Association of central arterial stiffness with the presence and severity of diabetic retinopathy in Asians with type 2 diabetes

Abstract

PurposeOsteopontin (OPN) is a proinflammatory cytokine with diverse functions. Increased levels of OPN in vitreous fluid have been reported in patients with diabetic retinopathy (DR); however, studies on circulating OPN levels in DR are limited. We aim to examine the association of plasma OPN levels with the presence and severity of DR in a multiethnic cohort with type 2 diabetes mellitus (type 2 diabetes) in Singapore.MethodsPlasma levels of OPN were measured using enzyme-linked immunosorbent assay. Digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR). Gradable fundus photographs and OPN measurements for 443 patients were used for analysis. A logistic regression model was used to evaluate the association of OPN with DR.ResultsDR was diagnosed in 174 (39.3%) patients, including 132 (75.9%) with NPDR and 42 (24.1%) with PDR. The median of OPN was higher in the patients with DR (64.7 [49.7–89.5] ng/ml) than in the patients without DR (51.7 [38.9–66.9] ng/ml; p<0.001). After adjustment for clinical and biochemical factors, a 1-unit increase in nature logarithm (ln)-transformed OPN was associated with the presence of DR (2.770 [1.599–3.800], p<0.001). The area under the curve (AUC) increased statistically significantly after the addition of OPN (0.805[0.763–0.846] versus 0.825 [0.785–0.865], p=0.011). In the severity analyses, the median of OPN was statistically significantly higher in the patients with PDR (76.8 [55.0–103.6] ng/ml) than in the patients with NPDR (61.7 [47.7–87.3] ng/ml; p=0.017). After adjustment, the 1-unit increase in lnOPN remained associated with NPDR (2.673 [1.519–4.704], p=0.001) and PDR (3.389 [1.254–9.226], p=0.017), respectively (p-trend=0.001).ConclusionsPlasma OPN levels were associated with the presence and severity of DR in patients with type 2 diabetes, suggesting OPN may be useful as a potential biomarker for DR.

Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium‐glucose co‐transporter‐2 inhibitors

“…Finally, it has been previously shown that patients with proliferative diabetic retinopathy featured significantly greater PWV compared to those having either background diabetic retinopathy or a normal fundoscopy, after adjustment for other risk factors . In a more recent study, it was demonstrated that arterial stiffness evolves as a determinant of the presence and severity of diabetic retinopathy among patients with T2DM, increasing the odds for both non‐proliferative (OR: 1.10, 95% CI 1.03‐1.17) and proliferative diabetic retinopathy (OR: 1.15, 95% CI 1.06‐1.25) …”

Measuring the Interaction Between the Macro- and Micro-Vasculature

“…As a consequence, the outer retinal layers may be more exposed, and damaged by increased flow pulsatility related to increased large artery stiffness, although this hypothesis needs to be confirmed. Large artery stiffness has been shown to be related to diabetic retinopathy (58), age-related macular degeneration (59) and retinal microvascular impairment (60, 61). Exaggerated pulsed retinal capillary flow, in contrast to unchanged mean retinal capillary flow, and stiffer wall properties of retinal arterioles has been observed in patients with treated resistant hypertension compared with patients with grade 1–2 hypertension (62).…”

The relationship between carotid disease and retinopathy in diabetes: a systematic review

“…A significant association between carotid disease and changes in the retinal microvasculature has also been found in adolescents with T1D [38]. Diabetic retinopathy has also been associated with other markers of peripheral arterial disease [39], peripheral vascular disease in T1D [40], and arterial stiffness [41].…”