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

Published on Feb 4, 2020in Cell Metabolism22.415
· DOI :10.1016/j.cmet.2019.11.018
Ahmad Al-Mrabeh10
Estimated H-index: 10
(Newcastle University),
Sviatlana Zhyzhneuskaya5
Estimated H-index: 5
(Newcastle University)
+ 10 AuthorsRoy Taylor47
Estimated H-index: 47
(Newcastle University)
Abstract
Summary 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.
  • References (78)
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References78
Newest
#1Roy Taylor (Newcastle University)H-Index: 47
#2Ahmad Al-Mrabeh (Newcastle University)H-Index: 10
Last. Naveed Sattar (Glas.: University of Glasgow)H-Index: 119
view all 3 authors...
Summary Clinical and pathophysiological studies have shown type 2 diabetes to be a condition mainly caused by excess, yet reversible, fat accumulation in the liver and pancreas. Within the liver, excess fat worsens hepatic responsiveness to insulin, leading to increased glucose production. Within the pancreas, the β cell seems to enter a survival mode and fails to function because of the fat-induced metabolic stress. Removal of excess fat from these organs via substantial weight loss can normali...
3 CitationsSource
#1Michael E. J. Lean (Glas.: University of Glasgow)H-Index: 79
#2W. S. Leslie (Glas.: University of Glasgow)H-Index: 16
Last. Roy Taylor (Newcastle University)H-Index: 47
view all 24 authors...
Summary Background The DiRECT trial assessed remission of type 2 diabetes during a primary care-led weight-management programme. At 1 year, 68 (46%) of 149 intervention participants were in remission and 36 (24%) had achieved at least 15 kg weight loss. The aim of this 2-year analysis is to assess the durability of the intervention effect. Methods DiRECT is an open-label, cluster-randomised, controlled trial done at primary care practices in the UK. Practices were randomly assigned (1:1) via a c...
24 CitationsSource
#1Jeff Ji (McGill University)H-Index: 3
#2Maria Petropavlovskaia (McGill University)H-Index: 6
Last. Dusica Maysinger (McGill University)H-Index: 44
view all 7 authors...
5 CitationsSource
#1Melanie J. Davies (University of Leicester)H-Index: 82
#2David A. D'Alessio (Duke University)H-Index: 71
Last. John B. Buse (UNC: University of North Carolina at Chapel Hill)H-Index: 97
view all 10 authors...
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication ...
258 CitationsSource
#1Melanie J. Davies (University of Leicester)H-Index: 82
#2David A. D'Alessio (Duke University)H-Index: 71
Last. John B. Buse (UNC: University of North Carolina at Chapel Hill)H-Index: 97
view all 10 authors...
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication,...
299 CitationsSource
#1Roy Taylor (Newcastle University)H-Index: 47
#2Ahmad Al-Mrabeh (Newcastle University)H-Index: 10
Last. Michael E. J. Lean (Glas.: University of Glasgow)H-Index: 79
view all 10 authors...
Summary The Diabetes Remission Clinical Trial reported return and persistence of non-diabetic blood glucose control in 46% of people with type 2 diabetes of up to 6 years duration. Detailed metabolic studies were performed on a subgroup (intervention, n = 64; control, n = 26). In the intervention group, liver fat content decreased (16.0% ± 1.3% to 3.1% ± 0.5%, p 2 , p 2 , p = 0.0001). Responders were similar to non-responders at baseline but had shorter diabetes duration (2.7 ± 0.3 versus 3.8 ± ...
31 CitationsSource
#1Petr JežekH-Index: 25
#2Martin JabůrekH-Index: 15
Last. Lydie Plecitá-HlavatáH-Index: 14
view all 4 authors...
Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly in...
7 CitationsSource
#1N. H. Cho (International Diabetes Federation)H-Index: 40
#2Jonathan E. ShawH-Index: 96
Last. Belma Malanda (International Diabetes Federation)H-Index: 7
view all 7 authors...
Abstract Introduction Since the year 2000, IDF has been measuring the prevalence of diabetes nationally, regionally and globally. Aim To produce estimates of the global burden of diabetes and its impact for 2017 and projections for 2045. Methods A systematic literature review was conducted to identify published studies on the prevalence of diabetes, impaired glucose tolerance and hyperglycaemia in pregnancy in the period from 1990 to 2016. The highest quality studies on diabetes prevalence were ...
453 CitationsSource
#1Roy Taylor (Newcastle University)H-Index: 47
#2W. S. Leslie (Glas.: University of Glasgow)H-Index: 16
Last. Michael E. J. Lean (Glas.: University of Glasgow)H-Index: 79
view all 23 authors...
Aims/hypothesis Substantial weight loss in type 2 diabetes can achieve a return to non-diabetic biochemical status, without the need for medication. The Diabetes Remission Clinical Trial (DiRECT), a cluster-randomised controlled trial, is testing a structured intervention designed to achieve and sustain this over 2 years in a primary care setting to determine practicability for routine clinical practice. This paper reports the characteristics of the baseline cohort.
10 CitationsSource
#1Marc Diedisheim (Paris V: Paris Descartes University)H-Index: 2
#2Masaya Oshima (Paris V: Paris Descartes University)H-Index: 3
Last. Raphael Scharfmann (Paris V: Paris Descartes University)H-Index: 39
view all 15 authors...
Abstract Objective Dedifferentiation could explain reduced functional pancreatic β-cell mass in type 2 diabetes (T2D). Methods Here we model human β-cell dedifferentiation using growth factor stimulation in the human β-cell line, EndoC-βH1, and human pancreatic islets. Results Fibroblast growth factor 2 (FGF2) treatment reduced expression of β-cell markers, ( INS, MAFB, SLC2A2, SLC30A8 , and GCK ) and activated ectopic expression of MYC, HES1, SOX9 , and NEUROG3 . FGF2-induced dedifferentiation ...
7 CitationsSource
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