Diabetic eyes are at risk – what if blood sugar control was not enough?

Diabetic retinopathy (DR) remains a leading cause of vision loss worldwide. Although the pathogenesis is well documented — beginning with hyperglycemia-induced oxidative stress and progressing through retinal microvascular and neuronal damage —intervening before irreversible changes occur remains a clinical priority.  

Diabetic Retinopathy Etiology – Pathogenesis – Clinical Outcome 

Pathogenesis scheme of diabetic retinopathy and points of micronutrient intervention, by Dr. rer. nat. F. Wirth with kind support from Prof. C. Erb, M.D.

↓ Download explanatory PDF. 

Etiology 

Diabetic retinopathy is caused by chronic hyperglycemia in diabetes mellitus. Capillary endothelial cells of the retina are especially vulnerable because they cannot downregulate intracellular glucose transport in response to elevated blood glucose levels.^11-13 As a result, they absorb excessive glucose, leading to intracellular hyperglycemia. 

Pathogenesis 

Excess intracellular glucose stimulates glycolysis and the citric acid cycle, increasing mitochondrial respiratory chain activity. Once the proton gradient at the mitochondrial membrane reaches a critical limit, electron transport becomes impaired.^11,14 The excess electrons react with molecular oxygen to form superoxide radicals, triggering oxidative stress. This oxidative stress inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key glycolytic enzyme, leading to accumulation of upstream glycolytic intermediates such as glyceraldehyde-3-phosphate and fructose-6-phosphate. These intermediates are diverted into alternative metabolic routes — the polyol pathway, the hexosamine pathway, protein kinase C activation, and the formation of advanced glycation end products (AGEs). 

Clinical Outcome 

These processes amplify oxidative stress, cause abnormal gene and protein expression, disrupt cell–matrix interactions, and increase production of inflammatory cytokines and growth factors.^11,15-17 In the retina, this cascade results in hypoxia, uncontrolled neovascularisation, and retinal hemorrhage, ultimately causing degeneration of pericytes, endothelial cells, and neurons — the three hallmark features of diabetic retinopathy.^16,17 

Is ‘blood sugar control’ enough in preventing and slowing the progression of diabetic retinopathy?

Optimal blood sugar control (HbA1c target <7%) is considered the most important factor in preventing the onset and slowing the progression of diabetic retinopathy. Multiple landmark studies such as the DCCT (Diabetes Control and Complications Trial)²³ and UKPDS (United Kingdom Prospective Diabetes Study)²⁴ confirm this.

However:

• Achieving optimal glycemic control is challenging: Tight glucose management is difficult to sustain in daily clinical practice due to factors such as patient compliance, risk of hypoglycemia, and variability in disease progression.^23,24,25
• Retinopathy may progress despite good glycemic control: In some patients, once the pathological cascade has been triggered, retinopathy can continue to progress even when glycemic control is within target. This suggests that additional factors — such as oxidative stress, chronic inflammation, genetic susceptibility, dyslipidemia, and hypertension — also play a critical role in disease progression.^23,24,26

This is where micronutrients — like those contained in RetiCap^®DR — may offer valuable additional support. In the above-mentioned clinical studies, patients with diabetes showed significant improvements in contrast sensitivity, retinal thickness, and visual acuity after supplementation with RetiCap^®DR. 

Effects of RetiCap^®DR supplementation over three – six months on visual function parameters, supported by published studies

Moreover, the ingredients in RetiCap^®DR — alpha-lipoic acid (ALA), rutin, and vitamin B1 — have been shown to positively influence diabetes-related biochemical pathways, such as the hexosamine pathway and the formation of advanced glycation end-products (AGEs). For example, a study by Prince et al. (2006)⁴ found that rutin supplementation significantly reduced HbA1c levels in a diabetic animal model.

This biochemical rationale was also assessed clinically: in a randomised study by Gebka (2014)²⁹, the researchers evaluated HbA1c levels before and after six months of supplementation with RetiCap^®DR. They observed a significant HbA1c reduction in the type 1 diabetes group (from 7.8 ± 0.6 to 7.5 ± 0.8%, p = 0.0130), while the change in the type 2 diabetes group was not statistically significant (from 7.3 ± 1.7 to 7.2 ± 1.6%, p = 0.3066).

Key nutrients can intervene in the pathogenesis of DR

Micronutrient research now suggests that key nutrients can intervene in this cascade.

R-alpha-lipoic acid

• Improves the uptake of glucose in fat cells and skeletal muscle cells and thus contributes to lowering blood sugar levels^6,7
• Reduces nitrosative and oxidative stress³
• Normalises NFκB activation (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells) and reduces Ang-2 (angiopoietin-2) and VEGF (vascular endothelial growth factor) in the diabetic retina^1,3
• Reduces the hexosamine modification of proteins^3,5
• Decreases the formation of AGEs.^3,5

Vitamin B1 (thiamine)

• Reduces the hexosamine modification of proteins⁵
• Decreases the formation of AGEs.⁵

Vitamin B2 (riboflavin)

• Has a beneficial effect on hyperglycaemia¹⁰
• Reduces oxidative stress.¹⁰

Rutin

• Increases plasma insulin levels and lowers plasma glucose levels⁴
• Reduces oxidative stress⁴
• Improves glucose homeostasis⁴
• Reduces glycosylation of circulating proteins.⁴

These mechanisms are not merely theoretical.

Four peer-reviewed clinical studies have confirmed measurable retinal benefits in diabetic patients:

• Wirth et al. (2025): review and effect size analysis of 4 studies done before.³³
• Wirth et al. (2024): In 46 Type 1, 51 Type 2 diabetics without DR and 20 healthy controls, six months of supplementation improved contrast sensitivity. Non-supplemented diabetics experienced functional decline. The effect size was moderate in Type 1 diabetics and healthy controls.³²
• Mulak et al. (2019): Among 25 patients with non-proliferative DR, supplementation led to improved best-corrected visual acuity (BCVA) and reduced central retinal thickness.³¹
• Ciszewska et al. (2017): In diabetics with pathological macular integrity, retinal sensitivity improved significantly over six months.³⁰
• Gebka et al. (2014): Both Type 1 and Type 2 diabetics showed preservation of contrast vision with supplementation, in contrast to deterioration in control groups.²⁹

Taken together, these findings support the use of targeted micronutrients as a complementary strategy to traditional glycaemic control. By addressing biochemical changes before structural damage occurs, clinicians may improve functional outcomes and delay DR progression.