|
1
|
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.
Collapse
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.
| |
Collapse
|
|
2
|
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.
Collapse
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
| |
Collapse
|
|
3
|
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.
Collapse
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
| |
Collapse
|
|
4
|
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.
Collapse
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
| |
Collapse
|
|
5
|
Cao MJ, Wu WJ, Chen JW, Fang XM, Ren Y, Zhu XW, Cheng HY, Tang QF. Quantification of ectopic fat storage in the liver and pancreas using six-point Dixon MRI and its association with insulin sensitivity and β-cell function in patients with central obesity. Eur Radiol 2023; 33:9213-9222. [PMID: 37410109 DOI: 10.1007/s00330-023-09856-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 04/26/2023] [Accepted: 05/14/2023] [Indexed: 07/07/2023]
Abstract
OBJECTIVES To assess the association of ectopic fat deposition in the liver and pancreas quantified by Dixon magnetic resonance imaging (MRI) with insulin sensitivity and β-cell function in patients with central obesity. MATERIALS AND METHODS A cross-sectional study of 143 patients with central obesity with normal glucose tolerance (NGT), prediabetes (PreD), and untreated type 2 diabetes mellitus (T2DM) was conducted between December 2019 and March 2022. All participants underwent routine medical history taking, anthropometric measurements, and laboratory tests, including a standard glucose tolerance test to quantify insulin sensitivity and β-cell function. The fat content in the liver and pancreas was measured with MRI using the six-point Dixon technique. RESULTS Patients with T2DM and PreD had a higher liver fat fraction (LFF) than those with NGT, while those with T2DM had a higher pancreatic fat fraction (PFF) than those with PreD and NGT. LFF was positively correlated with homeostatic model assessment of insulin resistance (HOMA-IR), while PFF was negatively correlated with homeostatic model assessment of insulin secretion (HOMA-β). Furthermore, using a structured equation model, we found LFF and PFF to be positively associated with glycosylated hemoglobin via HOMA-IR and HOMA-β, respectively. CONCLUSIONS In patients with central obesity, the effects of LFF and PFF on glucose metabolism. were associated with HOMA-IR and HOMA-β, respectively. Ectopic fat storage in the liver and pancreas quantified by MR Dixon imaging potentially plays a notable role in the onset ofT2DM. CLINICAL RELEVANCE STATEMENT We highlight the potential role of ectopic fat deposition in the liver and pancreas in the development of type 2 diabetes in patients with central obesity, providing valuable insights into the pathogenesis of the disease and potential targets for intervention. KEY POINTS • Ectopic fat deposition in the liver and pancreas is associated with T2DM. • T2DM and prediabetes patients had higher liver and pancreatic fat fractions than normal individuals. • The results provide valuable insights into pathogenesis of T2DM and potential targets for intervention.
Collapse
Affiliation(s)
- Meng-Jiao Cao
- Department of Radiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China
| | - Wen-Jun Wu
- Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China.
| | - Jing-Wen Chen
- Department of Radiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China
| | - Xiang-Ming Fang
- Department of Radiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China
| | - Ye Ren
- Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China
| | - Xiao-Wen Zhu
- Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China
| | - Hai-Yan Cheng
- Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China
| | - Qun-Feng Tang
- Department of Radiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No. 299 Qingyang Road, Wuxi , Jiangsu Province, 214000, China.
| |
Collapse
|
|
6
|
Ramzan F, Sequeira-Bisson IR, Lu LW, Mitchell CJ, D’Souza RF, Vickers MH, Poppitt SD, Cameron-Smith D. Circulatory miRNAs as Correlates of Elevated Intra-Pancreatic Fat Deposition in a Mixed Ethnic Female Cohort: The TOFI_Asia Study. Int J Mol Sci 2023; 24:14393. [PMID: 37762694 PMCID: PMC10532072 DOI: 10.3390/ijms241814393] [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: 08/07/2023] [Revised: 09/12/2023] [Accepted: 09/15/2023] [Indexed: 09/29/2023] Open
Abstract
Ectopic lipid accumulation, including intra-pancreatic fat deposition (IPFD), exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified as correlating with clinical measures of pancreatitis, pancreatic cancer and type 1 diabetes. The aim of the current study was therefore to examine the association between circulating abundances of candidate miRNAs, IPFD and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS). Asian Chinese (n = 34; BMI = 26.7 ± 4.2 kg/m2) and European Caucasian (n = 34; BMI = 28.0 ± 4.5 kg/m2) females from the TOFI_Asia cohort underwent MRI and MRS analysis of pancreas (MR-%IPFD) and liver fat (MR-%liver fat), respectively, to quantify ectopic lipid deposition. Plasma miRNA abundances of a subset of circulatory miRNAs associated with IPFD and liver fat deposition were quantified by qRT-PCR. miR-21-3p and miR-320a-5p correlated with MR-%IPFD, plasma insulin and HOMA2-IR, but not MR-%liver fat. MR-%IPFD remained associated with decreasing miR-21-3p abundance following multivariate regression analysis. miR-21-3p and miR-320a were demonstrated to be negatively correlated with MR-%IPFD, independent of ethnicity. For miR-21-3p, this relationship persists with the inclusion of MR-%liver fat in the model, suggesting the potential for a wider application as a specific circulatory correlate of IPFD.
Collapse
Affiliation(s)
- Farha Ramzan
- Liggins Institute, The University of Auckland, Auckland 1023, New Zealand (D.C.-S.)
| | - Ivana R. Sequeira-Bisson
- The High-Value Nutrition National Science Challenge, Auckland 1023, New Zealand (S.D.P.)
- Human Nutrition Unit, School of Biological Sciences, Faculty of Science, The University of Auckland, Auckland 1010, New Zealand
- The Riddet Institute, Massey University, Palmerston North 4410, New Zealand
| | - Louise W. Lu
- The High-Value Nutrition National Science Challenge, Auckland 1023, New Zealand (S.D.P.)
- Human Nutrition Unit, School of Biological Sciences, Faculty of Science, The University of Auckland, Auckland 1010, New Zealand
| | - Cameron J. Mitchell
- School of Kinesiology, The University of British Columbia, Vancouver, BC V6T 1Z1, Canada
| | - Randall F. D’Souza
- School of Medical Sciences, The University of Auckland, Auckland 1023, New Zealand
| | - Mark H. Vickers
- Liggins Institute, The University of Auckland, Auckland 1023, New Zealand (D.C.-S.)
| | - Sally D. Poppitt
- The High-Value Nutrition National Science Challenge, Auckland 1023, New Zealand (S.D.P.)
- Human Nutrition Unit, School of Biological Sciences, Faculty of Science, The University of Auckland, Auckland 1010, New Zealand
- The Riddet Institute, Massey University, Palmerston North 4410, New Zealand
- Department of Medicine, The University of Auckland, Auckland 1023, New Zealand
| | - David Cameron-Smith
- Liggins Institute, The University of Auckland, Auckland 1023, New Zealand (D.C.-S.)
- School of Agriculture, Food and Ecosystem Sciences, The University of Melbourne, Melbourne 3010, Australia
| |
Collapse
|
|
7
|
Zhang QH, Chen LH, An Q, Pi P, Dong YF, Zhao Y, Wang N, Fang X, Pu RW, Song QW, Lin LJ, Liu JH, Liu AL. Quantification of the renal sinus fat and exploration of its relationship with ectopic fat deposition in normal subjects using MRI fat fraction mapping. Front Endocrinol (Lausanne) 2023; 14:1187781. [PMID: 37621645 PMCID: PMC10446762 DOI: 10.3389/fendo.2023.1187781] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 05/29/2023] [Indexed: 08/26/2023] Open
Abstract
Purpose To determine the renal sinus fat (RSF) volume and fat fraction (FF) in normal Chinese subjects using MRI fat fraction mapping and to explore their associations with age, gender, body mass index (BMI) and ectopic fat deposition. Methods A total of 126 subjects were included in the analysis. RSF volume and FF, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, and hepatic and pancreatic FFs were measured for each subject. The comparisons in gender were determined using two-tailed t-tests or the nonparametric Mann-Whitney U-test for normally or non-normally distributed data for continuous variables and the chi-square test for categorical variables. Comparisons of RFS volume and FF between right and left kidneys were determined using paired sample t-tests. Multivariable logistic models were performed to confirm whether RSF differences between men and women are independent of VAT or SAT area. When parameters were normally distributed, the Pearson correlation coefficient was used; otherwise, the Spearman correlation coefficient was applied. Results The RSF volumes (cm3) of both kidneys in men (26.86 ± 8.81 for right and 31.62 ± 10.32 for left kidneys) were significantly bigger than those of women (21.47 ± 6.90 for right and 26.03 ± 8.55 for left kidneys) (P < 0.05). The RSF FFs (%) of both kidneys in men (28.33 ± 6.73 for right and 31.21 ± 6.29 for left kidneys) were significantly higher than those of the women (23.82 ± 7.74 for right and 27.92 ± 8.15 for left kidneys) (P < 0.05). The RSF differences between men and women are independent of SAT area and dependent of VAT area (except for right RSF volume). In addition, the RSF volumes and FFs in both kidneys in the overall subjects show significant correlations with age, BMI, VAT area, hepatic fat fraction and pancreatic fat fraction (P < 0.05). However, the patterns of these correlations varied by gender. The RSF volume and FF of left kidney were significantly larger than those of the right kidney (P < 0.05). Conclusion The association between renal sinus fat and ectopic fat deposition explored in this study may help establish a consensus on the normal values of RSF volume and FF for the Chinese population. This will facilitate the identification of clinicopathological changes and aid in the investigation of whether RSF volume and FF can serve as early biomarkers for metabolic diseases and renal dysfunction in future studies.
Collapse
Affiliation(s)
- Qin-He Zhang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Li-Hua Chen
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qi An
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Peng Pi
- Department of Medical Imaging, Dalian Medical University, Dalian, China
| | - Yi-Fan Dong
- Department of Medical Imaging, Dalian Medical University, Dalian, China
| | - Ying Zhao
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Nan Wang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xin Fang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ren-Wang Pu
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qing-Wei Song
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Liang-Jie Lin
- Clinical & Technical Solutions, Philips Healthcare, Beijing, China
| | - Jing-Hong Liu
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ai-Lian Liu
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| |
Collapse
|
|
8
|
Hassan S, Gujral UP, Quarells RC, Rhodes EC, Shah MK, Obi J, Lee WH, Shamambo L, Weber MB, Narayan KMV. Disparities in diabetes prevalence and management by race and ethnicity in the USA: defining a path forward. Lancet Diabetes Endocrinol 2023; 11:509-524. [PMID: 37356445 PMCID: PMC11070656 DOI: 10.1016/s2213-8587(23)00129-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 06/27/2023]
Abstract
Type 2 diabetes disparities in the USA persist in both the prevalence of disease and diabetes-related complications. We conducted a literature review related to diabetes prevention, management, and complications across racial and ethnic groups in the USA. The objective of this review is to summarise the current understanding of diabetes disparities by examining differences between and within racial and ethnic groups and among young people (aged <18 years). We also examine the pathophysiology of diabetes as it relates to race and ethnic differences. We use a conceptual framework built on the socioecological model to categorise the causes of diabetes disparities across the lifespan looking at factors in five domains of health behaviours and social norms, public awareness, structural racism, economic development, and access to high-quality care. The range of disparities in diabetes prevalence and management in the USA calls for a community-engaged and multidisciplinary approach that must involve community partners, researchers, practitioners, health system administrators, and policy makers. We offer recommendations for each of these groups to help to promote equity in diabetes prevention and care in the USA.
Collapse
Affiliation(s)
- Saria Hassan
- Department of Medicine, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA.
| | - Unjali P Gujral
- Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
| | - Rakale C Quarells
- Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Department of Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, GA, USA
| | - Elizabeth C Rhodes
- Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
| | - Megha K Shah
- Department of Family and Preventive Medicine, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA
| | - Jane Obi
- Emory School of Medicine, and the Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA
| | - Wei-Hsuan Lee
- Department of Medicine, Emory University, Atlanta, GA, USA
| | - Luwi Shamambo
- Department of Medicine, Emory University, Atlanta, GA, USA
| | - Mary Beth Weber
- Emory School of Medicine, and the Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
| | - K M Venkat Narayan
- Department of Medicine, Emory University, Atlanta, GA, USA; Emory School of Medicine, and the Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
| |
Collapse
|
|
9
|
Viriyasaranon T, Chun JW, Koh YH, Cho JH, Jung MK, Kim SH, Kim HJ, Lee WJ, Choi JH, Woo SM. Annotation-Efficient Deep Learning Model for Pancreatic Cancer Diagnosis and Classification Using CT Images: A Retrospective Diagnostic Study. Cancers (Basel) 2023; 15:3392. [PMID: 37444502 DOI: 10.3390/cancers15133392] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/26/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
The aim of this study was to develop a novel deep learning (DL) model without requiring large-annotated training datasets for detecting pancreatic cancer (PC) using computed tomography (CT) images. This retrospective diagnostic study was conducted using CT images collected from 2004 and 2019 from 4287 patients diagnosed with PC. We proposed a self-supervised learning algorithm (pseudo-lesion segmentation (PS)) for PC classification, which was trained with and without PS and validated on randomly divided training and validation sets. We further performed cross-racial external validation using open-access CT images from 361 patients. For internal validation, the accuracy and sensitivity for PC classification were 94.3% (92.8-95.4%) and 92.5% (90.0-94.4%), and 95.7% (94.5-96.7%) and 99.3 (98.4-99.7%) for the convolutional neural network (CNN) and transformer-based DL models (both with PS), respectively. Implementing PS on a small-sized training dataset (randomly sampled 10%) increased accuracy by 20.5% and sensitivity by 37.0%. For external validation, the accuracy and sensitivity were 82.5% (78.3-86.1%) and 81.7% (77.3-85.4%) and 87.8% (84.0-90.8%) and 86.5% (82.3-89.8%) for the CNN and transformer-based DL models (both with PS), respectively. PS self-supervised learning can increase DL-based PC classification performance, reliability, and robustness of the model for unseen, and even small, datasets. The proposed DL model is potentially useful for PC diagnosis.
Collapse
Affiliation(s)
- Thanaporn Viriyasaranon
- Graduate Program in System Health Science and Engineering, Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Jung Won Chun
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Republic of Korea
| | - Young Hwan Koh
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Republic of Korea
| | - Jae Hee Cho
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Min Kyu Jung
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu 41944, Republic of Korea
| | - Seong-Hun Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
| | - Hyo Jung Kim
- Department of Gastroenterology, Korea University Guro Hospital, Seoul 10408, Republic of Korea
| | - Woo Jin Lee
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Republic of Korea
| | - Jang-Hwan Choi
- Graduate Program in System Health Science and Engineering, Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Sang Myung Woo
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Republic of Korea
| |
Collapse
|
|
10
|
Mukherjee S, Maheshwari D, Pal R, Sachdeva N. Pancreatic fat in type 2 diabetes: Causal or coincidental? World J Meta-Anal 2023; 11:68-78. [DOI: 10.13105/wjma.v11.i3.68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/27/2022] [Accepted: 02/15/2023] [Indexed: 03/01/2023] Open
|
|
11
|
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.
Collapse
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
| |
Collapse
|
|
12
|
Story JD, Ghahremani S, Kafali SG, Shih SF, Kuwahara KJ, Calkins KL, Wu HH. Using Free-Breathing MRI to Quantify Pancreatic Fat and Investigate Spatial Heterogeneity in Children. J Magn Reson Imaging 2023; 57:508-518. [PMID: 35778376 PMCID: PMC9805469 DOI: 10.1002/jmri.28337] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 06/17/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND MRI acquisition for pediatric pancreatic fat quantification is limited by breath-holds (BH). Full segmentation (FS) or small region of interest (ROI) analysis methods may not account for pancreatic fat spatial heterogeneity, which may limit accuracy. PURPOSE To improve MRI acquisition and analysis for quantifying pancreatic proton-density fat fraction (pPDFF) in children by investigating free-breathing (FB)-MRI, characterizing pPDFF spatial heterogeneity, and relating pPDFF to clinical markers. STUDY TYPE Prospective. POPULATION A total of 34 children, including healthy (N = 16, 8 female) and overweight (N = 18, 5 female) subjects. FIELD STRENGTH AND SEQUENCES 3 T; multiecho gradient-echo three-dimensional (3D) stack-of-stars FB-MRI, multiecho gradient-echo 3D Cartesian BH-MRI. ASSESSMENT A radiologist measured FS- and ROI-based pPDFF on FB-MRI and BH-MRI PDFF maps, with anatomical images as references. Regional pPDFF in the pancreatic head, body, and tail were measured on FB-MRI. FS-pPDFF, ROI-pPDFF, and regional pPDFF were compared, and related to clinical markers, including hemoglobin A1c. STATISTICAL TESTS T-test, Bland-Altman analysis, Lin's concordance correlation coefficient (CCC), one-way analysis of variance, and Spearman's rank correlation coefficient were used. P < 0.05 was considered significant. RESULTS FS-pPDFF and ROI-pPDFF from FB-MRI and BH-MRI had mean difference = 0.4%; CCC was 0.95 for FS-pPDFF and 0.62 for ROI-pPDFF. FS-pPDFF was higher than ROI-pPDFF (10.4% ± 6.4% vs. 4.2% ± 2.8%). Tail-pPDFF (11.6% ± 8.1%) was higher than body-pPDFF (8.9% ± 6.3%) and head-pPDFF (8.7% ± 5.2%). Head-pPDFF and body-pPDFF positively correlated with hemoglobin A1c. DATA CONCLUSION FB-MRI pPDFF is comparable to BH-MRI. Spatial heterogeneity affects pPDFF quantification. Regional measurements of pPDFF in the head and body were correlated with hemoglobin A1c, a marker of insulin sensitivity. EVIDENCE LEVEL 2 TECHNICAL EFFICACY: Stage 2.
Collapse
Affiliation(s)
- Jacob D. Story
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Shahnaz Ghahremani
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Sevgi Gokce Kafali
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, United States
| | - Shu-Fu Shih
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, United States
| | - Kelsey J. Kuwahara
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
| | - Kara L. Calkins
- Department of Pediatrics, Division of Neonatology and Developmental Biology, and the UCLA Children’s Discovery and Innovation Institute, University of California Los Angeles, Los Angeles, CA, United States
| | - Holden H. Wu
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, United States
| |
Collapse
|
|
13
|
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.
Collapse
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
| |
Collapse
|
|
14
|
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.
Collapse
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:
| |
Collapse
|
|
15
|
Choudhury SR, Verma M, Gupta P, Singh H, Sharma V, Kochhar R. Ultrasound Shear Wave Elastography of Normal Pancreas in Adult Subjects. JOURNAL OF GASTROINTESTINAL AND ABDOMINAL RADIOLOGY 2022. [DOI: 10.1055/s-0042-1758126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Abstract
Background and Purpose Transabdominal ultrasound (US)-based shear wave elastography (SWE) provides an attractive method of estimating pancreatic stiffness. There is limited data on the SWE values of the healthy pancreas in Indian subjects. The current study aimed to evaluate SWE of the normal pancreas.
Methods We performed a study from January 2019 to March 2019. We included adult patients who presented for the US of the upper abdomen for vague abdominal symptoms, unrelated to the pancreas. The SWE values were obtained from the pancreatic head and body. The association of pancreatic SWE with age, gender, fatty liver, chronic liver disease, and cholelithiasis was recorded.
Results During the study period, 205 subjects underwent SWE of the pancreas. The mean age of subjects was 41.3 (standard deviation [SD] 15.3) years. There were 93 males and 112 females. The mean SWE value in the head of the pancreas was 8.98 (SD 2.46 kPa), and that in the body region was 8.67 (SD 2.67 kPa). There was a positive correlation of SWE with age. The SWE of the pancreatic body was significantly higher in patients who had a fatty liver on US (p < 0.05). There was no significant association of SWE of the pancreas with gender, presence of chronic liver disease, or gallstones.
Conclusion The normal values of pancreatic SWE are correlated with age and fatty change in the liver.
Collapse
Affiliation(s)
- Shayeri Roy Choudhury
- Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Mansi Verma
- Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pankaj Gupta
- Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Harjeet Singh
- Department of Surgical Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
16
|
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.
Collapse
|
|
17
|
Cadenas-Sanchez C, Cabeza R, Idoate F, Osés M, Medrano M, Villanueva A, Arenaza L, Sanz A, Ortega FB, Ruiz JR, Labayen I. Effects of a Family-Based Lifestyle Intervention Plus Supervised Exercise Training on Abdominal Fat Depots in Children With Overweight or Obesity: A Secondary Analysis of a Nonrandomized Clinical Trial. JAMA Netw Open 2022; 5:e2243864. [PMID: 36441551 PMCID: PMC9706365 DOI: 10.1001/jamanetworkopen.2022.43864] [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: 11/29/2022] Open
Abstract
IMPORTANCE Excess abdominal fat is a major determinant in the development of insulin resistance and other metabolic disorders. Increased visceral adipose tissue (VAT) seems to precede the development of insulin resistance and is therefore a prime target of childhood lifestyle interventions aimed at preventing diabetes. OBJECTIVES To examine the effect of added exercise to a family-based lifestyle intervention program designed to reduce VAT plus subcutaneous (ASAT), intermuscular (IMAAT), and pancreatic (PAT) adipose tissue in children with overweight or obesity and to explore the effect of changes in VAT on insulin resistance. DESIGN, SETTING, AND PARTICIPANTS This 2-group, parallel-design clinical trial was conducted in Vitoria-Gasteiz, Spain. A total of 116 children with overweight or obesity participated and were assigned to a 22-week family-based lifestyle program (control group [n = 57]) or the same program plus an exercise intervention (exercise group [n = 59]). Data were collected between September 1, 2014, and June 30, 2017, and imaging processing for fat depot assessments and data analysis were performed between May 1, 2019, and February 12, 2021. INTERVENTIONS The compared interventions consisted of a family-based lifestyle and psychoeducation program (two 90-minute sessions per month) and the same program plus supervised exercise (three 90-minute sessions per week). MAIN OUTCOMES AND MEASURES The primary outcome of this study was the change in VAT between baseline and 22 weeks as estimated by magnetic resonance imaging. The secondary outcomes were changes in ASAT, IMAAT, and PAT. The effect of changes in VAT area on insulin resistance was also recorded. RESULTS The 116 participants included in the analysis (62 girls [53.4%]) had a mean (SD) age of 10.6 (1.1) years, and 67 (57.8%) presented with obesity. Significantly greater reductions were recorded for the exercise group in terms of reduction in VAT (-18.1% vs -8.5% for the control group; P = .004), ASAT (-9.9% vs -3.0%; P = .001), and IMAAT (-6.0% vs -2.6%; P = .02) fat fractions compared with the control group. Changes in VAT explained 87.6% of the improvement seen in insulin resistance (β = -0.102 [95% CI, -0.230 to -0.002]). CONCLUSIONS AND RELEVANCE These findings suggest that the addition of exercise to a lifestyle intervention program substantially enhanced the positive effects on abdominal fat depots in children with overweight or obesity. In addition, the reduction in VAT seemed to largely mediate the improvement of insulin sensitivity. These results highlight the importance of including exercise as part of lifestyle therapies aimed at treating childhood obesity and preventing the development of type 2 diabetes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02258126.
Collapse
Affiliation(s)
- Cristina Cadenas-Sanchez
- Institute for Sustainability & Food Chain Innovation, Department of Health Sciences, Public University of Navarre, Pamplona, Spain
- Navarra Institute for Health Research, Pamplona, Spain
- PROFITH (Promoting Fitness and Health Through Physical Activity) Research Group, Sport and Health University Research Institute, Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Cabeza
- Department of Electrical, Electronic and Communications Engineering, Public University of Navarre, Pamplona, Spain
| | - Fernando Idoate
- Department of Radiology, Mutua Navarra, Pamplona, Spain
- Department of Health Sciences, Public University of Navarre, Pamplona, Spain
| | - Maddi Osés
- Institute for Sustainability & Food Chain Innovation, Department of Health Sciences, Public University of Navarre, Pamplona, Spain
- Navarra Institute for Health Research, Pamplona, Spain
| | - María Medrano
- Institute for Sustainability & Food Chain Innovation, Department of Health Sciences, Public University of Navarre, Pamplona, Spain
- Navarra Institute for Health Research, Pamplona, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| | - Arantxa Villanueva
- Navarra Institute for Health Research, Pamplona, Spain
- Department of Electrical, Electronic and Communications Engineering, Public University of Navarre, Pamplona, Spain
- Smart Cities Institute, Public University of Navarre, Pamplona, Spain
| | - Lide Arenaza
- Institute for Sustainability & Food Chain Innovation, Department of Health Sciences, Public University of Navarre, Pamplona, Spain
- Navarra Institute for Health Research, Pamplona, Spain
| | - Aritz Sanz
- Department of Electrical, Electronic and Communications Engineering, Public University of Navarre, Pamplona, Spain
| | - Francisco B. Ortega
- PROFITH (Promoting Fitness and Health Through Physical Activity) Research Group, Sport and Health University Research Institute, Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
| | - Jonatan R. Ruiz
- PROFITH (Promoting Fitness and Health Through Physical Activity) Research Group, Sport and Health University Research Institute, Department of Physical and Sports Education, Faculty of Sport Sciences, University of Granada, Granada, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Biosanitaria, ibs.Granada, Granada, Spain
| | - Idoia Labayen
- Institute for Sustainability & Food Chain Innovation, Department of Health Sciences, Public University of Navarre, Pamplona, Spain
- Navarra Institute for Health Research, Pamplona, Spain
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
| |
Collapse
|
|
18
|
Anwar MY, Baldassari AR, Polikowsky HG, Sitlani CM, Highland HM, Chami N, Chen HH, Graff M, Howard AG, Jung SY, Petty LE, Wang Z, Zhu W, Buyske S, Cheng I, Kaplan R, Kooperberg C, Loos RJF, Peters U, McCormick JB, Fisher-Hoch SP, Avery CL, Taylor KC, Below JE, North KE. Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations. BMC Med Genomics 2022; 15:192. [PMID: 36088317 PMCID: PMC9464371 DOI: 10.1186/s12920-022-01352-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 09/02/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations. METHODS Using multi-trait Adaptive Sum of Powered Score (aSPU) method, we examined individual and shared genetic effects underlying inflammatory (CRP) and adiposity-related traits (Body Mass Index [BMI]), and central adiposity (Waist to Hip Ratio [WHR]) in HLA participating in the Population Architecture Using Genomics and Epidemiology (PAGE) cohort (N = 35,871) with replication of effects in the Cameron County Hispanic Cohort (CCHC) which consists of Mexican American individuals. RESULTS Of the > 16 million SNPs tested, variants representing 7 independent loci were found to illustrate significant association with multiple traits. Two out of 7 variants were replicated at statistically significant level in multi-trait analyses in CCHC. The lead variant on APOE (rs439401) and rs11208712 were found to harbor multi-trait associations with adiposity and inflammation. CONCLUSIONS Results from this study demonstrate the importance of considering pleiotropy for improving our understanding of the etiology of the various metabolic pathways that regulate cardiovascular disease development.
Collapse
Affiliation(s)
- Mohammad Yaser Anwar
- Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, CVD Genetic Epidemiology Lab, Fl #4, Room A7, Chapel Hill, NC, 27599, USA.
| | - Antoine R Baldassari
- Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, CVD Genetic Epidemiology Lab, Fl #4, Room A7, Chapel Hill, NC, 27599, USA
| | - Hannah G Polikowsky
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Colleen M Sitlani
- Department of Medicine, University of Washington, Seattle, WA, 98195, USA
| | - Heather M Highland
- Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, CVD Genetic Epidemiology Lab, Fl #4, Room A7, Chapel Hill, NC, 27599, USA
| | - Nathalie Chami
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Hung-Hsin Chen
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Mariaelisa Graff
- Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, CVD Genetic Epidemiology Lab, Fl #4, Room A7, Chapel Hill, NC, 27599, USA
| | - Annie Green Howard
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
- Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA
| | - Su Yon Jung
- Translational Sciences Section, School of Nursing, University of California, Los Angeles, Los Angeles, CA, 90095, USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA
| | - Lauren E Petty
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Zhe Wang
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Wanying Zhu
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Steven Buyske
- Department of Statistics, Rutgers University, Piscataway, NJ, 08854, USA
| | - Iona Cheng
- Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, 94115, USA
| | - Robert Kaplan
- Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Charles Kooperberg
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA
| | - Ruth J F Loos
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ulrike Peters
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA
| | - Joseph B McCormick
- School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional Campus, Brownsville, TX, 78520, USA
| | - Susan P Fisher-Hoch
- School of Public Health, University of Texas Health Science Center at Houston, Brownsville Regional Campus, Brownsville, TX, 78520, USA
| | - Christy L Avery
- Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, CVD Genetic Epidemiology Lab, Fl #4, Room A7, Chapel Hill, NC, 27599, USA
- Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27516, USA
| | - Kira C Taylor
- Department of Epidemiology and Population Health, University of Louisville School of Public Health and Information Sciences, Louisville, KT, 40202, USA
| | - Jennifer E Below
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Kari E North
- Department of Epidemiology, University of North Carolina at Chapel Hill, 123 West Franklin Street, CVD Genetic Epidemiology Lab, Fl #4, Room A7, Chapel Hill, NC, 27599, USA
| |
Collapse
|
|
19
|
Bi Y, Lin HY, Li ML, Zhou J, Sun XL. The Association Between Pancreatic Steatosis and Metabolic Syndrome: A 5-Year Follow-up Study Among a General Chinese Population. Pancreas 2022; 51:1000-1006. [PMID: 36607946 DOI: 10.1097/mpa.0000000000002138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
OBJECTIVES To date, the complete natural history of pancreatic steatosis is unknown. This study aimed to investigate the association of fatty pancreas (FP) in the incidence of metabolic syndrome and its components among Chinese patients with a 5-year follow-up. METHODS Three independent cross-sectional surveys were carried out in 2013, 2015, and 2018. Fatty pancreas was diagnosed via transabdominal sonography. Logistic regression analysis was used to estimate the correlation between FP and metabolic syndrome. New cases of metabolic syndrome and its components were estimated by Cox proportional hazards models. RESULTS At baseline, 12,551 individuals classified into FP (n = 1010) and non-FP (n = 11,541) groups were finally enrolled. In cross-sectional analyses, odds ratio of FP was 2.378 (95% confidence interval [CI], 2.085-2.713; P < 0.001). In longitudinal analyses, FP was associated with the occurrence of metabolic syndrome (hazard ratio [HR], 3.179; 95% CI, 2.197-4.6; P < 0.001), type 2 diabetes mellitus (HR, 13.99; 95% CI, 7.865-24.883; P < 0.001), nonalcoholic fatty liver disease (HR, 31.843; 95% CI, 7.73-131.171; P < 0.001), and hypertension (HR, 12.801; 95% CI, 7.323-22.38; P < 0.001). CONCLUSIONS Pancreatic steatosis is strongly associated with the occurrence of metabolic syndrome and its components such as hypertension and diabetes.
Collapse
Affiliation(s)
- Ye Bi
- From the Department of Geriatric Endocrinology
| | - Hai-Yan Lin
- Physical Examination Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | | | - Jie Zhou
- From the Department of Geriatric Endocrinology
| | | |
Collapse
|
|
20
|
Yığman M, Tangal S. Effects of body fat components on early renal functions of individuals following kidney donation. JOURNAL OF CLINICAL UROLOGY 2022. [DOI: 10.1177/20514158221109411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective: Obesity stands as a risk factor for the chronic kidney disease. The objective of this study was to investigate the relationship between early renal function following kidney donation and the measurements of body fat components. Methods: In total, 86 donors followed up for at least 6 months postoperatively were included. Height and weight measurements and results of laboratory analysis of all donors were recorded retrospectively. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), hepatic fat (HF), pancreatic fat (PF) and splenic fat (SF) measurements were performed, and pancreatic splenic fat fraction difference (P−S) and pancreatic splenic fat fraction ratio (P/S) were calculated by a radiologist using the records of preoperative computed tomography scans of donors. Results: The estimated glomerular filtration rate (eGFR), serum creatinine and spot urinary microalbumin/creatinine ratio values of the donors at the sixth month postoperatively were statistically different from those of the preoperative values ( p < 0.001). In addition, the individuals were divided into two categories based on the postoperative eGFR: ⩾ 60 mL/min/1.73 m2 and < 60 mL/min/1.73 m2. Age, low-density lipoprotein (LDL) level and VAT/SAT ratio were lower in group eGFR: ⩾ 60 ( p < 0.001, p = 0.03, p = 0.007, respectively). Age and VAT/SAT ratio were the parameters found to be affecting the eGFR significantly, and VAT/SAT ratio (0.729, 95% CI: 0.602–0.856, p = 0.007) had higher predictive value in receiver operating characteristic curve (ROC). Conclusion: Preoperative measurements of body fat components may provide significant information to predict postoperative renal functions of kidney donor candidates. Level of evidence: Not applicable.
Collapse
Affiliation(s)
- Metin Yığman
- Department of Urology, Faculty of Medicine, Dr. Ridvan Ege Hospital, Ufuk University, Turkey
| | - Semih Tangal
- Department of Urology, Faculty of Medicine, Dr. Ridvan Ege Hospital, Ufuk University, Turkey
| |
Collapse
|
|
21
|
Pimentel JL, Vander Wyst KB, Soltero EG, Peña A, Hu HH, Bailey S, Pokorney A, Ayers S, Valencia AM, Olson ML, Shaibi GQ. Organ fat in Latino youth at risk for type 2 diabetes. Pediatr Diabetes 2022; 23:286-290. [PMID: 35001468 PMCID: PMC8983449 DOI: 10.1111/pedi.13311] [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: 10/01/2021] [Revised: 12/13/2021] [Accepted: 01/03/2022] [Indexed: 11/26/2022] Open
Abstract
PURPOSE Obesity in youth increases the risk for type 2 diabetes (T2D) and elevated abdominal adipose tissue and organ fat may be particularly deleterious. The purpose of this study was to examine associations among measures of adiposity including total, visceral, and organ fat (hepatic and pancreatic) and whether these measures were independently associated with glycemia in Latino youth at risk for diabetes. METHODS Latino adolescents (47 boys and 32 girls, 13.7 ± 1.4 years) with obesity (BMIz 2.3 ± 0.3) were assessed for total fat by DXA and visceral and organ fat by 3 T magnetic resonance imaging. Glycemic indicators included HbA1c, fasting glucose (FG), and 2-h glucose (2-HrG) following an oral glucose tolerance test. Pearson correlations and stepwise linear regression analyses controlling for age and sex were used to examine independent associations between adiposity and glycemia. RESULTS Total fat was associated with visceral (r = 0.66, p = 0.001) and hepatic fat (r = 0.34, p < 0.01) while visceral fat was associated with hepatic (r = 0.42, p < 0.001) and pancreatic fat (r = 0.36, p < 0.001). In stepwise linear regression analysis, hepatic and pancreatic fat were significant predictors of FG, explaining 4.7% and 5.2% of the variance, respectively (total R2 = 0.14, p = 0.02). Hepatic fat was the only significant predictor of 2-HrG explaining 9.9% of the variance in the model (total R2 = 0.12, p = 0.03). No measure of adiposity was retained as a significant predictor of HbA1c. CONCLUSION Hepatic and pancreatic fat were the only adiposity measures independently associated with glycemia but the small amount of variance explained underscores the need for additional T2D biomarkers in high risk youth.
Collapse
Affiliation(s)
- Janiel L. Pimentel
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Division of Pediatric Endocrinology and Diabetes, Phoenix Children’s Hospital, Phoenix, AZ
| | - Kiley B. Vander Wyst
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Master of Public Health Program, College of Graduate Studies, Midwestern University, Glendale, AZ
| | - Erica G. Soltero
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Armando Peña
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ
| | - Houchun H. Hu
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Hyperfine, Inc., Guilford, CT
| | - Smita Bailey
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Department of Radiology, Phoenix Children’s Hospital, Phoenix, AZ
| | - Amber Pokorney
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Department of Radiology, Phoenix Children’s Hospital, Phoenix, AZ
| | - Stephanie Ayers
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ
| | - Ana Martinez Valencia
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ
| | - Micah L. Olson
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Division of Pediatric Endocrinology and Diabetes, Phoenix Children’s Hospital, Phoenix, AZ
| | - Gabriel Q. Shaibi
- Center for Health Promotion and Disease Prevention, Edson College of Nursing and Health Innovation, Arizona State University, Phoenix, AZ,Division of Pediatric Endocrinology and Diabetes, Phoenix Children’s Hospital, Phoenix, AZ
| |
Collapse
|
|
22
|
Araújo MC, Soczek SHS, Pontes JP, Marques LAC, Santos GS, Simão G, Bueno LR, Maria-Ferreira D, Muscará MN, Fernandes ES. An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches. Cells 2022; 11:cells11081292. [PMID: 35455971 PMCID: PMC9030853 DOI: 10.3390/cells11081292] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/19/2022] [Accepted: 04/05/2022] [Indexed: 02/06/2023] Open
Abstract
Metabolic syndrome (MS) is a complex pathology characterized by visceral adiposity, insulin resistance, arterial hypertension, and dyslipidaemia. It has become a global epidemic associated with increased consumption of high-calorie, low-fibre food and sedentary habits. Some of its underlying mechanisms have been identified, with hypoadiponectinemia, inflammation and oxidative stress as important factors for MS establishment and progression. Alterations in adipokine levels may favour glucotoxicity and lipotoxicity which, in turn, contribute to inflammation and cellular stress responses within the adipose, pancreatic and liver tissues, in addition to hepatic steatosis. The multiple mechanisms of MS make its clinical management difficult, involving both non-pharmacological and pharmacological interventions. Transient receptor potential (TRP) channels are non-selective calcium channels involved in a plethora of physiological events, including energy balance, inflammation and oxidative stress. Evidence from animal models of disease has contributed to identify their specific contributions to MS and may help to tailor clinical trials for the disease. In this context, the oxidative stress sensors TRPV1, TRPA1 and TRPC5, play major roles in regulating inflammatory responses, thermogenesis and energy expenditure. Here, the interplay between these TRP channels and oxidative stress in MS is discussed in the light of novel therapies to treat this syndrome.
Collapse
Affiliation(s)
- Mizael C. Araújo
- Programa de Pós-Graduação, Universidade CEUMA, São Luís 65075-120, MA, Brazil; (M.C.A.); (G.S.S.)
| | - Suzany H. S. Soczek
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, PR, Brazil; (S.H.S.S.); (G.S.); (L.R.B.); (D.M.-F.)
- Programa de Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Faculdades Pequeno Príncipe, Curitiba 80230-020, PR, Brazil
| | - Jaqueline P. Pontes
- Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Maranhão, São Luís 565085-080, MA, Brazil;
| | - Leonardo A. C. Marques
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil; (L.A.C.M.); (M.N.M.)
| | - Gabriela S. Santos
- Programa de Pós-Graduação, Universidade CEUMA, São Luís 65075-120, MA, Brazil; (M.C.A.); (G.S.S.)
| | - Gisele Simão
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, PR, Brazil; (S.H.S.S.); (G.S.); (L.R.B.); (D.M.-F.)
- Programa de Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Faculdades Pequeno Príncipe, Curitiba 80230-020, PR, Brazil
| | - Laryssa R. Bueno
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, PR, Brazil; (S.H.S.S.); (G.S.); (L.R.B.); (D.M.-F.)
- Programa de Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Faculdades Pequeno Príncipe, Curitiba 80230-020, PR, Brazil
| | - Daniele Maria-Ferreira
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, PR, Brazil; (S.H.S.S.); (G.S.); (L.R.B.); (D.M.-F.)
- Programa de Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Faculdades Pequeno Príncipe, Curitiba 80230-020, PR, Brazil
| | - Marcelo N. Muscará
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil; (L.A.C.M.); (M.N.M.)
| | - Elizabeth S. Fernandes
- Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, PR, Brazil; (S.H.S.S.); (G.S.); (L.R.B.); (D.M.-F.)
- Programa de Pós-Graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Faculdades Pequeno Príncipe, Curitiba 80230-020, PR, Brazil
- Correspondence:
| |
Collapse
|
|
23
|
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.
Collapse
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
| |
Collapse
|
|
24
|
Fatty Pancreas-Centered Metabolic Basis of Pancreatic Adenocarcinoma: From Obesity, Diabetes and Pancreatitis to Oncogenesis. Biomedicines 2022; 10:biomedicines10030692. [PMID: 35327494 PMCID: PMC8945032 DOI: 10.3390/biomedicines10030692] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 12/13/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, and it is currently the third most common cause of cancer death in the U.S.A. Progress in the fight against PDAC has been hampered by an inability to detect it early in the overwhelming majority of patients, and also by the reduced oxygen levels and nutrient perfusion caused by new matrix formation through the activation of stromal cells in the context of desmoplasia. One harbinger of PDAC is excess intrapancreatic fat deposition, namely, fatty pancreas, which specifically affects the tumor macro- and microenvironment in the organ. Over half of PDAC patients have diabetes mellitus (DM) at the time of diagnosis, and fatty pancreas is associated with subsequent DM development. Moreover, there is a strong association between fatty pancreas and fatty liver through obesity, and a higher intrapancreatic fat percentage has been noted in acute pancreatitis patients with DM than in those without DM. All these findings suggest that the link between fatty pancreas and PDAC might occur through metabolic alterations, either DM-related or non-DM-related. Based on clinical, in vivo and in vitro evidence, the current review highlights the etiologies of fatty pancreas (including fatty infiltration and replacement) and the fatty pancreas-associated metabolic alterations involved in oncogenesis to provide crucial targets to prevent, detect, and/or effectively treat PDAC.
Collapse
|
|
25
|
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: 103] [Impact Index Per Article: 34.3] [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.
Collapse
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
| |
Collapse
|
|
26
|
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.
Collapse
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.
| |
Collapse
|
|
27
|
Pancreatic Steatosis Is Associated with Both Metabolic Syndrome and Pancreatic Stiffness Detected by Ultrasound Elastography. Dig Dis Sci 2022; 67:293-304. [PMID: 33651254 DOI: 10.1007/s10620-021-06844-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 01/10/2021] [Indexed: 12/16/2022]
Abstract
INTRODUCTION There is increasing evidence that pancreatic steatosis (PS) is associated with metabolic syndrome (MS). However, it is not known whether it is associated with PS grade and pancreatic stiffness, or not. We aimed to evaluate the relationship between PS and its grade detected by transabdominal ultrasound, and pancreatic stiffness determined by two-dimensional shearwave elastography (2D-SWE), whether it has clinical significance and its relationship with MS. METHODS Patients with and without PS were evaluated prospectively. RESULTS Patients with PS had higher odds ratio for MS (OR 5.49). Also, ultrasonographic grade of PS was associated with MS parameters and hepatosteatosis. Pancreatic SWE value was significantly higher in PS group and positively correlated with PS grade, liver fat, MS, number of MS criteria. DISCUSSION/CONCLUSION PS and its grade were associated with MS. In this first comprehensive PS-SWE study, we found that pancreas stiffness increased in the presence of PS, in correlation with PS grade and MS.
Collapse
|
|
28
|
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: 85] [Impact Index Per Article: 28.3] [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.
Collapse
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.
| |
Collapse
|
|
29
|
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.
Collapse
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
| |
Collapse
|
|
30
|
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.
Collapse
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
| |
Collapse
|
|
31
|
Altinmakas E, Guler B, Copur S, Siriopol D, Sag AA, Guneyli S, Dogan H, Afsar B, Balik E, Covic A, Johnson RJ, Kanbay M. Determinants of Pancreatic Steatosis: A Retrospective Observational Study. Middle East J Dig Dis 2021; 13:343-349. [PMID: 36606009 PMCID: PMC9489440 DOI: 10.34172/mejdd.2021.245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 04/04/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Metabolic syndrome affects 35% of the adult population in developed countries associated with non-alcoholic steatohepatitis, insulin resistance, and cardiovascular events. Fatty infiltration of the pancreas, or pancreatic steatosis, is a risk factor for acute pancreatitis, pancreatic malignancies, and diabetes mellitus, yet its relationship with metabolic syndrome is not well defined. METHODS We performed a single-centered retrospective observational study of 322 healthy subjects (subjects volunteering to be kidney transplant donors, mean age=46.3±13.5, 163 men and 159 women) in the last 2 years (July 2018-February 2020) from our institution. Pancreatic steatosis and hepatosteatosis were confirmed by computed tomography. RESULTS Pancreatic steatosis was present in 26.3% (85/322) of the subjects, and this finding correlated with age, body mass index (BMI), male sex, a family history of diabetes, creatinine, cystatin C, uric acid, low-density lipoprotein (LDL) cholesterol, triglycerides, glycemia, hemoglobin, transverse body diameter, and subcutaneous fat thickness levels by univariable logistic regression. On multiple linear regression only age (95% CI 1.01, 1.06), BMI (95% CI 1.01, 1.19), male sex (95% CI 1.49-5.99), uric acid (95% CI 1.01, 1.76), and subcutaneous fat thickness levels (95% CI 1.21-2.36) remained independently associated with pancreatic steatosis. CONCLUSION Pancreatic steatosis is common and associated with obesity, elevated serum uric acid, subcutaneous fat thickness, and male sex. Future studies are needed to evaluate if there are specific clinical consequences to the presence of pancreatic steatosis.
Collapse
Affiliation(s)
- Emre Altinmakas
- Department of Radiology, Koc University School of Medicine, Istanbul, Turkey
| | - Begum Guler
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Dimitrie Siriopol
- Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, and ‘Grigore T. Popa’ University of Medicine, Iasi, Romania
| | - Alan A. Sag
- Division of Vascular and Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, USA
| | - Serkan Guneyli
- Department of Radiology, Koc University School of Medicine, Istanbul, Turkey
| | - Hakan Dogan
- Department of Radiology, Koc University School of Medicine, Istanbul, Turkey
| | - Baris Afsar
- Department of Medicine, Division of Nephrology, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Emre Balik
- Department of General Surgery, Koc University School of Medicine, Istanbul, Turkey
| | - Adrian Covic
- Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, and ‘Grigore T. Popa’ University of Medicine, Iasi, Romania
| | - Richard J. Johnson
- Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO, USA
| | - Mehmet Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey.
,Corresponding Author: Mehmet Kanbay, MD Department of Medicine, Division of Nephrology Koc University School of Medicine 34010, Istanbul, Turkey Tel: + 90 212 2508250 Fax: + 90 850 2508250 E-mail:
| |
Collapse
|
|
32
|
Zhang CL, Wang JJ, Li JN, Yang Y. Nonalcoholic fatty pancreas disease: An emerging clinical challenge. World J Clin Cases 2021; 9:6624-6638. [PMID: 34447810 PMCID: PMC8362510 DOI: 10.12998/wjcc.v9.i23.6624] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/20/2021] [Accepted: 06/01/2021] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty pancreas disease (NAFPD) is an emerging disease that has gained an increasing amount of attention in recent years. It describes fat accumulation in the pancreas with insignificant alcohol consumption, but the pathogenesis is largely unknown. A wide range of terms have been used to describe the phenomenon of pancreatic fat accumulation, but NAFPD remains an under-recognized and non-independent disorder. Obesity, age, sex, race, and unhealthy lifestyle are established independent risk factors for NAFPD, which is strongly associated with metabolic syndrome, type 2 diabetes, pancreatitis, pancreatic fistula, pancreatic cancer, and nonalcoholic fatty liver disease. At present, imaging techniques are common diagnostic aids, but uniform criteria and consensus are lacking. Therapeutically, healthy diet, weight loss, and exercise are the mainstays to reduce pancreatic fat accumulation. It can be seen that there is a limited understanding of NAFPD at this stage and further exploration is needed. Previous studies have revealed that NAFPD may directly affect diagnosis and clinical decision-making. Therefore, exploring the pathophysiological mechanism and clinical associations of NAFPD is a major challenge for researchers and clinicians.
Collapse
Affiliation(s)
- Cheng-Lei Zhang
- Department of Clinical Laboratory, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- The Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Jing-Jiao Wang
- Department of Stomatology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Jian-Ning Li
- The Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Yang
- The Institute of Endocrinology, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| |
Collapse
|
|
33
|
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.
Collapse
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
| |
Collapse
|
|
34
|
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.
Collapse
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
| |
Collapse
|
|
35
|
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.
Collapse
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
| |
Collapse
|
|
36
|
Vinuesa A, Pomilio C, Gregosa A, Bentivegna M, Presa J, Bellotto M, Saravia F, Beauquis J. Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer's Disease. Front Neurosci 2021; 15:653651. [PMID: 33967682 PMCID: PMC8102834 DOI: 10.3389/fnins.2021.653651] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 03/31/2021] [Indexed: 12/21/2022] Open
Abstract
Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer's disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets.
Collapse
Affiliation(s)
- Angeles Vinuesa
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Carlos Pomilio
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Amal Gregosa
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Melisa Bentivegna
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Jessica Presa
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Melina Bellotto
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Flavia Saravia
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Juan Beauquis
- Laboratorio de Neurobiología del Envejecimiento, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
- Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| |
Collapse
|
|
37
|
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.
Collapse
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
| |
Collapse
|
|
38
|
Chi ZC. Research status and prgoress of nonalcoholic fatty pancreatic disease. Shijie Huaren Xiaohua Zazhi 2020; 28:933-950. [DOI: 10.11569/wcjd.v28.i19.933] [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] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty pancreatic disease (NAFPD) is a disease characterized by an increase in pancreatic fat accumulation. It is a component of the metabolic syndrome and often coexists with nonalcoholic fatty liver disease. Once the diagnosis is established, it is closely related to acute and chronic pancreatitis, type 2 diabetes mellitus, pancreatic fibrosis, and pancreatic cancer. In recent years, it has been confirmed that NAFPD is closely related to cardiovascular disease, liver fibrosis, and liver cancer. The prevalence of NAFPD ranges between 11% and 69%, and increases with age. It is worth noting that the prevalence in obese children is twice as high as that in non-obese children. The high prevalence rate and complexity of the disease have aroused people's high attention. Therefore, to improve the understanding of NAFPD, fully understand the clinical significance of NAFPD, and further study its pathogenesis, diagnosis, and treatment require the collaboration and joint efforts of multiple disciplines, including hepatopathy, gastroenterology, endocrine metabolism, cardiovascular disease, imaging, pathology, and others. In this paper, we review the clinical significance, pathogenesis, and imaging diagnosis of NAFPD and propose our personal understanding of the key points in future research.
Collapse
Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
| |
Collapse
|
|
39
|
Chiyanika C, Chan DFY, Hui SCN, So H, Deng M, Yeung DKW, Nelson EAS, Chu WCW. The relationship between pancreas steatosis and the risk of metabolic syndrome and insulin resistance in Chinese adolescents with concurrent obesity and non-alcoholic fatty liver disease. Pediatr Obes 2020; 15:e12653. [PMID: 32351030 PMCID: PMC7507143 DOI: 10.1111/ijpo.12653] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 03/17/2020] [Accepted: 04/17/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The incidence of childhood obesity and associated comorbidities are on an increasing trend worldwide. More than 340 million children and adolescents aged between 5 and 19 years old were overweight or had obesity in 2016, from which over 124 million children and adolescents (6% of girls and 8% of boys) had obesity. OBJECTIVE To describe the relationship between pancreas steatosis, body fat and the risk of metabolic syndrome, insulin resistance in Hong Kong Chinese adolescents with both obesity and non-alcoholic fatty liver disease (NAFLD). METHODS Fifty two adolescents with obesity and NAFLD were analysed (14-18 years), stratified into fatty and non-fatty pancreas groups using chemical shift encoded MRI-pancreas proton density fat fraction ≥5%. Pancreatic, abdominal subcutaneous adipose tissue (SAT)/visceral adipose tissue (VAT) volumes, biochemical and anthropometric parameters were measured. Mann-Whitney U test, multiple linear/binary logistic regression analyses and odds ratios were used. RESULTS Fifty percent had fatty pancreas, 38% had metabolic syndrome and 81% had insulin resistance. Liver proton density fat fraction (PDFF) and VAT were independent predictors of insulin resistance (P = .006, .016). Pancreas and liver PDFF were both independent predictors of beta cells dysfunction (P = .015, .050) and metabolic syndrome (P = .021, .041). Presence of fatty pancreas in obesity was associated with insulin resistance (OR = 1.58, 95% CI = 0.39-6.4) and metabolic syndrome (OR = 1.70, 95% CI = 0.53-5.5). CONCLUSION A significant causal relationship exists between fatty pancreas, fatty liver, body fat and the risk of developing metabolic syndrome and insulin resistance. KEY POINTS Fatty pancreas is a common finding in adolescents with obesity, with a prevalence rate of 50% in this study cohort. Liver PDFF and VAT are independent predictors of insulin resistance while pancreas PDFF and liver PDFF are independent predictors of both beta cells dysfunction and metabolic syndrome. Presence of fatty pancreas at imaging should not be considered as a benign finding but rather as an imaging biomarker of emerging pancreatic metabolic and endocrine dysfunction.
Collapse
Affiliation(s)
- Chileka Chiyanika
- Department of Imaging and Interventional RadiologyThe Chinese University of Hong KongHong KongChina
| | - Dorothy F. Y. Chan
- Department of PaediatricsThe Chinese University of Hong KongHong KongChina
| | - Steve C. N. Hui
- Department of Imaging and Interventional RadiologyThe Chinese University of Hong KongHong KongChina,Russell H. Morgan Department of Radiology and Radiological ScienceThe Johns Hopkins University School of MedicineBaltimoreMarylandUSA
| | - Hung‐kwan So
- Department of Paediatrics and Adolescent MedicineThe University of Hong KongHong KongChina
| | - Min Deng
- Department of Imaging and Interventional RadiologyThe Chinese University of Hong KongHong KongChina
| | - David K. W. Yeung
- Department of Imaging and Interventional RadiologyThe Chinese University of Hong KongHong KongChina,Department of Clinical OncologyThe Chinese University of Hong KongHong KongChina
| | | | - Winnie C. W. Chu
- Department of Imaging and Interventional RadiologyThe Chinese University of Hong KongHong KongChina
| |
Collapse
|
|
40
|
Yamazaki H, Tauchi S, Wang J, Dohke M, Hanawa N, Kodama Y, Katanuma A, Saisho Y, Kamitani T, Fukuhara S, Yamamoto Y. Longitudinal association of fatty pancreas with the incidence of type-2 diabetes in lean individuals: a 6-year computed tomography-based cohort study. J Gastroenterol 2020; 55:712-721. [PMID: 32246380 DOI: 10.1007/s00535-020-01683-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Only a few studies have longitudinally evaluated whether fatty pancreas increases the risk of type-2 diabetes (T2D), and their results were inconsistent. Fatty pancreas is closely linked to overweight and obesity, but previous studies did not exclude overweight or obese individuals. Therefore, in this cohort study, we investigated the association between fatty pancreas and T2D incidence in lean individuals. METHODS Between 2008 and 2013, 1478 nondiabetic lean individuals (i.e. body-mass index < 25 kg/m2) underwent health examinations including computed tomography (CT) and were followed for a median of 6.19 years. Fatty pancreas was evaluated by a histologically-validated method using pancreas attenuation (Hounsfield units [HU]) on CT at baseline; lower pancreas attenuation indicates more pancreatic fat. To detect incident T2D, we used fasting plasma glucose, HbA1c, and self-reports of prescribed anti-diabetes medications. Odds ratios (OR) for the association between pancreas attenuation and incident T2D were estimated using logistic regression models adjusted for likely confounders. RESULTS T2D occurred in 61 participants (4.13%) during the follow-up period. Lower pancreas attenuation (i.e. more pancreatic fat) at baseline was associated with incident T2D (unadjusted OR per 10 HU lower attenuation: 1.56 [95% CI 1.28-1.91], p < 0.001). The multivariable-adjusted analysis revealed a similar association (adjusted OR per 10 HU lower attenuation: 1.32 [95% CI 1.06-1.63], p = 0.012). CONCLUSIONS T2D was likely to develop in lean individuals with the fatty pancreas. Among people who are neither obese nor overweight, the fatty pancreas can be used to define a group at high risk for T2D.
Collapse
Affiliation(s)
- Hajime Yamazaki
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. .,Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Syogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Shinichi Tauchi
- Department of Radiology, Keijinkai Maruyama Clinic, 3-16, Odori Nishi 26-chome, Chuo-ku, Sapporo, 064-0820, Japan
| | - Jui Wang
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Room 517, No. 17, Xu-Zhou Road, Taipei, 100, Taiwan
| | - Mitsuru Dohke
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, 3-16, Odori Nishi 26-chome, Chuo-ku, Sapporo, 064-0820, Japan
| | - Nagisa Hanawa
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, 3-16, Odori Nishi 26-chome, Chuo-ku, Sapporo, 064-0820, Japan
| | - Yoshihisa Kodama
- Department of Radiology, Teine Keijinkai Hospital, 1-40, 1-jo 12-chome, Maeda, Teine-ku, Sapporo, 006-8555, Japan
| | - Akio Katanuma
- Center for Gastroenterology, Teine Keijinkai Hospital, 1-40, 1-jo 12-chome, Maeda, Teine-ku, Sapporo, 006-8555, Japan
| | - Yoshifumi Saisho
- Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Tsukasa Kamitani
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Shunichi Fukuhara
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Yosuke Yamamoto
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| |
Collapse
|
|
41
|
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]
|
|
42
|
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.
Collapse
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
| |
Collapse
|
|
43
|
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.
Collapse
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
| |
Collapse
|
|
44
|
Ishibashi C, Kozawa J, Hosakawa Y, Yoneda S, Kimura T, Fujita Y, Fukui K, Iwahashi H, Shimomura I. Pancreatic fat is related to the longitudinal decrease in the increment of C-peptide in glucagon stimulation test in type 2 diabetes patients. J Diabetes Investig 2020; 11:80-87. [PMID: 31240874 PMCID: PMC6944841 DOI: 10.1111/jdi.13108] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Revised: 06/11/2019] [Accepted: 06/23/2019] [Indexed: 02/06/2023] Open
Abstract
AIMS/INTRODUCTION The relationship between pancreatic fatty infiltration and diabetes is widely known, whereas the causal relationship is not clear. Furthermore, it is uncertain whether pathogenesis of pancreatic fat is similar to that of liver fat. We aimed to clarify the contribution of this type of fat to glucose metabolism in type 2 diabetes patients by cross-sectional and longitudinal analyses. MATERIAL AND METHODS A total of 56 patients with type 2 diabetes who had been hospitalized twice were analyzed. We evaluated the mean computed tomography values of the pancreas (P), liver (L) and spleen (S). Lower computed tomography values indicate a greater fat content. We defined indices of pancreatic or liver fat content as the differences between P or L and S. We assessed the associations among fat content for the two organs (P-S, L-S) and clinical parameters at the first hospitalization, and then analyzed the associations between these fat contents and changes in glycometabolic markers (the second data values minus the first). RESULTS In the cross-sectional study, P-S negatively correlated with the increment of C-peptide in the glucagon stimulation test (r = -0.71, P < 0.0001) and body mass index (r = -0.28, P = 0.034). L-S negatively correlated with homeostasis model assessment of insulin resistance (r = -0.73, P < 0.0001), body mass index (r = -0.62, P < 0.0001) and some other obesity-related indicators, but not with the increment of C-peptide in the glucagon stimulation test. In the longitudinal study, P-S positively correlated with the change of the increment of C-peptide in the glucagon stimulation test (r = 0.49, P = 0.021). CONCLUSIONS In type 2 diabetes patients, pancreatic fat was less associated with obesity-related indicators than liver fat, but was more strongly associated with the longitudinal decrease in endogenous insulin-secreting capacity.
Collapse
Affiliation(s)
- Chisaki Ishibashi
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Junji Kozawa
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Yoshiya Hosakawa
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Sho Yoneda
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Takekazu Kimura
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Yukari Fujita
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
- Department of Community MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Kenji Fukui
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Hiromi Iwahashi
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
- Department of Diabetes Care MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| | - Iichiro Shimomura
- Department of Metabolic MedicineGraduate School of MedicineOsaka UniversitySuitaJapan
| |
Collapse
|
|
45
|
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]
|
|
46
|
Raczkowska E, Bronkowska M. The Effect of the Body Mass Indexes of Young Healthy Individuals on the Glyacemic Indexes of Traditional and Modified Vegetarian Meals. Nutrients 2019; 11:E2546. [PMID: 31652553 PMCID: PMC6835997 DOI: 10.3390/nu11102546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 10/08/2019] [Accepted: 10/14/2019] [Indexed: 11/16/2022] Open
Abstract
Blood glucose concentration increases after the consumption of any carbohydrate-containing meal. Several factors affect the course of glucose metabolism, including nutritional status. This study evaluated the effect of the nutritional statuses of adults on their glycaemic responses after the consumption of some vegetarian meals (dumplings with potato and curd cheese stuffing; curd cheese dumplings; pancakes with curd cheese), prepared according to the traditional recipe and a partly modified recipe. The 105 participants, aged 20-27 years, with different body mass indexes (BMI), took an oral glucose tolerance test after the intake of a standard glucose solution, and also after each meal (previously analysed for energy value and approximate composition). The consumption of each meal by participants with different nutritional statuses elicited different glycaemic responses, which were reflected in the diverse glycaemic indexes (GIs). The partial modification of the meal recipes contributed to lowering their GIs. Vast differences were observed in the glycaemic responses among the surveyed participants after the consumption of the same meals. The GIs of meals should be determined in different groups of people.
Collapse
Affiliation(s)
- Ewa Raczkowska
- Department of Human Nutrition, Faculty of Biotechnology and Food Sciences, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland.
| | - Monika Bronkowska
- Department of Human Nutrition, Faculty of Biotechnology and Food Sciences, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland.
| |
Collapse
|
|
47
|
Abstract
OBJECTIVES Pancreatic steatosis or fatty pancreas refers to the fat accumulation in the pancreas, which can lead to inflammation and fibrosis, β-cell dysfunction, fibrosis, and, possibly, pancreatic cancer. This study aimed to study the prevalence of fatty pancreas and its risk factors in patients referred to an endosonography center. METHODS During 18 months, 228 patients who were referred to our endosonography center for various reasons were evaluated for fatty pancreas. Fatty pancreas was defined as hyperechoic pancreas echotexture compared with spleen echotexture. Demographic characteristics, past medical history, and laboratory measurements were compared between groups with and without fatty pancreas to determine the risk factors for fatty pancreas. RESULTS The prevalence of fatty pancreas was 25.9%. Patients with fatty pancreas had a significantly higher mean level of uric acid (P = 0.04), frequency of ischemic heart disease (P = 0.03), hyperlipidemia (P = 0.04), frequency of fatty liver (P < 0.001), and aortic intima thickness (P = 0.01). There was no significant difference in age, sex, body mass index, smoking status, substance abuse, and use of oral contraceptives in the 2 groups. CONCLUSIONS Fatty pancreas is a common disorder. There are meaningful relationships between coronary artery disease, nonalcoholic fatty liver, and atherosclerosis with fatty pancreas.
Collapse
|
|
48
|
Trout AT, Hunte DE, Mouzaki M, Xanthakos SA, Su W, Zhang B, Dillman JR. Relationship between abdominal fat stores and liver fat, pancreatic fat, and metabolic comorbidities in a pediatric population with non-alcoholic fatty liver disease. Abdom Radiol (NY) 2019; 44:3107-3114. [PMID: 31312893 DOI: 10.1007/s00261-019-02123-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE To define the relationship between compartmental abdominal fat stores, liver and pancreatic fat fractions, and type 2 diabetes mellitus (T2DM) in children with non-alcoholic fatty liver disease (NAFLD). METHODS This was a retrospective study of patients with NAFLD who underwent abdominal MRI between August 2015 and July 2017. Using an axial multi-echo Dixon-based sequence, liver fat fraction (LFF) and pancreatic fat fraction (PFF) were measured. The fat image was used to quantify abdominal fat depots (thickness, cross-sectional area) at the L2 vertebral level. Multivariable models with stepwise selection were created for prediction of LFF, PFF, and T2DM status based upon variables of clinical interest. RESULTS 86 patients (70% male, 25% Hispanic, 58% Caucasian, 11% African American) with a mean age of 14.2 ± 3.2 years were included. 19 (22%) patients were pre-diabetic or diabetic. Only ethnicity was a predictor of LFF (P = 0.0023) with Hispanic ethnicity associated with the highest LFF. Depending on the model, either total abdominal fat area (P = 0.0003) or patient weight (P = 0.008) were the only predictors of PFF. No patient variable predicted T2DM status. CONCLUSIONS In our population, there was an association between ethnicity and LFF, with the highest LFF in Hispanics. The presence or severity of hepatic steatosis could not be predicted based on patient size or the distribution of abdominal fat in our cohort. Neither LFF nor PFF were predictive of T2DM.
Collapse
Affiliation(s)
- Andrew T Trout
- Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 5031, Cincinnati, OH, 45229, USA.
- Department of Radiology, University of Cincinnati Medical Center, Cincinnati, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, USA.
| | - David E Hunte
- Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 5031, Cincinnati, OH, 45229, USA
| | - Marialena Mouzaki
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, USA
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, USA
| | - Stavra A Xanthakos
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, USA
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, USA
| | - Weizhe Su
- Department of Mathematical Sciences, University of Cincinnati, Cincinnati, USA
| | - Bin Zhang
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, USA
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, USA
| | - Jonathan R Dillman
- Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 5031, Cincinnati, OH, 45229, USA
- Department of Radiology, University of Cincinnati Medical Center, Cincinnati, USA
| |
Collapse
|
|
49
|
Singh RG, Nguyen NN, Cervantes A, Alarcon Ramos GC, Cho J, Petrov MS. Associations between intra-pancreatic fat deposition and circulating levels of cytokines. Cytokine 2019; 120:107-114. [DOI: 10.1016/j.cyto.2019.04.011] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 03/29/2019] [Accepted: 04/18/2019] [Indexed: 12/12/2022]
|
|
50
|
Ethnic distinctions in the pathophysiology of type 2 diabetes: a focus on black African-Caribbean populations. Proc Nutr Soc 2019; 79:184-193. [PMID: 31307560 DOI: 10.1017/s0029665119001034] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Type 2 diabetes (T2D) is a global public health priority, particularly for populations of black African-Caribbean ethnicity, who suffer disproportionately high rates of the disease. While the mechanisms underlying the development of T2D are well documented, there is growing evidence describing distinctions among black African-Caribbean populations. In the present paper, we review the evidence describing the impact of black African-Caribbean ethnicity on T2D pathophysiology. Ethnic differences were first recognised through evidence that metabolic syndrome diagnostic criteria fail to detect T2D risk in black populations due to less central obesity and dyslipidaemia. Subsequently more detailed investigations have recognised other mechanistic differences, particularly lower visceral and hepatic fat accumulation and a distinctly hyperinsulinaemic response to glucose stimulation. While epidemiological studies have reported exaggerated insulin resistance in black populations, more detailed and direct measures of insulin sensitivity have provided evidence that insulin sensitivity is not markedly different to other ethnic groups and does not explain the hyperinsulinaemia that is exhibited. These findings lead us to hypothesise that ectopic fat does not play a pivotal role in driving insulin resistance in black populations. Furthermore, we hypothesise that hyperinsulinaemia is driven by lower rates of hepatic insulin clearance rather than heightened insulin resistance and is a primary defect rather than occurring in compensation for insulin resistance. These hypotheses are being investigated in our ongoing South London Diabetes and Ethnicity Phenotyping study, which will enable a more detailed understanding of ethnic distinctions in the pathophysiology of T2D between men of black African and white European ethnicity.
Collapse
|