Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemSerum Apolipoproteins Are Associated With Systemic and Retinal Microvascular Function in People With Diabetes(AMER DIABETES ASSOC, 2012-07)Serum apolipoprotein (apo)AI and -B have been shown to be associated with diabetic retinopathy, but the underlying mechanisms are unclear. We investigated whether apoAI and apoB levels are associated with measures of systemic and retinal microvascular function in patients with diabetes. We recruited 224 diabetic patients (85 type 1 and 139 type 2) and assessed serum lipids and lipoproteins from fasting blood, skin responses to sodium nitroprusside (endothelium independent) and acetylcholine (ACh) (endothelium dependent) iontophoresis, flicker-light-induced retinal vasodilatation, and retinal vascular tortuosity. After adjustment for age and sex, every SD increase in apoAI level was associated with ACh-induced skin perfusion (mean change 1.27%; P < 0.001 for apoAI) and flicker-light retinal arteriolar vasodilatation (0.33%; P = 0.003) and was associated inversely with arteriolar tortuosity (-2.83 × 10(-5); P = 0.044). Each SD increase in apoB was associated with arteriolar tortuosity only (1.75 × 10(-5); P = 0.050). These associations, except for apoB, remained in multivariate models. Serum apoAI was associated with increased vasomotor responsiveness to ACh and flickering light and inversely related to retinal vessel tortuosity--a characteristic that has both structural and functional dimensions. These findings provide additional insights into the potential mechanisms of apos in the pathogenesis of diabetic retinopathy and other diabetic microvascular complications.
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ItemDiabetic Retinopathy Is Related to Both Endothelium-Dependent and -Independent Responses of Skin Microvascular Flow(AMER DIABETES ASSOC, 2011-06)OBJECTIVE: Endothelial dysfunction has been hypothesized as a possible pathogenic factor in the development of diabetic retinopathy (DR). We examined the relationship of DR to endothelium-dependent and endothelium-independent responses in skin microvascular flow. RESEARCH DESIGN AND METHODS: Participants consisted of 224 individuals with diabetes: 85 with type 1 diabetes and 139 with type 2 diabetes. Sodium nitroprusside (SNP) and acetylcholine (ACh) were delivered across the skin by iontophoresis. Laser Doppler flowmetry was used to assess the skin microcirculation response to SNP (endothelium-independent response) and ACh (endothelium-dependent response). The presence and severity of DR were graded from retinal photographs using a standard protocol. RESULTS: Of 224 participants, 64.3% had DR. After multivariable adjustment, participants with reduced responses to SNP or ACh were more likely to have DR, with an odds ratio (OR) of 2.33 (95% CI 1.09-5.01) for SNP and 2.20 (1.05-4.61) for ACh, comparing participants with responses below and above the median values. Participants with reduced responses (below the median) to both SNP and ACh were nearly four times more likely to have DR (OR 3.86 [1.45-10.3]) than those with SNP and ACh both above the median values. CONCLUSIONS: The presence of DR was associated with a reduction in skin microcirculation responses to iontophoresis of both SNP and ACh, suggesting that vascular processes associated with both endothelial dysfunction and endothelial function-independent mechanisms may be pathogenically related to DR.
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ItemSerum Apolipoprotein AI and B Are Stronger Biomarkers of Diabetic Retinopathy Than Traditional Lipids(AMER DIABETES ASSOC, 2011-02)OBJECTIVE: To describe and compare the associations of serum lipoproteins and apolipoproteins with diabetic retinopathy. RESEARCH DESIGN AND METHODS: This was a cross-sectional study of 224 diabetic patients (85 type 1 and 139 type 2) from a diabetes clinic. Diabetic retinopathy was graded from fundus photographs according to the Airlie House Classification system and categorized into mild, moderate, and vision-threatening diabetic retinopathy (VTDR). Serum traditional lipids (total, LDL, non-HDL, and HDL cholesterol and triglycerides) and apolipoprotein AI (apoAI), apolipoprotein B (apoB), and the apoB-to-apoAI ratio were assessed. RESULTS: Diabetic retinopathy was present in 133 (59.4%) individuals. After adjustment for age, sex, diabetes duration, A1C, systolic blood pressure, and diabetes medications, the HDL cholesterol level was inversely associated with diabetic retinopathy (odds ratio 0.39 [95% CI 0.16-0.94], highest versus lowest quartile; P(trend) = 0.017). The ApoAI level was inversely associated with diabetic retinopathy (per SD increase, 0.76 [95% CI 0.59-0.98]), whereas apoB (per SD increase, 1.31 [1.02-1.68]) and the apoB-to-apoAI ratio (per SD increase, 1.48 [1.13-1.95]) were positively associated with diabetic retinopathy. Results were similar for mild to moderate diabetic retinopathy and VTDR. Traditional lipid levels improved the area under the receiver operating curve by 1.8%, whereas apolipoproteins improved the area by 8.2%. CONCLUSIONS: ApoAI and apoB and the apoB-to-apoAI ratio were significantly and independently associated with diabetic retinopathy and diabetic retinopathy severity and improved the ability to discriminate diabetic retinopathy by 8%. Serum apolipoprotein levels may therefore be stronger biomarkers of diabetic retinopathy than traditional lipid measures.
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ItemNovel versus traditional risk markers for diabetic retinopathy(SPRINGER, 2012-03)AIMS/HYPOTHESIS: To explore the relative contribution of novel and traditional risk markers for diabetic retinopathy (DR). METHODS: A clinic-based study of 224 diabetic patients (85 type 1, 139 type 2) from a diabetes clinic was performed. DR was graded from fundus photographs according to the Airlie House Classification system and classified as absent or present (at least ETDRS level 14). Novel risk markers assessed included serum apolipoprotein (Apo) AI and B, skin microvascular responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) iontophoresis, flicker-light-induced retinal vasodilation and retinal vascular tortuosity. Relative contribution was determined by semi-partial correlation coefficient generated from a logistic regression model containing all traditional and novel risk markers simultaneously. RESULTS: There were 144 (64.3%) participants with DR. Of the novel markers, ApoAI, flicker-light-induced vasodilation and retinal arteriolar tortuosity were significantly associated with DR, independently of traditional measures (all p < 0.03). Diabetes duration contributed most (51%) to the risk of DR, followed by ApoAI (16%), systolic blood pressure (13%), retinal arteriolar tortuosity (8%) and flicker-light-induced venular and arteriolar dilation (3% and 0.5%, respectively). CONCLUSIONS/INTERPRETATION: ApoAI and retinal arteriolar tortuosity made considerable contributions to DR risk, independently of traditional risk markers. Findings from this study suggest that serum ApoAI and retinal arteriolar tortuosity may be novel and independent risk markers of DR.