Type 2 diabetes and HbA_1c are independently associated with wider retinal arterioles: the Maastricht study

Aims/hypothesis: Retinal microvascular diameters are biomarkers of cardio-metabolic risk. However, the association of (pre)diabetes with retinal microvascular diameters remains unclear. We aimed to investigate the association of prediabetes (impaired fasting glucose or impaired glucose tolerance) and type 2 diabetes with retinal microvascular diameters in a predominantly white population. Methods: In a population-based cohort study with oversampling of type 2 diabetes (N = 2876; n = 1630 normal glucose metabolism [NGM], n = 433 prediabetes and n = 813 type 2 diabetes, 51.2% men, aged 59.8 ± 8.2 years; 98.6% white), we determined retinal microvascular diameters (measurement unit as measured by retinal health information and notification system [RHINO] software) and glucose metabolism status (using OGTT). Associations were assessed with multivariable regression analyses adjusted for age, sex, waist circumference, smoking, systolic blood pressure, lipid profile and the use of lipid-modifying and/or antihypertensive medication. Results: Multivariable regression analyses showed a significant association for type 2 diabetes but not for prediabetes with arteriolar width (vs NGM; prediabetes: β = 0.62 [95%CI −1.58, 2.83]; type 2 diabetes: 2.89 [0.69, 5.08]; measurement unit); however, there was a linear trend for the arteriolar width across glucose metabolism status (p for trend = 0.013). The association with wider venules was not statistically significant (prediabetes: 2.40 [−1.03, 5.84]; type 2 diabetes: 2.87 [−0.55, 6.29], p for trend = 0.083; measurement unit). Higher HbA_1c levels were associated with wider retinal arterioles (standardised β = 0.043 [95% CI 0.00002, 0.085]; p = 0.050) but the association with wider venules did not reach statistical significance (0.037 [−0.006, 0.080]; p = 0.092) after adjustment for potential confounders. Conclusions/interpretation: Type 2 diabetes, higher levels of HbA_1c and, possibly, prediabetes, are independently associated with wider retinal arterioles in a predominantly white population. These findings indicate that microvascular dysfunction is an early phenomenon in impaired glucose metabolism.