Altered Volume, Morphology and Composition of the Pancreas in Type 2 Diabetes

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 diabet...

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Published inPloS one Vol. 10; no. 5; p. e0126825
Main Authors Macauley, Mavin, Percival, Katie, Thelwall, Peter E., Hollingsworth, Kieren G., Taylor, Roy
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 07.05.2015
Public Library of Science (PLoS)
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Summary: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. 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. 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. 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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Conceived and designed the experiments: RT. Performed the experiments: MM KP PET KGH. Analyzed the data: MM KP PET KGH. Contributed reagents/materials/analysis tools: PET KGH. Wrote the paper: MM KP PET KGH RT.
Joint senior authors
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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0126825