TY - JOUR
T1 - Nuclear Magnetic Resonance Derived Biomarkers for Evaluating Cardiometabolic Risk in Youth and Young Adults Across the Spectrum of Glucose Tolerance
AU - Chung, Stephanie T.
AU - Matta, Samantha T.
AU - Meyers, Abby G.
AU - Cravalho, Celeste K.
AU - Villalobos-Perez, Alfredo
AU - Dawson, Joshua M.
AU - Sharma, Vandhna R.
AU - Sampson, Maureen L.
AU - Otvos, James D.
AU - Magge, Sheela N.
N1 - Funding Information:
We would like to thank the volunteers (and their families) whose participation made this study possible.
Publisher Copyright:
© 2021, At least a portion of this work is authored by Stephanie T. Chung on behalf of the U.S. Government and, as regards Dr. Chung and the U.S. Government, is not subject to copyright protection in the United States.
PY - 2021/5/18
Y1 - 2021/5/18
N2 - 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.
AB - 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.
KW - GlycA
KW - NMR
KW - cardiometabolic risk
KW - glucose tolerance
KW - insulin resistance
KW - lipoprotein insulin resistance index
KW - youth
UR - http://www.scopus.com/inward/record.url?scp=85107068140&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107068140&partnerID=8YFLogxK
U2 - 10.3389/fendo.2021.665292
DO - 10.3389/fendo.2021.665292
M3 - Article
C2 - 34084151
AN - SCOPUS:85107068140
SN - 1664-2392
VL - 12
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 665292
ER -