The effect of HgbA1c and diabetes duration as risk factors for proliferative diabetic retinopathy is determined by common mitochondrial haplogroups in patients with Type 2 diabetes

Abstract

Purpose : We previously reported that European mitochondrial haplogroups H and UK are associated with severity, but not presence of, diabetic retinopathy (DR) in Caucasian patients with Type 2 diabetes. The purpose of this study was to determine if haplogroups H and UK affect hyperglycemia and duration of diabetes, the most important risk factors for proliferative DR (PDR).

Methods : Medical records for Caucasian patients with Type 2 diabetes were obtained from BioVU, Vanderbilt’s electronic, de-identified DNA databank. International Statistical Classification of Diseases (ICD-9) codes for diabetes with or without DR and manual medical record reviews were used to identify patients with diabetes and classify each as having nonproliferative DR (NPDR), PDR, or no DR. Additional Caucasian patients with Type 2 diabetes were recruited from the Vanderbilt Eye Institute and classified by DR severity. A total of 857 patients (229 NPDR, 148 PDR, 480 no DR) were analyzed. Genotype data were used to determine the mitochondrial haplogroup of all subjects. Logistic regression was used to measure the strength of age, sex, duration of diabetes, and hemoglobin A1c (HgbA1c) as risk factors for DR severity. These measurements were performed separately in patients with haplogroup H and UK.

Results : The strength of HgbA1c and diabetes duration as risk factors for DR among patients with Type 2 diabetes was equivalent among the haplogroups. In contrast, among DR patients, elevated HgbA1c (>8%) was a significant risk factor for PDR in haplogroup H (OR = 2.38 [1.22-4.69], p=0.0113) but not in haplogroup UK (OR=1.24 [0.44-3.50], p=0.68). Diabetes duration was also a significant risk factor for PDR in haplogroup H (OR = 1.08 [1.04-1.13], p=0.0001), but not in haplogroup UK (OR=1.02 [0.96-1.08], p=0.56). The prevalence of PDR increased with increasing HgbA1c levels in patients with haplogroup H, but not in patients with other European mitochondrial haplogroups.

Conclusions : These data indicate that patients with Type 2 diabetes from haplogroup UK are less likely to have PDR even in the face of poor glycemic control and longer duration of diabetes. Additionally, patients with haplogroup H are much more likely to have PDR than patients with other European mitochondrial haplogroups and should be monitored more closely.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.