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Longitudinal effects of MRI-measured hepatic steatosis on biomarkers of glucose homeostasis and hepatic apoptosis in obese youth.

Kim G, Giannini C, Pierpont B, Feldstein AE, Santoro N, Kursawe R, Shaw M, Duran E, Goldberg R, Dziura J, Caprio S - Diabetes Care (2012)

Bottom Line: Over time, markers of insulin sensitivity and 2-h glucose improved significantly in the group without fatty liver, in contrast with the persistence of the insulin resistance and associated correlates in the fatty liver group.In a multivariate analysis, we showed that baseline HFF is an independent predictor of 2-h glucose and whole-body insulin sensitivity.Baseline HFF strongly modulates longitudinally 2-h blood glucose, biomarkers of insulin resistance, and hepatocellular apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.

ABSTRACT

Objective: We used fast-gradient magnetic resonance imaging (MRI) to determine the longitudinal associations between the hepatic fat content (HFF), glucose homeostasis, and a biomarker of hepatocellular apoptosis in obese youth.

Research design and methods: Baseline and longitudinal liver and abdominal MRI were performed with an oral glucose tolerance test in 76 obese youth followed for an average of 1.9 years. Cytokeratin-18 (CK-18) was measured at baseline and follow-up as a biomarker of hepatic apoptosis. The relationship between baseline HFF and metabolic parameters and circulating levels of CK-18 at follow-up were assessed using a bivariate correlation.

Results: At baseline, 38% had hepatic steatosis based on %HFF ≥5.5% with alterations in indices of insulin sensitivity and secretion. At follow-up, BMI increased in both groups and baseline %HFF correlated strongly with the follow-up %HFF (r = 0.81, P < 0.001). Over time, markers of insulin sensitivity and 2-h glucose improved significantly in the group without fatty liver, in contrast with the persistence of the insulin resistance and associated correlates in the fatty liver group. Baseline HFF correlated with 2-h glucose (r = 0.38, P = 0.001), whole-body insulin sensitivity (r = -0.405, P = 0.001), adiponectin (r = -0.44, P < 0.001), CK-18 levels, (r = 0.63, P < 0.001), and disposition index (r = -0.272, P = 0.021) at follow-up. In a multivariate analysis, we showed that baseline HFF is an independent predictor of 2-h glucose and whole-body insulin sensitivity.

Conclusions: In obese youth, the phenotype of MRI-measured hepatic steatosis is persistent. Baseline HFF strongly modulates longitudinally 2-h blood glucose, biomarkers of insulin resistance, and hepatocellular apoptosis.

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Correlations between baseline HFF (%) and HFF (%), CK-18, and metabolic parameters at follow-up.
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Figure 2: Correlations between baseline HFF (%) and HFF (%), CK-18, and metabolic parameters at follow-up.

Mentions: Baseline %HFF correlated strongly with the follow-up %HFF (r = 0.81, P < 0.001). Thus, obese adolescents with a high fat content at baseline remained in the same category over time. As for biomarkers of hepatocellular injury, we found a strong association between baseline HFF (%) and CK-18 levels (r = 0.613, P < 0.001) (Fig. 2). Furthermore, both ALT (r = 0.667) and AST (r = 0.606) correlated strongly with baseline %HFF (P = 0.001).


Longitudinal effects of MRI-measured hepatic steatosis on biomarkers of glucose homeostasis and hepatic apoptosis in obese youth.

Kim G, Giannini C, Pierpont B, Feldstein AE, Santoro N, Kursawe R, Shaw M, Duran E, Goldberg R, Dziura J, Caprio S - Diabetes Care (2012)

Correlations between baseline HFF (%) and HFF (%), CK-18, and metabolic parameters at follow-up.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3526202&req=5

Figure 2: Correlations between baseline HFF (%) and HFF (%), CK-18, and metabolic parameters at follow-up.
Mentions: Baseline %HFF correlated strongly with the follow-up %HFF (r = 0.81, P < 0.001). Thus, obese adolescents with a high fat content at baseline remained in the same category over time. As for biomarkers of hepatocellular injury, we found a strong association between baseline HFF (%) and CK-18 levels (r = 0.613, P < 0.001) (Fig. 2). Furthermore, both ALT (r = 0.667) and AST (r = 0.606) correlated strongly with baseline %HFF (P = 0.001).

Bottom Line: Over time, markers of insulin sensitivity and 2-h glucose improved significantly in the group without fatty liver, in contrast with the persistence of the insulin resistance and associated correlates in the fatty liver group.In a multivariate analysis, we showed that baseline HFF is an independent predictor of 2-h glucose and whole-body insulin sensitivity.Baseline HFF strongly modulates longitudinally 2-h blood glucose, biomarkers of insulin resistance, and hepatocellular apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.

ABSTRACT

Objective: We used fast-gradient magnetic resonance imaging (MRI) to determine the longitudinal associations between the hepatic fat content (HFF), glucose homeostasis, and a biomarker of hepatocellular apoptosis in obese youth.

Research design and methods: Baseline and longitudinal liver and abdominal MRI were performed with an oral glucose tolerance test in 76 obese youth followed for an average of 1.9 years. Cytokeratin-18 (CK-18) was measured at baseline and follow-up as a biomarker of hepatic apoptosis. The relationship between baseline HFF and metabolic parameters and circulating levels of CK-18 at follow-up were assessed using a bivariate correlation.

Results: At baseline, 38% had hepatic steatosis based on %HFF ≥5.5% with alterations in indices of insulin sensitivity and secretion. At follow-up, BMI increased in both groups and baseline %HFF correlated strongly with the follow-up %HFF (r = 0.81, P < 0.001). Over time, markers of insulin sensitivity and 2-h glucose improved significantly in the group without fatty liver, in contrast with the persistence of the insulin resistance and associated correlates in the fatty liver group. Baseline HFF correlated with 2-h glucose (r = 0.38, P = 0.001), whole-body insulin sensitivity (r = -0.405, P = 0.001), adiponectin (r = -0.44, P < 0.001), CK-18 levels, (r = 0.63, P < 0.001), and disposition index (r = -0.272, P = 0.021) at follow-up. In a multivariate analysis, we showed that baseline HFF is an independent predictor of 2-h glucose and whole-body insulin sensitivity.

Conclusions: In obese youth, the phenotype of MRI-measured hepatic steatosis is persistent. Baseline HFF strongly modulates longitudinally 2-h blood glucose, biomarkers of insulin resistance, and hepatocellular apoptosis.

Show MeSH
Related in: MedlinePlus