The obesity paradox: Retinopathy, obesity, and circulating risk markers in youth with type 2 diabetes in the TODAY Study

Abstract

Aim: To understand the relationship of obesity and 27 circulating inflammatory biomarkers to the prevalence of non-proliferative diabetic retinopathy (NPDR) in youth with type 2 diabetes.

Methods: Youth with type 2 diabetes who participated in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study were followed for 2-6.5 years. Digital fundus photographs were obtained in the last year of the study. Blood samples during the study were processed for inflammatory biomarkers, and these were correlated with obesity tertiles and presence of retinopathy.

Results: Higher BMI was associated with an increase in circulating levels of metabolic biomarkers including high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, LDL-cholesterol (LDL-C) and Apolipoprotein B (ApoB), tumor necrosis factor receptors 1 and 2 (TNFR-1 and -2), interleukin 6 (IL-6), E-selectin, and homocysteine, as well as a decrease in the metabolic risk markers HDL-cholesterol (HDLC), and insulin-like growth factor binding protein 1 (IGFBP-1). Although NPDR risk decreased with increasing obesity, it was not associated with any of the measured biomarkers.

Conclusions: Circulating levels of measured biomarkers did not elucidate the "obesity paradox" of decreased NPDR in the most obese participants in the TODAY study.

Trial registration: clinicaltrials.govNCT00081328.

Keywords: Biomarkers; Obesity; Obesity paradox; Retinopathy; Type 2 diabetes; Youth.

Conflict of interest statement

Declaration of competing interest Ruth S. Weinstock participates in multicenter clinical trials, through her institution, sponsored by Medtronic, Insulet, Eli Lilly, Boehringer Ingelheim, Kowa and Tolerion Inc.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.