The Diabetes Visual Function Supplement Study (DiVFuSS)

Abstract

Background: Diabetes is known to affect visual function before onset of retinopathy (diabetic retinopathy (DR)). Protection of visual function may signal disruption of mechanisms underlying DR.

Methods: This was a 6-month randomised, controlled clinical trial of patients with type 1 and type 2 diabetes with no retinopathy or mild to moderate non-proliferative retinopathy assigned to twice daily consumption of placebo or a novel, multi-component formula containing xanthophyll pigments, antioxidants and selected botanical extracts. Measurement of contrast sensitivity, macular pigment optical density, colour discrimination, 5-2 macular threshold perimetry, Diabetic Peripheral Neuropathy Symptoms, foveal and retinal nerve fibre layer thickness, glycohaemoglobin (HbA1c), serum lipids, 25-OH-vitamin D, tumour necrosis factor α (TNF-a) and high-sensitivity C reactive protein (hsCRP) were taken at baseline and 6 months. Outcomes were assessed by differences between and within groups at baseline and at study conclusion using meand ± SDs and t tests (p<0.05) for continuous variables.

Results: There were no significant intergroup differences at baseline. At 6 months, subjects on active supplement compared with placebo had significantly better visual function on all measures (p values ranging from 0.008 to <0.0001), significant improvements in most serum lipids (p values ranging from 0.01 to 0.0004), hsCRP (p=0.01) and diabetic peripheral neuropathy (Fisher's exact test, p=0.0024) No significant changes in retinal thickness, HbA1c, total cholesterol or TNF-α were found between the groups.

Conclusions: This study provides strong evidence of clinically meaningful improvements in visual function, hsCRP and peripheral neuropathy in patients with diabetes, both with and without retinopathy, and without affecting glycaemic control.

Trial registration number: www.ClinicalTrials.gov Identifier: NCT01646047.

Keywords: Clinical Trial; Colour vision; Field of vision; Macula; Retina.

Figure 1

Diabetic Peripheral Neuropathy Symptom Score (DPNSS).

Figure 2

Mean change over 6 months by eye for contrast sensitivity function at (A) 1.5 cycles/degree (c/d), (B) 3 c/d, (C) 6 c/d, (D) 12 c/d and (E) 18 c/d for supplement and placebo groups. OD, right eye; OS, left eye.

Figure 3

Mean change over 6 months for total colour error score by eye for supplement and placebo groups. A higher colour error score denotes less normal/more abnormal colour discrimination.

Figure 4

Mean change over 6 months in five to two threshold visual field mean deviation by eye for supplement and placebo groups.

Figure 5

Mean change over 6 months in macular pigment optical density (MPOD) by eye for supplement and placebo groups. MPOD was measured in one eye at baseline and the same eye at trial completion.

Figure 6

Mean change over 6 months in foveal thickness by eye for supplement and placebo groups.

Figure 7

Mean change over 6 months in retinal nerve fibre layer by eye for supplement and placebo groups.

Figure 8

Biological mechanisms implicated in diabetic retinopathy. AGEs, advanced glycation endproducts; BDNF, brain-derived neurotrophic factor; BRB, blood-retinal barrier; ET-1, endothelin-1; ICAM, intercellular adhesion molecule 1; LDL, low-density lipoprotein; IGF, insulin-like growth factor; MMP, matrix metalloproteinase; NFkB, nuclear factor kappa beta; PDGF, platelet-derived growth factor; PEDF, pigment-epithelium derived factor; PKC, protein kinase C; RAAS, renin-angiotensin-aldostrerone system; RGC, retinal ganglion cell; ROS, reactive oxygen species; TGF, transforming growth factor; VEGF, vascular endothelial growth factor.

Figure 9

Rationale for inclusion of specific Diabetes Visual Function Supplement Study (DiVFuSS) micronutrients. AGE, advanced glycation endproduct; AREDS, Age-Related Eye Disease Study; DHA/EPA, decosahexaenoic acid/eicosapentaenoic acid; DPN, Diabetic Peripheral Neuropathy; DR, diabetic retinopathy; HbA1c, glycohaemoglobin; NFkB, nuclear factor kappa beta; PKC, protein kinase C; VEGF, vascular endothelial growth factor.