Format

Send to

Choose Destination
Cell Metab. 2020 Feb 4;31(2):233-249.e4. doi: 10.1016/j.cmet.2019.11.018. Epub 2019 Dec 19.

Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss.

Author information

1
Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Electronic address: ahmad.al-mrabeh2@ncl.ac.uk.
2
Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
3
Human Nutrition Research Centre, Population and Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
4
School of Medical Education, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
5
Computer Science Department, Lagos State University, Lagos PMB 0001, Nigeria.
6
Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow G12 8TA, UK.
7
School of Medicine, Dentistry and Nursing, Glasgow University, Glasgow G31 2ER, UK.
8
Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Electronic address: roy.taylor@ncl.ac.uk.

Abstract

The role of hepatic lipoprotein metabolism in diet-induced remission of type 2 diabetes is currently unclear. Here, we determined the contributions of hepatic VLDL1-triglyceride production rate and VLDL1-palmitic acid content to changes in intra-pancreatic fat and return of first phase insulin response in a subgroup of the Diabetes Remission Clinical Trial. Liver fat, VLDL1-triglyceride production, and intra-pancreatic fat decreased after weight loss and remained normalized after 24 months of remission. First-phase insulin response remained increased only in those maintaining diabetes remission. Compared with those in remission at 24 months, individuals who relapsed after initial remission had a greater rise in the content of VLDL1-triglyceride and VLDL1-palmitic acid, re-accumulated intra-pancreatic fat, and lost first-phase response by 24 months. Thus, we observed temporal relationships between VLDL1-triglyceride production, hepatic palmitic acid flux, intra-pancreatic fat, and β-cell function. Weight-related disordered fat metabolism appears to drive development and reversal of type 2 diabetes.

KEYWORDS:

VLDL1-triglycerides; diabetes remission; human; intra-pancreatic fat; liver fat; palmitic acid; pathophysiology; twin cycle hypothesis; type 2 diabetes; β-cell function

PMID:
31866441
DOI:
10.1016/j.cmet.2019.11.018

Conflict of interest statement

Declaration of Interests R.T. reports grants from Diabetes UK, and lecture fees from Novartis, Lilly, and Jansen during the conduct of the study. A.A.-M. reports a grant from Diabetes UK to conduct the Re-TUNE study. N.S. reports grants and personal fees from Boehringer Ingelheim and personal fees from, Astrazenica, Eli Lilly, Sanofi, and NovoNordisk, and M.E.J.L. reports personal fees from Counterweight and Cambridge Weight Plan not related to the present work. All other authors declare no competing interests.

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center