Retinal vascular calibre predictors in children and adolescents with type 1 diabetes

Submission note: A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Allied Health, Faculty of Health Science, La Trobe University, Bundoora.

Aim/s: To investigate the relationship between a variety of pre-, peri- and post-natal factors and retinal vascular calibre in children and adolescents with type 1 diabetes. A secondary aim was to evaluate the relationship between retinal vascular calibre and kidney function and diabetic retinopathy. Methods: This was a hospital-based cross-sectional (study 1, n = 483) and longitudinal (study 2, baseline = 483, T2 = 112, T3 = 11) study of children and adolescents with type 1 diabetes. The medical files of participants who had retinal images taken were audited to collect all relevant clinical data. An additional 83 participants (study 3) provided cross-sectional dietary, physical activity data, and maternal information via two questionnaires. Retinal vascular calibre was measured by a trained grader and summarised as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) using a semi-automated computer program. Results: In this population, the mean ([plus or minus] SD) CRAE and CRVE were 164.21 micrometres ([plus or minus] 12.55) and 232.75 micrometres ([plus or minus] 17.18), respectively. In study 1, after multivariable adjustments, a vascular risk profile that included: older age, higher serum creatinine, higher SBP, higher BMI, abnormal eGFR, lower HDL cholesterol, longer duration of diabetes and higher serum sodium predicted an increased risk of narrower CRAE (95 percent CI = -4.10/-0.76, p = 0.004). A second vascular risk profile that included: higher total cholesterol level, higher BMI, lower physical activity level, higher HbA1c and higher triglyceride levels predicted wider CRVE (95 percent CI = 1.14/5.62, p = 0.003). Regression models revealed narrower CRAE and CRVE were associated with the presence of microalbuminuria (CRAE: 95 percent CI = 0.08/0.24, p = [less than]0.0001 and CRVE: 95 percent CI = 0.15/0.38, p = [less than]0.0001). In study 3, after multivariable adjustments, lower physical activity levels were related to wider CRVE (p = 0.036), while longer time spent playing computer or video games was related to wider CRVE (p = 0.011) and narrower CRAE (p = 0.001). Three major dietary patterns were identified in study 3: 1) processed foods, 2) plant-based foods and 3) vegetable/fish avoidance pattern. Adjusted regression analysis revealed the “vegetable/fish avoidance” dietary pattern predicted a wider CRVE (95 percent CI = 0.12/7.24, p = 0.039). Conclusions: In children and adolescents with type 1 diabetes, retinal arteriolar and venular calibres appear to reflect different mediating pathways. The finding of narrower retinal arterioles in individuals with microalbuminuria suggests that retinal microvascular changes may accompany a decline in kidney function. Furthermore, exposure to modifiable risk 17 factors, notably higher blood pressure, may be related to retinal microvasculature, and this has possible implications for vascular disease preventative action early in life.