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

Tomsa, Anca; Bartz, Sara Klinepeter; Krishnamurthy, Rajesh; Bacha, Fida

doi:10.1016/j.jpeds.2016.07.025

Cited by 24 publications

(31 citation statements)

References 36 publications

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“…In adults, the presence of insulin resistance in obesity may mediate this relationship . The relationship of endothelial function to insulin sensitivity in adolescents is less clear as a relationship has been found in some, but not all studies, and may be dependent on how endothelial function and insulin sensitivity are assessed . In the current study we did not find a relationship between endothelial function and insulin sensitivity.…”

Section: Discussioncontrasting

confidence: 75%

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Increased body fat and reduced insulin sensitivity are associated with impaired endothelial function and subendocardial viability in healthy, non‐Hispanic white adolescents

et al. 2019

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Background Cardiovascular disease has its origins in adolescents. Endothelial dysfunction, arterial stiffness, and decreased endocardial oxygen supply: demand ratios are early functional markers of cardiovascular risk. The goal of this study was to determine the relationships of these markers to physical, inflammatory, and metabolic markers in healthy non‐Hispanic, white adolescents. Methods Thirty‐four of the 75 subjects were female. Mean age was 15.0 ± 1.7 years and mean body mass index (BMI) was 22.0 ± 5.8 kg/m2 (mean ± SD). Reactive hyperemia was measured using venous occlusion plethysmography. Arterial tonometry was used to measure the augmentation index (AIx75) and the Buckberg subendocardial viability ratio. Blood samples were taken to measure inflammatory and lipid markers and oral glucose tolerance test was used to assess insulin sensitivity. Results Reactive hyperemia decreased as body mass and fat mass increased. It also decreased with increasing neutrophil count. The Buckberg index was higher in males and was positively related to insulin sensitivity even when accounting for age, sex, and resting heart rate. AIx75 was not related to any of the other variables. Conclusions These results demonstrate that increased fat mass and decreased insulin sensitivity are related to poorer vascular function and cardiac risk in adolescents before the development of actual cardiovascular disease.

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Section: Discussioncontrasting

confidence: 75%

“…This may indicate that we used the wrong markers. Tomosa et al, however, found no relationship between reactive hyperemia and tissue necrosing factor‐α, but did find a relationship for AIx 75 . It is, also, possible that these relationships may not develop until a later age.…”

Section: Discussionmentioning

confidence: 94%

Increased body fat and reduced insulin sensitivity are associated with impaired endothelial function and subendocardial viability in healthy, non‐Hispanic white adolescents

et al. 2019

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“…The reduction of insulin-induced vasodilatation in overfed rats may be related to a general impairment of arterial vasodilatation during the first stages of weight gain, as both the relaxation in response to acetylcholine, which is mediated by nitric oxide release from the endothelium, and to sodium nitroprusside, which acts directly on the vascular smooth muscle, were reduced in early overfed rats. Likewise, it is reported that vasodilatation to reactive hyperemia correlates negatively with body fat in adolescents [37]. As previously reported [38,39], the vascular insulin resistance may be due to both increased vascular inflammation and oxidative stress, since both the mRNA levels of pro-inflammatory and pro-oxidant markers were upregulated in overfed rats.…”

Section: Discussionsupporting

confidence: 61%

Overfeeding during Lactation in Rats is Associated with Cardiovascular Insulin Resistance in the Short-Term

et al. 2020

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Childhood obesity is associated with metabolic and cardiovascular comorbidities. The development of these alterations may have its origin in early life stages such as the lactation period through metabolic programming. Insulin resistance is a common complication in obese patients and may be responsible for the cardiovascular alterations associated with this condition. This study analyzed the development of cardiovascular insulin resistance in a rat model of childhood overweight induced by overfeeding during the lactation period. On birth day, litters were divided into twelve (L12) or three pups per mother (L3). Overfed rats showed a lower increase in myocardial contractility in response to insulin perfusion and a reduced insulin-induced vasodilation, suggesting a state of cardiovascular insulin resistance. Vascular insulin resistance was due to decreased activation of phosphoinositide 3-kinase (PI3K)/Akt pathway, whereas cardiac insulin resistance was associated with mitogen-activated protein kinase (MAPK) hyperactivity. Early overfeeding was also associated with a proinflammatory and pro-oxidant state; endothelial dysfunction; decreased release of nitrites and nitrates; and decreased gene expression of insulin receptor (IR), glucose transporter-4 (GLUT-4), and endothelial nitric oxide synthase (eNOS) in response to insulin. In conclusion, overweight induced by lactational overnutrition in rat pups is associated with cardiovascular insulin resistance that could be related to the cardiovascular alterations associated with this condition.

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“…In OHAs with dysglycemia (prediabetes and T2DM), the presence of NAFLD is associated with worse endothelial function, a biomarker of subclinical atherosclerosis, as indicated by lower reactive hyperemia index (nitric oxide dependent vascular function), higher augmentation index (a measure of peripheral vascular stiffness) [ 27 , 29 ], and higher levels of circulating inflammatory markers. These measures of vascular function were related to the hepatic fat content, independent of total body and visceral adiposity, and other CVD risk markers of glycemia, and blood pressure.…”

Section: Discussionmentioning

confidence: 99%

“…The augmentation index (AIx) is a measure of arterial stiffness. It is usually a negative number calculated as the difference between the early (P1) and late (P2) systolic peaks of the pulse wave relative to the early peak wave (P2 – P1 / P1) expressed as a percentage [ 28 ], and adjusted to a standard heart rate of 75 beats per minute (AIx-75) [ 29 ]. A higher AIx (less negative number) reflects greater arterial stiffness.…”

Section: Methodsmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease in Hispanic Youth With Dysglycemia: Risk for Subclinical Atherosclerosis?

Bacha

Tomsa

Bartz

et al. 2017

Journal of the Endocrine Society

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Context:Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden.Objective:To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth.Design:Cross-sectional study.Setting:Academic institution.Participants:Thirty-six OHAs (15.3 ± 0.4 years), 20 with prediabetes and 16 with type 2 diabetes, with and without NAFLD.Intervention:Evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) by peripheral arterial tonometry; muscle, hepatic, and adipose tissue insulin sensitivity (IS; hyperinsulinemic-euglycemic clamp 80 mu/m2/min, with [6,6 2H2]glucose and [2H5] glycerol); body composition; and abdominal and hepatic fat by magnetic resonance imaging/spectroscopy.Outcome Measures:RHI and AIx.Hypothesis:OHAs with dysglycemia and NAFLD have worse RHI and AIx vs those without NAFLD.Results:The NAFLD (n = 23) and non-NAFLD (n = 13) groups were of similar age, sex, glycemic status, body mass index, % body fat and abdominal fat. The NAFLD group had higher hepatic fat (P < 0.001) lower skeletal muscle IS (P = 0.01), hepatic IS (P = 0.01), and adipose tissue IS (P = 0.04). The NAFLD vs non-NAFLD group had lower RHI (1.4 ± 0.05 vs 1.7 ± 0.09, P = 0.002), greater AIx (–6.0 ± 1.6 vs –12.0 ± 2.1, P = 0.03). Hepatic fat was inversely related to RHI (r = –0.49, P = 0.002) and positively related to AIx (r = 0.45, P = 0.006). Hepatic IS (r = –0.42, P = 0.01) and adipose IS (r = –.54, P = 0.001) correlated with arterial stiffness (AIx).Conclusion:In OHAs with dysglycemia, NAFLD is associated with worse endothelial function. RHI and AIx were related to hepatic fat content. Vascular stiffness was related to hepatic and adipose tissue insulin resistance.

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

Abstract: 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.

Cited by 24 publications

References 36 publications

Increased body fat and reduced insulin sensitivity are associated with impaired endothelial function and subendocardial viability in healthy, non‐Hispanic white adolescents

Increased body fat and reduced insulin sensitivity are associated with impaired endothelial function and subendocardial viability in healthy, non‐Hispanic white adolescents

Overfeeding during Lactation in Rats is Associated with Cardiovascular Insulin Resistance in the Short-Term

Nonalcoholic Fatty Liver Disease in Hispanic Youth With Dysglycemia: Risk for Subclinical Atherosclerosis?

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