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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
Open accessAbstract
Background The pancreas is small and irregular in shape in people with type 2 diabetes. If these abnormalities are caused by the disease state itself rather than being a predisposing factor, remission of type 2 diabetes should restore normal pancreas morphology. The objective of this study was to determine whether changes in pancreas volume and shape occurred during 2 years of remission.Methods For this post-hoc analysis, we included a subset of adult participants of the Diabetes Remission Clinical Trial (DiRECT), who had type 2 diabetes and were randomly assigned to a weight management intervention or routine diabetes management. Intervention group participants were categorised as responders (HbA 1c <6·5% [48 mmol/mol] and fasting blood glucose <7·0 mmol/L, off all anti-diabetes medication) and non-responders, who were classified as remaining diabetic. Data on pancreas volume and irregularity of pancreas border at baseline, 5 months, 12 months, and 24 months after intervention were compared between responders and non-responders; additional comparisons were made between control group participants with type 2 diabetes and a non-diabetic comparator (NDC) group, who were matched to the intervention group by age, sex, and post-weight-loss weight, to determine the extent of any normalisation. We used a mixed-effects regression model based on repeated measures ANOVA with correction for potential confounding. Magnetic resonance techniques were employed to quantify pancreas volume, the irregularity of the pancreas borders, and intrapancreatic fat content. β-cell function and biomarkers of tissue growth were also measured.Findings Between July 25, 2015, and Aug 5, 2016, 90 participants with type 2 diabetes in the DiRECT subset were randomly assigned to intervention (n=64) or control (n=26) and were assessed at baseline; a further 25 non-diabetic participants were enrolled into the NDC group. At baseline, mean pancreas volume was 61·7 cm 3 (SD 16·0) in all participants with type 2 diabetes and 79·8 cm 3 (14·3) in the NDC group (p<0·0001). At 24 months, pancreas volume had increased by 9·4 cm 3 (95% CI 6·1 to 12·8) in responders compared with 6·4 cm 3 (2·5 to 10·3) in non-responders (p=0·0008). Pancreas borders at baseline were more irregular in participants with type 2 diabetes than in the NDC group (fractal dimension 1·138 [SD 0·027] vs 1·097 [0·025]; p<0·0001) and had normalised by 24 months in responders only (1·099 [0·028]). Intrapancreatic fat declined by 1·02 percentage points (95% CI 0·53 to 1·51) in 32 responders and 0·51% (-0·17 to 1·19) in 13 non-responders (p=0·23).Interpretation These data show for the first time, to our knowledge, reversibility of the abnormal pancreas morphology of type 2 diabetes by weight loss-induced remission.Funding Diabetes UK.
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“A non-diabetic state can be restored for 2 years for 70–80% of people with type 2 diabetes by interventions that maintain over 10 kg weight loss (36/149, 24% of participants in the Diabetes Remission Clinical Trial [DiRECT]) [7], which sustains loss of ectopic fat, reversing the pathophysiology and normalising pancreas morphology [8].”
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Metadata
- Authors
- Al-Mrabeh, A., Hollingsworth, K. G., Shaw, J. A. M., McConnachie, A., Sattar, N., Lean, M. E. J., & Taylor, R.
- Affiliations
- Newcastle University (GB)
- University of Glasgow (GB)
- Corresponding author
- Al-Mrabeh, Ahmad
- ORCID
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 8
- Issue
- 12
- Pages
- 939-948
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W3090835260
- Cited by
- 122
- References
- 36
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 17 · 2023: 25 · 2022: 22 · 2021: 26 · 2020: 1
- FWCI
- 13.95
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-12-01)
- Open access
- green
- eprints.gla.ac.uk
- Licence
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
- Funders
- Diabetes UK
- Newcastle University
- University of Glasgow
- Newcastle upon Tyne Hospitals NHS Foundation Trust
- European Association for the Study of Diabetes
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes remission, pancreas volume, pancreas morphology, weight management interventions, bariatric surgery, beta-cell function, pancreatic regeneration, HbA1c, fasting blood glucose, DIRECT trial, insulin resistance
- MeSH terms
- Adult, Aged, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Middle Aged, Pancreas, Prognosis, Remission Induction, Biomarkers, Weight Loss, Young Adult
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