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 ◽  
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.

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

2020 ◽  
Vol 52 (11) ◽  
pp. 809-814
Author(s):  
Sabrina Reif ◽  
Sarah Moschko ◽  
Christina Gar ◽  
Uta Ferrari ◽  
Nina Hesse ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Young Women ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Fetuin A ◽  
The Metabolic Syndrome ◽  
Independent Association

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.

scholarly journals Fetuin-A and Risk of Diabetes Independent of Liver Fat Content

2016 ◽  
Vol 185 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Sarah A. Aroner ◽  
Kenneth J. Mukamal ◽  
David E. St-Jules ◽  
Matthew J. Budoff ◽  
Ronit Katz ◽  
...  
Keyword(s):  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Fetuin A

scholarly journals Association of fetuin-A with incident type 2 diabetes: results from the MONICA/KORA Augsburg study and a systematic meta-analysis

2018 ◽  
Vol 178 (4) ◽  
pp. 389-398 ◽  
Author(s):  
Chaterina Sujana ◽  
Cornelia Huth ◽  
Astrid Zierer ◽  
Sophie Meesters ◽  
Julie Sudduth-Klinger ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Meta Analysis ◽  
Fat Content ◽  
Cox Proportional Hazards ◽  
Liver Fat ◽  
Subclinical Inflammation ◽  
Liver Fat Content ◽  
Fetuin A ◽  
Incident Type ◽  
Males And Females

Objective We investigated the association of circulating fetuin-A with incident T2D particularly examining potential sex differences. Additionally, we determined whether putative associations were independent of subclinical inflammation, adiponectin and liver fat content. Design Case-cohort study plus systematic meta-analysis. Methods We investigated the association between baseline fetuin-A levels and incident T2D in the MONICA/KORA Augsburg study using Cox proportional hazards analyses. Furthermore, we conducted a systematic review within PubMed and EMBASE and pooled association estimates of eligible studies with the MONICA/KORA Augsburg data using a DerSimonian-Laird random effects model. Results Within MONICA/KORA Augsburg, 930 participants developed incident T2D (median follow-up: 14 years). We observed a significant association between fetuin-A and T2D risk after multivariable adjustment including C-reactive protein and adiponectin. The strength of the association was similar in males and females (P value for sex interaction >0.55). Seven eligible published studies were identified in addition to the MONICA/KORA Augsburg study for the meta-analysis. The pooled hazard ratio (95% CI) for incident T2D per 1 standard deviation (s.d.) increment of fetuin-A was 1.24 (1.14–1.34) for the multivariable adjusted model. Our sex-stratified meta-analysis yielded relative risk estimates per 1 s.d. of 1.19 (1.04–1.38) in males and 1.29 (1.15–1.46) in females. Further individual adjustment for subclinical inflammation, adiponectin and liver fat content had almost no impact on the strength of the association. Conclusions Higher fetuin-A levels are associated with incident T2D in both males and females independently of subclinical inflammation, adiponectin and liver fat content.

Diabetes Remission Clinical Trial (DiRECT)—Plasma Liver Function Tests Reflect Change in Liver Fat Content in Early Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1834-P
Author(s):  
SVIATLANA V. ZHYZHNEUSKAYA ◽  
AHMAD AL-MRABEH ◽  
CARL PETERS ◽  
ALISON C. BARNES ◽  
KIEREN G. HOLLINGSWORTH ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Liver Function ◽  
Liver Function Tests ◽  
Fat Content ◽  
Diabetes Remission ◽  
Liver Fat ◽  
Early Type ◽  
Liver Fat Content

115-LB: Oral Insulin–Induced Reduction in Liver Fat Content in T2DM Patients with Nonalcoholic Steatohepatitis

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 115-LB
Author(s):  
MIRIAM KIDRON ◽  
SHARON PERLES ◽  
REEM KALOTI ◽  
RAMI GHANTOUS ◽  
SUHA F. SANDOUKA ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Fat Content ◽  
Liver Fat ◽  
Oral Insulin ◽  
Liver Fat Content

scholarly journals Liver fat content is independently associated with microalbuminuria in a normotensive, euglycaemic Chinese population: a community-based, cross-sectional study

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044237
Author(s):  
Xiaoming Li ◽  
Mingfeng Xia ◽  
Hui Ma ◽  
Yu Hu ◽  
Hongmei Yan ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Blood Glucose ◽  
Density Lipoprotein ◽  
Fat Content ◽  
Lipoprotein Cholesterol ◽  
Liver Fat ◽  
Community Based ◽  
Liver Fat Content ◽  
Cross Sectional ◽  
Multivariable Logistic Regression

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is associated with microalbuminuria (MA) in patients with diabetes/pre-diabetes. Whether this association is mediated by blood glucose and blood pressure (BP) remains unclear. This study investigated whether liver fat content (LFC) was associated with MA in a normotensive and non-diabetic population.DesignA cross-sectional substudy.SettingsLFC was determined from the hepatic/renal echogenicity ratio at ultrasound. MA was defined as an albumin-to-creatinine ratio (ACR) of 30–300 µg/mg (early- morning urine sample). Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate LFC as a predictor of MA.ParticipantsBetween May 2010 and June 2011, this cross-sectional, community-based study enrolled residents from Shanghai (China), aged ≥40 years and with normal glucose tolerance and BP.ResultsA total of 550 residents (median age, 57 years; 174 men) were enrolled and stratified according to LFC quartiles. ACR (p<0.001) and MA prevalence (p=0.012) increased across the LFC quartiles. Multivariable logistic regression showed that the OR for MA (per SD increase in LFC) was 1.840 (95% CI 1.173 to 2.887, p=0.008) after adjustment for potential confounders including age, gender, waist-hip ratio, blood urea nitrogen, systolic and diastolic BP, fasting blood glucose, postprandial glucose, low-density lipoprotein-cholesterol, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, estimated glomerular filtration rate and lipid-lowering drugs. The ROC analysis revealed that the optimal LFC cut-off value for predicting MA was 6.82%.ConclusionLFC is independently associated with MA in normotensive, euglycaemic middle-aged and elderly Chinese individuals. Screening for MA in people with NAFLD might facilitate early intervention to minimise kidney disease risk.

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

2006 ◽  
Vol 291 (2) ◽  
pp. E282-E290 ◽  
Author(s):  
Riikka Lautamäki ◽  
Ronald Borra ◽  
Patricia Iozzo ◽  
Markku Komu ◽  
Terho Lehtimäki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Liver Steatosis ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Artery Disease ◽  
Myocardial Insulin Resistance ◽  
High Liver

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

Choline requirement of the preruminant lamb during the first two or three weeks of life

1985 ◽  
Vol 36 (6) ◽  
pp. 829 ◽  
Author(s):  
SJ Al-Ali ◽  
NM Malouf ◽  
DM Walker
Keyword(s):  
Choline Chloride ◽  
Ammonia Excretion ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Butter Oil ◽  
Protein Energy ◽  
Gross Energy ◽  
Ad Libitum ◽  
Milk Replacers

Preruminant male crossbred lambs, aged 1-2 days at the start of the experiment, were bottle-fed on milk replacers containing casein as the sole source of protein for an experimental period of 15-21 days. Choline-deficient diets were used in experiment 1 to determine the effect on the performance of the lambs of thc dictary protein concentration (10, 15 and 25% protein energy), and in experiment 2 of different sources of fat (butter oil, maize oil or lard), unsupplemented, or with supplements of choline chloride or L-cystine. Supplements of choline chloride decreased liver fat content and decreased urinary creatine excretion, irrespective of dietary protein concentration or source of dietary fat. Ira general, urinary ammonia excretion increased as the sulfur amino acid content of the diets increased, but there were interactions with the source of fat, so that although sulfur intake remained constant ammonia excretion was higher with diets containing lard than with those containing maize oil or butter oil. The effect of the supplements of 1,-cystine on liver fat content and urinary creatine excretion was not significantly different from that of the unsupplemented choline-deficient diets. In experiments 3 and 4 a choline-deficient diet with 25% protein energy and butter oil as the source of fat was supplemented with graded amounts of choline chloride. Energy intake was ad libitum, or restricted to 80% of ad libitum. When the lambs were fed ad libitum there was a significant decrease in liver fat content even with the smallest supplement of choline chloride (c. 9 mg MJ-1 gross energy), but no significant effect when energy intake was restricted. Since liveweight gains and nitrogen balances were unaffected by the presence or absence of the choline supplements it was concluded that in milk replacers containing 25% protein energy from casein, with butter oil as the source of fat, supplementation with choline chloride to provide 9 mg MJ-1 gross energy (233 mg kg-1 dry matter) would be sufficient to prevent the increased deposition of fat in the liver during the 6rst three weeks of life.

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