Abstract
Purpose :
Despite the risk of rare serious complications in people with sickle trait (traumatic hyphema, medullary carcinoma, splenic infarction at high altitudes, rhabdomyolysis), life expectancy is reported to be the same as the general population. Mortality of people with both sickle trait and diabetes (affecting the microvasculature) is poorly understood. We investigate the association of sickle cell trait with all-cause mortality in a large diverse cohort of people with diabetes and standardized DR grading.
Methods :
Cohort study (Jan 2012-Dec 2021) of 176,876 people with diabetes registered in the North East of London diabetic eye screening programme with linked primary and secondary healthcare records. Hazard ratios (HR) for all-cause mortality with adjustment for diagnosis of sickle cell trait, sickle cell disease, hypertension, chronic kidney disease, age, sex, ethnicity, type and duration of diabetes, HbA1c, DR severity (coded in order of increasing severity: R0M0, R1M0, R1M1, R2M0, R2M1, R3M0, R3M1), and deprivation, were estimated using Cox regression.
Results :
A total of 1,917/176,876 (1.1%) people had a diagnosis of sickle trait, 202/176,876 (0.1%) had sickle cell disease. There were 28,988 deaths over a median of 7.91 years (IQR 4.47-10.19). Compared with people with no haemoglobinopathies, people with sickle trait had a 19% (95%CI 1.06-1.35, p=0.005) increase in hazards of death, and people with sickle cell disease had a 54% (95%CI 1.09-2.18, p=0.015) increase in hazards of death. Each step rise in DR severity was associated with a 20% increase in hazards of death (p-for-linear-trend <0.001). Compared with people with no DR at first screen, people with R3M1 had a 2.86-fold increase in hazards of death (95%CI 2.58-3.17, p<0.001). Compared with people with highest deprivation, the least deprived people showed a HR of 0.70 (95%CI 0.67-0.74, p-for-linear-trend<0.001).
Conclusions :
In the context of a strong linear all-cause mortality association with each DR severity step increase, a potential interplay between subclinical chronic microvascular changes in the diabetic milieu and sickle trait may contribute to a higher mortality risk. Future work is warranted to investigate the associations of sickle trait with sight-threatening DR development. Our works lays foundations for prediction model refinement to prevent major diabetes complications.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.