Clinical Context

Diabetes is a prevalent, chronic childhood disease associated with chronic hyperglycemia and end-organ damage often causing the microvascular triad of nephropathy, neuropathy, and retinopathy. Subsequent retinal neurodegeneration and blood-retinal barrier breakdown lead to diabetic retinopathy, the leading cause of blindness in working-age and young adults.

Study Synopsis and Perspective

Children diagnosed with type 2 diabetes (T2D) appear significantly more likely to develop retinopathy and other ocular complications over time than children who are diagnosed with type 1 diabetes (T1D), researchers report.

Among a population-based cohort of children (defined as younger than 22 years), the risk for diabetic retinopathy was 88% greater in those with T2D than those with T1D within the first 15 years of disease diagnosis.

"The purpose of this study was to assess the risk of developing diabetes-associated ocular complications...among a population-based cohort of children diagnosed with either T1D or T2D during a 50-year period," lead author Patricia Bai, from the Mayo Clinic, Phoenix, Arizona, and colleagues reported in JAMA Ophthalmology.^[1]

The researchers retrospectively reviewed medical records from all residents of Olmsted County, Minnesota, from 1970 to 2019. The study cohort included 606 children with a confirmed a diagnosis of T1D or T2D, 525 (86.6%) of whom had at least 1 ocular examination.

The mean age at diabetes diagnosis was 12.1 years (standard deviation, 5.4 years); most participants were White (95.7% in 1990), and half (50.3%) were male. Diabetes-associated ocular complications occurred in 31.9% and 26.6% of children with T1D and T2D, respectively.

The hazard ratios illustrating the risk between T2D and T1D rates were 1.88 (95% confidence interval [CI], 1.13-3.12; P=.02) for any diabetic retinopathy, 2.33 (95% CI, 0.99-5.50; P=.048) for proliferative diabetic retinopathy (PDR), 1.49 (95% CI, 0.46-4.89; P=.50) for diabetic macular edema, 2.43 (95% CI, 0.54-11.07; P=.24) for a visually significant cataract, and 4.06 (95% CI, 1.34-12.33; P=.007) for requiring pars plana vitrectomy (PPV) within the first 15 years of diagnosis.

These results suggest that earlier surveillance and intervention may help prevent vision-threatening complications, the researchers explained.

"After adjusting for race using self-identified categories of White or not White, the adjusted HR of developing any retinopathy was 1.63 (95% CI, 0.96-2.79; P = .07), and the adjusted [hazard ratio] of developing PDR was 2.02 (95% CI, 0.79-5.16; P = .14)" in patients with T2D versus T1D, the researchers wrote.

"We would expect the reported rate of type 2 diabetes to be potentially underestimated in our study cohort," Bai commented in an interview. "Race has been suggested to be a surrogate for other social determinants of health, such as lower rates of optimal follow-up care received by racial and ethnic minorities, which could influence subsequent retinopathy rates."

In an accompanying editorial, Jennifer K. Sun, MD, MPH, from Harvard Medical School, Boston, wrote that the present study indicates that the natural history of retinopathy may differ between patients with T1D and T2D.^[2]

Although the pathophysiology of diabetic retinopathy in T1D and T2D appears similar, other patient-related factors such as lipid profiles, the presence of hypertension, and body mass index may differ between the 2 disease states.

She wrote that "there is a particular need to document retinopathy outcomes and risk factors for advanced disease in youth with T2D, for whom there is a paucity of information."

Bai and colleagues acknowledged that a key limitation of the study was the retrospective design. As a result, irregular follow-up and incomplete data may limit the applicability of the findings.

"Some children with milder forms of diabetes may have eluded detection, a limitation that is more likely to affect T2D, which may exist undetected for years before a diagnosis," Bai explained.

Dr Sun recommended that further epidemiologic studies are needed to help optimize guidelines for screening and follow-up for young people diagnosed with diabetes. "Such efforts may potentially lead to increased understanding of the mechanistic differences between pathology in T1D versus T2D," she concluded.

This study used the resources of the Rochester Epidemiology Project (REP) medical records linkage system, which is supported by grant funding from the National Institute on Aging, the Mayo Clinic Research Committee, and by fees paid annually by REP users. The study authors have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online December 2, 2021.

Clinical Implications

• Diabetic retinopathy, PDR, and the need for PPV occurred within a shorter diabetes duration for children with T2D vs T1D, and children with T2D had nearly twice the risk of developing retinopathy.
• The natural history of developing retinopathy may differ in youth diagnosed with T2D vs those with T1D, in that they may be more susceptible to developing retinopathy despite controlling for diabetes duration.
• Implications for the Health Care Team: To prevent serious ocular complications, children with T2D may need earlier surveillance and intervention, including ophthalmoscopic examinations at least as often or more often than children with T1D.

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