: n. 425 (54.9%); MD1: 250 (32.3%); MD2: 75 (9.7%); MD3: 24 (3.1%). Distribution was unchanged after esclusion of 41 T1D (5.3%) with previous CV events (CV+; 57.0%, 32.2%, 8.5% and 2.3%, respectively). Compared to no-MD, MD1-3 groups showed an adverse CV risk profile with steeply increase in age, DD, BMI, WHR, BP, HbA1c, uric acid and EURODIAB PCS risk score for major vascular outcomes (p<0.0001); total and LDL cholesterol, and triglycerides (p<0.05). eGFR (CKD-EPI) decreased, albuminuria progressively increased (p<0.0001). Rate of CV events and that of EURODIAB score ≥20 increased with MD: 1.6%, 5.6%, 17.3%, and 29.2%; 4.0%, 14.4%, 41.3% and 79.2%, respectively (p<0.0001). Consistently, rate of subjects on BP-lowering agents, RAS-blockers, statins e anti-platelet drugs increased (p<0.0001). A total of 52 deaths occurred during the 8,184 person-years of follow-up (6.7%; 6.36 x1000 person-years). Death rate increased with MD: no-MD 1.9%; MD1 6.8% (HR: 3.75, 95% CI 1.62-8.69); MD2 14.7% (7.10, 2.85-17.67); MD3 66.7% (45.64, 19.50-106.79; K-M, p<0.0001). Death rate was unchanged after esclusion of 41 CV+: 1.9%, 6.4%, 12.9% and 64.7% (p<0.0001). After adjustment for age and sex, HRs were: MD1 2.61 (95% CI 1.11-6.14); MD2 3.42 (1.29-9.06); MD3 16.21 (6.20-42.35; p<0.0001). In fully adjusted model, HRs were: MD1 2.51 (95% CI 1.01-6.23); MD2 2.97 (1.07-8.25); MD3 9.68 (3.19-29.36; p=0.001), with independent effects for age (HR 1.06), uric acid (HR 1.37) and smoking history (HR 2.45). Thus, the cumulative burden of MD independently affects the risk of all-cause death in T1D.