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Randomized Controlled Trial
. 2015 May 7;10(5):e0126825.
doi: 10.1371/journal.pone.0126825. eCollection 2015.

Altered volume, morphology and composition of the pancreas in type 2 diabetes

Mavin Macauley  1 , Katie Percival  2 , Peter E Thelwall  1 , Kieren G Hollingsworth  1 , Roy Taylor  1
Affiliations
Randomized Controlled Trial

Altered volume, morphology and composition of the pancreas in type 2 diabetes

Mavin Macauley et al. PLoS One. .

Abstract

Objective: Although impairment in pancreatic insulin secretion is known to precede the clinical diagnosis of type 2 diabetes by up to a decade, fasting blood glucose concentration only rises abnormally once the impairment reaches a critical threshold. Despite its centrality to the pathogenesis of type 2 diabetes, the pancreas is the least studied organ due to its inaccessible anatomical position. Previous ultrasound and CT studies have suggested a possible decrease in pancreatic volume in type 2 diabetes. However, ultrasound techniques are relatively insensitive while CT uses ionizing radiation, making these modalities unsuitable for precise, longitudinal studies designed to explore the underlying mechanisms of type 2 diabetes. Hence there is a need to develop a non-invasive, safe and precise method to quantitate pancreas volume.

Methods: We developed and applied magnetic resonance imaging at 3.0T to obtain balanced turbo field echo (BTFE) structural images of the pancreas, together with 3-point Dixon images to quantify pancreatic triglyceride content. Pancreas volume, morphology and triglyceride content was quantified in a group of 41 subjects with well-controlled type 2 diabetes (HbA1c ≤ 7.6%) taking only metformin (duration of T2DM 5.7 ± 0.7 years), and a control group of 14 normal glucose tolerance subjects matched for age, weight and sex.

Results: The mean pancreatic volume was found to be 33% less in type 2 diabetes than in normal glucose tolerant subjects (55.5 ± 2.8 vs. 82.6 ± 4.8 cm3; p < 0.0001). Pancreas volume was positively correlated with HOMA-β in the type 2 diabetes subjects (r = 0.31; p = 0.03) and controls (r = 0.46; p = 0.05) considered separately; and in the whole population studied (r = 0.37; p = 0.003). In type 2 diabetes, the pancreas was typically involuted with a serrated border. Pancreatic triglyceride content was 23% greater (5.4 ± 0.3 vs. 4.4 ± 0.4%; p = 0.02) in the type 2 diabetes group.

Conclusion: This study describes for the first time gross abnormalities of the pancreas in early type 2 diabetes and quantifies the decrease in pancreas size, the irregular morphology and increase in fat content.

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Conflict of interest statement

Competing Interests: Novartis International AG (http://www.novartis.com/about-novartis/locations/basel-headquarters.shtml) funded the clinical trial CLAF237A2389 and the investigator led project 2419T on normal control subjects. There are no patents, products in development, nor marketed products relevant to this work. RT has provided consultancy input into a Novartis advisory board and has received lecture fees from Novartis. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Mean pancreas volume in the type 2 diabetes and control groups (error bars show standard error of the mean).
Pancreas volume was decreased by 33% (p<0.001 by Mann- Whitney U test).
Fig 2
Fig 2. Relationships between HOMA-β (%) and pancreas volume (cm3) in T2DM group (panel a), control group (panel b) and all subjects combined (panel c).
In each case there was a positive correlation between pancreas volume and insulin secretion (Spearman test).
Fig 3
Fig 3. Bland-Altman plots for intra-observer (panel a) and inter-observer (panel b) analysis of pancreas volume measurement (cm3).
The Bland Altman statistic confirmed lack of bias and defined 95% limits of agreeement.
Fig 4
Fig 4. Comparison of the morphology of the pancreata of T2DM subjects (left) and NGT subjects (right) demonstrating the more irregular anterior (uppermost) border of the pancreata.
In the upper panel anatomical landmarks around the pancreas have been labelledto allow interpretation of the comparative pancreas views below.
Fig 5
Fig 5. Semi-quantitive analysis of the irregularity of pancreas outline.
Red: type 2 diabetes individuals; Green: non-diabetic control individuals. Most irregular = 1 and least irregular = 5. It can be seen that most non-diabetic individual have a smooth pancreas outline whereas many people with type 2 diabetes have an irregular pancreas border. The distributions of scores are significantly different (p<0.002; Mann-Whitney U test).
Fig 6
Fig 6. Pancreas triglyceride content in the T2DM and control group.
The 23% higher triglyceride content in the T2DM group was significant (p = 0.02; Student’s t test).
See this image and copyright information in PMC

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