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2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DiRECT open-label, cluster-randomised trial

Lookup NU author(s): Dr Ahmad Al-Mrabeh, Dr Kieren Hollingsworth, Professor James Shaw, Professor Roy Taylor

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

Summary Background: The pancreas is small and irregular in shape in type 2 diabetes (T2DM). If these abnormalities are caused by the disease state itself rather than being a predisposing factor, remission of T2DM should restore normal morphology. The objective of this study was to determine whether such changes occurred during two years of remission. Methods: intervention group participants in the Diabetes Remission Clinical Trial were divided into ‘Responders’ (HbA1c <6.5%; 48 mmol/mol and fasting blood glucose <7.0 mmol/l off all anti-diabetes medication; n=39) and non-responders (n=16) who remained diabetic. The main statistical analyses were carried out using ANOVA with correction for potential confounding. Novel magnetic resonance techniques were employed to quantify pancreas volume, the irregularity of the pancreas borders, and intra-pancreatic fat content. β-cell function and biomarkers of tissue growth were also measured. Data were compared with matched non-diabetic controls. Findings: At baseline, pancreas volume was 61.7(SD 16.0)cm3 in T2DM and 79.8 (14.3) cm3 in non-diabetic controls (p<0.0001). At 24 months, pancreas volume had increased by 9.4(95% CI: 6.1,12.8)cm3 in responders compared with 6.4(2.5,10.3) cm3 in non-responders (p=0.001) . The pancreas borders were more irregular in T2DM at baseline compared with non-diabetic controls (Fractal Dimension 1.138(0.027) vs 1.097(0.025), p<0.0001) and normalised by 24 months in responders only (1.099(0.028)). Intra-pancreatic fat declined by -1.02 (-1.51, -0.53)% in responders and -0.51(-1.19, 0.17)% in non-responders (p=0.23). Interpretation: These data demonstrate for the first time, to our knowledge, reversibility of the abnormal pancreas morphology of T2DM by weight loss-induced remission.


Publication metadata

Author(s): Al-Mrabeh A, Hollingsworth KG, Shaw JAM, McConnachie A, Sattar N, Lean MEJ, Taylor R

Publication type: Article

Publication status: Published

Journal: The Lancet Diabetes and Endocrinology

Year: 2020

Volume: 8

Issue: 12

Pages: 939-948

Print publication date: 01/12/2020

Online publication date: 05/10/2020

Acceptance date: 02/04/2018

Date deposited: 22/10/2020

ISSN (print): 2213-8587

ISSN (electronic): 2213-8595

Publisher: The Lancet Publishing Group

URL: https://doi.org/10.1016/S2213-8587(20)30303-X

DOI: 10.1016/S2213-8587(20)30303-X


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