Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity

Abstract

Background: The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions.

Aim: To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity.

Methods: Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart.

Results: During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at < 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed < 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed < 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed < 45 years of age [β 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The β (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073).

Conclusion: The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

Keywords: Age at diagnosis; Age-related macular disease; Cataract; Diabetes; Glaucoma; Vision acuity.

Figure 1

Flowchart for population selection for analysis of ocular conditions from the UK Biobank. Propensity score matching was to select two controls for each diabetic participant. The analysis was conducted for age groups of diabetes diagnosis separately. The median age at diagnosis type 1 was 17 years. Propensity score accounted for age, gender, ethnicity, education, household income, physical activity, smoking, alcohol consumption, sleep duration, depression, hypertension, heart disease, stroke, body mass index, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride. AMD: Age-related macular degeneration; T1D: Type 1 diabetes; T2D: Type 2 diabetes.

Figure 2

Risk for ocular conditions associated with age at diagnosis of diabetes. Cox proportional hazard regression models were used to examine the association between diabetes and incident ocular condition for each group of diabetes diagnosis age. Model 1 was adjusted for age, gender, ethnicity, income, education, alcohol consumption, physical activity, sleep duration, smoking, body mass index, depression, hypertension, heart disease, stroke, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride. Central squares of each horizontal line represent the hazard ratio for each subgroup. Horizontal lines indicate the range of the 95%CI. The vertical dash lines indicate the hazard ratio of 1.0. AMD: Age-related macular degeneration; T1D: Type 1 diabetes; T2D: Type 2 diabetes; HbA1C: Glycated haemoglobin.

Figure 3

Vision acuity associated with age at diagnosis of diabetes. General linear regression models were used to test the difference in LogMAR between diabetic participants and controls for each group of diabetes diagnosis age. Model 1 was adjusted for age, gender, ethnicity, income, education, alcohol consumption, physical activity, sleep duration, smoking, BMI, depression, hypertension, heart disease, stroke, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride. Central squares of each horizontal line represent the β for each subgroup. Horizontal lines indicate the range of the 95%CI. The vertical dash lines represent the β of 0. T1D: Type 1 diabetes; T2D: Type 2 diabetes; HbA1C: Glycated haemoglobin.

Figure 4

Intraocular pressure associated with age at diagnosis of diabetes. General linear regression models were used to test the difference in intraocular pressure between diabetic participants and controls for each group of diabetes diagnosis age. Model 1 was adjusted for age, gender, ethnicity, income, education, alcohol consumption, physical activity, sleep duration, smoking, body mass index, depression, hypertension, heart disease, stroke, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride. T2D: Type 2 diabetes; IOP: Intraocular pressure.

Figure 5

Risk for ocular conditions associated with age at diagnosis of diabetes with the same reference. Sensitivity analysis was conducted to randomly select controls for each individual with type 2 diabetes with all diabetic patients as a whole. Cox proportional hazard regression models were used to estimate hazard ratios for ocular conditions associated with age at diagnosis of diabetes with controls as the reference for each group of diabetes diagnosed age. The multivariable model was adjusted for age, gender, ethnicity, income, education, alcohol consumption, physical activity, sleep duration, smoking, body mass index, depression, hypertension, heart disease, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and glycated haemoglobin. Central squares of each horizontal line represent the hazard ratio for each subgroup. Horizontal lines indicate the range of the 95%CI. The vertical dash lines indicate the hazard ratio of 1.0. T2D: Type 2 diabetes; AMD: Age-related macular degeneration.