Nuclear Magnetic Resonance Derived Biomarkers for Evaluating Cardiometabolic Risk in Youth and Young Adults Across the Spectrum of Glucose Tolerance.

Vandhna R Sharma,Samantha T Matta,Stephanie T Chung,Abby G Meyers,James D Otvos,Sheela N Magge,Alfredo Villalobos-Perez,Celeste K Cravalho,Joshua M Dawson,Maureen L Sampson

doi:10.3389/fendo.2021.665292

Abstract

Youth with obesity have an increased risk for cardiometabolic disease, but identifying those at highest risk remains a challenge. Four biomarkers that might serve this purpose are “by products” of clinical NMR LipoProfile® lipid testing: LPIR (Lipoprotein Insulin Resistance Index), GlycA (inflammation marker), BCAA (total branched-chain amino acids), and glycine. All are strongly related to insulin resistance and type 2 diabetes (T2DM) in adults (glycine inversely) and are independent of biological and methodological variations in insulin assays. However, their clinical utility in youth is unclear. We compared fasting levels of these biomarkers in 186 youth (42 lean normal glucose tolerant (NGT), 88 obese NGT, 23 with prediabetes (PreDM), and 33 with T2DM. All four biomarkers were associated with obesity and glycemia in youth. LPIR and GlycA were highest in youth with PreDM and T2DM, whereas glycine was lowest in youth with T2DM. While all four were correlated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LPIR had the strongest correlation (LPIR: r = 0.6; GlycA: r = 0.4, glycine: r = −0.4, BCAA: r = 0.2, all P < 0.01). All four markers correlated with HbA1c (LPIR, GlycA, BCAA: r ≥ 0.3 and glycine: r = −0.3, all P < 0.001). In multi-variable regression models, LPIR, GlycA, and glycine were independently associated with HOMA-IR (Adjusted R2 = 0.473, P < 0.001) and LPIR, glycine, and BCAA were independently associated with HbA1c (Adjusted R2 = 0.33, P < 0.001). An LPIR index of >44 was associated with elevated blood pressure, BMI, and dyslipidemia. Plasma NMR-derived markers were related to adverse markers of cardiometabolic risk in youth. LPIR, either alone or in combination with GlycA, should be explored as a non-insulin dependent predictive tool for development of insulin resistance and diabetes in youth.Clinical Trial Registration Clinicaltrials.gov, identifier NCT:02960659

Highlights

Cardiometabolic diseases are a major cause of morbidity and mortality worldwide
This was a secondary analysis of participants enrolled in two observational cohort cross-sectional studies that were designed to evaluate the pathophysiology of T2DM in youth: The MIGHTY study (Metformin Influences Gut Hormones in Youth) cohort was recruited from two clinical sites (Baylor College of Medicine, Houston TX and National Institutes of Health (NIH), Bethesda, MD) and The Dyslipidemia and Cardiovascular (CV) Risk Factors in Pediatric Obesity and Type 2 Diabetes study cohort was recruited from the Children’s Hospital of Philadelphia (CHOP)
Participants in quartile 4 with an lipoprotein insulin resistance index (LPIR) score of >44 had significantly higher BMI, blood pressure, and metabolic markers of dyslipidemia and dysglycemia (P < 0.001). This analysis confirms the association of nuclear magnetic resonance (NMR) biomarkers (LPIR, GlycA, branched chain amino acids (BCAA), and glycine) with insulin resistance and glycemia and provides new information on the distribution of these variables in a predominantly African American youth and young adult cohort who were at risk for or who had T2DM

Summary

Introduction

Cardiometabolic diseases are a major cause of morbidity and mortality worldwide. Excess adiposity in childhood is an important modifiable risk factor and one of the strongest predictors of future disease in adults [1, 2]. Global rates of childhood obesity continue to rise unabatedly despite numerous primary prevention campaigns [3] To tackle this growing public health problem, prevention and intervention strategies should be coupled and targeted to youth and young adults at highest risk [4]. Current approaches in pediatrics rely heavily on clinical and single laboratory parameters, such as BMI percentile and screening tests for hyperglycemia, to help clinicians diagnose and assess risk for cardiometabolic diseases. These tools are useful for the diagnosis of obesity and diabetes among growing children, they are relatively insensitive to risk stratification of insulin resistance, a primary pathophysiologic factor in cardiometabolic diseases [5]

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