scholarly journals Variants in Genes Controlling Oxidative Metabolism Contribute to Lower Hepatic ATP Independent of Liver Fat Content in Type 1 Diabetes

Diabetes ◽  
2016 ◽  
Vol 65 (7) ◽  
pp. 1849-1857 ◽  
Author(s):  
Sofiya Gancheva ◽  
Alessandra Bierwagen ◽  
Kirti Kaul ◽  
Christian Herder ◽  
Peter Nowotny ◽  
...  
2015 ◽  
Vol 100 (2) ◽  
pp. 607-616 ◽  
Author(s):  
Gemma Llauradó ◽  
Ksenia Sevastianova ◽  
Sanja Sädevirta ◽  
Antti Hakkarainen ◽  
Nina Lundbom ◽  
...  

Diabetes Care ◽  
2021 ◽  
Author(s):  
Susan Martin ◽  
Elena P. Sorokin ◽  
E. Louise Thomas ◽  
Naveed Sattar ◽  
Madeleine Cule ◽  
...  

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.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1888-P
Author(s):  
SOFIA ANTONIOU ◽  
OANA P. ZAHARIA ◽  
KLAUS STRASSBURGER ◽  
YANISLAVA KARUSHEVA ◽  
KALMAN BODIS ◽  
...  

2022 ◽  
Author(s):  
Susan Martin ◽  
Elena P Sorokin ◽  
E. Louise Thomas ◽  
Naveed Sattar ◽  
Madeleine Cule ◽  
...  

<b>Objective:</b> 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. <p> </p> <p><b>Research design and methods:</b> We used genetic variants associated (p < 5×10<sup>−8</sup>) 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. </p> <p> </p> <p><b>Results:</b> Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio (OR) per one standard deviation (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 on 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.</p> <p> </p> <p><b>Conclusions:</b> 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.</p> <p> </p>


2022 ◽  
Author(s):  
Susan Martin ◽  
Elena P Sorokin ◽  
E. Louise Thomas ◽  
Naveed Sattar ◽  
Madeleine Cule ◽  
...  

<b>Objective:</b> 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. <p> </p> <p><b>Research design and methods:</b> We used genetic variants associated (p < 5×10<sup>−8</sup>) 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. </p> <p> </p> <p><b>Results:</b> Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio (OR) per one standard deviation (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 on 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.</p> <p> </p> <p><b>Conclusions:</b> 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.</p> <p> </p>


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