Differential Association of Microvascular Attributions With Cardiovascular Disease in Patients With Long Duration of Type 1 Diabetes

Abstract

Objective: Independent association of chronic kidney disease (CKD) and proliferative diabetic retinopathy (PDR) with cardiovascular disease (CVD) has not been established. In the Joslin 50-Year Medalist study, characterizing individuals with type 1 diabetes for 50 years or more, we examined the associations of CKD and PDR with CVD, which was validated by another cohort with type 1 diabetes from Finland.

Research design and methods: This cross-sectional study characterized U.S. residents (n = 762) with type 1 diabetes of 50 years or longer (Medalists) at a single site by questionnaire, clinical, ophthalmic, and laboratory studies. A replication cohort (n = 675) from the longitudinal Finnish Diabetic Nephropathy Study (FinnDiane) was used. CKD and PDR were defined as estimated glomerular filtration rate <45 mL/min/1.73 m² (CKD stage 3b) and according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, respectively. CVD was based on questionnaires and/or hospital discharge registers. Associations of CVD status with CKD and PDR were analyzed by multivariable logistic regression.

Results: CVD prevalence in the Medalists with CKD and without PDR (+CKD/-PDR) (n = 30) and CVD prevalence in the -CKD/+PDR group (n = 339) were half the prevalence in the +CKD/+PDR group (n = 66) (34.5% and 42.8% vs. 68.2%, P = 0.002). PDR status was independently associated with CVD (odds ratio 0.21 [95% CI 0.08-0.58], P = 0.003) in patients with CKD. Among the Finnish cohort, a trend toward a lower prevalence of CVD in the +CKD/-PDR group (n = 21) compared with the +CKD/+PDR group (n = 170) (19.1% vs. 37.1%, P = 0.10) was also observed.

Conclusions: Absence of PDR in people with type 1 diabetes and CKD was associated with a decreased prevalence of CVD, suggesting that common protective factors for PDR and CVD may exist.

Figure 1

Differences in CVD prevalence across patients with and without CKD and PDR. Data are % (n per group) in Medalist patients (A) and FinnDiane patients (B). Overall P < 0.001 in both cohorts.

Figure 2

Kidney (A) and retinal (B) photographs of a 72-year old Medalist patient with 66 years of type 1 diabetes and severe diabetic nephropathy (DN class III), but only mild DR (nonproliferative DR [NPDR]), and no CVD, showing differential protection. PAS, periodic acid-Schiff staining; Tub, tubule. *Kimmelstiel-Wilson nodule. †Mesangial expansion.