Kids with T2D Developed Retinopathy Faster, More Often Than Kids with T1D

Kids with type 2 diabetes (T2D) were nearly twice as likely to develop diabetic retinopathy compared to kids with type 1 diabetes (T1D), and the ocular condition also developed more rapidly, according to findings from a 50-year retrospective study.

Diabetes is a relatively common chronic disease among children, and resulting diabetic retinopathy is the leading cause of blindness among working-age and young adults. However, while the ocular sequelae of T1D and adult-onset T2D are well established, little is known regarding progression to diabetic retinopathy in kids with T2D—a growing concern, given the increased incidence of T2D in this population in recent years, Brian G. Mohney, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues explained in JAMA Ophthalmology.

Mohney and colleagues conducted an analysis to assess the risk of developing diabetes-associated ocular complications (DAOC)—including diabetic retinopathy, proliferative diabetic retinopathy (PDR), diabetic macular edema, cataracts, and a need for pars plana vitrectomy—among a population of children younger than 22 years from Minnesota diagnosed with either type 1 or type 2 diabetes from 1970 through 2019.

“In this 50-year population-based cohort, children diagnosed with T2D had a higher risk of developing diabetic retinopathy, developing PDR, and requiring [pars plana vitrectomy] compared with those diagnosed with T1D,” Mohney and colleagues reported. “The duration between the diagnosis of diabetes and the development of diabetic retinopathy was shorter in the T2D cohort compared with the T1D cohort, and patients with T2D developed vision-threatening retinopathy at a higher rate than those with T1D. This suggests that the natural history of retinopathy development among youth diagnosed with T2D may differ from that in youth diagnosed with T1D, where patients with T2D may be more susceptible to developing retinopathy than those with T1D despite controlling for diabetes disease duration.”

The study authors concluded that their findings “suggest that to prevent serious ocular complications, children with T2D may require ophthalmoscopic evaluations at least as frequently as or more frequently than children with T1D.”

Updated strategies for managing ocular complications will be vital in the near future, as diabetes prevalence is projected to skyrocket in the next few decades, Jennifer K. Sun, MD, MPH, of the Beetham Eye Institute at Joslin Diabetes Center in Boston, stressed in an editorial accompanying the study.

“Diabetes is a growing epidemic that will affect more than 700 million individuals worldwide by the year 2045,” Sun wrote. “The rising prevalence of diabetes affects youth as well as adults; it has been projected that the number of young people with T1D will increase by almost 3-fold and those with T2D will nearly quadruple by the year 2050. Although better patient education and advances in medical care have led to improvements in systemic control for populations with diabetes in developed countries such as the U.S., the increased global incidence of diabetes implies that there will be a growing number of individuals at risk for vision loss due to diabetic retinopathy during the following decades. These statistics highlight the need to better understand when and how vision-threatening complications occur in youth with diabetes to optimize strategies to preserve vision in these vulnerable individuals.”

In light of this, Sun noted that Mohney et al “have made a valuable contribution that highlights several issues critical to developing a thorough understanding of diabetic eye disease in both pediatric and adult populations. Accurate risk estimates for onset of vision-threatening complications such as proliferative diabetic retinopathy and diabetic macular edema are crucial in setting appropriate screening guidelines for baseline and follow-up retinal examinations.”

She concluded that similar studies across diverse cohorts will be necessary to help optimize guidelines for baseline screening and follow-up for kids diagnosed with diabetes. “Such efforts may potentially lead to increased understanding of the mechanistic differences between pathology in T1D versus T2D and ideally provide insight into therapeutic targets to preserve vision in youth with diabetes across subsequent decades of hyperglycemia,” she wrote.

For their analysis, Mohney and colleagues retrospectively reviewed medical records of all patients younger than 22 years who were newly diagnosed with diabetes from Jan. 1, 1970, through Dec. 31, 2019, in Olmsted County, Minnesota. Exclusion criteria included patients living outside Olmsted County at the time of diabetes diagnosis, those diagnosed after 21 years of age or outside the study period, or denial of research authorization by the patient or guardian. The primary study outcome was risk of developing DAOCs over time.

The final study cohort consisted of 525 children with confirmed T1D or T2D who underwent at least one eye examination after their diagnosis. Of these, 461 patients had T1D and 64 had T2D. Median follow-up was 13.6 years and 8.6 years for patients with T1D and T2D, respectively; mean (SD) age at diabetes diagnosis was 12.1 (5.4) years; and just over half of children (n=264; 50.3%) were male.

“Diabetes-associated ocular complications occurred in 147 of the 461 children (31.9%) with T1D and in 17 of the 64 children (26.6%) with T2D,” Mohney and colleagues found. “The hazard ratio illustrating the risk between T2D and T1D rates was 1.88 (95% CI, 1.13-3.12; P=0.02) for developing any diabetic retinopathy (nonproliferative or greater), 2.33 (95% CI, 0.99-5.50; P=0.048) for proliferative diabetic retinopathy, 1.49 (95% CI, 0.46-4.89; P=0.50) for diabetic macular edema, 2.43 (95% CI, 0.54-11.07; P=0.24) for a visually significant cataract, and 4.06 (95% CI, 1.34-12.33; P=0.007) for requiring pars plana vitrectomy by 15 years after the diagnosis of diabetes.”

The Kaplan-Meier risks for ocular sequelae in children with T1D versus T2D were as follows:

• Developing any retinopathy: 31% versus 53%.
• Developing proliferative diabetic retinopathy: 5% versus 8%.
• Developing diabetic macular edema: 5% versus 4%.
• Developing a visually significant cataract: 1% versus 9%.
• Requiring pars plana vitrectomy within 15 years: 2% versus 8%.

As youth-onset T2D was relatively infrequent prior to the 21st century, follow-up time for the T2D cohort was shorter than for the T1D cohort, and therefore Kaplan-Meier risks for developing DAOCs in T2D beyond 15 years after diagnosis “were too unstable to calculate,” the study authors noted.

While Sun praised the study by Mohney et al for “[leveraging] the strength of multiple decades of medical care continuity provided to residents of Olmsted County, Minnesota, by the Mayo Clinic,” she also argued that there are limitations to the study data “beyond the variability of clinical follow-up and missing observations typically found in a retrospective study.”

For example, she noted that diabetes diagnoses were generally made based on clinical evaluation, “with fundus photographs reviewed for diabetic retinopathy severity only if there was no corresponding clinical examination. Not all diabetic retinal pathology may have been identified or recorded. Indeed, clinical management and grading of diabetic eye disease evolved substantially during the study period.” She specifically pointed to the Early Treatment Diabetic Retinopathy severity scale, which was not published until 1991, and the development of the National Glycohemoglobin Standardization Program in 1996 as major changes in clinical management of DAOCs that may impact the earlier data included in the analysis.

What’s more, Sun pointed out that the population of Olmsted County is “overwhelmingly White (95.7% in 1990),” which may limit the generalizability of the findings, a limitation that Mohney and colleagues also acknowledged.

Additional study limitations include that some children with milder forms of diabetes may not have been detected; the number of children diagnosed with T2D was relatively small; and DAOCs may have been underestimated if patients moved out of state or were lost to follow-up.

1. Children with type 2 diabetes (T2D) were nearly twice as likely to develop diabetic retinopathy compared to children with type 1 diabetes (T1D), and they also experienced ocular complications sooner after initial diagnosis, according to a 50-year retrospective analysis.

2. These findings suggest that children with T2D may require ophthalmoscopic evaluations at least as frequently as or more frequently than children with T1D in order to prevent serious ocular complications.

John McKenna, Associate Editor, BreakingMED™

Cat ID: 240

Topic ID: 92,240,730,12,138,139,669,918,240