Chronic kidney disease and proliferative diabetic retinopathy in people with type 1 diabetes may be tied to microvascular complications, researchers reported.
Among older patients with type 1 diabetes, cardiovascular disease prevalence was 68.2% among those with both chronic kidney disease (CKD) and proliferative diabetic retinopathy (PDR). This was significantly higher compared to patients who only had CKD (34.5%) or PDR (42.8%) (P=0.002), according to Daniel Gordin, MD, PhD, of Joslin Diabetes Center in Boston, and colleagues.
The lowest prevalence of cardiovascular disease was seen in patients without either CKD or PDR (28.8%), they wrote in Diabetes Care.
However, PDR was also independently tied to cardiovascular disease among patients with type 1 diabetes and CKD (OR 0.21, 95% CI 0.08-0.58, P=0.003), while CKD without PDR was not tied to cardiovascular disease risk.
“The co-occurrence of CKD and PDR is not surprising since chronic hyperglycemia is the major contributor to diabetic microvascular complications,” the group wrote.
However, “these unexpected findings suggest that PDR adds to the toxicity of chronic kidney disease in the development of cardiovascular disease, or that there could be a common protective factor against hyperglycemic toxicity for severe diabetic eye disease and CVD,” they added.
A total of 762 individuals who participated in the Joslin Medalist Study were included in the current cross-sectional analysis. All participants had type 1 diabetes with insulin treatment for 50 years or more.
Estimated glomerular filtration rate was determined using the Chronic Kidney Disease Epidemiology Collaboration formula, while CKD was defined as stage 3b CKD (eGFR <45 mL/min/1.73m2). PDR was determined using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, defined as a score of over 53.
Among the cohort, the majority of individuals did not have CKD but did have PDR (n=339). The second largest group included those without CKD and PDR (n=327), while there were 66 individuals with both conditions. Although all groups had no significant differences in HbA1c levels, those with CKD and without PDR were notably older at the time of type 1 diabetes diagnosis. This group also had the highest prevalence of random detectable C-peptide versus all other groups.
A secondary analysis was also performed by the group, which included 675 individuals with type 1 diabetes for 25 years or more from the FinnDiane Study. This study utilized the same definition for CKD, while PDR was defined as a score of 60 or greater on the ETDRS scale.
This analysis found similar trends as the Medalist cohort, with a trend towards a lower prevalence of cardiovascular disease seen among the group with CKD but without PDR (19.1%) versus those with both conditions (37.1%, P=0.10). The group noted this relationship likely didn’t reach significance “due to small sample size and number of events.”
Similar to the Medalist study, the lowest prevalence of cardiovascular disease was seen in the group without either CKD or PDR (6.6%).
“Multiple possible factors could be involved in this differential protection on the retinal, renal and cardiovascular tissue in diabetes,” the authors suggested. “Of particular interest could be insulin and vascular endothelial growth factor (VEGF), which have been targets of therapeutic modulations for all three complications.”
“Interestingly, VEGF expressions are elevated in the retina and renal glomeruli, yet decreased by diabetes in the myocardium. This differential tissue expression of VEGF in diabetes made systemic treatments targeting VEGF difficult, but may provide an explanation for differential contributions to CKD, PDR, and neuropathy in addition to CVD.”
Study limitations included the long duration of type 1 diabetes in patients from both cohorts. The authors suggested future studies include patients with a shorter duration of diabetes aimed at determining whether CKD with PDR “is a marker of more generalized vascular dysfunction or whether tissue specific protective factors are in play.”
Click here for the American Association of Clinical Endocrinologists’ clinical practice guidelines for developing a diabetes mellitus comprehensive care plan.
The study was supported by the Iacocca Foundation, the Folkhälsan Research Foundation, the Wilhelm and Else Stockmann Foundation, the Livoch Hälsa Foundation, The Medical Society of Finland (Finska Läkaresällskapet), the Finnish Medical Foundation, The Swedish Cultural Foundation in Finland, the Biomedicum Helsinki Foundation, the Dorothea Olivia, Karl Walter och Jarl Walter Perkléns Foundation, Academy of Finland, Novo Nordisk Foundation, Päivikki and Sakari Sohlberg Foundation, and by EVO governmental grants.
Gordin disclosed no relevant relationships with industry. One co-author disclosed relevant relationships with Eli Lilly, Roche, AbbVie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Novartis, and Sanofi, Genzyme, Novartis, Novo Nordisk, and Sanofi.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner