ESPE Yearbook of Paediatric Endocrinology

Brief summary: This study aimed to decipher the pathophysiology of the lower prevalence of diabetic retinopathy observed among youth with T2D who also have severe obesity. None of the several biomarkers assessed was found to be associated with the obesity paradox. The biomarkers included: inflammatory factors, acute phase reactants or cytokines (VEGF, hsCRP, ICAM-1, VCAM-1, homocysteine, adiponectin, E-selectin, MCP-1, TNF-α, IL-6, fibrinogen, and ApoB).

Comment: High rates of diabetes complications have been reported in youth with T2D. Data from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that 13.7% of youth developed retinopathy after a mean 4.9 years of disease. Diabetic retinopathy increases with diabetes duration. The estimated pooled global prevalence of diabetic retinopathy in paediatric T2D increases with disease duration, from 1.1% at less than 2.5 years after diagnosis, to 9.0% at 2.5 to 5.0 years after T2D diagnosis, and 28.1% at more than 5 years after T2D diagnosis.¹

The ‘obesity paradox’ describes the association of overweight or mild obesity, compared to normal weight or underweight, with a lower risk of mortality in such conditions as heart disease, diabetes, chronic kidney disease and heart failure. It is called a ‘paradox’ because it contradicts the generally accepted notion that obesity is a risk factor for various health problems and increased mortality. Using body mass index (BMI) as a surrogate for obesity, the TODAY study found that among 524 youth with T2D who were followed 2–6.5 years, and who underwent retinal examinations with digital fundus photographs, those with greater obesity were less likely to have retinopathy than were those with less obesity. The prevalence of non-proliferative diabetes retinopathy was 16.3% for the lowest BMI tertile (21.6–31.5 kg/m²), 15.0% for the middle BMI tertile (31.5–37.9 kg/m2) and 9.8% for the highest BMI tertile (37.9–68.7 kg/m²). Comparing the highest to the lowest BMI tertile, the OR was =0.565 95% CI (0.387, 0.824).

In an attempt to elucidate factors associated with the ‘obesity paradox’, the TODAY study assessed serum levels of circulating factors that have been identified as associated etiopathologically in the development of diabetic retinopathy. Inflammatory factors, acute phase reactants, cytokines and other factors implicated in the pathogenesis of diabetic retinopathy were obtained (VEGF, hsCRP, ICAM-1, VCAM-1, homocysteine, adiponectin, E-selectin, MCP-1, TNF-α, IL-6, fibrinogen, and ApoB, levels). None of these parameters could explain the lower rate of retinopathy in the highest BMI tertile. Presently, however, the well-known epidemiologic risk factors of hyperglycemia, diabetes duration and hypertension remain the most important markers for an increased risk of diabetic retinopathy in youth with T2D.

Reference: 1. Cioana M, Deng J, Nadarajah A, Hou M, Qiu Y, Chen SSJ, Rivas A, Toor PP, Banfield L, Thabane L, Chaudhary V, Samaan MC. Global prevalence of diabetic retinopathy in pediatric type 2 diabetes: A systematic review and meta-analysis. JAMA Netw Open. 2023 Mar 1;6(3):e231887. doi: 10.1001/jamanetworkopen.2023.1887.