Endothelial Function in Youth: A Biomarker Modulated by Adiposity-Related Insulin Resistance

• Published in: The Journal of pediatrics Vol. 178; pp. 171 - 177
• Main Authors: Tomsa, Anca, MD, Klinepeter Bartz, Sara, MD, Krishnamurthy, Rajesh, MD, Krishnamurthy, Ramkumar, PhD, Bacha, Fida, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016
• Subjects: Adipose Tissue; Adiposity - physiology; Adolescent; Biomarkers - metabolism; Child; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - physiopathology; endothelial function; Endothelium - physiopathology; Female; Glucose Tolerance Test; Humans; inflammatory markers; insulin resistance; Insulin Resistance - physiology; Male; Overweight - complications; Overweight - physiopathology; Pediatrics; Young Adult; inflammatory markers; T2DM; PAT; Fat-free mass; Reactive hyperemia index; Type 2 diabetes mellitus; FFM; Impaired glucose regulation; TNF; BP; AIx; Body mass index; HDL; RHI; LDL; Hemoglobin; Blood pressure; Hb; insulin resistance; AIx-75; Peripheral arterial tonometry; BMI; Plasminogen activator inhibition; endothelial function; Normal glucose tolerance; AIx at heart rate 75 bpm; Augmentation index; PWV; Low-density lipoprotein; High-density lipoprotein; IGR; Tumor necrosis factor; Pulse wave velocity; PAI; NGT
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2016.07.025

Objective To investigate the physical and metabolic determinants of endothelial dysfunction, an early marker of subclinical atherosclerosis, in normal weight and overweight adolescents with and without type 2 diabetes mellitus. Study design A cross-sectional study of 81 adolescents: 21 normal weight, 25 overweight with normal glucose tolerance, 19 overweight with impaired glucose regulation, and 16 with type 2 diabetes mellitus underwent evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) at heart rate 75 bpm by peripheral arterial tonometry; oral glucose tolerance test, lipid profile, and hyperinsulinemic-euglycemic clamp to measure insulin sensitivity; and dual energy X-ray absorptiometry scan and abdominal magnetic resonance imaging for percentage of body fat and abdominal fat partitioning. Results Participants across tertiles of RHI (1.2 ± 0.02, 1.5 ± 0.02, and 2.0 ± 0.05, P  < .001) had similar age, sex, race, lipid profile, and blood pressure. Body mass index z-score, percentage body fat, abdominal fat, and hemoglobin A1c decreased, and insulin sensitivity increased from the first to third tertile. RHI was inversely related to percentage body fat (r = −0.29, P  = .008), total (r = −0.37, P  = .004), subcutaneous (r = −0.39, P  = .003), and visceral (r = −0.26, P  = .04) abdominal fat. AIx at heart rate 75 bpm was higher (worse) in the lower RHI tertiles ( P  = .04), was positively related to percentage body fat (r = 0.26, P  = .021), and inversely related to age, insulin sensitivity, and inflammatory markers (tumor necrosis factor-α and plasminogen activator inhibition-1). Conclusions Childhood obesity, particularly abdominal adiposity, is associated with endothelial dysfunction manifested by worse reactive hyperemia and higher AIx. Insulin resistance appears to mediate this relationship.