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Parlar MA, Mutlu H, Doğantekin B, Musaoğlu İS, Albayrakoğlu ND, Yavuz ML, Özbolat ZB, Kaplan M. The Association of Statin Therapy with Liver and Pancreatic Fat Fraction in Type 2 Diabetes Mellitus. Diagnostics (Basel) 2025; 15:426. [PMID: 40002577 PMCID: PMC11854770 DOI: 10.3390/diagnostics15040426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 02/02/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: It has been shown that the use of statins in patients with type 2 diabetes mellitus (T2DM) worsens hyperglycemia and hemoglobin A1c levels but may help in the preservation of pancreatic β-cell function. The potential role of a high pancreatic fat fraction (PFF) in this process has not yet been clarified. This study aimed to investigate whether the liver fat fraction (LFF) and PFF in T2DM patients is affected by statin therapy. Methods: This cross-sectional study involved a total of 140 T2DM patients, including both those who were receiving (n = 70) and those who were not receiving (n = 70) statin therapy. The mapping of the LFF and PFF utilizing the IDEAL-IQ sequence was conducted in magnetic resonance imaging. Results: In T2DM patients who used statins, the median PFF was higher compared to those who did not use statins (8.4 vs. 6.2%, p = 0.021), while the median LFF was found to be similar (8.4 vs. 8.9, p = 0.572). Variations in PFF were associated with the use of various statins (non-statin group: 6.2 vs. atovastatin: 8.7 vs. rosuvastatin: 3.2 vs. pitavastatin: 9.2, p = 0.004). The multivariable regression analysis indicated that insulin usage decreased log(LFF) by a factor of 0.16-fold (ꞵ ± SE = -0.16 ± 0.05, p = 0.010), and rosuvastatin usage reduced log(PFF) by 0.16-fold (ꞵ ± SE = -0.16 ± 0.07, p = 0.025), irrespective of other risk factors. Furthermore, the use of atorvastatin (ꞵ ± SE = 0.17 ± 0.06, p = 0.011) and pitavastatin (ꞵ ± SE = 0.19 ± 0.07, p = 0.008) were independently associated with an increase in log(PFF). Conclusions: In patients with T2DM, statin use did not show a significant effect on the liver fat fraction, but it caused differences in the pancreatic fat fraction. The observation of a lower pancreatic fat fraction in patients taking a rosuvastatin and atorvastatin dose of 40 mg/day suggests that different types and doses of statins may have varying effects on pancreatic fat accumulation.
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Affiliation(s)
- Mehmet Akif Parlar
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Hakan Mutlu
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Betül Doğantekin
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - İsmail Serhat Musaoğlu
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Nisa Demirboşnak Albayrakoğlu
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
| | - Mustafa Lütfi Yavuz
- Department of Cardiology, Istanbul University Faculty of Medicine, 34093 Istanbul, Turkey;
| | - Zehra Buşra Özbolat
- Deparment of Chest Diseases, Çerkezköy State Hospital, Tekirdağ Provincial Health Directorate, 59100 Tekirdağ, Turkey;
| | - Mustafa Kaplan
- Department of Internal Medicine, Sultan 2. Abdülhamid Han Training and Research Hospital, University of Health Sciences, Selimiye Neighborhood, Tıbbiye Street, 34668 Istanbul, Turkey; (H.M.); (B.D.); (İ.S.M.); (N.D.A.); (M.K.)
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Souza M, Silva GP, Junior CRO, Amaral MJM, Lima LCV, Charatcharoenwitthaya P. Prevalence, clinical characteristics, and outcomes of fatty pancreas disease: an updated systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2025; 37:137-146. [PMID: 39589806 DOI: 10.1097/meg.0000000000002893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2024]
Abstract
Fatty pancreas disease (FPD) is a condition characterized by diffuse excessive intrapancreatic fat deposition with relevant metabolic implications but often overlooked by healthcare professionals. Our study aims to provide a comprehensive overview of the prevalence, clinical characteristics, and outcomes of FPD. PubMed and Embase databases were searched from inception to 10 April 2024. Pairwise meta-analysis was performed using the DerSimonian-Laird method. Meta-analysis of proportions was conducted using the inverse-variance method with logit transformation. Between-study heterogeneity was examined, with subsequent subgroup and meta-regression analyses, and publication bias was assessed. Eighteen studies with 111 682 individuals were included in this meta-analysis. The overall prevalence of FPD was 21.11% [95% confidence interval (CI): 11.04-36.58]. Diagnostic method influenced FPD prevalence ( P < 0.01), with pooled prevalences of 17.53% (95% CI: 16.20-18.95), 30.05% (95% CI: 24.14-36.70), and 21.23% (95% CI: 8.52-43.88) for MRI, computed tomography, and transabdominal ultrasound, respectively. Patients with FPD were more likely to be older, have higher BMI, male, and have metabolic dysfunction. They also had an increased risk of metabolic syndrome, endocrine-related outcomes (i.e. diabetes and glycemic progression), and exocrine-related outcomes (i.e. acute pancreatitis and pancreatic cancer) compared with those without FPD. This study summarizes the epidemiology of FPD and highlights its clinical and prognostic significance. Increased multidisciplinary collaboration is needed to improve understanding of the disease and raise awareness among healthcare professionals. This study was a priori registered in International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024514116).
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Affiliation(s)
- Matheus Souza
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gabriel P Silva
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos R O Junior
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcio J M Amaral
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luan C V Lima
- Department of Internal Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Pan Z, Chen Q, Lin H, Huang W, Li J, Meng F, Zhong Z, Liu W, Li Z, Qin H, Huang B, Chen Y. Enhanced accuracy and stability in automated intra-pancreatic fat deposition monitoring of type 2 diabetes mellitus using Dixon MRI and deep learning. Abdom Radiol (NY) 2025:10.1007/s00261-025-04804-3. [PMID: 39841227 DOI: 10.1007/s00261-025-04804-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 01/08/2025] [Accepted: 01/08/2025] [Indexed: 01/23/2025]
Abstract
PURPOSE Intra-pancreatic fat deposition (IPFD) is closely associated with the onset and progression of type 2 diabetes mellitus (T2DM). We aimed to develop an accurate and automated method for assessing IPFD on multi-echo Dixon MRI. MATERIALS AND METHODS In this retrospective study, 534 patients from two centers who underwent upper abdomen MRI and completed multi-echo and double-echo Dixon MRI were included. A pancreatic segmentation model was trained on double-echo Dixon water images using nnU-Net. Predicted masks were registered to the proton density fat fraction (PDFF) maps of the multi-echo Dixon sequence. Deep semantic segmentation feature-based radiomics (DSFR) and radiomics features were separately extracted on the PDFF maps and modeled using the support vector machine method with 5-fold cross-validation. The first deep learning radiomics (DLR) model was constructed to distinguish T2DM from non-diabetes and pre-diabetes by averaging the output scores of the DSFR and radiomics models. The second DLR model was then developed to distinguish pre-diabetes from non-diabetes. Two radiologist models were constructed based on the mean PDFF of three pancreatic regions of interest. RESULTS The mean Dice similarity coefficient for pancreas segmentation was 0.958 in the total test cohort. The AUCs of the DLR and two radiologist models in distinguishing T2DM from non-diabetes and pre-diabetes were 0.868, 0.760, and 0.782 in the training cohort, and 0.741, 0.724, and 0.653 in the external test cohort, respectively. For distinguishing pre-diabetes from non-diabetes, the AUCs were 0.881, 0.688, and 0.688 in the training cohort, which included data combined from both centers. Testing was not conducted due to limited pre-diabetic patients. Intraclass correlation coefficients between radiologists' pancreatic PDFF measurements were 0.800 and 0.699 at two centers, suggesting good and moderate reproducibility, respectively. CONCLUSION The DLR model demonstrated superior performance over radiologists, providing a more efficient, accurate and stable method for monitoring IPFD and predicting the risk of T2DM and pre-diabetes. This enables IPFD assessment to potentially serve as an early biomarker for T2DM, providing richer clinical information for disease progression and management.
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Affiliation(s)
- Zhongxian Pan
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Qiuyi Chen
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Haiwei Lin
- Medical AI Lab, School of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, China
| | - Wensheng Huang
- Department of Radiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Junfeng Li
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Fanqi Meng
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Zhangnan Zhong
- Medical AI Lab, School of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, China
| | - Wenxi Liu
- Medical AI Lab, School of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, China
| | - Zhujing Li
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Haodong Qin
- MR Research Collaboration, Siemens Healthineers, Shanghai, China
| | - Bingsheng Huang
- Medical AI Lab, School of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, China.
| | - Yueyao Chen
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China.
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Ye J, Wang JG, Liu RQ, Shi Q, Wang WX. Association between intra-pancreatic fat deposition and diseases of the exocrine pancreas: A narrative review. World J Gastroenterol 2025; 31:101180. [PMID: 39811515 PMCID: PMC11684206 DOI: 10.3748/wjg.v31.i2.101180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/26/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
Intrapancreatic fat deposition (IPFD) has garnered increasing attention in recent years. The prevalence of IPFD is relatively high and associated with factors such as obesity, age, and sex. However, the pathophysiological mechanisms underlying IPFD remain unclear, with several potential contributing factors, including oxidative stress, alterations in the gut microbiota, and hormonal imbalances. IPFD was found to be highly correlated with the occurrence and prognosis of exocrine pancreatic diseases. Although imaging techniques remain the primary diagnostic approach for IPFD, an expanding array of biomarkers and clinical scoring systems have been identified for screening purposes. Currently, effective treatments for IPFD are not available; however, existing medications, such as glucagon-like peptide-1 receptor agonists, and new therapeutic approaches explored in animal models have shown considerable potential for managing this disease. This paper reviews the pathogenesis of IPFD, its association with exocrine pancreatic diseases, and recent advancements in its diagnosis and treatment, emphasizing the significant clinical relevance of IPFD.
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Affiliation(s)
- Jing Ye
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Jian-Guo Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Rong-Qiang Liu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Qiao Shi
- Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Wei-Xing Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
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Della Pepa G, Salamone D, Testa R, Bozzetto L, Costabile G. Intrapancreatic fat deposition and nutritional treatment: the role of various dietary approaches. Nutr Rev 2024; 82:1820-1834. [PMID: 38153345 DOI: 10.1093/nutrit/nuad159] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2023] Open
Abstract
Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD.
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Affiliation(s)
- Giuseppe Della Pepa
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, National Research Council-CNR, Pisa, Italy
| | - Dominic Salamone
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Roberta Testa
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Lutgarda Bozzetto
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Giuseppina Costabile
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
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Bergman BC, Zemski Berry K, Garfield A, Keller A, Zarini S, Bowen S, McKenna C, Kahn D, Pavelka J, Macias E, Uhlson C, Johnson C, Russ HA, Viesi CH, Seldin M, Liu C, Doliba N, Schoen J, Rothchild K, Hazel K, Naji A. Human peripancreatic adipose tissue paracrine signaling impacts insulin secretion, blood flow, and gene transcription. J Clin Endocrinol Metab 2024:dgae767. [PMID: 39484843 DOI: 10.1210/clinem/dgae767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/14/2024] [Accepted: 10/29/2024] [Indexed: 11/03/2024]
Abstract
CONTEXT Adipose tissue accumulation around non-adipose tissues is associated with obesity and metabolic disease. One relatively unstudied depot is peripancreatic adipose tissue (PAT) that accumulates in obesity and insulin resistance and may impact beta cell function. Pancreatic lipid accumulation and PAT content are negatively related to metabolic outcomes in humans, but these studies are limited by the inability to pursue mechanisms. OBJECTIVE We obtained PAT from human donors through the Human Pancreas Analysis Program to evaluate differences in paracrine signaling compared to subcutaneous adipose tissue (SAT), as well as effects of the PAT secretome on aortic vasodilation, human islet insulin secretion, and gene transcription using RNAseq. RESULTS PAT had greater secretion of IFN-γ and most inflammatory eicosanoids compared to SAT. Secretion of adipokines negatively related to metabolic health were also increased in PAT compared to SAT. We found no overall effects of PAT compared to SAT on human islet insulin secretion, however, insulin secretion was suppressed after PAT exposure from men compared to women. Vasodilation was significantly dampened by PAT conditioned media, an effect explained almost completely by PAT from men and not women. Islets treated with PAT showed selective changes in lipid metabolism pathways while SAT altered cellular signaling and growth. RNAseq analysis showed changes in islet gene transcription impacted by PAT compared to SAT, with the biggest changes found between PAT based on sex. CONCLUSION The PAT secretome is metabolically negative compared to SAT, and impacts islet insulin secretion, blood flow, and gene transcription in a sex dependent manner.
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Affiliation(s)
- Bryan C Bergman
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Karin Zemski Berry
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Amanda Garfield
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Amy Keller
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
| | - Simona Zarini
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Sophia Bowen
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Colleen McKenna
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Darcy Kahn
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jay Pavelka
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Emily Macias
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Charis Uhlson
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Chris Johnson
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Holger A Russ
- College of Medicine, Department of Pharmacology and Therapeutics, University of Florida USA
- Diabetes Institute, University of Florida USA
| | - Carlos H Viesi
- Department of Biological Chemistry and the Center for Epigenetics and Metabolism, University of California, Irvine, CA, USA
| | - Marcus Seldin
- Department of Biological Chemistry and the Center for Epigenetics and Metabolism, University of California, Irvine, CA, USA
| | - Chengyang Liu
- University of Pennsylvania Medical Center, Philadelphia, PA, USA
| | - Nicolai Doliba
- University of Pennsylvania Medical Center, Philadelphia, PA, USA
| | - Jonathan Schoen
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kevin Rothchild
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kweku Hazel
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Ali Naji
- University of Pennsylvania Medical Center, Philadelphia, PA, USA
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Habas E, Farfar K, Habas E, Rayani A, Elzouki AN. Extended Review and Updates of Nonalcoholic Fatty Pancreas Disease. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2024; 12:284-291. [PMID: 39539795 PMCID: PMC11556510 DOI: 10.4103/sjmms.sjmms_526_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 11/16/2024]
Abstract
Non-alcoholic fatty pancreatic disease (NAFPD), also known as pancreatic steatosis, is a benign condition characterized by deposition of lipids in the pancreas and is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, aging, and absence of heavy alcohol intake or infection. Similar to nonalcoholic fatty liver disease, NAFPD is a phenotypic entity that includes fat buildup in the pancreas, pancreatic inflammation, and subsequent fibrosis. The extent to which pancreatic fat infiltration is clinically important remains unclear. Despite these clinical associations, most of the clinical effects of NAFPD are not known. NAFPD may be identified by transabdominal and elastography ultrasound, computed tomography scan, or magnetic resonance imaging modalities, but a confirmatory diagnosis can only be made through tissue histology. In addition to complications such as acute and chronic pancreatitis, NAFPD may progress to pancreatic ductal adenocarcinoma. However, further research is required to fully understand the associations, pathophysiology, and effects of NAFPD. This review provides a narrative synthesis of the current literature on the epidemiology, pathophysiology, complications, diagnostic and imaging tools, and management of NAFPD.
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Affiliation(s)
- Elmukhtar Habas
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
| | - Kalifa Farfar
- Department of Medicine, Alwakra General Hospital, Alwakra, Qatar
| | - Eshrak Habas
- Department of Medicine, Tripoli Central Hospital, Tripoli, Libya
| | - Amnna Rayani
- Tripoli Children Hospital, Medical College, Tripoli University, Tripoli, Libya
| | - Abdul-Naser Elzouki
- Department of Medicine, Hamad Medical Corporation, Doha, Qatar
- Department of Medicine, College of Medicine, Qatar University, Doha, Qatar
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Pang C, Dong P, Yang J, Fan Z, Cheng Z, Zhan H. Non-alcoholic fatty pancreas disease: an updated review. JOURNAL OF PANCREATOLOGY 2024; 7:212-221. [DOI: 10.1097/jp9.0000000000000157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Ectopic accumulation of fat can cause a variety of metabolic diseases, and the emerging non-alcoholic fatty pancreas disease (NAFPD) is increasingly being recognized by clinicians as a cause for concern. NAFPD is a disease caused by abnormal accumulation of adipose tissue in the pancreas, which is related to obesity. The main feature of NAFPD is death of acinar cells, which are then replaced by adipose cells. However, the underlying molecular mechanisms have not been fully explored. Obesity, aging, and metabolic syndrome are independent risk factors for the occurrence and development of NAFPD. Studies have shown that NAFPD leads to insulin resistance and pancreatic dysfunction, increases the risk of diabetes mellitus, worsens the severity of pancreatitis, and is significantly correlated with pancreatic cancer and postoperative pancreatic fistula. There is no standard treatment for NAFPD; exercise, a balanced diet, and lifestyle can help reduce pancreatic fat; however, other treatment modalities such as drugs and bariatric surgery are still being explored. The specific pathological mechanism of NAFPD remains unclear, and its potential association with various clinical diseases requires further study. This review summarizes the etiology, diagnosis, clinical consequences, and potential therapeutic strategies of NAFPD.
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Affiliation(s)
- Chaoyu Pang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Peng Dong
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Jian Yang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Zhiqiang Cheng
- Division of Colorectal Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
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Wu WJ. Diabetes remission and nonalcoholic fatty pancreas disease. World J Diabetes 2024; 15:1390-1393. [PMID: 39099818 PMCID: PMC11292330 DOI: 10.4239/wjd.v15.i7.1390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 03/13/2024] [Accepted: 04/09/2024] [Indexed: 07/08/2024] Open
Abstract
This editorial focuses on the relationship between nonalcoholic fatty pancreas disease (NAFPD) and the development and remission of type 2 diabetes (T2D). NAFPD is characterized by intrapancreatic fatty deposition associated with obesity and not associated with alcohol abuse, viral infections, and other factors. Ectopic fat deposition in the pancreas is associated with the development of T2D, and the underlying mechanism is lipotoxic β-cell dysfunction. However, the results on the relationship between intrapancreatic fat deposition (IPFD) and β-cell function are conflicting. Regardless of the therapeutic approach, weight loss improves IPFD, glycemia, and β-cell function. Pancreatic imaging is valuable for clinically monitoring and evaluating the management of T2D.
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Affiliation(s)
- Wen-Jun Wu
- Department of Endocrinology, Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai 201500, China
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Li C, Chen X, Zhu X, Cao M, Tang Q, Wu W. MRI-Measured Pancreatic Fat Correlates with Increased Arterial Stiffness in Patients Who are Overweight and Obese. Diabetes Metab Syndr Obes 2024; 17:2283-2291. [PMID: 38859996 PMCID: PMC11164197 DOI: 10.2147/dmso.s456172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 05/23/2024] [Indexed: 06/12/2024] Open
Abstract
Purpose Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT. Patients and methods We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF<10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases. Results Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index. Conclusion NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.
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Affiliation(s)
- Chenxi Li
- Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China
| | - Xiaolei Chen
- Department of Neurology, Jiangnan University Medical Center, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of China
| | - Xiaowen Zhu
- Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China
| | - Mengjiao Cao
- Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China
| | - Qunfeng Tang
- Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China
| | - Wenjun Wu
- Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China
- Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China
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11
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Thomas P, Gallagher MT, Da Silva Xavier G. Beta cell lipotoxicity in the development of type 2 diabetes: the need for species-specific understanding. Front Endocrinol (Lausanne) 2023; 14:1275835. [PMID: 38144558 PMCID: PMC10739424 DOI: 10.3389/fendo.2023.1275835] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 11/13/2023] [Indexed: 12/26/2023] Open
Abstract
The propensity to develop type 2 diabetes (T2D) is known to have both environmental and hereditary components. In those with a genetic predisposition to T2D, it is widely believed that elevated concentrations of circulatory long-chain fatty acids (LC-FFA) significantly contribute towards the demise of insulin-producing pancreatic β-cells - the fundamental feature of the development of T2D. Over 25 years of research support that LC-FFA are deleterious to β-cells, through a process termed lipotoxicity. However, the work underpinning the theory of β-cell lipotoxicity is mostly based on rodent studies. Doubts have been raised as to whether lipotoxicity also occurs in humans. In this review, we examine the evidence, both in vivo and in vitro, for the pathogenic effects of LC-FFA on β-cell viability and function in humans, highlighting key species differences. In this way, we aim to uncover the role of lipotoxicity in the human pathogenesis of T2D and motivate the need for species-specific understanding.
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Affiliation(s)
- Patricia Thomas
- Centre for Systems Modelling and Quantitative Biomedicine, University of Birmingham, Birmingham, United Kingdom
- Institute for Metabolism and Systems Research, Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
| | - Meurig T. Gallagher
- Centre for Systems Modelling and Quantitative Biomedicine, University of Birmingham, Birmingham, United Kingdom
- Institute for Metabolism and Systems Research, Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
| | - Gabriela Da Silva Xavier
- Institute for Metabolism and Systems Research, Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
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12
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Couch CA, Fowler LA, Goss AM, Gower BA. Associations of renal sinus fat with blood pressure and ectopic fat in a diverse cohort of adults. INTERNATIONAL JOURNAL OF CARDIOLOGY. CARDIOVASCULAR RISK AND PREVENTION 2023; 16:200165. [PMID: 36874041 PMCID: PMC9975207 DOI: 10.1016/j.ijcrp.2022.200165] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 12/04/2022] [Accepted: 12/10/2022] [Indexed: 12/23/2022]
Abstract
Background Renal sinus fat (RSF) is an ectopic fat depot shown to be associated with visceral adiposity and hypertension in predominantly white populations. The purpose of this analysis is to investigate RSF and associations between RSF and blood pressure in a cohort of African American (AA) and European American (EA) adults. A secondary purpose was to explore risk factors associated with RSF. Methods Participants were 116 A A and EA adult men and women. Ectopic fat depots were assessed with MRI: RSF, intraabdominal adipose tissue (IAAT), intermuscular adipose tissue (IMAT), perimuscular adipose tissue (PMAT), and liver fat. Cardiovascular measures included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure, mean arterial pressure, and flow mediated dilation. Matsuda index was calculated for insulin sensitivity. Pearson correlations were used to investigate associations of RSF with cardiovascular measures. Multiple linear regression was used to evaluate contributions of RSF on SBP and DBP and to explore factors associated with RSF. Results No difference was observed in RSF between AA and EA participants. RSF was positively associated with DBP in AA participants, but this was not independent of age and sex. Age, male sex, and total body fat were positively associated with RSF in AA participants. Insulin sensitivity was inversely and IAAT and PMAT were positively associated with RSF in EA participants. Conclusions Differential associations of RSF with age, insulin sensitivity, and adipose depots among AA and EA adults suggest unique pathophysiological mechanisms influence RSF deposition, which may contribute to chronic disease etiology and progression.
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Affiliation(s)
- Catharine A. Couch
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Lauren A. Fowler
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Amy M. Goss
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Barbara A. Gower
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
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13
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Sevim BC, Chela H, Ertugrul H, Malik LS, Malik S, Basar O, Daglilar E, Samiullah S, Gaballah AH, Tahan V. Non-Alcoholic Fatty Pancreas Disease: The Unsung Disease. Endocr Metab Immune Disord Drug Targets 2023; 23:485-493. [PMID: 36177623 DOI: 10.2174/1871530322666220929142905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/04/2022] [Accepted: 08/01/2022] [Indexed: 01/10/2023]
Abstract
Non-alcoholic fatty pancreas disease (NAFPD) is a relatively new and emerging disease that is increasingly diagnosed yearly, like non-alcoholic fatty liver disease (NAFLD). It is associated especially with metabolic syndrome and obesity. As awareness of pancreatic steatosis and its clinical implications increase, it is diagnosed more frequently. The researchers have explained the clinical importance of NAFPD and the diseases it causes, such as pancreatitis, pancreatic insufficiency, and pancreatic cancer. Although the definitive treatment is not yet established, the primary treatment approach is weight loss since NAFPD is associated with metabolic syndrome as well as obesity. Although pharmacological agents, such as oral hypoglycemic agents, have been investigated in animal experiments, studies on humans have not been conducted. Since the research on NAFPD is still insufficient, it is a subject that needs to be investigated, and further studies are needed to explore its pathophysiology, clinical impact, and its management.
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Affiliation(s)
- Burak C Sevim
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
| | - Harleen Chela
- Department of Internal Medicine, Division of Gastroenterology, West Virginia University- Charleston Campus, Charleston, West Virginia, USA
| | - Hamza Ertugrul
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
| | - Lyiba S Malik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
- Milwaukee College of Letters & Science, Milwaukee, University of Wisconsin, Wisconsin, USA
| | - Suha Malik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
- Milwaukee College of Letters & Science, Milwaukee, University of Wisconsin, Wisconsin, USA
| | - Omer Basar
- Department of Internal Medicine, Division of Gastroenterology, Summa Health System and Northeast Ohio Medical University, Akron, Ohio, USA
| | - Ebubekir Daglilar
- Department of Internal Medicine, Division of Gastroenterology, West Virginia University- Charleston Campus, Charleston, West Virginia, USA
| | - Sami Samiullah
- Department of Internal Medicine, Division of Gastroenterology, Summa Health System and Northeast Ohio Medical University, Akron, Ohio, USA
| | - Ayman H Gaballah
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
| | - Veysel Tahan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
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14
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Sequeira IR, Yip W, Lu LW, Jiang Y, Murphy R, Plank LD, Cooper GJS, Peters CN, Aribsala BS, Hollingsworth KG, Poppitt SD. Exploring the relationship between pancreatic fat and insulin secretion in overweight or obese women without type 2 diabetes mellitus: A preliminary investigation of the TOFI_Asia cohort. PLoS One 2022; 17:e0279085. [PMID: 36584200 PMCID: PMC9803309 DOI: 10.1371/journal.pone.0279085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 10/02/2022] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE While there is an emerging role of pancreatic fat in the aetiology of type 2 diabetes mellitus (T2DM), its impact on the associated decrease in insulin secretion remains controversial. We aimed to determine whether pancreatic fat negatively affects β-cell function and insulin secretion in women with overweight or obesity but without T2DM. METHODS 20 women, with normo- or dysglycaemia based on fasting plasma glucose levels, and low (< 4.5%) vs high (≥ 4.5%) magnetic resonance (MR) quantified pancreatic fat, completed a 1-hr intravenous glucose tolerance test (ivGTT) which included two consecutive 30-min square-wave steps of hyperglycaemia generated by using 25% dextrose. Plasma glucose, insulin and C-peptide were measured, and insulin secretion rate (ISR) calculated using regularisation deconvolution method from C-peptide kinetics. Repeated measures linear mixed models, adjusted for ethnicity and baseline analyte concentrations, were used to compare changes during the ivGTT between high and low percentage pancreatic fat (PPF) groups. RESULTS No ethnic differences in anthropomorphic variables, body composition, visceral adipose tissue (MR-VAT) or PPF were measured and hence data were combined. Nine women (47%) were identified as having high PPF values. PPF was significantly associated with baseline C-peptide (p = 0.04) and ISR (p = 0.04) in all. During the 1-hr ivGTT, plasma glucose (p<0.0001), insulin (p<0.0001) and ISR (p = 0.02) increased significantly from baseline in both high and low PPF groups but did not differ between the two groups at any given time during the test (PPF x time, p > 0.05). Notably, the incremental areas under the curves for both first and second phase ISR were 0.04 units lower in the high than low PPF groups, but this was not significant (p > 0.05). CONCLUSION In women with overweight or obesity but without T2DM, PPF did not modify β-cell function as determined by ivGTT-assessed ISR. However, the salient feature in biphasic insulin secretion in those with ≥4.5% PPF may be of clinical importance, particularly in early stages of dysglycaemia may warrant further investigation.
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Affiliation(s)
- Ivana R. Sequeira
- Human Nutrition Unit, School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- * E-mail:
| | - Wilson Yip
- Human Nutrition Unit, School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Louise W. Lu
- Human Nutrition Unit, School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Yannan Jiang
- Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand
| | - Rinki Murphy
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Auckland District Health Board, Auckland, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
| | - Lindsay D. Plank
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Garth J. S. Cooper
- Division of Cardiovascular Sciences, Centre for Advanced Discovery and Experimental Therapeutics (CADET), Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand
- Division of Medical Sciences, Department of Pharmacology, University of Oxford, Oxford, United Kingdom
| | - Carl N. Peters
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Waitemata District Health Board, Auckland, New Zealand
| | - Benjamin S. Aribsala
- Newcastle Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Science, Newcastle University, Newcastle Upon Tyne, United Kingdom
- Department of Computer Science, Faculty of Science, Lagos State University, Lagos, Nigeria
| | - Kieren G. Hollingsworth
- Newcastle Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Science, Newcastle University, Newcastle Upon Tyne, United Kingdom
| | - Sally D. Poppitt
- Human Nutrition Unit, School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, Auckland, New Zealand
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Riddet Centre of Research Excellence (CoRE) for Food and Nutrition, Palmerston North, New Zealand
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15
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Rugivarodom M, Geeratragool T, Pausawasdi N, Charatcharoenwitthaya P. Fatty Pancreas: Linking Pancreas Pathophysiology to Nonalcoholic Fatty Liver Disease. J Clin Transl Hepatol 2022; 10:1229-1239. [PMID: 36381092 PMCID: PMC9634764 DOI: 10.14218/jcth.2022.00085] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 06/05/2022] [Accepted: 06/27/2022] [Indexed: 12/04/2022] Open
Abstract
Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired β-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD.
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Affiliation(s)
| | | | | | - Phunchai Charatcharoenwitthaya
- Correspondence to: Phunchai Charatcharoenwitthaya, Division of Gastroenterology, Medicine Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Wang-Lang Road, Bangkok 10700, Thailand. ORCID: https://orcid.org/0000-0002-8334-0267. Tel: +66-2-4197282, Fax: +66-2-4115013, E-mail:
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16
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An Adapted Deep Convolutional Neural Network for Automatic Measurement of Pancreatic Fat and Pancreatic Volume in Clinical Multi-Protocol Magnetic Resonance Images: A Retrospective Study with Multi-Ethnic External Validation. Biomedicines 2022; 10:biomedicines10112991. [PMID: 36428558 PMCID: PMC9687882 DOI: 10.3390/biomedicines10112991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 11/08/2022] [Accepted: 11/17/2022] [Indexed: 11/23/2022] Open
Abstract
Pancreatic volume and fat fraction are critical prognoses for metabolic diseases like type 2 diabetes (T2D). Magnetic Resonance Imaging (MRI) is a required non-invasive quantification method for the pancreatic fat fraction. The dramatic development of deep learning has enabled the automatic measurement of MR images. Therefore, based on MRI, we intend to develop a deep convolutional neural network (DCNN) that can accurately segment and measure pancreatic volume and fat fraction. This retrospective study involved abdominal MR images from 148 diabetic patients and 246 healthy normoglycemic participants. We randomly separated them into training and testing sets according to the proportion of 80:20. There were 2364 recognizable pancreas images labeled and pre-treated by an upgraded superpixel algorithm for a discernible pancreatic boundary. We then applied them to the novel DCNN model, mimicking the most accurate and latest manual pancreatic segmentation process. Fat phantom and erosion algorithms were employed to increase the accuracy. The results were evaluated by dice similarity coefficient (DSC). External validation datasets included 240 MR images from 10 additional patients. We assessed the pancreas and pancreatic fat volume using the DCNN and compared them with those of specialists. This DCNN employed the cutting-edge idea of manual pancreas segmentation and achieved the highest DSC (91.2%) compared with any reported models. It is the first framework to measure intra-pancreatic fat volume and fat deposition. Performance validation reflected by regression R2 value between manual operation and trained DCNN segmentation on the pancreas and pancreatic fat volume were 0.9764 and 0.9675, respectively. The performance of the novel DCNN enables accurate pancreas segmentation, pancreatic fat volume, fraction measurement, and calculation. It achieves the same segmentation level of experts. With further training, it may well surpass any expert and provide accurate measurements, which may have significant clinical relevance.
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17
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Leiu KH, Poppitt SD, Miles-Chan JL, Sequeira IR. Fatty Pancreas and Cardiometabolic Risk: Response of Ectopic Fat to Lifestyle and Surgical Interventions. Nutrients 2022; 14:nu14224873. [PMID: 36432559 PMCID: PMC9693202 DOI: 10.3390/nu14224873] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/11/2022] [Accepted: 11/14/2022] [Indexed: 11/19/2022] Open
Abstract
Ectopic fat accumulation in non-adipose organs, such as the pancreas and liver, is associated with an increased risk of cardiometabolic disease. While clinical trials have focused on interventions to decrease body weight and liver fat, ameliorating pancreatic fat can be crucial but successful intervention strategies are not yet defined. We identified twenty-two published studies which quantified pancreatic fat during dietary, physical activity, and/or bariatric surgery interventions targeted at body weight and adipose mass loss alongside their subsequent effect on metabolic outcomes. Thirteen studies reported a significant decrease in body weight, utilising weight-loss diets (n = 2), very low-energy diets (VLED) (n = 2), isocaloric diets (n = 1), a combination of diet and physical activity (n = 2), and bariatric surgery (n = 5) including a comparison with VLED (n = 1). Surgical intervention achieved the largest decrease in pancreatic fat (range: -18.2% to -67.2%) vs. a combination of weight-loss diets, isocaloric diets, and/or VLED (range: -10.2% to -42.3%) vs. diet and physical activity combined (range: -0.6% to -3.9%), with a concurrent decrease in metabolic outcomes. While surgical intervention purportedly is the most effective strategy to decrease pancreas fat content and improve cardiometabolic health, the procedure is invasive and may not be accessible to most individuals. Given that dietary intervention is the cornerstone for the prevention of adverse metabolic health, the alternative approaches appear to be the use of weight-loss diets or VLED meal replacements, which are shown to decrease pancreatic fat and associated cardiometabolic risk.
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Affiliation(s)
- Kok Hong Leiu
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- High Value Nutrition, National Science Challenge, Auckland 1010, New Zealand
| | - Sally D. Poppitt
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- High Value Nutrition, National Science Challenge, Auckland 1010, New Zealand
- Department of Medicine, University of Auckland, Auckland 1010, New Zealand
- Riddet Centre of Research Excellence (CoRE) for Food and Nutrition, Palmerston North 4442, New Zealand
| | - Jennifer L. Miles-Chan
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- High Value Nutrition, National Science Challenge, Auckland 1010, New Zealand
- Riddet Centre of Research Excellence (CoRE) for Food and Nutrition, Palmerston North 4442, New Zealand
| | - Ivana R. Sequeira
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand
- High Value Nutrition, National Science Challenge, Auckland 1010, New Zealand
- Correspondence: ; Tel.: +64-09-6301162
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18
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Salman AA, Salman MA, Said M, El Sherbiny M, Elkassar H, Hassan MB, Marwan A, Morad MA, Ashoush O, Labib S, Aon MH, Awad A, Sayed M, Taha AE, Moustafa A, Shaaban HED, Khater A, Elewa A, Khalaf AM, Mostafa AA, Matter M, Youssef A. Improvement of Pancreatic Steatosis and Indices of Insulin Resistance After Metabolic Surgery. Front Med (Lausanne) 2022; 9:894465. [PMID: 35733870 PMCID: PMC9207952 DOI: 10.3389/fmed.2022.894465] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/27/2022] [Indexed: 11/13/2022] Open
Abstract
PURPOSE Obesity is associated with fat accumulation in ectopic sites such as the pancreas, the so-called pancreatic steatosis (PS). Bariatric surgery has been shown to be associated with reducing pancreatic fat. This study investigated the effect of laparoscopic sleeve gastrectomy (LSG) on pancreatic volume and its fat content and glucose homeostasis. METHODS The study enrolled 54 patients subjected to LSG. Metabolic variables and pancreatic exocrine function were assessed immediately before surgery and 12 months after. MRI of the abdomen was performed to measure pancreatic fat content and its total volume and visceral adipose tissue (VAT). RESULTS Surgery resulted in a significant reduction in body weight and BMI. HbA1c, fasting insulin, C-peptide levels, HOMA-IR, and Hs-CRP levels decreased significantly. Surgery resulted in significant improvement in lipid profile except for HDL-cholesterol and liver function tests. Total VAT volume decreased significantly. Total pancreas volume decreased by a mean of 9.0 cm3 (95% CI: 6.6-11.3). The median change of pancreatic fat was -26.1% (range: -55.6 to 58.3%). Pancreatic lipase decreased significantly (P < 0.001). There was a positive correlation between the percentage of total weight loss and decrease in pancreatic fat volume (r = 0.295, P = 0.030). CONCLUSION Weight loss after LSG is associated with a reduction of total VAT volume, total pancreatic volume, and pancreatic fat content. These changes are associated with improved glucose homeostasis, reduced systemic inflammation, and decreased pancreatic lipase secretion.
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Affiliation(s)
| | | | - Mostafa Said
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohammad El Sherbiny
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elkassar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Badr Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Marwan
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | | | - Omar Ashoush
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Safa Labib
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed H. Aon
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Abeer Awad
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Sayed
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed E. Taha
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Moustafa
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hossam El-Din Shaaban
- Tropical and Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Amir Khater
- Tropical and Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Ahmed Elewa
- General Surgery Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Adel M. Khalaf
- Department of General Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Ahmed A. Mostafa
- Department of General Surgery, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohamed Matter
- Radiodiagnosis Department, Faculty of Medicine, Alazhar University, Cairo, Egypt
| | - Ahmed Youssef
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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19
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Skudder-Hill L, Sequeira IR, Cho J, Ko J, Poppitt SD, Petrov MS. Fat Distribution Within the Pancreas According to Diabetes Status and Insulin Traits. Diabetes 2022; 71:1182-1192. [PMID: 35234845 DOI: 10.2337/db21-0976] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 02/22/2022] [Indexed: 11/13/2022]
Abstract
A growing body of evidence suggests that intrapancreatic fat is associated with diabetes, but whether distribution of intrapancreatic fat across the regions of the pancreas has a pathophysiologic role is unknown. The aim of this study was to investigate the differences in intrapancreatic fat deposition between the head, body, and tail of the pancreas, as well as the relationship between regional intrapancreatic fat deposition and diabetes status and insulin traits. A total of 368 adults from the general population underwent MRI on a 3 Tesla scanner, and intrapancreatic fat was manually quantified in duplicate. Statistical models included adjustment for age, sex, ethnicity, BMI, and liver fat. Intrapancreatic fat deposition in the head, body, and tail of the pancreas did not differ significantly in adjusted models in either the overall cohort or the three subgroups based on diabetes status. HOMA of insulin resistance and fasting insulin were significantly positively associated with fat in the tail and body of the pancreas. There was no significant association between regional intrapancreatic fat and HOMA of β-cell function. The association of increased intrapancreatic fat deposition in the tail and body regions with increased insulin resistance may have an important role in the early identification of patients at risk for developing insulin resistance and diseases that stem from it.
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Affiliation(s)
- Loren Skudder-Hill
- School of Medicine, University of Auckland, Auckland, New Zealand
- Department of Neurosurgery, Yuquan Hospital Affiliated to Tsinghua University School of Clinical Medicine, Beijing, People's Republic of China
| | - Ivana R Sequeira
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, University of Auckland, Auckland, New Zealand
| | - Jaelim Cho
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Juyeon Ko
- School of Medicine, University of Auckland, Auckland, New Zealand
| | - Sally D Poppitt
- School of Medicine, University of Auckland, Auckland, New Zealand
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High-Value Nutrition National Science Challenge, University of Auckland, Auckland, New Zealand
- Riddet Institute, Centre of Research Excellence (CoRE) for Food and Nutrition, Palmerston North, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand
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20
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Wen Y, Chen C, Kong X, Xia Z, Kong W, Si K, Han P, Vivian Liu W, Li X. Pancreatic fat infiltration, β-cell function and insulin resistance: A study of the young patients with obesity. Diabetes Res Clin Pract 2022; 187:109860. [PMID: 35367311 DOI: 10.1016/j.diabres.2022.109860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 03/07/2022] [Accepted: 03/29/2022] [Indexed: 11/25/2022]
Abstract
OBJECTIVE This study aimed to investigate the relationship between pancreatic fat infiltration (PFI) and glucose metabolism disorder, β-cell function and insulin resistance in patients with obesity. METHODS Pancreatic fat fraction (PFF) was quantified by MRI IDEAL-IQ technique. PFF greater than 6.2 % was defined as PFI, and 34 obese patients were divided into PFI and non-PFI groups. The 5-point plasma glucose and insulin values during oral glucose tolerance test (OGTT) were recorded. OGTT-derived indices of insulin resistance and β-cell function were calculated. RESULTS Glucose values levels at 0-120 min during OGTT were significantly higher and β-cell function variables were lower in PFI group than non-PFI group. While indices of insulin resistance were not significantly different between two groups. Correlation analysis showed that PFF was positively correlated with glucose levels at 0, 30 and 60 min, negatively correlated with β-cell function variables and not significantly correlated with indices of insulin resistance. However, these associations of PFF with β-cell function and glucose levels were only present in type 2 diabetes mellitus (T2DM) group but not in non-T2DM group. CONCLUSION There is an association between PFI and impaired β-cell function, and increased pancreatic fat may be a potential risk factor for the development of T2DM.
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Affiliation(s)
- Yu Wen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Cen Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xiangchuang Kong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Zefeng Xia
- Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Wen Kong
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Keke Si
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Ping Han
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | | | - Xin Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.
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21
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Kahn DE, Bergman BC. Keeping It Local in Metabolic Disease: Adipose Tissue Paracrine Signaling and Insulin Resistance. Diabetes 2022; 71:599-609. [PMID: 35316835 PMCID: PMC8965661 DOI: 10.2337/dbi21-0020] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 01/03/2022] [Indexed: 01/04/2023]
Abstract
Alterations in adipose tissue composition and function are associated with obesity and contribute to the development of type 2 diabetes. While the significance of this relationship has been cemented, our understanding of the multifaceted role of adipose tissue in metabolic heath and disease continues to evolve and expand. Heterogenous populations of cells that make up adipose tissue throughout the body generate diverse secretomes containing a mosaic of bioactive compounds with vast structural and signaling capabilities. While there are many reports highlighting the important role of adipose tissue endocrine signaling in insulin resistance and type 2 diabetes, the direct, local, paracrine effect of adipose tissue has received less attention. Recent studies have begun to underscore the importance of considering anatomically discrete adipose depots for their specific impact on local microenvironments and metabolic function in neighboring tissues as well as regulation of whole-body physiology. This article highlights the important role of adipose tissue paracrine signaling on metabolic function and insulin sensitivity in nearby tissues and organs, specifically focusing on visceral, pancreatic, subcutaneous, intermuscular, and perivascular adipose tissue depots.
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Affiliation(s)
- Darcy E. Kahn
- University of Colorado Anschutz Medical Campus, Aurora, CO
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22
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Sequeira IR, Yip WC, Lu LWW, Jiang Y, Murphy R, Plank LD, Cooper GJS, Peters CN, Lu J, Hollingsworth KG, Poppitt SD. Pancreas Fat, an Early Marker of Metabolic Risk? A Magnetic Resonance Study of Chinese and Caucasian Women: TOFI_Asia Study. Front Physiol 2022; 13:819606. [PMID: 35431998 PMCID: PMC9008457 DOI: 10.3389/fphys.2022.819606] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 02/17/2022] [Indexed: 11/13/2022] Open
Abstract
ObjectivePrevalence of type 2 diabetes (T2D) is disproportionately higher in younger outwardly lean Asian Chinese compared to matched Caucasians. Susceptibility to T2D is hypothesised due to dysfunctional adipose tissue expansion resulting in adverse abdominal visceral and organ fat accumulation. Impact on early risk, particularly in individuals characterised by the thin-on-the-outside-fat-on-the-inside (TOFI) phenotype, is undetermined.MethodsSixty-eight women [34 Chinese, 34 Caucasian; 18–70 years; body mass index (BMI), 20–45 kg/m2] from the TOFI_Asia study underwent magnetic resonance imaging and spectroscopy to quantify visceral, pancreas, and liver fat. Total body fat was (TBF) assessed by dual-energy x-ray absorptiometry, and fasting blood biomarkers were measured. Ethnic comparisons, conducted using two-sample tests and multivariate regressions adjusted for age, % TBF and ethnicity, identified relationships between abdominal ectopic fat depots with fasting plasma glucose (FPG), insulin resistance (HOMA2-IR), and related metabolic clinical risk markers in all, and within ethnic groups.ResultsDespite being younger and of lower bodyweight, Chinese women in the cohort had similar BMI and % TBF compared to their Caucasian counterparts. Protective high-density lipoprotein cholesterol, total- and high-molecular weight adiponectin were significantly lower, while glucoregulatory glucagon-like peptide-1 and glucagon significantly higher, in Chinese. There were no ethnic differences between % pancreas fat and % liver fat. However, at low BMI, % pancreas and % liver fat were ∼1 and ∼2% higher in Chinese compared to Caucasian women. In all women, % pancreas and visceral adipose tissue had the strongest correlation with FPG, independent of age and % TBF. Percentage (%) pancreas fat and age positively contributed to variance in FPG, whereas % TBF, amylin and C-peptide contributed to IR which was 0.3 units higher in Chinese.ConclusionPancreas fat accumulation may be an early adverse event, in TOFI individuals, with peptides highlighting pancreatic dysfunction as drivers of T2D susceptibility. Follow-up is warranted to explore causality.
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Affiliation(s)
- Ivana R. Sequeira
- Human Nutrition Unit, Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High Value Nutrition National Science Challenge, Auckland, New Zealand
- *Correspondence: Ivana R. Sequeira, ; orcid.org/0000-0001-5414-9925
| | - Wilson C. Yip
- Human Nutrition Unit, Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Louise W. W. Lu
- Human Nutrition Unit, Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High Value Nutrition National Science Challenge, Auckland, New Zealand
| | - Yannan Jiang
- Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand
| | - Rinki Murphy
- High Value Nutrition National Science Challenge, Auckland, New Zealand
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Auckland District Health Board, Auckland, New Zealand
- Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
| | - Lindsay D. Plank
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Garth J. S. Cooper
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Centre for Advanced Discovery and Experimental Therapeutics (CADET), Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- Division of Medical Sciences, Department of Pharmacology, University of Oxford, Oxford, United Kingdom
| | - Carl N. Peters
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Waitemata District Health Board, Auckland, New Zealand
| | - Jun Lu
- Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
| | - Kieren G. Hollingsworth
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Sally D. Poppitt
- Human Nutrition Unit, Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand
- High Value Nutrition National Science Challenge, Auckland, New Zealand
- Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
- Faculty of Science, School of Biological Sciences, University of Auckland, Auckland, New Zealand
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23
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Petrov MS, Taylor R. Intra-pancreatic fat deposition: bringing hidden fat to the fore. Nat Rev Gastroenterol Hepatol 2022; 19:153-168. [PMID: 34880411 DOI: 10.1038/s41575-021-00551-0] [Citation(s) in RCA: 99] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2021] [Indexed: 02/07/2023]
Abstract
Development of advanced modalities for detection of fat within the pancreas has transformed understanding of the role of intra-pancreatic fat deposition (IPFD) in health and disease. There is now strong evidence for the presence of minimal (but not negligible) IPFD in healthy human pancreas. Diffuse excess IPFD, or fatty pancreas disease (FPD), is more frequent than type 2 diabetes mellitus (T2DM) (the most common disease of the endocrine pancreas) and acute pancreatitis (the most common disease of the exocrine pancreas) combined. FPD is not strictly a function of high BMI; it can result from the excess deposition of fat in the islets of Langerhans, acinar cells, inter-lobular stroma, acinar-to-adipocyte trans-differentiation or replacement of apoptotic acinar cells. This process leads to a wide array of diseases characterized by excess IPFD, including but not limited to acute pancreatitis, chronic pancreatitis, pancreatic cancer, T2DM, diabetes of the exocrine pancreas. There is ample evidence for FPD being potentially reversible. Weight loss-induced decrease of intra-pancreatic fat is tightly associated with remission of T2DM and its re-deposition with recurrence of the disease. Reversing FPD will open up opportunities for preventing or intercepting progression of major diseases of the exocrine pancreas in the future.
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Affiliation(s)
- Maxim S Petrov
- School of Medicine, University of Auckland, Auckland, New Zealand.
| | - Roy Taylor
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
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24
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Koh HCE, Patterson BW, Reeds DN, Mittendorfer B. Insulin sensitivity and kinetics in African American and White people with obesity: Insights from different study protocols. Obesity (Silver Spring) 2022; 30:655-665. [PMID: 35083870 PMCID: PMC8866210 DOI: 10.1002/oby.23363] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/28/2021] [Accepted: 12/02/2021] [Indexed: 01/03/2023]
Abstract
OBJECTIVE Studies that used an intravenous glucose tolerance test (IVGTT) have suggested that race is an important modulator of insulin sensitivity, β-cell function, and insulin clearance. However, the validity of the IVGTT has been challenged. METHODS This study assessed insulin sensitivity and insulin kinetics in non-Hispanic White (NHW, n = 29) and African American (AA, n = 14) people with obesity by using a hyperinsulinemic-euglycemic pancreatic clamp with glucose tracer infusion, an oral glucose tolerance test (OGTT), and an IVGTT. RESULTS Hepatic insulin sensitivity was better in AA participants than in NHW participants. Muscle insulin sensitivity, insulin secretion in relation to plasma glucose during the OGTT, and insulin clearance during basal conditions during the hyperinsulinemic-euglycemic pancreatic clamp and during the OGTT were not different between AA participants and NHW participants. The acute insulin response to the large glucose bolus administered during the IVGTT was double in AA participants compared with NHW participants because of increased insulin secretion and reduced insulin clearance. CONCLUSIONS AA individuals are not more insulin resistant than NHW individuals, and the β-cell response to glucose ingestion and postprandial insulin clearance are not different between AA individuals and NHW individuals. However, AA individuals have greater insulin secretory capacity and reduced insulin clearance capacity than NHW individuals and might be susceptible to hyperinsulinemia after consuming very large amounts of glucose.
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Affiliation(s)
- Han-Chow E Koh
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Bruce W Patterson
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Dominic N Reeds
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Bettina Mittendorfer
- Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA
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25
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Reed RM, Nevitt SJ, Kemp GJ, Cuthbertson DJ, Whyte MB, Goff LM. Ectopic fat deposition in populations of black African ancestry: A systematic review and meta-analysis. Acta Diabetol 2022; 59:171-187. [PMID: 34518896 PMCID: PMC8841318 DOI: 10.1007/s00592-021-01797-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/02/2021] [Indexed: 02/07/2023]
Abstract
AIMS In populations of black African ancestry (BA), a paradox exists whereby lower visceral adipose tissue is found despite their high risk for type 2 diabetes (T2D). This systematic review investigates ethnic differences in other ectopic fat depots (intrahepatic lipid: IHL; intramyocellular lipid: IMCL and intrapancreatic lipid; IPL) to help contextualise their potential contribution to T2D risk. METHODS A systematic literature search was performed in December 2020 to identify studies reporting at least one ectopic fat comparison between BA and one/more other ethnicity. For IHL, a meta-analysis was carried out with studies considered comparable based on the method of measurement. RESULTS Twenty-eight studies were included (IHL: n = 20; IMCL: n = 8; IPL: n = 4). Meta-analysis of 11 studies investigating IHL revealed that it was lower in BA populations vs pooled ethnic comparators (MD -1.35%, 95% CI -1.55 to -1.16, I2 = 85%, P < 0.00001), white European ancestry (MD -0.94%, 95% CI -1.17 to -0.70, I2 = 79%, P < 0.00001), Hispanic ancestry (MD -2.06%, 95% CI -2.49 to -1.63, I2 = 81%, P < 0.00001) and South Asian ancestry comparators (MD -1.92%, 95% CI -3.26 to -0.57, I2 = 78%, P = 0.005). However, heterogeneity was high in all analyses. Most studies found no significant differences in IMCL between BA and WE. Few studies investigated IPL, however, indicated that IPL is lower in BA compared to WE and HIS. CONCLUSION The discordance between ectopic fat and greater risk for T2D in BA populations raises questions around its contribution to T2D pathophysiology in BA.
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Affiliation(s)
- Reuben M Reed
- Department of Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Sarah J Nevitt
- Department of Health Data Science, Institute of Population Health, University of Liverpool, Liverpool, UK
| | - Graham J Kemp
- Department of Musculoskeletal and Ageing Science. Institute of Life Course and Medical Sciences, Liverpool Magnetic Resonance Imaging Centre (LiMRIC), University of Liverpool, Liverpool, UK
| | - Daniel J Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course Sciences, University of Liverpool, Liverpool, UK
| | - Martin B Whyte
- Faculty of Health & Medical Sciences, University of Surrey, Guildford, Surrey, UK
| | - Louise M Goff
- Department of Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
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26
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Wagner R, Eckstein SS, Yamazaki H, Gerst F, Machann J, Jaghutriz BA, Schürmann A, Solimena M, Singer S, Königsrainer A, Birkenfeld AL, Häring HU, Fritsche A, Ullrich S, Heni M. Metabolic implications of pancreatic fat accumulation. Nat Rev Endocrinol 2022; 18:43-54. [PMID: 34671102 DOI: 10.1038/s41574-021-00573-3] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/13/2021] [Indexed: 12/15/2022]
Abstract
Fat accumulation outside subcutaneous adipose tissue often has unfavourable effects on systemic metabolism. In addition to non-alcoholic fatty liver disease, which has received considerable attention, pancreatic fat has become an important area of research throughout the past 10 years. While a number of diagnostic approaches are available to quantify pancreatic fat, multi-echo Dixon MRI is currently the most developed method. Initial studies have shown associations between pancreatic fat and the metabolic syndrome, impaired glucose metabolism and type 2 diabetes mellitus. Pancreatic fat is linked to reduced insulin secretion, at least under specific circumstances such as prediabetes, low BMI and increased genetic risk of type 2 diabetes mellitus. This Review summarizes the possible causes and metabolic consequences of pancreatic fat accumulation. In addition, potential therapeutic approaches for addressing pancreatic fat accumulation are discussed.
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Affiliation(s)
- Robert Wagner
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Sabine S Eckstein
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Felicia Gerst
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Jürgen Machann
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Section of Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Benjamin Assad Jaghutriz
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Annette Schürmann
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany
- Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
| | - Michele Solimena
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Molecular Diabetology, University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
- Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Stephan Singer
- Institute of Pathology, University of Tübingen, Tübingen, Germany
| | - Alfred Königsrainer
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Andreas L Birkenfeld
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Hans-Ulrich Häring
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Andreas Fritsche
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Susanne Ullrich
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Martin Heni
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
- German Center for Diabetes Research (DZD), Tübingen, Germany.
- Department of Internal Medicine, Division of Diabetology, Endocrinology, and Nephrology, Eberhard Karls University Tübingen, Tübingen, Germany.
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany.
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27
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Filippatos TD, Alexakis K, Mavrikaki V, Mikhailidis DP. Nonalcoholic Fatty Pancreas Disease: Role in Metabolic Syndrome, "Prediabetes," Diabetes and Atherosclerosis. Dig Dis Sci 2022; 67:26-41. [PMID: 33469809 DOI: 10.1007/s10620-021-06824-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 01/05/2021] [Indexed: 02/06/2023]
Abstract
Fat accumulation in the pancreas associated with obesity and the metabolic syndrome (MetS) has been defined as "non-alcoholic fatty pancreas disease" (NAFPD). The aim of this review is to describe the association of NAFPD with obesity, MetS, type 2 diabetes mellitus (T2DM) and atherosclerosis and also increase awareness regarding NAFPD. Various methods are used for the detection and quantification of pancreatic fat accumulation that may play a significant role in the differences that have been observed in the prevalence of NAFPD. Endoscopic ultrasound provides detailed images of the pancreas and its use is expected to increase in the future. Obesity and MetS have been recognized as NAFPD risk factors. NAFPD is strongly associated with non-alcoholic fatty liver disease (NAFLD) and it seems that the presence of both may be related with aggravation of NAFLD. A role of NAFPD in the development of "prediabetes" and T2DM has also been suggested by most human studies. Accumulation of fat in pancreatic tissue possibly initiates a vicious cycle of beta-cell deterioration and further pancreatic fat accumulation. Additionally, some evidence indicates a correlation between NAFPD and atherosclerotic markers (e.g., carotid intima-media thickness). Weight loss and bariatric surgery decreases pancreatic triglyceride content but pharmacologic treatments for NAFPD have not been evaluated in specifically designed studies. Hence, NAFPD is a marker of local fat accumulation possibly associated with beta-cell function impairment, carbohydrate metabolism disorders and atherosclerosis.
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Affiliation(s)
- T D Filippatos
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece.
| | - K Alexakis
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - V Mavrikaki
- Metabolic Diseases Research Unit, Internal Medicine Laboratory, School of Medicine, Faculty of Medicine, University of Crete, P.O. Box 2208, Heraklion, Crete, Greece
| | - D P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, NW3 2QG, UK.,Mohammed Bin Rashid University (MBRU) of Medicine and Health Sciences, Dubai, United Arab Emirates
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28
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Hayashi H, Uemura N, Matsumura K, Zhao L, Sato H, Shiraishi Y, Yamashita YI, Baba H. Recent advances in artificial intelligence for pancreatic ductal adenocarcinoma. World J Gastroenterol 2021; 27:7480-7496. [PMID: 34887644 PMCID: PMC8613738 DOI: 10.3748/wjg.v27.i43.7480] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 08/02/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal type of cancer. The 5-year survival rate for patients with early-stage diagnosis can be as high as 20%, suggesting that early diagnosis plays a pivotal role in the prognostic improvement of PDAC cases. In the medical field, the broad availability of biomedical data has led to the advent of the "big data" era. To overcome this deadly disease, how to fully exploit big data is a new challenge in the era of precision medicine. Artificial intelligence (AI) is the ability of a machine to learn and display intelligence to solve problems. AI can help to transform big data into clinically actionable insights more efficiently, reduce inevitable errors to improve diagnostic accuracy, and make real-time predictions. AI-based omics analyses will become the next alterative approach to overcome this poor-prognostic disease by discovering biomarkers for early detection, providing molecular/genomic subtyping, offering treatment guidance, and predicting recurrence and survival. Advances in AI may therefore improve PDAC survival outcomes in the near future. The present review mainly focuses on recent advances of AI in PDAC for clinicians. We believe that breakthroughs will soon emerge to fight this deadly disease using AI-navigated precision medicine.
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Affiliation(s)
- Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Norio Uemura
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Kazuki Matsumura
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Liu Zhao
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Hiroki Sato
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Yuta Shiraishi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Yo-ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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29
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Swislocki A. Fatty Pancreas: An Underappreciated Intersection of the Metabolic Profile and Pancreatic Adenocarcinoma. Metab Syndr Relat Disord 2021; 19:317-324. [PMID: 33656378 DOI: 10.1089/met.2020.0070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Although the prevalence of pancreatic cancer is increasing, treatment strategies remain limited, and success is rare. A growing body of evidence links pancreatic cancer to pre-existing metabolic disorders, including, but not limited to, type 2 diabetes mellitus and obesity. An infrequently described finding, fatty pancreas, initially described in the context of obesity in the early 20th century, appears to be at the crossroads of type 2 diabetes and obesity on the one hand, and the development of pancreatic cancer on the other. Similarly, other conditions of the pancreas, such as intrapancreatic mucinous neoplasms, also seem to be related to diabetes while increasing the subsequent risk of pancreatic cancer. In this review, the author explores the diagnostic criteria for, and prevalence of, fatty pancreas and the potential link to other pancreatic conditions, including pancreatic cancer. Diagnostic limitations, and areas of controversy are also addressed, as are potential therapeutic approaches to fatty pancreas intended to reduce the subsequent risk of pancreatic cancer.
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Affiliation(s)
- Arthur Swislocki
- Medical Service (612/111), Veterans Affairs Northern California Health Care System (VANCHCS), Martinez, California, USA
- Department of Medicine, UC Davis School of Medicine, Sacramento, California, USA
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Streicher SA, Lim U, Park SL, Li Y, Sheng X, Hom V, Xia L, Pooler L, Shepherd J, Loo LWM, Darst BF, Highland HM, Polfus LM, Bogumil D, Ernst T, Buchthal S, Franke AA, Setiawan VW, Tiirikainen M, Wilkens LR, Haiman CA, Stram DO, Cheng I, Le Marchand L. Genome-wide association study of pancreatic fat: The Multiethnic Cohort Adiposity Phenotype Study. PLoS One 2021; 16:e0249615. [PMID: 34329319 PMCID: PMC8323875 DOI: 10.1371/journal.pone.0249615] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 06/15/2021] [Indexed: 01/26/2023] Open
Abstract
Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO, and rs79967607 is in intron 1 of EPM2A. PLUTO, a lncRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.
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Affiliation(s)
- Samantha A. Streicher
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Unhee Lim
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - S. Lani Park
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Yuqing Li
- Department of Epidemiology and Biostatistics, University of California – San Francisco, San Francisco, California, United States of America
| | - Xin Sheng
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Victor Hom
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Lucy Xia
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Loreall Pooler
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - John Shepherd
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Lenora W. M. Loo
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Burcu F. Darst
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Heather M. Highland
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
| | - Linda M. Polfus
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - David Bogumil
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Thomas Ernst
- University of Maryland School of Medicine, Baltimore, Maryland, United States of America
| | - Steven Buchthal
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Adrian A. Franke
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Veronica Wendy Setiawan
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Maarit Tiirikainen
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Lynne R. Wilkens
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
| | - Christopher A. Haiman
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Daniel O. Stram
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Iona Cheng
- Department of Epidemiology and Biostatistics, University of California – San Francisco, San Francisco, California, United States of America
| | - Loïc Le Marchand
- University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America
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Taylor R. Type 2 diabetes and remission: practical management guided by pathophysiology. J Intern Med 2021; 289:754-770. [PMID: 33289165 PMCID: PMC8247294 DOI: 10.1111/joim.13214] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 09/10/2020] [Accepted: 09/15/2020] [Indexed: 12/13/2022]
Abstract
The twin cycle hypothesis postulated that type 2 diabetes was a result of excess liver fat causing excess supply of fat to the pancreas with resulting dysfunction of both organs. If this was so, the condition should be able to be returned to normal by calorie restriction. The Counterpoint study tested this prediction in short-duration type 2 diabetes and showed that liver glucose handling returned to normal within 7 days and that beta-cell function returned close to normal over 8 weeks. Subsequent studies have demonstrated the durability of remission from type 2 diabetes. Remarkably, during the first 12 months of remission, the maximum functional beta-cell mass returns completely to normal and remains so for at least 24 months, consistent with regain of insulin secretory function of beta cells which had dedifferentiated in the face of chronic nutrient oversupply. The likelihood of achieving remission after 15% weight loss has been shown to be mainly determined by the duration of diabetes, with responders having better beta-cell function at baseline. Remission is independent of BMI, underscoring the personal fat threshold concept that type 2 diabetes develops when an individual acquires more fat than can be individually tolerated even at a BMI which in the nonobese range. Observations on people of South Asian or Afro-American ethnicity confirm that substantial weight loss achieves remission in the same way as in the largely White Europeans studied in detail. Diagnosis of type 2 diabetes can now be regarded as an urgent signal that weight loss must be achieved to avoid a progressive decline of health.
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Affiliation(s)
- Roy Taylor
- Magnetic Resonance CentreInstitute of Cellular MedicineNewcastle UniversityNewcastleUK
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Fortuin-de Smidt MC, Mendham AE, Hauksson J, Alhamud A, Stefanovski D, Hakim O, Swart J, Goff LM, Kahn SE, Olsson T, Goedecke JH. β-cell function in black South African women: exploratory associations with insulin clearance, visceral and ectopic fat. Endocr Connect 2021; 10:550-560. [PMID: 33884957 PMCID: PMC8183622 DOI: 10.1530/ec-21-0153] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 04/22/2021] [Indexed: 11/08/2022]
Abstract
The role of ectopic fat, insulin secretion and clearance in the preservation ofβ-cell function in black African women with obesity who typically present with hyperinsulinaemia is not clear. We aim to examine the associations between disposition index (DI, an estimate of β-cell function), insulin secretion and clearance and ectopic fat deposition. This is a cross-sectional study of 43 black South African women (age 20-35 years) with obesity (BMI 30-40 kg/m2) and without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently sampled i.v. glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal s.c. adipose tissue (aSAT) volume (MRI), intra-myocellular (IMCL) and extra-myocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance (β 55.80, P = 0.002). Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (P = 0.033) and lower hepatic insulin extraction (P = 0.022) were associated with lower VAT, independent from SI, rather than with ectopic fat. In conclusion, peripheral insulin clearance emerged as an important correlate of DI. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, is associated with both lower insulin secretion and higher hepatic insulin extraction. Prevention of VAT accumulation in young black African women should, therefore, be an important target for beta cell preservation.
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Affiliation(s)
- Melony C Fortuin-de Smidt
- Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
- Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa
- Correspondence should be addressed to M C Fortuin-de Smidt:
| | - Amy E Mendham
- Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
- Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa
| | - Jon Hauksson
- Department of Radiation Sciences, Radiation Physics and Biomedical Engineering, Umea University, Umea, Sweden
| | - Ali Alhamud
- Department of Human Biology, MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa
- The Modern Pioneer Center and ArSMRM for MRI Training and Development, Tripoli, Libya
| | - Darko Stefanovski
- Department of Clinical Studies, New Bolton Centre, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA
| | - Olah Hakim
- Department of Diabetes, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK
| | - Jeroen Swart
- Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
| | - Louise M Goff
- Department of Diabetes, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK
| | - Steven E Kahn
- Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington, USA
| | - Tommy Olsson
- Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden
| | - Julia H Goedecke
- Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
- Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa
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Ladwa M, Bello O, Hakim O, Shojaee-Moradie F, Boselli ML, Charles-Edwards G, Peacock J, Umpleby AM, Amiel SA, Bonadonna RC, Goff LM. Ethnic differences in beta cell function occur independently of insulin sensitivity and pancreatic fat in black and white men. BMJ Open Diabetes Res Care 2021; 9:9/1/e002034. [PMID: 33762314 PMCID: PMC7993168 DOI: 10.1136/bmjdrc-2020-002034] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 01/21/2021] [Accepted: 02/11/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION It is increasingly recognized that type 2 diabetes (T2D) is a heterogenous disease with ethnic variations. Differences in insulin secretion, insulin resistance and ectopic fat are thought to contribute to these variations. Therefore, we aimed to compare postprandial insulin secretion and the relationships between insulin secretion, insulin sensitivity and pancreatic fat in men of black West African (BA) and white European (WE) ancestry. RESEARCH DESIGN AND METHODS A cross-sectional, observational study in which 23 WE and 23 BA men with normal glucose tolerance, matched for body mass index, underwent a mixed meal tolerance test with C peptide modeling to measure beta cell insulin secretion, an MRI to quantify intrapancreatic lipid (IPL), and a hyperinsulinemic-euglycemic clamp to measure whole-body insulin sensitivity. RESULTS Postprandial insulin secretion was lower in BA versus WE men following adjustment for insulin sensitivity (estimated marginal means, BA vs WE: 40.5 (95% CI 31.8 to 49.2) × 103 vs 56.4 (95% CI 48.9 to 63.8) × 103 pmol/m2 body surface area × 180 min, p=0.008). There was a significantly different relationship by ethnicity between IPL and insulin secretion, with a stronger relationship in WE than in BA (r=0.59 vs r=0.39, interaction p=0.036); however, IPL was not a predictor of insulin secretion in either ethnic group following adjustment for insulin sensitivity. CONCLUSIONS Ethnicity is an independent determinant of beta cell function in black and white men. In response to a meal, healthy BA men exhibit lower insulin secretion compared with their WE counterparts for their given insulin sensitivity. Ethnic differences in beta cell function may contribute to the greater risk of T2D in populations of African ancestry.
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Affiliation(s)
- Meera Ladwa
- Department of Diabetes, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Oluwatoyosi Bello
- Diabetes and Nutritional Sciences Division, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Olah Hakim
- Diabetes and Nutritional Sciences Division, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | | | | | - Geoff Charles-Edwards
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Janet Peacock
- Department of Epidemiology, Dartmouth College Geisel School of Medicine, Hanover, New Hampshire, USA
| | - A Margot Umpleby
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
| | - Stephanie A Amiel
- Department of Diabetes, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Riccardo C Bonadonna
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Endocrinologia e Malattie del Metabolismo, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Louise M Goff
- Diabetes and Nutritional Sciences Division, Faculty of Life Sciences and Medicine, King's College London, London, UK
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Andrisse S, Garcia-Reyes Y, Pyle L, Kelsey MM, Nadeau KJ, Cree-Green M. Racial and Ethnic Differences in Metabolic Disease in Adolescents With Obesity and Polycystic Ovary Syndrome. J Endocr Soc 2021; 5:bvab008. [PMID: 33644620 PMCID: PMC7896356 DOI: 10.1210/jendso/bvab008] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Indexed: 01/23/2023] Open
Abstract
Context Polycystic ovary syndrome (PCOS) is common and associated with metabolic syndrome. In the general population, metabolic disease varies by race and ethnicity. Objective This work aimed to examine in depth the interaction of race and ethnicity with PCOS-related metabolic disease in adolescent youth. Methods A secondary analysis was conducted of data from girls (age 12-21 years) with overweight or obesity (> 90 body mass index [BMI] percentile) and PCOS. Measurements included fasting hormone and metabolic measures, a 2-hour oral glucose tolerance test (OGTT), and magnetic resonance imaging for hepatic fat. Groups were categorized by race or ethnicity. Results Participants included 39 non-Hispanic White (NHW, age 15.7 ± 0.2 years; BMI 97.7 ± 0.2 percentile), 50 Hispanic (HW, 15.2 ± 0.3 years; 97.9 ± 0.3 percentile), and 12 non-Hispanic Black (NHB, 16.0 ± 0.6 years; 98.6 ± 0.4 percentile) adolescents. Hepatic markers of insulin resistance were worse in NHW, including lower sex hormone-binding globulin and higher triglycerides over high-density lipoprotein cholesterol (TGs/HDL-C) ratio (P = .002 overall, HW vs NHB [P = .009] vs NHW [P = 0.020]), although homeostasis model assessment of estimated insulin resistance was worst in NHB (P = .010 overall, NHW vs NHB P = .014). Fasting and 2-hour OGTT glucose were not different between groups, although glycated hemoglobin A1c (HbA1c) was lowest in NHW (overall P < .001, NHW 5.2 ± 0.3 vs HW 5.5 ± 0.3 P < .001 vs 5.7 ± 0.4%, P < .001). The frequency of hepatic steatosis (HW 62%, NHW 42%, NHB 25%, P = .032); low HDL-C < 40 mg/dL (HW 82%, NHW 61%, NHB 50%, P < .001) and prediabetes HbA1c 5.7% to 6.4% (NHB 50%, HW 36%, NHW 5%, P < .001) were different between the groups. Conclusion Adolescents with PCOS appear to show similar racial and ethnic variation to the general population in terms of metabolic disease components.
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Affiliation(s)
- Stanley Andrisse
- Howard University College of Medicine, Physiology and Biophysics, Baltimore, Maryland, USA.,Johns Hopkins Medicine, Pediatric Endocrinology, Baltimore, Maryland, USA
| | - Yesenia Garcia-Reyes
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Laura Pyle
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado, USA
| | - Megan M Kelsey
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Center for Women's Health Research, Aurora, Colorado, USA
| | - Kristen J Nadeau
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Center for Women's Health Research, Aurora, Colorado, USA
| | - Melanie Cree-Green
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.,Center for Women's Health Research, Aurora, Colorado, USA
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Al-Mrabeh A, Hollingsworth KG, Shaw JAM, McConnachie A, Sattar N, Lean MEJ, Taylor R. 2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 2020; 8:939-948. [PMID: 33031736 DOI: 10.1016/s2213-8587(20)30303-x] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 08/14/2020] [Accepted: 08/18/2020] [Indexed: 01/03/2023]
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 (HbA1c <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 cm3 (SD 16·0) in all participants with type 2 diabetes and 79·8 cm3 (14·3) in the NDC group (p<0·0001). At 24 months, pancreas volume had increased by 9·4 cm3 (95% CI 6·1 to 12·8) in responders compared with 6·4 cm3 (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.
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Affiliation(s)
- Ahmad Al-Mrabeh
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
| | - Kieren G Hollingsworth
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - James A M Shaw
- Regenerative Medicine, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Alex McConnachie
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK
| | - Michael E J Lean
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Roy Taylor
- Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
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Beta Cell Physiological Dynamics and Dysfunctional Transitions in Response to Islet Inflammation in Obesity and Diabetes. Metabolites 2020; 10:metabo10110452. [PMID: 33182622 PMCID: PMC7697558 DOI: 10.3390/metabo10110452] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 10/02/2020] [Accepted: 10/10/2020] [Indexed: 02/07/2023] Open
Abstract
Beta cells adapt their function to respond to fluctuating glucose concentrations and variable insulin demand. The highly specialized beta cells have well-established endoplasmic reticulum to handle their high metabolic load for insulin biosynthesis and secretion. Beta cell endoplasmic reticulum therefore recognize and remove misfolded proteins thereby limiting their accumulation. Beta cells function optimally when they sense glucose and, in response, biosynthesize and secrete sufficient insulin. Overnutrition drives the pathogenesis of obesity and diabetes, with adverse effects on beta cells. The interleukin signaling system maintains beta cell physiology and plays a role in beta cell inflammation. In pre-diabetes and compromised metabolic states such as obesity, insulin resistance, and glucose intolerance, beta cells biosynthesize and secrete more insulin, i.e., hyperfunction. Obesity is entwined with inflammation, characterized by compensatory hyperinsulinemia, for a defined period, to normalize glycemia. However, with chronic hyperglycemia and diabetes, there is a perpetual high demand for insulin, and beta cells become exhausted resulting in insufficient insulin biosynthesis and secretion, i.e., they hypofunction in response to elevated glycemia. Therefore, beta cell hyperfunction progresses to hypofunction, and may progressively worsen towards failure. Preserving beta cell physiology, through healthy nutrition and lifestyles, and therapies that are aligned with beta cell functional transitions, is key for diabetes prevention and management.
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Ko J, Skudder-Hill L, Cho J, Bharmal SH, Petrov MS. The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis. Nutrients 2020; 12:nu12092883. [PMID: 32967240 PMCID: PMC7551376 DOI: 10.3390/nu12092883] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 12/14/2022] Open
Abstract
Both type 2 prediabetes/diabetes (T2DM) and new-onset prediabetes/diabetes after acute pancreatitis (NODAP) are characterized by impaired tissue sensitivity to insulin action. Although the outcomes of NODAP and T2DM are different, it is unknown whether drivers of insulin resistance are different in the two types of diabetes. This study aimed to investigate the associations between abdominal fat phenotypes and indices of insulin sensitivity in non-obese individuals with NODAP, T2DM, and healthy controls. Indices of insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA-IS), Raynaud index, triglyceride and glucose (TyG) index, Matsuda index) were calculated in fasting and postprandial states. Fat phenotypes (intra-pancreatic fat, intra-hepatic fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using magnetic resonance imaging and spectroscopy. Linear regression and relative importance analyses were conducted. Age, sex, and glycated hemoglobin A1c were adjusted for. A total of 78 non-obese individuals (26 NODAP, 20 T2DM, and 32 healthy controls) were included. Intra-pancreatic fat was significantly associated with all the indices of insulin sensitivity in the NODAP group, consistently in both the unadjusted and adjusted models. Intra-pancreatic fat was not significantly associated with any index of insulin sensitivity in the T2DM and healthy controls groups. The variance in HOMA-IS was explained the most by intra-pancreatic fat (R2 = 29%) in the NODAP group and by visceral fat (R2 = 21%) in the T2DM group. The variance in the Raynaud index was explained the most by intra-pancreatic fat (R2 = 18%) in the NODAP group and by visceral fat (R2 = 15%) in the T2DM group. The variance in the TyG index was explained the most by visceral fat in both the NODAP group (R2 = 49%) and in the T2DM group (R2 = 25%). The variance in the Matsuda index was explained the most by intra-pancreatic fat (R2 = 48%) in the NODAP group and by visceral fat (R2 = 38%) in the T2DM group. The differing association between intra-pancreatic fat and insulin resistance can be used to differentiate NODAP from T2DM. Insulin resistance in NODAP appears to be predominantly driven by increased intra-pancreatic fat deposition.
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Goedecke JH, Olsson T. Pathogenesis of type 2 diabetes risk in black Africans: a South African perspective. J Intern Med 2020; 288:284-294. [PMID: 32303113 DOI: 10.1111/joim.13083] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 02/25/2020] [Accepted: 03/02/2020] [Indexed: 12/16/2022]
Abstract
The prevalence of type 2 diabetes (T2D) is higher in black Africans than their European counterparts. This review summarizes the research exploring the pathogenesis of T2D in populations of African ancestry compared to white Europeans and shows that the pathogenesis differs by ethnicity. Black Africans present with a phenotype of low insulin sensitivity and hyperinsulinaemia as a result of increased insulin secretion and reduced hepatic insulin clearance. Whether hyperinsulinaemia precedes insulin resistance or is merely a compensatory mechanism is yet to be determined. Black Africans have lower visceral adipose tissue and ectopic fat deposition and greater peripheral (gluteo-femoral) fat deposition than their European counterparts. This suggests that black Africans are more sensitive to the effects of ectopic fat deposition, or alternatively, that ectopic fat is not an important mediator of T2D in black Africans. Importantly, ethnic disparities in T2D risk factors may be confounded by differences in sociocultural and lifestyle factors. Future longitudinal and dietary intervention studies, in combination with genetic analyses, are needed for a better understanding of the pathophysiology of T2D in black Africans. This will be key for effective prevention and management strategies.
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Affiliation(s)
- J H Goedecke
- From the, Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
| | - T Olsson
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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Boga S, Koksal AR, Sen İ, Kurul Yeniay M, Yilmaz Ozguven MB, Serin E, Erturk SM, Alkim H, Alkim C. Liver and pancreas: 'Castor and Pollux' regarding the relationship between hepatic steatosis and pancreas exocrine insufficiency. Pancreatology 2020; 20:880-886. [PMID: 32475757 DOI: 10.1016/j.pan.2020.04.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 04/07/2020] [Accepted: 04/27/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) is found in 30-50% of diabetes mellitus (DM). Insulin resistance is triggering factor in both DM and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to investigate frequency of PEI in NAFLD, and relationship of fecal pancreatic elastase (PE) levels with liver histology and pancreatic fat. METHODS Ninety-seven biopsy proven NAFLD patients and 50 controls were enrolled. Pancreas exocrine functions were measured by PE. Magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) was used to quantify fat. RESULTS NAFLD patients had significantly lower PE levels than controls (297 [204-517] vs. 500 [298-678] μg/g, p < 0.01). PEI (PE < 200 μg/g) ratio of NAFLD patients (22.7%, n = 22) was higher than PEI ratio of controls (6%, n = 3) (p = 0.011). Among diabetic (n = 35) NAFLD patients, 9 (25.7%) exhibited PEI, compared to 13 (21%) of non-diabetics. There was no significant difference in patients with and without DM in terms of PEI (p = 0.592). Among NASH (n = 68) patients 16 (23.5%) exhibited PEI, compared to (20.7%) of non-NASH (p = 0.76). Multiple analysis revealed NAFLD as a predictor of PEI independent of age, sex and DM (OR = 4.892, p = 0,021). Mean pancreas MRI-PDFF was significantly higher in diabetics (13.7% ± 3.6% vs. 8.7% ± 5.1%, p = 0.001). There was no significant pancreas MRI-PDFF difference between NASH and non-NASH (P = 0.95). Mean pancreas MRI-PDFF was significantly higher in patients with PEI (13.7% ± 3.4% vs. 8.9% ± 5.2%, P < 0.01). CONCLUSION This is the first study demonstrating the high frequency of PEI in NAFLD independent of DM. Moreover, increasing pancreatic steatosis appears to be associated with higher frequency of PEI in NAFLD.
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Affiliation(s)
- Salih Boga
- Associate Professor of Gastroenterology, Department of Gastroenterology, Bahcelievler Memorial Hospital, Turkey.
| | - Ali Riza Koksal
- Tulane University, School of Medicine, Department of Medicine, Section of Gastroenterology and Hepatology, USA.
| | - İlker Sen
- Specialist of Gastroenterology and Internal Medicine, Department of Gastroenterology, Sisli Hamidiye Etfal Education and Research Hospital, Turkey.
| | - Muge Kurul Yeniay
- Specialist of Internal Medicine, Department of Internal Medicine, Sisli Hamidiye Etfal Education and Research Hospital, Turkey.
| | - Muveddet Banu Yilmaz Ozguven
- Associate Professor of of Pathology, Department of Pathology, Sisli Hamidiye Etfal Education and Research Hospital, Turkey.
| | - Erdinc Serin
- Associate Professor of of Medical Biochemistry, Department of Biochemistry, Sisli Hamidiye Etfal Education and Research Hospital, Turkey.
| | - Sukru Mehmet Erturk
- Professor of of Radiology, Department of Radiology, Sisli Hamidiye Etfal Education and Research Hospital, Turkey.
| | - Huseyin Alkim
- Professor of Gastroenterology, Department of Gastroenterology, Sisli Hamidiye Etfal Education and Research Hospital, Turkey.
| | - Canan Alkim
- Professor of Gastroenterology, Department of Gastroenterology, Sisli Hamidiye Etfal Education and Research Hospital, Turkey.
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Shah N, Rocha JP, Bhutiani N, Endashaw O. Nonalcoholic Fatty Pancreas Disease. Nutr Clin Pract 2020; 34 Suppl 1:S49-S56. [PMID: 31535735 DOI: 10.1002/ncp.10397] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Nonalcoholic fatty pancreas disease (NAFPD) describes a phenotype of pancreatic steatosis (PS) that is not caused by alcohol consumption, viral infections, toxins, or congenital metabolic syndromes but is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, or increasing age. NAFPD is a relatively new disease entity, as the clinical significance of fatty infiltration of pancreas has gained attention recently. Clinical consequences of NAFPD remain largely unknown despite clinical associations. This review aims to study similarities and differences between hepatic and PS and explore recent advances in NAFPD.
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Affiliation(s)
- Nihar Shah
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky, USA
| | - Jason P Rocha
- Division of Gastroenterology and Nutrition, University of Texas Health San Antonio, San Antonio, Texas, USA
| | - Neal Bhutiani
- Department of Surgery and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA
| | - Omer Endashaw
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky, USA
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Liu KL, Wu T, Chen PT, Tsai YM, Roth H, Wu MS, Liao WC, Wang W. Deep learning to distinguish pancreatic cancer tissue from non-cancerous pancreatic tissue: a retrospective study with cross-racial external validation. LANCET DIGITAL HEALTH 2020; 2:e303-e313. [DOI: 10.1016/s2589-7500(20)30078-9] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 03/24/2020] [Accepted: 03/25/2020] [Indexed: 02/08/2023]
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Vieira J, Amorim J, Martí-Bonmatí L, Alberich-Bayarri Á, França M. Quantifying steatosis in the liver and pancreas with MRI in patient with chronic liver disease. RADIOLOGIA 2020. [DOI: 10.1016/j.rxeng.2019.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Tremmel DM, Feeney AK, Mitchell SA, Chlebeck PJ, Raglin S, Fernandez LA, Odorico JS, Sackett SD. Hypertension, but not body mass index, is predictive of increased pancreatic lipid content and islet dysfunction. Am J Transplant 2020; 20:1105-1115. [PMID: 31715064 PMCID: PMC7103563 DOI: 10.1111/ajt.15698] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 10/15/2019] [Accepted: 11/04/2019] [Indexed: 01/25/2023]
Abstract
Pancreatic steatosis is thought to be a negative risk factor for pancreas transplant outcomes. Despite considering donor body mass index (BMI) and the visualization of intercalated fat as indicators of donor pancreas lipid content, transplant surgeons do not use a quantitative method to directly measure steatosis when deciding to transplant a pancreas. In this study, we used nondiabetic human pancreata donated for research to measure the pancreatic and islet-specific lipid content to determine which clinical markers correlate best with lipid content. Interestingly, we found that BMI and age correlate with increased pancreatic lipid content (Panc-LC) in men, but not women. Our findings further suggest that total Panc-LC correlates with an increase in islet lipid content for both men and women. We noted that pancreata donated from individuals with a history of hypertension have increased Panc-LC independent of donor BMI or sex. Moreover, we identify hypertension as a risk factor for reduced islet function after islet isolation. Together, our findings emphasize differences in pancreas graft quality related to pancreatic and islet lipid content, which may not be predicted by assessing BMI alone but may be influenced by a donor history of hypertension.
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Affiliation(s)
- Daniel M. Tremmel
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA.,Co-first authors
| | - Austin K. Feeney
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA.,Co-first authors
| | - Samantha A. Mitchell
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA
| | - Peter J. Chlebeck
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA
| | - Sierra Raglin
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA
| | - Luis A. Fernandez
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA
| | - Jon S. Odorico
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA
| | - Sara D. Sackett
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, 53705, USA
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Marinho TDS, Borges CC, Aguila MB, Mandarim-de-Lacerda CA. Intermittent fasting benefits on alpha- and beta-cell arrangement in diet-induced obese mice pancreatic islet. J Diabetes Complications 2020; 34:107497. [PMID: 31866258 DOI: 10.1016/j.jdiacomp.2019.107497] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 12/21/2022]
Abstract
AIMS There is a pancreatic islet adaptation in obese subjects, resulting in insulin resistance and diabetes type 2. We studied the effect of intermittent fasting (IntF) on the islet structure of diet-induced obese (DIO) mice. METHODS Three-month-old male mice fed a control diet (C, 10% Kcal fat) or a high-fat diet (HF, 50% Kcal fat) for two months (n = 20 each group). Then, half of each group did IntF (alternating 24 h fed/24 h fast), continuing in their diets four more weeks: C, C-IntF, HF, HF-IntF. Islets were prepared to microscopy or isolated for molecular analysis. RESULTS HF group (vs. C group) showed hyperglycemia, hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, glucose intolerance, insulin resistance, and islet hypertrophy with a consequent higher both the alpha-cell and beta-cell masses. In the HF group (vs. C), there was low PDX1 (pancreatic and duodenal homeobox 1), and IntF did not alter PDX1. There was a low p-AKT/AKT ratio (protein kinase B), and IntF enhanced it. Also, tumor suppressor p53 was increased, and IntF decreased it. IL (interleukin) -6 was higher in the HF group (vs. C), and HF-IntF (vs. C-IntF). Any significant change in NFkB was seen among groups. CONCLUSIONS IntF improves pancreatic islet structure in DIO mice, even with continued HF diet intake, primarily considering on the alpha- and beta-cell masses regulation, then improving insulin signaling and decreasing cell apoptosis. Future research should explore whether the shortening of the IntF extend could maintain the benefits observed in the long term.
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Affiliation(s)
- Thatiany de Souza Marinho
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Celina Carvalho Borges
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcia Barbosa Aguila
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos Alberto Mandarim-de-Lacerda
- Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
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45
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Vieira J, Amorim J, Martí-Bonmatí L, Alberich-Bayarri Á, França M. Quantifying steatosis in the liver and pancreas with MRI in patient with chronic liver disease. RADIOLOGIA 2020; 62:222-228. [PMID: 31932016 DOI: 10.1016/j.rx.2019.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 09/08/2019] [Accepted: 11/04/2019] [Indexed: 12/13/2022]
Abstract
AIM To compare pancreatic and hepatic steatosis quantified by proton density fat fraction (PDFF) on magnetic resonance imaging (MRI) in patients with chronic liver disease. MATERIAL AND METHODS This cross-sectional study included 46 adult patients who underwent liver biopsy for chronic viral hepatitis (n=19) or other chronic non-alcoholic liver diseases (NALD) (n=27). Liver biopsy was used as the gold standard for diagnosing and grading hepatic steatosis. All patients underwent clinical evaluation and MRI with a multi-echo chemical shift-encoded (MECSE) gradient-echo sequence for liver and pancreas PDFF quantification. We used Spearman's correlation coefficient to determine the degree of association between hepatic PDFF and steatosis grade, and between pancreatic PDFF and steatosis grade and hepatic PDFF. To compare the chronic viral hepatitis group and the NALD group, we used t-tests for continuous or ordinal variables and chi-square tests for categorical variables. RESULTS Hepatic PDFF measurements correlated with steatosis grades (RS=0.875, p<0.001). Pancreatic PDFF correlated with hepatic steatosis grades (RS=0.573, p<0.001) and hepatic PDFF measurements (RS=0.536, p<0.001). In the subgroup of patients with chronic NALD, the correlations remained significant between pancreatic PDFF and hepatic PDFF (RS=0.632, p<0.001) and between pancreatic PDFF and liver steatosis (RS=0.608, p<0.001); however, in the subgroup of patients with viral hepatitis these correlations were no longer significant. CONCLUSION Pancreatic fat deposition correlates with hepatic steatosis in patients with chronic NALD, but not in those with chronic viral hepatitis.
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Affiliation(s)
- J Vieira
- Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidad de Oporto, Oporto, Portugal.
| | - J Amorim
- Departamento de Diagnóstico por la Imagen, Centro Hospitalar do Porto, Oporto, Portugal; Escola de Medicina, Universidade do Minho, Braga, Portugal; ICVS/3B's, Instituto de Investigación de Ciencias de la Vida y la Salud, Universidade do Minho, Braga, Portugal
| | - L Martí-Bonmatí
- Departamento de Radiología y Grupo de Investigación Biomédica en Imagen GIBI2(30). Hospital Universitario y Politécnico La Fe e Instituto de Investigación Sanitaria La Fe, Valencia, España
| | - Á Alberich-Bayarri
- Departamento de Radiología y Grupo de Investigación Biomédica en Imagen GIBI2(30). Hospital Universitario y Politécnico La Fe e Instituto de Investigación Sanitaria La Fe, Valencia, España; Quantitative Imaging Biomarkers in Medicine (QUIBIM), Valencia, España
| | - M França
- Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidad de Oporto, Oporto, Portugal; Departamento de Diagnóstico por la Imagen, Centro Hospitalar do Porto, Oporto, Portugal; i3S, Instituto de Investigacão e Inovação em Saúde, IBMC, Instituto de Biología Molecular y Celular, Oporto, Portugal
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Li YX, Sang YQ, Sun Y, Liu XK, Geng HF, Zha M, Wang B, Teng F, Sun HJ, Wang Y, Qiu QQ, Zang X, Wang Y, Wu TT, Jones PM, Liang J, Xu W. Pancreatic Fat is not significantly correlated with β-cell Dysfunction in Patients with new-onset Type 2 Diabetes Mellitus using quantitative Computed Tomography. Int J Med Sci 2020; 17:1673-1682. [PMID: 32714070 PMCID: PMC7378671 DOI: 10.7150/ijms.46395] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 06/19/2020] [Indexed: 12/14/2022] Open
Abstract
Objective: Type 2 diabetes mellitus (T2DM) is a chronic condition resulting from insulin resistance and insufficient β-cell secretion, leading to improper glycaemic regulation. Previous studies have found that excessive fat deposits in organs such as the liver and muscle can cause insulin resistance through lipotoxicity that affects β-cell function. The relationships between fat deposits in pancreatic tissue, the function of β-cells, the method of visceral fat evaluation and T2DM have been sought by researchers. This study aims to elucidate the role of pancreatic fat deposits in the development of T2DM using quantitative computed tomography (QCT), especially their effects on islet β-cell function. Methods: We examined 106 subjects at the onset of T2DM who had undergone abdominal QCT. Estimated pancreatic fat and liver fat were quantified using QCT and calculated. We analysed the correlations with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores and other oral glucose tolerance test-derived parameters that reflect islet function. Furthermore, correlations of estimated pancreatic fat and liver fat with the area under the curve for insulin (AUCINS) and HOMA-IR were assessed with partial correlation analysis and demonstrated by scatter plots. Results: Associations were found between estimated liver fat and HOMA-IR, AUCINS, the modified β-cell function index (MBCI) and Homeostatic Model Assessment β (HOMA-β). However, no significant differences existed between estimated pancreas fat and those parameters. Similarly, after adjustment for sex, age and body mass index, only estimated liver fat was correlated with HOMA-IR and AUCINS. Conclusions: This study suggests no significant correlation between pancreatic fat deposition and β-cell dysfunction in the early stages of T2DM using QCT as a screening tool. The deposits of fat in the pancreas and the resulting lipotoxicity may play an important role in the late stage of islet cell function dysfunction as the course of T2DM progresses.
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Affiliation(s)
- Y X Li
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China.,Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Y Q Sang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Yan Sun
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - X K Liu
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - H F Geng
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Min Zha
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Jiangsu, China
| | - Ben Wang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Fei Teng
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - H J Sun
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Yu Wang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Q Q Qiu
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Xiu Zang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Yun Wang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - T T Wu
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Peter M Jones
- Diabetes Research Group, Division of Diabetes & Nutritional Sciences, School of Medicine, King's College London, London, UK
| | - Jun Liang
- Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China
| | - Wei Xu
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China.,Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Nanjing Medical University, Affiliated Hospital of Medical School of Southeast University, Jiangsu, China.,Diabetes Research Group, Division of Diabetes & Nutritional Sciences, School of Medicine, King's College London, London, UK
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47
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Al Juboori A, Chela H, Samiullah S, Tahan V. Nonalcoholic Fatty Pancreatic Disease (NAFPD). OBESITY AND DIABETES 2020:335-345. [DOI: 10.1007/978-3-030-53370-0_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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49
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Kim M, Kim SK, Jung J. Obese Subjects with Non-Alcoholic Fatty Liver Disease Have a Higher Risk of Thyroid Dysfunction. KOSIN MEDICAL JOURNAL 2019. [DOI: 10.7180/kmj.2019.34.2.117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Objectives The effects of obesity on thyroid function have not been well established. The aim of this study was to investigate the effects of body mass index (BMI) and/or non-alcoholic fatty liver disease (NAFLD) on thyroid function. Methods A retrospective longitudinal analysis was conducted among subjects who underwent comprehensive health check-ups at least four times between 2008 and 2017. Thyroid function was investigated according to BMI or presence of NAFLD at the end of follow-up. The subjects were divided into four groups: control (n = 216), subjects with obese (n = 94), subjects with NAFLD (n = 48), and subjects with obese + NAFLD (n = 93). Obesity was defined as BMI ≥ 25 kg/m2. Results During the mean follow-up of 6.8 years (6.8 ± 1.2 years), 42 of the 451 subjects (9.3%) had subclinical hypothyroidism (SCH) but no subjects developed overt hypothyroidism. In multivariate Cox proportional hazard analysis, after adjustment for age, sex, smoking, and baseline thyroid stimulating hormone level, obese subjects with NAFLD had a higher risk of SCH than the control group. Conclusions The obese subjects with NAFLD had a higher risk for SCH in the future.
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50
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Abstract
Pancreatic steatosis is an emerging clinical entity whose pathophysiology, natural history, and long-term complications are poorly characterized in the current literature. Epidemiological and prospective studies have described prevalence rates between 16% and 35%. Although the natural history is not well known, there are strong associations with obesity, metabolic syndrome, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Ectopic fat accumulation of the pancreas can cause chronic, low-grade inflammation from adipocytokine imbalances that involve beta cells and acinar cells. This mechanism can lead to pancreatic endocrine and exocrine dysfunction and initiate carcinogenesis. Although it is associated with morbid conditions, pancreatic steatosis may be amendable to treatment with a healthy diet, less meat consumption, exercise, and smoking cessation. Pancreatic steatosis should factor into clinical decision-making and prognostication of patients with pancreatic and systemic disease. This review seeks to describe the pathophysiology, natural history, diagnosis, and complications of this emerging clinically relevant entity.
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