Plasma apolipoprotein C1 concentration is associated with plasma triglyceride concentration but not with visceral fat and liver fat content in people with type 1 diabetes

Abstract Intoduction Excess visceral and liver fat are known risk factors for cardiometabolic disorders. Metabolomics might allow for easier quantification of these ectopic fat depots, instead of using invasive and costly tools such as MRI or approximations such as waist circumference. Objective We explored the potential use of plasma metabolites as biomarkers of visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC). Methods We performed a cross-sectional analysis of a subset of the Netherlands Epidemiology of Obesity study. Plasma metabolite profiles were determined using the Biocrates AbsoluteIDQ p150 kit in 176 individuals with normal fasting plasma glucose. VAT was assessed with magnetic resonance imaging and HTGC with proton-MR spectroscopy. We used linear regression to investigate the associations of 190 metabolite variables with VAT and HTGC. Results After adjustment for age, sex, total body fat, currently used approximations of visceral and liver fat, and multiple testing, three metabolite ratios were associated with VAT. The strongest association was the lysophosphatidylcholines to total phosphatidylcholines (PCs) ratio [− 14.1 (95% CI − 21.7; − 6.6) cm2 VAT per SD of metabolite concentration]. Four individual metabolites were associated with HTGC, especially the diacyl PCs of which C32:1 was the strongest at a 1.31 (95% CI 1.14; 1.51) fold increased HTGC per SD of metabolite concentration. Conclusion Metabolomics may be a useful tool to identify biomarkers of visceral fat and liver fat content that have added diagnostic value over current approximations. Replication studies are required to validate the diagnostic value of these metabolites.

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Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study

Diabetes Care ◽

10.2337/dc21-1262 ◽

2021 ◽

Author(s):

Susan Martin ◽

Elena P. Sorokin ◽

E. Louise Thomas ◽

Naveed Sattar ◽

Madeleine Cule ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Mendelian Randomization ◽

Fat Content ◽

Liver Fat ◽

Liver And Pancreas ◽

Pancreas Volume

OBJECTIVE Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations. RESEARCH DESIGN AND METHODS We used genetic variants associated (P < 5 × 10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n = 32,859). We obtained summary-level data for risk of type 1 (9,358 cases) and type 2 (55,005 cases) diabetes from the largest available genome-wide association studies. We performed inverse–variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects. RESULTS Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27% increased risk and 0.76 [0.62, 0.94] or 24% decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes. CONCLUSIONS Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and 2 diabetes.

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1888-P: Impaired Insulin Clearance Relates to Increased Liver Fat Content in Recent-Onset Type 2 Diabetes and to Impaired Glucose Control in Recent-Onset Type 1 Diabetes

Diabetes ◽

10.2337/db19-1888-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1888-P

Author(s):

SOFIA ANTONIOU ◽

OANA P. ZAHARIA ◽

KLAUS STRASSBURGER ◽

YANISLAVA KARUSHEVA ◽

KALMAN BODIS ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Glucose Control ◽

Liver Fat ◽

Liver Fat Content ◽

Recent Onset ◽

Onset Type ◽

Impaired Insulin

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Elevated Circulating Glutamate Is Associated With Subclinical Atherosclerosis Independently of Established Risk Markers: A Cross-Sectional Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa898 ◽

2020 ◽

Author(s):

Angela Lehn-Stefan ◽

Andreas Peter ◽

Jürgen Machann ◽

Fritz Schick ◽

Elko Randrianarisoa ◽

...

Keyword(s):

Insulin Sensitivity ◽

Body Fat ◽

Fat Mass ◽

Visceral Fat ◽

Fat Content ◽

Liver Fat ◽

Body Fat Mass ◽

Elevated Plasma ◽

Liver Fat Content ◽

Increased Risk

Abstract Objective Elevated plasma glutamate levels are associated with an increased risk of cardiovascular disease (CVD). Because plasma glutamate levels are also strongly associated with visceral adiposity, nonalcoholic fatty liver disease, insulin resistance, and high circulating levels of branched-chain amino acids (BCAAs), it is unknown to what extent elevated circulating glutamate is an independent marker of an increased risk of atherosclerosis. Methods Plasma levels of glutamate and BCAAs were measured in 102 individuals who were precisely phenotyped for body fat mass and distribution (magnetic resonance [MR] tomography), liver fat content (1H-MR spectroscopy), insulin sensitivity (oral glucose tolerance test and hyperinsulinemic, euglycemic clamp [N = 57]), and carotid intima media thickness (cIMT). Results Plasma glutamate levels, adjusted for age, sex, body fat mass, and visceral fat mass, correlated positively with liver fat content and cIMT (all std β ≥ .22, all P ≤ .023) and negatively with insulin sensitivity (std β ≤ –.31, P ≤ .002). Glutamate levels also were associated with cIMT, independently of additional adjustment for liver fat content, insulin sensitivity and BCAAs levels (std β ≥ .24, P ≤ .02). Furthermore, an independent positive association of glutamate and interleukin-6 (IL-6) levels was observed (N = 50; std β = .39, P = .03). Although glutamate, adjusted for age, sex, body fat mass, and visceral fat mass, also correlated positively with cIMT in this subgroup (std β = .31, P = .02), after additional adjustment for the parameters liver fat content, insulin sensitivity, BCAAs, or IL-6 levels, adjustment for IL-6 most strongly attenuated this relationship (std β = .28, P = .05). Conclusions Elevated plasma glutamate levels are associated with increased cIMT, independently of established CVD risk factors, and this relationship may in part be explained by IL-6-associated subclinical inflammation.

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