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

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  • Additional Information
    • Source:
      Publisher: The Lancet, Diabetes & Endocrinology Country of Publication: England NLM ID: 101618821 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-8595 (Electronic) Linking ISSN: 22138587 NLM ISO Abbreviation: Lancet Diabetes Endocrinol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : The Lancet, Diabetes & Endocrinology, [2013]-
    • Subject Terms:
      Body Weight* ; Weight Loss*; Biomarkers/*analysis ; Diabetes Mellitus, Type 2/*drug therapy ; Hypoglycemic Agents/*therapeutic use ; Pancreas/*drug effects; Adult ; Aged ; Blood Glucose/analysis ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Female ; Follow-Up Studies ; Glycated Hemoglobin/analysis ; Humans ; Male ; Middle Aged ; Pancreas/physiopathology ; Prognosis ; Remission Induction ; Young Adult
    • Abstract:
      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.
      (Copyright © 2020 Elsevier Ltd. All rights reserved.)
    • Comments:
      Erratum in: Lancet Diabetes Endocrinol. 2020 Dec;8(12):e7. (PMID: 33217336)
    • Grant Information:
      G1100160 United Kingdom MRC_ Medical Research Council
    • Accession Number:
      0 (Biomarkers)
      0 (Blood Glucose)
      0 (Glycated Hemoglobin A)
      0 (Hypoglycemic Agents)
      0 (hemoglobin A1c protein, human)
    • Publication Date:
      Date Created: 20201008 Date Completed: 20201207 Latest Revision: 20221207
    • Publication Date:
      20240628
    • Accession Number:
      10.1016/S2213-8587(20)30303-X
    • Accession Number:
      33031736