Pancreas Fat and β Cell Mass in Humans With and Without Diabetes: An Analysis in the Japanese Population.
Murakami Rie,Saisho Yoshifumi,Watanabe Yuusuke,Inaishi Jun,Tsuchiya Tami,Kou Kinsei,Sato Seiji,Kitago Minoru,Kitagawa Yuko,Yamada Taketo,Itoh Hiroshi
The Journal of clinical endocrinology and metabolism
Context:The mechanisms by which β cell mass is reduced in patients with type 2 diabetes remain unclear. It has been postulated that ectopic fat deposits in the pancreas induce β cell apoptosis, leading to the development of diabetes. Objective:The aim of this study was to clarify the effects of intrapancreatic fat on β and α cell mass in humans with and without diabetes. Design and Subjects:Using our tissue database, pancreas sections of 72 Japanese nondiabetic (NDM) autopsy cases and 50 diabetic and 49 age- and body mass index (BMI)-matched NDM patients who underwent pancreatic surgery were analyzed. In addition to histological grading, intrapancreatic fat area (IPFA) was quantified as fractional intralobular, but not interlobular, fat area to the whole pancreas area. Results:Although IPFA was positively correlated with age and BMI, there was no significant difference in IPFA between cases with and without diabetes. Moreover, no association was found between IPFA and either β or α cell area, or glycated hemoglobin. Conclusion:These findings suggest that pancreatic fat deposits have little effect on β cell mass and the development of diabetes in humans.
No Correlation of Pancreatic Fat and β-Cell Function in Young Women With and Without a History of Gestational Diabetes.
Popp Daniel,Aertsen Stephanie,Luetke-Daldrup Charlotte,Coppenrath Eva,Hetterich Holger,Saam Tobias,Rottenkolber Marietta,Seissler Jochen,Lechner Andreas,Sommer Nora N
The Journal of clinical endocrinology and metabolism
Context:Pancreatic steatosis may contribute to β-cell dysfunction in type 2 diabetes (T2D), but data are controversial. Women who had gestational diabetes mellitus (GDM) are at high risk for developing T2D. Objective:To examine the association of pancreatic fat content with early/first-phase insulin secretion (as markers of β-cell function). Design:Cross-sectional analysis of a subcohort of the monocentric, prospective cohort study titled Prediction, Prevention, and Subclassification of Type 2 Diabetes. Setting:Ludwig Maximilians University Hospital, Munich, Germany. Participants:Ninety-seven women, 3 to 16 months after pregnancy [41 normoglycemic women post-GDM, 19 women post-GDM with pathological glucose metabolism, and 37 normoglycemic women after a normoglycemic pregnancy (controls)]. Main Outcome Measures:Correlation of MRI-measured pancreatic fat content with early insulin release in an oral glucose tolerance test (OGGT) [insulin increment within the first 30 minutes of the OGTT (IR30)] and first-phase insulin response (FPIR) in an intravenous glucose tolerance test (n = 65), both adjusted for insulin sensitivity index (ISI). Results:Pancreatic fat content did not correlate with IR30 and FPIR adjusted for ISI. It correlated positively with body mass index, waist circumference, liver fat, and intraabdominal fat volume. Conclusion:Pancreatic fat content does not correlate with β-cell function in a cohort of young women with different degrees of T2D risk.
Pancreatic size and fat content in diabetes: A systematic review and meta-analysis of imaging studies.
Garcia Tiago Severo,Rech Tatiana Helena,Leitão Cristiane Bauermann
OBJECTIVES:Imaging studies are expected to produce reliable information regarding the size and fat content of the pancreas. However, the available studies have produced inconclusive results. The aim of this study was to perform a systematic review and meta-analysis of imaging studies assessing pancreas size and fat content in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). METHODS:Medline and Embase databases were performed. Studies evaluating pancreatic size (diameter, area or volume) and/or fat content by ultrasound, computed tomography, or magnetic resonance imaging in patients with T1DM and/or T2DM as compared to healthy controls were selected. Seventeen studies including 3,403 subjects (284 T1DM patients, 1,139 T2DM patients, and 1,980 control subjects) were selected for meta-analyses. Pancreas diameter, area, volume, density, and fat percentage were evaluated. RESULTS:Pancreatic volume was reduced in T1DM and T2DM vs. controls (T1DM vs. controls: -38.72 cm3, 95%CI: -52.25 to -25.19, I2 = 70.2%, p for heterogeneity = 0.018; and T2DM vs. controls: -12.18 cm3, 95%CI: -19.1 to -5.25, I2 = 79.3%, p for heterogeneity = 0.001). Fat content was higher in T2DM vs. controls (+2.73%, 95%CI 0.55 to 4.91, I2 = 82.0%, p for heterogeneity<0.001). CONCLUSIONS:Individuals with T1DM and T2DM have reduced pancreas size in comparison with control subjects. Patients with T2DM have increased pancreatic fat content.
Beta-Cell Mass in Obesity and Type 2 Diabetes, and Its Relation to Pancreas Fat: A Mini-Review.
Inaishi Jun,Saisho Yoshifumi
Type 2 diabetes (T2DM) is characterized by insulin resistance and beta-cell dysfunction. Although insulin resistance is assumed to be a main pathophysiological feature of the development of T2DM, recent studies have revealed that a deficit of functional beta-cell mass is an essential factor for the pathophysiology of T2DM. Pancreatic fat contents increase with obesity and are suggested to cause beta-cell dysfunction. Since the beta-cell dysfunction induced by obesity or progressive decline with disease duration results in a worsening glycemic control, and treatment failure, preserving beta-cell mass is an important treatment strategy for T2DM. In this mini-review, we summarize the current knowledge on beta-cell mass, beta-cell function, and pancreas fat in obesity and T2DM, and we discuss treatment strategies for T2DM in relation to beta-cell preservation.
Pancreas fat quantification with quantitative CT: an MRI correlation analysis.
Yao W J,Guo Z,Wang L,Li K,Saba L,Guglielmi G,Cheng X G,Brown J K,Blake G M,Liu B
AIM:To assess the fat content of the pancreas using quantitative computed tomography (QCT) and to correlate the results with chemical-shift-encoded magnetic resonance imaging (CSE-MRI) measurements of proton density fat fraction (PDFF). MATERIAL AND METHODS:Institutional review board approval for this research was obtained and 52 participants (25 men, 27 women; mean age 35.1 years; age range 22-50 years), who were enrolled in the Prospective Urban Rural Epidemiology (PURE) Study, underwent QCT and CSE-MRI for quantification of fat content in the pancreas. Two observers placed regions of interest (area of 100-130 mm) in the head, body, and tail of the pancreas as closely matched as possible on the two scans. Pearson correlation and Bland-Altman analysis were performed to evaluate the correlation between the QCT and CSE-MRI measurements and the systematic difference between the two techniques. RESULTS:The QCT and CSE-MRI measurements of pancreatic fat content were well correlated (r=0.805, p<0.0001), although Bland-Altman analysis showed that the QCT measurements were systematically lower by 6.3% compared to CSE-MRI PDFF. CONCLUSION:In conclusion, the results of this study suggest good correlation between QCT and CSE-MRI measurements of pancreatic fat content. Further studies are required to improve the numerical agreement of QCT measurements with PDFF.
Quantification of pancreas fat on dual-energy computed tomography: comparison with six-point Dixon magnetic resonance imaging.
Kameda Fumi,Tanabe Masahiro,Onoda Hideko,Higashi Mayumi,Ariyoshi Shoko,Ihara Kenichiro,Iida Etsushi,Furukawa Matakazu,Okada Munemasa,Ito Katsuyoshi
Abdominal radiology (New York)
OBJECTIVES:Although it is important to quantify the degree of fatty degeneration of the pancreas, it is difficult to make such a quantification using conventional computed tomography (CT). The present study evaluated the feasibility of pancreatic fat quantification by dual-energy CT (DECT) compared with T2*-corrected six-point Dixon magnetic resonance imaging (MRI). MATERIALS AND METHODS:Twenty-eight patients who underwent both DECT (100 and 150 kVp) and Dixon MRI without the use of contrast agents were analyzed. The region of interest (ROI) was placed at the head and body/tail of the pancreas on fat volume fraction (FVF) maps generated using the multi-material decomposition (MMD) algorithm on DECT. The FVF (%) of pancreatic parenchyma measured by DECT (CT-FVF) was compared with that measured on FVF maps calculated using Dixon MRI (MR-FVF) using the Spearman rank correlation coefficient. RESULTS:The median CT-FVF (%) values of the head and body/tail of the pancreas on DECT were 14.2% (range 0.1-81.2%) and 9.4% (range 0-40.8%), respectively. The median MR-FVF (%) values of the head and body/tail of the pancreas on Dixon MRI were 12.2% (range 1.2-80.9%) and 8.1% (range 0.3-43.7%), respectively. CT-FVF (%) measured by DECT showed a significant correlation with the MR-FVF (%) measured by Dixon MRI in the head of the pancreas (ρ = 0.631, P < 0.001) as well as the body/tail of the pancreas (ρ = 0.526, P = 0.004). CONCLUSION:DECT may be useful for quantifying the degree of fatty degeneration of the pancreas.
Ectopic fat accumulation in the pancreas and its clinical relevance: A systematic review, meta-analysis, and meta-regression.
Singh Ruma G,Yoon Harry D,Wu Landy M,Lu Jun,Plank Lindsay D,Petrov Maxim S
Metabolism: clinical and experimental
OBJECTIVE:Growing evidence suggests that individuals with excessive fat in the pancreas are at an increased risk of chronic metabolic disorders. The aim was to systematically review studies on non-alcoholic fatty pancreas disease (NAFPD) with a view to determine its prevalence, associations with metabolic co-morbidities, and to suggest normal pancreatic fat percentage threshold. METHODS:Three electronic databases (MEDLINE, Scopus, and Embase) were queried. Studies in humans were eligible for inclusion if they provided data on NAFPD and/or pancreatic fat percentage. Where possible, data were pooled using random-effects meta-analysis and the effect of covariates analysed using meta-regression. RESULTS:Pooling data on pancreatic fat percentage from nine studies (1209 healthy individuals who underwent magnetic resonance imaging), yielded the weighted mean and weighted standard deviation of 4.48% and 0.87%, respectively. Pooling data on NAFPD from eleven studies (12,675 individuals), yielded the pooled prevalence of 33% (95% confidence interval, 24% - 41%). Meta-regression analysis showed that the prevalence of NAFPD was independent of age and sex. The presence of NAFPD was associated with a significantly increased risk of arterial hypertension (risk ratio 1.67; 95% confidence interval, 1.32-2.10; p<0.0001), diabetes mellitus (risk ratio 2.08; 95% confidence interval, 1.44-3.00; p=0.0001), and metabolic syndrome (risk ratio 2.37; 95% confidence interval, 2.07-2.71; p<0.0001). CONCLUSION:The findings indicate that NAFPD is a frequent clinical entity, associated with significantly increased risk of metabolic syndrome and its components. The normal pancreatic fat cut-off point of 6.2% may be recommended for use in future prospective studies.
Ectopic fat accumulation in the pancreas and its biomarkers: A systematic review and meta-analysis.
Singh Ruma G,Yoon Harry D,Poppitt Sally D,Plank Lindsay D,Petrov Maxim S
Diabetes/metabolism research and reviews
Presence of fat in the pancreas increases the risk of metabolic co-morbidities. Detection and quantification of pancreatic fat is not a routine clinical practice, at least in part because of need to use expensive imaging techniques. We aimed to systematically review common markers of pancreatic fat in blood and to investigate differences in these markers associated with fatty pancreas. The search was conducted in 3 databases (EMBASE, Scopus, and MEDLINE). Studies in humans were eligible for inclusion if they reported on biological markers and percentage of pancreatic fat or fatty pancreas prevalence. Data were pooled for correlation and effect size meta-analysis. A total of 17 studies including 11 967 individuals were eligible for meta-analysis. Markers of lipid metabolism, including circulating triglycerides (r = 0.38 [95% confidence interval (CI) 0.31, 0.46]) and high-density lipoprotein cholesterol (r = -0.33 [95% CI -0.35, -0.31]), and markers of glucose metabolism, including glycated haemoglobin (r = 0.39 [95% CI 0.30, 0.48], insulin (r = 0.38 [95% CI 0.33, 0.43]), and homeostasis model assessment-insulin resistance (r = 0.37 [95% CI 0.30, 0.44], yielded the best correlations with percentage of pancreatic fat. Further, effect size analysis showed large and medium effects for the above markers of lipid and glucose metabolism. Circulating levels of triglycerides and glycated haemoglobin appear to be the best currently available markers of pancreatic fat. The approach of non-invasive and accurate detection of pancreatic fat by blood analysis should be further explored in the future, by investigating other potential biological markers of pancreatic fat.
Comparison of pancreatic volume and fat amount linked with glucose homeostasis between healthy Caucasians and Koreans.
Roh Eun,Kim Kyoung M,Park Kyeong S,Kim Yoon J,Chun Eun J,Choi Sung H,Park Kyong S,Jang Hak C,Lim Soo
Diabetes, obesity & metabolism
AIM:To compare pancreatic volume and fat amount, and their associations with glucose homeostasis, in a Korean and a white population. MATERIALS AND METHODS:In 43 healthy Korean and 43 healthy white people, matched for age (±3 years) and body mass index (BMI; ±1 kg/m ), we measured pancreatic volume and fat amount in the pancreas and abdomen using computed tomography. Pancreatic β-cell function and insulin resistance were estimated according to biochemical characteristics and a 75-g oral glucose tolerance test. Body composition and resting energy expenditure (REE) were examined using bioimpedance and indirect calorimetry, respectively. RESULTS:The mean ±SD age of the participants was 29.9 ± 5.9 years and 30.0 ± 5.2 years, and BMI was 24.0 ±3.7 and 24.1 ±3.2 kg/m in the white participants and the Korean participants, respectively. Pancreatic volume in the white participants was greater than that in Korean participants (77.8 ±11.6 vs 68.2 ±12.1 cm ; P < .001). Pancreatic fat content in Korean participants was 22.8% higher than in white participants (P = .051). Insulinogenic index, disposition index, muscle mass and REE were significantly lower in Korean participants. Pancreatic volume was positively associated with indices linked to β-cell function; fat content in the pancreas was negatively associated with such indices, and positively with insulin resistance after adjusting for relevant variables including REE. CONCLUSIONS:A smaller pancreas and higher fat deposition might be crucial determinants of vulnerability to diabetes in Korean people compared with white people with similar BMI and body fat levels.
Glucose dysregulation in patients with iron overload: is there a relationship with quantitative pancreas and liver iron and fat content measured by MRI?
Shur Joshua,Kannengiesser Stephan A R,Menezes Ravi,Ward Richard,Kuo Kevin,Jhaveri Kartik
OBJECTIVES:The aim was to investigate the relationship between pancreatic and hepatic iron and fat to glucose metabolism in patients with iron overload and address conflicting results in literature as regards the relationship between pancreas iron and glucose dysregulation. METHODS:We retrospectively evaluated pancreatic and hepatic R2*, fat fraction (FF), liver iron concentration (LIC), and glucose metabolism in 105 patients with iron overload obtained with a multi-echo gradient echo R2* technique and assessed the correlation between pancreatic R2* and FF to glucose dysregulation. RESULTS:There were no significant differences in pancreatic R2*, liver R2*, and FF in patients with iron overload and glucose dysregulation compared to those with normoglycemia (p = 0.435, p = 0.674, and p = 0.976), whereas pancreatic FF was significantly higher, 23.5% vs 16.7% respectively (p = 0.011). Pancreatic FF and R2* demonstrated an area under the curve of 0.666 and 0.571 for discriminating glucose dysregulation. Pancreatic FF of 26.2% yielded specificity and sensitivity of 80% and 45% for prediction of glucose dysregulation. Pancreatic R2* weakly correlated with pancreatic FF, r = 0.388 (p < 0.001), and liver R2*, r = 0.201 (p = 0.033), and showed no correlation with hepatic FF r = -0.013 (p = 0.892) or LIC categories (p = 0.493). CONCLUSION:Pancreatic FF but not pancreatic R2* was associated with glucose dysregulation in patients with iron overload. Prior studies reporting correlation of pancreatic R2* to glucose dysregulation likely relate from inadequate MRI technique or analysis employed, which unlike our study did not perform simultaneous measurements of fat and iron essential to avoid their confounding effects during quantitative analysis. KEY POINTS:• Pancreatic fat fraction, unlike iron, is associated with glucose dysregulation in iron overload. • Simultaneous measurement of pancreatic iron and fat content with MRI is essential to avoid confounding effects of one another during quantitative analysis. • Pancreatic fat fraction could be utilized to predict glucose dysregulation in iron overload states.
Pancreatic Fat Content Detected by Computed Tomography and Its Significant Relationship With Intraductal Papillary Mucinous Neoplasm.
Kashiwagi Kazuhiro,Seino Takashi,Fukuhara Seiichirou,Minami Kazuhiro,Horibe Masayasu,Iwasaki Eisuke,Takaishi Hiromasa,Itoh Kazunari,Sugino Yoshinori,Inoue Nagamu,Iwao Yasushi,Kanai Takanori
OBJECTIVES:Intraductal papillary mucinous neoplasms (IPMNs) are premalignant lesions of pancreatic ductal adenocarcinomas (PDACs). Fat accumulation in the pancreas is increasingly recognized as a cause of PDAC. We aimed to identify factors that are relevant between IPMN and metabolic-related factors, including pancreatic fat. METHODS:The database for 781 subjects who underwent a health checkup and upper abdominal magnetic resonance imaging was searched and computed tomography attenuation indexes (pancreatic and spleen attenuation, pancreas-to-spleen attenuation ratio) were decided by measuring the regions of interest in the pancreas and spleen on nonenhanced images, using Hounsfield units. Eighty-five subjects from each of the IPMN and noncyst groups were matched for age, sex, and glycemic status and statistically compared in clinical characteristics. RESULTS:There was no difference in metabolic-related factors except for apolipoprotein A1 and high-density lipoprotein cholesterol between the 2 groups in univariate analysis. Multivariate logistic regression analysis showed that both indexes were significantly associated with IPMN (odds ratio, 0.905 [95% confidence intervals, 0.851-0.963; P = 0.002]; odds ratio, 0.006 [95% confidence intervals, 0.000-0.152; P = 0.002]). CONCLUSIONS:Pancreatic fat content measured by computed tomography was significantly associated with IPMN. These results suggest that IPMN may develop secondary to pancreatic steatosis that could be an overlapping risk factor for PDAC and IPMN.
A Systematic Review of Intra-pancreatic Fat Deposition and Pancreatic Carcinogenesis.
Sreedhar Uma L,DeSouza Steve V,Park Brittany,Petrov Maxim S
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
BACKGROUND:Excess adiposity is considered causally related to pancreatic cancer. While most knowledge on the topic comes from studies on general and visceral adiposity, the role of intra-pancreatic fat deposition in pancreatic carcinogenesis just begins to be elucidated. The aim was to conduct a comprehensive systematic review of clinical studies on intra-pancreatic fat deposition in individuals with pancreatic cancer or pre-malignant lesions. METHODS:A literature search was conducted independently by two reviewers using three electronic databases. Studies were included if they reported on intra-pancreatic fat deposition determined based on modern radiology or histology. Summary estimates were presented as pooled prevalence or relative risk and 95% confidence interval. RESULTS:A total of 13 studies (encompassing 2178 individuals) were included. The pooled prevalence of intra-pancreatic fat deposition in individuals with pancreatic cancer or pre-malignant lesions was 52% (95% confidence interval, 38-66%). The presence of pancreatic cancer or pre-malignant lesions was associated with a significantly increased risk of intra-pancreatic fat deposition (relative risk 2.78 (95% confidence interval, 1.56-4.94, p < 0.001). CONCLUSION:Individuals with pancreatic cancer or pre-malignant lesions are characterized by increased intra-pancreatic fat deposition. There are sound grounds for conceptually viewing intra-pancreatic fat deposition as a combination of fat accumulation in the pancreas (due to expansion of excess visceral fat) and fatty replacement of the pancreas (due to changes in cellular identity within the pancreas). Guidelines on reporting intra-pancreatic fat deposition need to be developed with a view to informing a comprehensive and standardized characterization of this clinical entity in future studies.
Evaluation of fatty pancreas by proton density fat fraction using 3-T magnetic resonance imaging and its association with pancreatic cancer.
Fukui Hideyuki,Hori Masatoshi,Fukuda Yasunari,Onishi Hiromitsu,Nakamoto Atsushi,Ota Takashi,Ogawa Kazuya,Ninomiya Keisuke,Tatsumi Mitsuaki,Osuga Keigo,Yamada Daisaku,Eguchi Hidetoshi,Miyoshi Eiji,Tomiyama Noriyuki
European journal of radiology
PURPOSE:To evaluate whether pancreatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) correlates with histological pancreatic fat fraction and its possible usefulness as a biomarker of pancreatic cancer compared with pancreatic index (PI) using computed tomography (CT number of the pancreas divided by that of the spleen). METHOD:We included 55 consecutive patients (24 with pancreatic cancer and 31 controls; median age, 72 years) who preoperatively underwent MRI-PDFF using IDEAL-IQ and unenhanced CT and did not receive preoperative therapy. Histologic pancreatic fat fraction was measured in non-tumorous pancreatic tissues at the resection stump. A board-certified radiologist evaluated MRI-PDFF and PI. Correlations were evaluated among MRI-PDFF, PI, and histologic pancreatic fat fraction; the usefulness of MRI-PDFF as a predictor of pancreatic cancer was assessed. RESULTS:Histologic pancreatic fat fraction significantly correlated with MRI-PDFF and PI (r = 0.802 and -0.534, respectively; P < 0.01). The absolute correlation coefficient was significantly higher for MRI-PDFF than for PI (P < 0.01). Compared with the control group, the pancreatic cancer group had higher MRI-PDFF and histologic pancreatic fat fraction (P < 0.01) but lower PI (P < 0.01). In multivariate analysis, MRI-PDFF was found to be the sole independent risk factor for pancreatic cancer (odds ratio: 1.19; P < 0.01). CONCLUSIONS:Pancreatic fat, which was associated with pancreatic cancer, could be quantified by MRI-PDFF measurement; therefore, MRI-PDFF should be considered as a promising and superior imaging biomarker for estimating the probability of pancreatic cancer than PI.