Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 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

Ahmad Al-Mrabeh  1 , Sviatlana V Zhyzhneuskaya  2 , Carl Peters  2 , Alison C Barnes  3 , Shaden Melhem  2 , Aaron Jesuthasan  4 , Benjamin Aribisala  5 , Kieren G Hollingsworth  2 , Georg Lietz  3 , John C Mathers  3 , Naveed Sattar  6 , Michael E J Lean  7 , Roy Taylor  8
Affiliations
Free article
Randomized Controlled Trial

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

Ahmad Al-Mrabeh et al. Cell Metab. .
Free article

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.

PubMed Disclaimer

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.

Publication types