The Centers for Disease Control (CDC) Division of Diabetes Translation released the National Diabetes Statistics Report, which presents the most current statistics on the “state of the disease” in the United States. The percentage of adults who have prediabetes who were aware they had the condition nearly tripled between 2005 and 2020, but most continue to be unaware, the report reveals. (For more statistics, see “Key Findings From the CDC’s National Diabetes Statistics Report,” p. 36).

Diabetic retinopathy (DR) is a major microvascular complication of diabetes and a leading cause of vision loss and blindness globally.¹ Nearly all patients with type 1 and >60% of patients with type 2 diabetes will have some form of DR within 20 years of developing diabetes.^2,3 With the rising numbers of younger people who have insulin resistance and diabetes, rates of DR will increase amongst these patients at a much higher rate.⁴ In fact, in a CDC report released December 2019, nearly one in five (18%) adolescents (ages 12 to 18) and one in four (24%) young adults (ages 19 to 34) were found to be living with prediabetes.⁵

However, nutrition can play an important role in curbing the effects of diabetes, and by extension DR. In this article, we’ll review specific nutrients – carotenoids, omega fatty acids, vitamin D, and B – and the affect they can have on diabetic patients.

DIETARY INTAKE AND RISK OF DR

The evidence linking dietary intake and DR is growing, although many questions remain. With more research dollars being allotted to study the relevance of dietary patterns and disease, our knowledge will continue to rapidly expand.

Microvascular complications are at the root of damage from diabetes; however, a growing body of evidence suggests that hyperglycemia-induced oxidative stress and inflammation play an integral role in the early pathogenesis of DR by potentiating retinal neurodegeneration.⁶ The onset of type 2 diabetes mellitus starts with insulin resistance leading to insulin deficiency, hyperglycemia, and dyslipidemia. This in turn enhances the pro-oxidant and pro-inflammatory pathways. Additionally, various poor dietary behaviors, along with obesity, worsen the physiological state in diabetics.

A wide variety of nutrients, by their natural physiological, biochemical, and molecular action, can preserve retinal structure and function by interfering with the various pathological steps that promote DR, thereby altering the risk of developing this ocular morbidity. Nutrients that are already commonly prescribed for age-related macular degeneration and dry eye disease are reviewed here:

Carotenoids

For well over two decades, the carotenoids lutein, zeaxanthin, and meso-zeaxanthin have been studied for their ability to mitigate oxidative stress in macular degeneration. Lem et al⁶ argue that decreased levels and depletion of the endogenous antioxidant defense system in the retina from diabetes can also be augmented via carotenoid vitamin therapy. They propose using macular pigment optical density measurements as an early biomarker of oxidative stress in the retina.

Supplementing with carotenoids for DR is not new. Lutein, zeaxanthin, and meso-zeaxanthin are shown to have antioxidant effects, reduce vascular permeability and leakage, and maintain blood vessel integrity.⁷ Some studies show they can reduce the risk of DR pathogenesis.^7,8,9 Brazionis et al reports that, similar to AMD, higher lutein and zeaxanthin levels were associated with significantly lower odds of DR.⁸ A two-year trial of 10 mg lutein plus 12 mg zeaxanthin in diabetic patients who did not have DR showed improved retinal response density on multifocal electroretinography and a mild non-edematous increase in foveal thickness.¹⁰ There is also evidence that lutein supplementation increases brain-derived neurotrophic factor (BDNF), preventing neurodegeneration, and preserving electroretinograms.^11,12

Key Findings From the CDC’s National Diabetes Statistics Report

34 million Americans — just over one in 10 — have diabetes.

 

88 million American adults — approximately one in three — have prediabetes.

 

 

New diabetes cases were higher among non-Hispanic Blacks and people of Hispanic origin than non-Hispanic Asians and non-Hispanic whites.

 

 

New cases of diabetes in adults significantly decreased from 2008 through 2019.

 

 

Newly diagnosed cases of type 1 and type 2 diabetes significantly increased among U.S. youth.

 

 

For ages 10 to 19, incidence of type 2 diabetes remained stable among non-Hispanic whites and increased for all others, especially non-Hispanic Blacks.

 

See cdc.gov/diabetes/library/features/diabetes-stat-report.html .

Omega-3 Fatty Acids

Evidence shows that omega-3s can also inhibit the development and progression of DR.^13-16 Omega-3 fatty acid metabolites, such as lipoxins, resolvins, and protectins, exhibit anti-inflammatory action by suppressing interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, VEGF, and reactive oxygen species (ROS), and restore antioxidant homeostasis.¹⁷

Sala-Vila et al examined this association in humans by conducting a long-term prospective study of 3,482 patients who had type 2 diabetes (mean age, 67 years; 48% men) enrolled in the PREDIMED trial. They found that consumption of omega-3 fatty acids (≥500 mg/d) significantly reduced the risk of DR.¹⁸ The relative risk of incident sight-threatening DR for these participants was 46% lower than for those who consumed less omega-3s (p = .001), regardless of the assigned diet. Risk reduction was even greater for patients who had hypertension or advanced diabetes. Participants who consumed at least two servings of oily fish per week at baseline also had a lower risk of DR.¹⁸ Omega-3s, in particular docosahexaenoic acid (DHA), has been shown to increase the production of BDNF, which can protect retinal neuronal cells from degeneration caused from DR.¹⁹

The omega-3 poly-unsaturated fatty acids eicosapentaenoic acid (EPA) and DHA prevent Interleukin 6 and tumor necrosis factor alpha production and suppress intercellular cell adhesion molecule expression and vascular endothelial growth factor secretion.¹⁹ High-glucose-induced retinal vascular endothelial damage is also reduced by omega-3s.¹⁹ While not all studies consistently show a benefit of omega-3 supplementation in DR, an overall pattern is emerging that a diet of two servings of oily fish per week is protective of DR.¹⁸

In contrast, omega-6 poly-unsaturated fatty acids are precursors of bioactive lipids, such as arachidonic acid, which would itself promote a pro-inflammatory environment and development of diabetic complications. Multiple studies suggest that dietary manipulations that increase the ratio of omega-3 to omega-6 fatty acids decrease the risk of diabetic complications in adult participants who have type 2 diabetes.^20,21

Vitamin D

Vitamin D is a fat-soluble vitamin that functions as a pro-hormone. Studies on dry eyes and AMD suggest that supplementing with vitamin D is beneficial to the pathophysiology of both disorders. Research also supports the role of vitamin D in DR. The prevalence of vitamin D deficiency in the United States is above 40%, higher in the elderly and in some ethnic groups.²² It is a potent inhibitor of angiogenesis and its angiogenic effect may be mediated by vitamin D receptors in the retina.^17,23

Vitamin D sufficiency is essential for insulin release, insulin sensitivity, reduction of inflammation, and reduction of arterial stiffness.^24-30 Recently, optimal vitamin D levels are shown to reduce the risk and severity of DR.³¹ Vitamin D also plays a role in pancreatic β-cell function.^32,33 Deficiency reduces insulin sensitivity and increases the risk of atherosclerosis, cardiovascular disease, type 2 diabetes mellitus, and hypertension.^33-36

By stimulating pancreatic beta cells, 1,25–dihydroxy vitamin D triggers the secretion of insulin.^29,30 Clinical trials show improvements in insulin sensitivity and HbA1c when patients were given vitamin D3.^36,37 Mutlu et al reports that lower vitamin D was associated with retinal microvascular damage after studying the associations in 5,675 participants who have diabetes.³⁸ Vitamin D deficiency is linked to type 1 diabetes mellitus.³⁹

Vitamin D deficiency is also linked to type 2 diabetes and supplementation, which is shown to decrease C-reactive protein (CRP), high-sensitive-CRP.⁴⁰ Serum levels of 25-hydroxy vitamin D above 30 ng/ml reduce the odds of DR.^31,41 Vitamin D supplementation reduces intracellular reactive oxygen species, decreasing VEGF expression.⁴² Low serum vitamin D levels among patients with DM are associated with a higher risk and severity of DR for all the above reasons. Cumulatively, this suggests that vitamin D supplementation is beneficial to reduce the risk and severity of DR.²²

B Vitamins

The B vitamins are a group of eight water soluble vitamins that perform closely interrelated roles in cellular functioning, acting as coenzymes in a vast array of catabolic and anabolic enzymatic reactions. Their effects are particularly prevalent in numerous aspects of brain and retinal function, including energy production, deoxyribonucleic acid/ribonucleic acid synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. An association between lower levels of B vitamins and a greater chance of DR, due to increased levels of homocysteine, has been reported.^43,44

A low concentration of folic acid (vitamin B9) and cobalamine (vitamin B12) increases the risk of vascular damage by homocysteine.⁴² High homocysteine levels are toxic to pericytes and endothelial cell walls of retinal blood vessels, causing vascular thrombosis and microaneurysms.⁴³ Also, a Croatian study shows a link between plasma homocysteine levels and non-proliferative DR in patients who have type 2 diabetes mellitus without renal disease.⁴⁵

Hyperglycemia promotes vascular superoxide production, sequentially inactivating nitric oxide (NO) expression by endothelial cells, which leads to vascular degeneration. B vitamins enhance NO production and are specifically essential in maintaining the overall vascular system integrity.⁴³

B vitamins work synergistically in energy production and mitochondrial function. In the central nervous system and retina, where metabolic rates are high, there is a synergistic benefit to using several of the B vitamins together.⁴⁶ For people who have diabetes, B vitamin serum concentrations are lower, possibly due to higher renal clearance and lower reabsorption.⁴⁷ This leads to further deficiencies and the need for even higher B vitamin levels.

DIETARY PATTERNS AND REDUCED DR RISK

Concentrating on dietary profiles rather than specific nutrients is proving to be more beneficial due to the synergistic effects of the different nutritional components in an entire diet. In 2018, Wong et al conducted a systematic review of dietary patterns and DR that showed higher intakes of dietary fiber, fruits and vegetables, oily fish, and a greater adherence to a Mediterranean diet were protective of DR.⁴⁸ Conversely, high total caloric intake was associated with a higher risk of DR. The ingestion of dietary fiber tends to modulate the postprandial glucose response and is, thus, proposed to reduce glucose-induced damage to the retina.⁴⁸

Kadri et al observed an inverse relationship between more frequent (>2 times/week) fish consumption and DR progression.⁴⁹ Two other large studies, one on Spanish adults and one on an Asian population, also shows that at least two servings of oily fish a week had a significantly lower risk of DR.^18,50

The findings of these studies support existing American Diabetic Association guidelines for overall diabetes management that acknowledge the beneficial effects of a Mediterranean diet, encourage people with diabetes to eat a diet rich in fruits and vegetables, and consume fewer calories.⁵¹

NUTRITION RESEARCH

In 2020, the National Institutes of Health (NIH) released a plan to accelerate nutrition research over the next 10 years. (See https://dpcpsi.nih.gov/onr/strategic-plan .) The objective, according to the NIH, is for practitioners to be able to recommend food to optimize health. It is known as “precision nutrition.” OM

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DR. POTEET is the president of the Ocular Wellness & Nutrition Society. She is a graduate of the New England College of Optometry where she completed a residency in ocular disease. She has a Master’s of Science in Human Nutrition and Functional Medicine, and is a Certified Nutrition Specialist. She practices in Acworth, Ga.