No Independent Association of Circulating Fetuin-A with Insulin
Sensitivity in Young Women

AbstractAnimal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association.

Download Full-text

MRI measurement of liver fat content predicts the metabolic syndrome

Diabetes & Metabolism ◽

10.1016/j.diabet.2013.01.007 ◽

2013 ◽

Vol 39 (4) ◽

pp. 314-321 ◽

Cited By ~ 14

Author(s):

P.-H. Ducluzeau ◽

J. Boursier ◽

S. Bertrais ◽

S. Dubois ◽

A. Gauthier ◽

...

Keyword(s):

Metabolic Syndrome ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

The Metabolic Syndrome

Download Full-text

Postprandial lipid and apolipoprotein responses following three consecutive meals associate with liver fat content in type 2 diabetes and the metabolic syndrome

Atherosclerosis ◽

10.1016/j.atherosclerosis.2010.02.002 ◽

2010 ◽

Vol 211 (1) ◽

pp. 308-314 ◽

Cited By ~ 22

Author(s):

Maarten E. Tushuizen ◽

Petra J. Pouwels ◽

Saskia Bontemps ◽

Cees Rustemeijer ◽

Niina Matikainen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

The Metabolic Syndrome ◽

Postprandial Lipid

Download Full-text

Insulin Sensitivity Is Correlated with Subcutaneous but Not Visceral Body Fat in Overweight and Obese Prepubertal Children

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2089 ◽

2008 ◽

Vol 93 (6) ◽

pp. 2122-2128 ◽

Cited By ~ 60

Author(s):

Claudio Maffeis ◽

Riccardo Manfredi ◽

Maddalena Trombetta ◽

Silvia Sordelli ◽

Monica Storti ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Body Fat ◽

Fat Distribution ◽

Fat Content ◽

Liver Fat ◽

P Value ◽

Inflammation Markers ◽

Liver Fat Content ◽

Prepubertal Children

Abstract Aim: Our aim was to explore the relationship between insulin sensitivity, body fat distribution, ectopic (liver and skeletal muscle) fat deposition, adipokines (leptin and adiponectin), and inflammation markers (highly sensitive C-reactive protein, IL-6, IL-10, and TNF-α) in prepubertal children. Subjects and Methods: Thirty overweight and obese children (16 males and 14 females with body mass index z-score range of 1.1–3.2) were recruited. Body fat distribution and fat accumulation in liver and skeletal muscle were measured using magnetic resonance imaging. Insulin sensitivity was assessed by iv glucose tolerance test. Results: Insulin sensitivity was associated with sc abdominal adipose tissue (SAT) (r = −0.52; P < 0.01) and liver fat content (r = −0.44; P < 0.02) but not with visceral abdominal adipose tissue (VAT) (r = −0.193; P value not significant) and fat accumulation in skeletal muscle (r = −0.210; P value not significant). Adipokines, but not inflammation markers, were significantly correlated to insulin sensitivity. VAT correlated with C-reactive protein (r = 0.55; P < 0.01) as well as adiponectin (r = −0.53; P <0.01). Multiple regression analysis showed that only SAT and liver fat content were independently correlated to insulin sensitivity (P < 0.01; 20 and 16% of explained variance, respectively). Conclusions: In overweight and moderately obese prepubertal children, insulin sensitivity was negatively correlated with SAT and liver fat content. Furthermore, contrary to adults, VAT and inflammation markers were not correlated with insulin sensitivity in children.

Download Full-text

Effect of liver fat on insulin clearance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00444.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. E1709-E1715 ◽

Cited By ~ 129

Author(s):

Anna Kotronen ◽

Satu Vehkavaara ◽

Anneli Seppälä-Lindroos ◽

Robert Bergholm ◽

Hannele Yki-Järvinen

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Fat Content ◽

Insulin Clearance ◽

Liver Fat ◽

Hepatic Insulin Resistance ◽

Model Assessment ◽

Liver Fat Content ◽

Hepatic Insulin Sensitivity ◽

Impaired Insulin

A fatty liver is associated with fasting hyperinsulinemia, which could reflect either impaired insulin clearance or hepatic insulin action. We determined the effect of liver fat on insulin clearance and hepatic insulin sensitivity in 80 nondiabetic subjects [age 43 ± 1 yr, body mass index (BMI) 26.3 ± 0.5 kg/m2]. Insulin clearance and hepatic insulin resistance were measured by the euglycemic hyperinsulinemic (insulin infusion rate 0.3 mU·kg−1·min−1for 240 min) clamp technique combined with the infusion of [3-3H]glucose and liver fat by proton magnetic resonance spectroscopy. During hyperinsulinemia, both serum insulin concentrations and increments above basal remained ∼40% higher ( P < 0.0001) in the high (15.0 ± 1.5%) compared with the low (1.8 ± 0.2%) liver fat group, independent of age, sex, and BMI. Insulin clearance (ml·kg fat free mass−1·min−1) was inversely related to liver fat content ( r = −0.52, P < 0.0001), independent of age, sex, and BMI ( r = −0.37, P = 0.001). The variation in insulin clearance due to that in liver fat (range 0–41%) explained on the average 27% of the variation in fasting serum (fS)-insulin concentrations. The contribution of impaired insulin clearance to fS-insulin concentrations increased as a function of liver fat. This implies that indirect indexes of insulin sensitivity, such as homeostatic model assessment, overestimate insulin resistance in subjects with high liver fat content. Liver fat content correlated significantly with fS-insulin concentrations adjusted for insulin clearance ( r = 0.43, P < 0.0001) and with directly measured hepatic insulin sensitivity ( r = −0.40, P = 0.0002). We conclude that increased liver fat is associated with both impaired insulin clearance and hepatic insulin resistance. Hepatic insulin sensitivity associates with liver fat content, independent of insulin clearance.

Download Full-text

Quantitative relationship between liver fat content and metabolic syndrome in obese children and adolescents

Clinical Endocrinology ◽

10.1111/cen.12758 ◽

2015 ◽

Vol 83 (1) ◽

pp. 43-49 ◽

Cited By ~ 6

Author(s):

Hongxi Zhang ◽

Huiping Yang ◽

Can Lai ◽

Xiaoqin Xu ◽

Ke Huang ◽

...

Keyword(s):

Metabolic Syndrome ◽

Children And Adolescents ◽

Quantitative Relationship ◽

Fat Content ◽

Liver Fat ◽

Obese Children ◽

Liver Fat Content

Download Full-text

Similar Weight Loss Induces Greater Improvements in Insulin Sensitivity and Liver Function among Individuals with NAFLD Compared to Individuals without NAFLD

Nutrients ◽

10.3390/nu11030544 ◽

2019 ◽

Vol 11 (3) ◽

pp. 544 ◽

Cited By ~ 2

Author(s):

Ruth Schübel ◽

Tobias Nonnenmacher ◽

Disorn Sookthai ◽

Sandra Gonzalez Maldonado ◽

Solomon Sowah ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Liver Function ◽

Dietary Intervention ◽

Fat Content ◽

Metabolic Parameters ◽

Liver Fat ◽

Metabolic Effects ◽

Liver Fat Content ◽

Alcoholic Fatty Liver

Background: Preliminary evidence suggests that weight loss among obese has differential metabolic effects depending on the presence of non-alcoholic fatty liver disease (NAFLD). We assessed whether NAFLD predisposes to differential changes in liver fat content, liver function, and metabolic parameters upon diet-induced weight loss in a 50-week intervention trial. Methods: 143 overweight and obese non-smokers underwent a 12-week dietary intervention and a 38-week follow-up. Diet-induced changes in anthropometric measures, circulating biomarkers, and magnetic resonance (MR)-derived liver fat content and adipose tissue volumes were evaluated by mixed linear models stratifying by NAFLD at baseline. Results: The prevalence of NAFLD at baseline was 52%. Diet-induced weight loss after 12 (NAFLD: 4.8 ± 0.5%, No NAFLD: 5.1 ± 0.5%) and 50 weeks (NAFLD: 3.5 ± 0.7%, No NAFLD: 3.5 ± 0.9%) was similar in both groups, while the decrease in liver fat was significantly greater in the NAFLD group (week 12: 32.9 ± 9.5% vs. 6.3 ± 4.0%; week 50: 23.3 ± 4.4% vs. 5.0 ± 4.2%). Decreases in biomarkers of liver dysfunction (GGT, ALT, AST) and HOMA IR were also significantly greater in the NAFLD group. Other metabolic parameters showed no significant differences. Conclusion: Our data suggest that individuals with NAFLD show greater improvements of liver function and insulin sensitivity after moderate diet-induced weight loss than individuals without NAFLD.

Download Full-text

1029-P: Teneligliptin Significantly Reduces Liver Fat Content (LFC) and Delays Progression of NASH in Type 2 Diabetes Mellitus Patients

Diabetes ◽

10.2337/db19-1029-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1029-P

Author(s):

VISHAL KUMAR GUPTA

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content

Download Full-text

Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3050 ◽

2015 ◽

Vol 100 (2) ◽

pp. 607-616 ◽

Cited By ~ 26

Author(s):

Gemma Llauradó ◽

Ksenia Sevastianova ◽

Sanja Sädevirta ◽

Antti Hakkarainen ◽

Nina Lundbom ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Sensitivity ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Hepatic Insulin Sensitivity

Download Full-text

Abstract MP45: Liver Fat Content Does Not Account for the Strong Association of Fetuin-A with Diabetes Risk in Women: The Multi-Ethnic Study of Atherosclerosis

Circulation ◽

10.1161/circ.131.suppl_1.mp45 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Sarah A Aroner ◽

Kenneth J Mukamal ◽

David E St-Jules ◽

Matthew J Budoff ◽

Ronit Katz ◽

...

Keyword(s):

Strong Association ◽

Secretory Protein ◽

Fat Content ◽

Diabetes Risk ◽

Liver Fat ◽

Enzyme Linked Immunosorbent Assay ◽

Liver Fat Content ◽

Fetuin A ◽

Minimal Impact ◽

Ethnic Study

Introduction: Fetuin-A, a hepatic secretory protein, has been associated with risk of diabetes. However, liver fat content may be an important confounder or effect modifier not fully accounted for in previous studies. Further, it remains unclear whether associations differ between women and men. Aim: In an ethnically diverse cohort of women and men, we assessed the association of fetuin-A with risk of diabetes and investigated the role of liver fat in this association. Methods: We conducted a case-cohort study nested in the Multi-Ethnic Study of Atherosclerosis among 1,957 subcohort members and 455 cases (265 of whom belonged to the subcohort) with follow-up from 2000-2012. Fetuin-A was measured from baseline plasma samples by enzyme-linked immunosorbent assay, and liver fat was assessed via computed tomography. Associations were estimated using multivariable-adjusted Cox models, with weighting to account for the case-cohort design. Results: The association of fetuin-A with risk of diabetes differed between women and men (p-interaction = 0.001). Each standard deviation (SD) higher fetuin-A concentration (0.10 g/L) was associated with a hazard ratio (HR) of 1.51 (95% CI: 1.32-1.74, p <0.0001) among women and an HR of 1.12 (95% CI: 0.94-1.32, p = 0.20) among men. With additional adjustment for liver fat, associations were slightly attenuated in both women (HR per SD fetuin-A = 1.37, 95% CI: 1.19-1.59, p<0.0001) and men (HR = 1.06, 95% CI: 0.90-1.24, p = 0.40). Additional adjustment for other clinical variables had minimal impact on multivariable-adjusted estimates (Figure). Associations did not differ by degree of liver fat content (p-heterogeneity >0.25 for both women and men). Conclusions: Fetuin-A was associated with diabetes risk, particularly in women, even after adjustment for liver fat.

Download Full-text