高脂肪食下におけるGIPの膵β細胞保護効果の非侵襲的評価

京都大学新制・課程博士博士(医学)甲第24200号医博第4894号京都大学大学院医学研究科医学専攻(主査)教授 長船 健二, 教授 中本 裕士, 教授 江木 盛時学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Noninvasive quantitative evaluation of viable islet grafts using ¹¹¹In-exendin-4 SPECT/CT

Islet transplantation (IT) is an effective β-cell replacement therapy for patients with type 1 diabetes; however, the lack of methods to detect islet grafts and evaluate their β-cell mass (BCM) has limited the further optimization of IT protocols. Therefore, the development of noninvasive β-cell imaging is required. In this study, we investigated the utility of the ¹¹¹Indium-labeled exendin-4 probe {[Lys12(111In-BnDTPA-Ahx)] exendin-4} (¹¹¹In exendin-4) to evaluate islet graft BCM after intraportal IT. The probe was cultured with various numbers of isolated islets. Streptozotocin-induced diabetic mice were intraportally transplanted with 150 or 400 syngeneic islets. After a 6-week observation following IT, the ex-vivo liver graft uptake of ¹¹¹In-exendin-4 was compared with the liver insulin content. In addition, the in-vivo liver graft uptake of ¹¹¹In exendin-4 using SPECT/CT was compared with that of liver graft BCM measured by a histological method. As a result, probe accumulation was significantly correlated with islet numbers. The ex-vivo liver graft uptake in the 400-islet-transplanted group was significantly higher than that in the control and the 150-islet-transplanted groups, consistent with glycemic control and liver insulin content. In conclusion, in-vivo SPECT/CT displayed liver islet grafts, and uptakes were corroborated by histological liver BCM. ¹¹¹In-exendin-4 SPECT/CT can be used to visualize and evaluate liver islet grafts noninvasively after intraportal IT

Voxel‐based specific regional analysis system for Alzheimer’s disease utility as a screening tool for unrecognized cognitive dysfunction of elderly patients in diabetes outpatient clinics: Multicenter retrospective exploratory study

AIMS/INTRODUCTION: An efficient screening strategy for identification of cognitive dysfunction remains a clinical issue in the management of elderly adults with diabetes. A magnetic resonance imaging voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) has been developed as an automated brain morphometry system that includes the hippocampus. We carried out a multicenter retrospective study to evaluate the utility of VSRAD for screening cognitive dysfunction in diabetes outpatient clinics. MATERIALS AND METHODS: We enrolled patients with diabetes aged >65 years who underwent brain magnetic resonance imaging scans for the purpose of a medical checkup between November 2018 and May 2019. Patients who were already suspected or diagnosed with mild cognitive impairment and/or dementia as well as those with a history of cerebrovascular disease were excluded. RESULTS: A total of 67 patients were enrolled. Five patients were diagnosed with mild cognitive impairment or dementia (clinical cognitive dysfunction). Patients with clinical cognitive dysfunction showed a significantly higher z-score in VSRAD analysis (2.57 ± 0.47 vs 1.15 ± 0.55, P < 0.01). The sensitivities and specificities for diagnosis of clinical cognitive dysfunction were 80 and 48% for the Mini-Mental State Examination, 100 and 89% for the z-score, and 100 and 90% for the combination of the Mini-Mental State Examination score and z-score, respectively. CONCLUSIONS: VSRAD analysis can distinguish patients with clinical cognitive dysfunction in the elderly with diabetes, and also shows reasonable sensitivity and specificity compared with the Mini-Mental State Examination alone. Thus, VSRAD analysis can be useful for early identification of clinical cognitive dysfunction in the elderly with diabetes

Noninvasive evaluation of donor and native pancreases following simultaneous pancreas–kidney transplantation using positron emission tomography/computed tomography

ABSTRACT It is crucial to develop practical and noninvasive methods to assess the functional beta‐cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney–pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin‐based probe, [18F]FB(ePEG12)12‐exendin‐4. Following transplantation, PET imaging with [18F]FB(ePEG12)12‐exendin‐4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [18F]FB(ePEG12)12‐exendin‐4 whole‐body maximum intensity projection and axial PET images. At 1 and 2 h after [18F]FB(ePEG12)12‐exendin‐4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [18F]FB(ePEG12)12‐exendin‐4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta‐cell mass following simultaneous kidney–pancreas transplantation