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[(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.ORCID iD: 0000-0002-6060-6229
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2017 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 5, p. 1286-1292Article in journal (Refereed) Published
Abstract [en]

[(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.

Place, publisher, year, edition, pages
2017. Vol. 66, no 5, p. 1286-1292
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-316831DOI: 10.2337/db16-1449ISI: 000399799800022PubMedID: 28246291OAI: oai:DiVA.org:uu-316831DiVA, id: diva2:1079108
Funder
Swedish Society for Medical Research (SSMF), K2015-54X-12219-19-4 K2013-64X-08268-26-3 K2013-55X-15043 921-2014-7054Novo NordiskSwedish Child Diabetes Foundation
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2018-01-25Bibliographically approved
In thesis
1. Positron Emission Tomography and Magnetic Resonance Techniques in Diabetes
Open this publication in new window or tab >>Positron Emission Tomography and Magnetic Resonance Techniques in Diabetes
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In order to further advance the field of diabetes research there is a great need for establishing validated non-invasive quantitative techniques to study the pancreas and other tissues of importance for blood glucose regulation. The general aim of this thesis was to explore magnetic resonance techniques and positron emission tomography as such tools.

In paper I pancreatic perfusion under basal conditions and in response to glucose in nondiabetic and type 1 diabetic individuals was studied with [15O]H2O PET/CT. Individuals with type 1 diabetes were found to have reduced basal pancreatic perfusion and a severely impaired pancreatic and splanchnic perfusion response to intravenous glucose stimulation.

In paper II four groups of subjects at different stages of type 2 diabetes development and a control group of individuals without diabetes were examined with PET/CT and MRI. The [11C]5-HTP uptake in pancreas was hypothesized to correlate with remaining functional capacity of the β-cells. The progressive loss of β-cell function indicated by metabolic testing was not mirrored by a decrease in [11C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased β-cell function, indicating that β-cell dysfunction or dedifferentiation, and not necessarily endocrine cell loss, constitutes a major cause of β-cell failure in type 2 diabetes.

In paper III the feasibility of using ex-vivo MR spectroscopy for assessment of viability of human pancreas grafts prior to transplantation was studied. It was found that 31P-MRS may provide quantitative parameters for evaluating graft viability ex vivo, and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts.

In paper IV the Imiomics method for automatic image analysis was validated in whole-body [18F]-FDG PET/MR images in subjects with varying degree of insulin resistance. Imiomics was found to provide association screening and timesaving analysis of whole-body data and detected differences in glucose uptake and tissue composition between subjects on voxel-level. However, it did not show complete correlation with traditional volume of interest based tissue analysis in a small cohort.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 61
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1422
Keyword
Positron emission tomography, Magnetic resonance imaging, Magnetic resonance spectroscopy, Type 1 diabetes, Type 2 diabetes, PET/MR, Pancreas transplantation, Perfusion
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-340008 (URN)978-91-513-0223-2 (ISBN)
Public defence
2018-03-15, Rosénsalen, ingång 95/96, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2018-02-21 Created: 2018-01-25 Last updated: 2018-03-07

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Carlbom, LinaEspes, DanielLubberink, MarkMartinell, MatsJohansson, LarsAhlström, HåkanCarlsson, Per-OlaKorsgren, OlleEriksson, Olof

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Carlbom, LinaEspes, DanielLubberink, MarkMartinell, MatsJohansson, LarsAhlström, HåkanCarlsson, Per-OlaKorsgren, OlleEriksson, Olof
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RadiologyDepartment of Medical Cell BiologyFamily Medicine and Preventive MedicineTransplantation and regenerative medicineClinical ImmunologyDepartment of Medicinal Chemistry
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