Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals

Abstract

Aims/hypothesis Insulin may link metabolic disorders to retinal microvascular pathology. The aim of the present study was to investigate the impact of early insulin resistance on retinal microcirculation. Methods Retinal diameter responses to flicker-light stimulation were investigated in 81 clinically healthy participants (32 ±6 years [mean±SD], 59% women) who were recruited according to their BMI. All participants underwent an OGTT and euglycaemic-hyperinsulinaemic clamp (40 mU/m 2 · min −1 insulin dose). After stratification by low and high insulin sensitivity based on a clamp-derived glucose disposal rate of ≤ or >4.9 mg/kg body mass, respectively, baseline retinal diameters and their relative changes to flicker stimulation were compared while controlling for mean arterial pressure, BMI and sex.Results The arterial vasodilator response at the end of flicker stimulation (p=0.044) and the area under the arterial reaction curve during flicker stimulation (p=0.015) were significantly higher in individuals with low vs high insulin sensitivity. Vasodilatory responses of retinal veins to flicker stimulation and baseline retinal diameters did not differ between insulinsensitive and insulin-resistant participants (p>0.05). In a stepwise linear regression analysis, fasting insulin remained the only predictor of the arterial vasodilator response to flicker-light (p<0.01). Waist circumference also contributed, although to a lesser extent, to the arterial vasodilator response (p=0.023). Conclusions/interpretation Insulin sensitivity is an important determinant of retinal microvascular function. We propose that the elevated arterial flicker response in insulin-resistant states is a result of higher circulating insulin levels.

Retinal microvascular dysfunction in patients with coronary artery disease with and without heart failure: a continuum?

“…The correlations with laboratory parameters support the role of LDL and triglycerides for retinal vessel function as well as for glucose metabolism . Significant impairment of retinal microvascular function has recently been described in patients with elevated LDL .…”

“…The correlations with laboratory parameters support the role of LDL and triglycerides 25 for retinal vessel function as well as for glucose metabolism. 33 Significant impairment of retinal microvascular function has recently been described in patients with elevated LDL. 6 To the best of our knowledge, the significance of HDL in association with retinal vessel function in atherosclerotic subjects has not been reported.…”

Retinal Neurodegeneration in Euglycemic Hyperinsulinemia, Prediabetes, and Diabetes

“…Insulin resistance can also affect arteriolar diameter changes in response to environmental stimulators. Furthermore, hyperinsulinemia leads to dilation of retinal arterioles in response to stimulation by flicker light, substantiating the fact that one of the ways hyperinsulinemia drives its vasodilatory effect is via nitric oxide (NO) [15, 16]. This effect of insulin may arise by inducing phosphatidylinositol 3-kinase (PI3K) activation [15].…”

“…Furthermore, hyperinsulinemia leads to dilation of retinal arterioles in response to stimulation by flicker light, substantiating the fact that one of the ways hyperinsulinemia drives its vasodilatory effect is via nitric oxide (NO) [15,16]. This effect of insulin may arise by inducing phosphatidylinositol 3-kinase (PI3K) activation [15]. Direct evidence of the role of NO in triggering oxidative stress preceding DR is limited.…”