Treating systemic inflammation may protect against diabetes

(Image credit: AdobeStock/Natallia)

Diet and lifestyle affect every part of the body, and the epidemic of diabetes is a product of this, according to Shree Kurup, MD, FACP. Kurup discussed the importance of lifestyle and inflammation in patients with diabetic retinopathy (DR) at the Fourth Annual Cleveland Eye Bank Foundation Virtual Vision Research Symposium.¹ Kurup is Distinguished Professor of Ophthalmology at Case Western Reserve University in Cleveland, Ohio, as well as vice chair of ophthalmology, director of vitreoretinal diseases and surgery, director of ocular immunology and uveitis, director of operations ophthalmology, and director of the Ret­ina Diseases Image Analysis Reading Center at University Hospital Eye Center in Cleveland.

Unraveling the inflammatory pathway

Inflammation is a complex topic. “Inflammation starts with leukocyte recruitment followed by cytokine production,” Kurup said. “Therefore, the clinical target is the cytokines. Currently, because there are numerous mechanisms and innovations that can interfere with cytokine production, such as gene therapy, this raises the question about how patients are being managed.”

He went on to discuss the pathway complexities of inflammation, noting that a problem associated with this is the redundancy in nature. Inflammation exerts a multifaceted attack on the retinal cells in patients with diabetes.

“We are constantly attacking [VEGF]. Although VEGF is a big player, perhaps the biggest player in diabetes, diabetes is by no means primarily driven by VEGF but results from an accumulation of numerous factors,” Kurup said. When patients present to a clinic for diabetes or glaucoma, for example, the systemic level of inflammation is very high. Because of the complex nature of the disease, treating VEGF is only part of the problem, given the presence of inflammatory cytokines and chemokines. “There is a great deal of value to treating the other components of the disease,” he added.

Treating systemic inflammation and thwarting diabetes

Kurup pointed to strong evidence supporting the notion that treating systemic inflammation may prevent diabetes. Findings from a study published in Scientific Reports concluded that systemic inhibition of inflammatory factors protects against the development of diabetes.²

IL-16 may be a key player in this scenario. There is evidence, according to Kurup, that although neutralization of IL-16 does not protect against nephrogenic diabetic disease, it is pathogenic for the kidney as well as the ret­ina.³ Illustrative of this are patients undergoing kidney dialysis, who experience significant improvements in the status of their retinas following kidney transplantation.

Currently, a primary reason for the lack of development of anti-interleukin drugs is the associated adverse effects. Some patients with proliferative DR have extensive tractional retinal detachments. Kurup speculated about avoiding blindness by treating patients with alternatives to monthly anti-VEGF intravitreal injections and encouraged clinicians to think outside the box to develop effective treatments.

Another consideration in treatment development is genomics. “In the future, we will be addressing this. Trials are already in the pipeline to investigate other treatments over and above anti-VEGF drugs to combat the cytokines in the eye,” he said.

Research endeavors

Patricia Taylor and Warren Sobel, MD, from the Cleveland Clinic are engaged in investigations into IL-17 and type 2 diabetes. Despite differences between type 1 and type 2 diabetes, IL-17, a proinflammatory cytokine, is expressed in the pancreas of patients with both disease types. IL-17 can lead to insulin resistance, which is the inception of the diabetic process in predisposed individuals, Kurup explained.

Kurup also underscored the importance of patient education about nutrition. Injecting an anti-VEGF agent and sending patients home is insufficient because of the systemic nature of diabetes.

Poor nutrition can promote oxidative stress. Antioxidants combined with anti-VEGF injections are more effective than anti-VEGF injections alone, he said. The cardiology diet used to combat heart disease is also valuable for patients with diabetes.⁴

Shree Kurup, MD, FACP

E: skkurup@gmail.com

Kurup is Distinguished Professor of Ophthalmology at Case Western Reserve University in Cleveland, Ohio, and vice chair of ophthalmology, director of vitreoretinal diseases and surgery, director of ocular immunology and uveitis, director of operations ophthalmology, and director of the Retina Diseases Image Analysis Reading Center at University Hospital Eye Center in Cleveland. He has no financial interest in this subject matter.

References

1. Kurup S. Inflammation, life and diabetes: a reflection in the eye. Presented at: Fourth Annual Cleveland Eye Bank Foundation Virtual Vision Research Symposium; October 15, 2024; Cleveland, Ohio.

2. Qiao Q, Liu X, Xue W, Chen L, Hou X. Analysis of the association between high antioxidant diet and lifestyle habits and diabetic retinopathy based on NHANES cross-sectional study. Sci Rep. 2024;14(1):11868. doi:10.1038/s41598-024-62707-7

3. Garcia-Medina JJ, Rubio-Velazquez E, Foulquie-Moreno E, et al. Update on the effects of antioxidants on diabetic retinopathy: in vitro experiments, animal studies and clinical trials. Antioxidants (Basel). 2020;9(6):561. doi:10.3390/antiox9060561

4. Lafuente M, Ortín L, Argente M, et al. Combined intravitreal ranibizumab and oral supplementation with docosahexaenoic acid and antioxidants for diabetic macular edema: two-year randomized single-blind controlled trial results. Retina. 2017;37(7):1277-1286.