Intra-pancreatic fat is associated with continuous glucose monitoring metrics.

AIM: To investigate the relationship of fat in the pancreas with time spent in different glycaemic ranges. METHODS: Abdominal magnetic resonance imaging at 3.0 Tesla was used to quantify fat in the pancreas as both continuous [i.e. intra-pancreatic fat deposition (IPFD)] and binary (i.e. fatty change of the pancreas vs. normal pancreas) variables. Dexcom G6 devices were used to collect continuous glucose monitoring data every 5 min over a continuous 7-day period. Time above range (TAR), time in range (TIR) and time below range were computed. Statistical models were built to adjust for age, sex, body composition, and other covariates in linear regression analysis and analysis of covariance. RESULTS: In total, 38 individuals were studied. IPFD was significantly associated with TAR (p = .036) and TIR (p = .042) after adjustment for covariates. For every 1% increase in IPFD, there was a 0.3 unit increase in TAR and a decrease in TIR. Individuals with fatty change of the pancreas, when compared with those with normal pancreas, had significantly higher TAR (p = .034) and lower TIR (p = .047) after adjustment for covariates. Neither IPFD (p = .805) nor fatty change of the pancreas (p = .555) was associated with time below range after adjustment for covariates. CONCLUSION: Increased fat in the pancreas is associated with excessive glycaemic variability. Fatty change of the pancreas may contribute to heightening the risk of cardiovascular diseases.

Serum lipid profile as a biomarker of intra-pancreatic fat deposition: A nested cross-sectional study.

BACKGROUND AND AIMS: The relationship between intra-pancreatic fat deposition (IPFD) and lipid profile has been investigated in individuals with obesity and/or type 2 diabetes, but not in healthy non-obese individuals and those after acute pancreatitis. The aim of the study was to investigate the association between serum lipid profile and IPFD in the latter individuals and to determine the effect of abdominal fat distribution and other covariates. METHODS AND RESULTS: A total of 90 individuals with a history of acute pancreatitis as well as 23 healthy non-obese individuals participated in the study. Magnetic resonance imaging was used to quantify IPFD and visceral-to-subcutaneous fat volume ratio, followed by fasting state measurement of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TC/HDL-C ratio, and triglycerides. In healthy non-obese individuals, IPFD was not significantly associated with any of the studied markers. In individuals after acute pancreatitis, IPFD was significantly associated with triglycerides in both unadjusted (ß = 0.360; 95% CI, 0.090-0.629; p = 0.009) and adjusted models, with a ß-coefficient of 0.280 [(95% CI, 0.016-0.545); p = 0.038] in the most adjusted model. Also, IPFD was significantly associated with TC/HDL-C ratio in both unadjusted (ß = 0.336; 95% CI, 0.045-0.626; p = 0.024) and adjusted models, with a ß-coefficient of 0.375 [(95% CI, 0.090-0.660); p = 0.010] in the most adjusted model. Multiple regression yielded triglycerides, but not TC/HDL-C ratio, as a significant marker of IPFD in individuals after acute pancreatitis. CONCLUSIONS: Serum lipid profile is not associated with IPFD in healthy non-obese. Triglycerides, but not other components of lipid profile, is a promising biomarker for IPFD in individuals following acute pancreatitis.

Relationship of Liver Blood Tests and T1 Relaxation Time With Intra-pancreatic Fat Deposition.

Background: Liver is well recognised as a metabolically active organ. While intra-pancreatic fat deposition (IPFD) is emerging as an important player in the whole-body metabolism, the interplay between the liver and IPFD has been poorly investigated. This study aimed to investigate the associations of liver blood tests and non-invasive tests for hepatic fibrosis with IPFD. Methods: Participants underwent a 3.0 Tesla magnetic resonance imaging to measure IPFD and map liver T1 (longitudinal relaxation time). Four liver tests were done on the same sample of blood. Hepatic fibrosis risk score (BARD) was calculated. Linear regression models were built, accounting for age, sex, visceral-to-subcutaneous fat ratio, and other covariates. Results: A total of 143 individuals were studied. In the most adjusted model, alkaline phosphatase (P < 0.001), alanine aminotransferase (P < 0.001), and γ-glutamyl transferase (P = 0.042) were significantly positively associated with IPFD. The BARD score was not significantly associated with IPFD in the most adjusted model (P = 0.295). T1 relaxation time of the liver was not significantly associated with IPFD in the most adjusted model (P = 0.782). Conclusions: Elevated alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transferase are associated with increased IPFD. Hepatic fibrosis does not appear to be associated with IPFD.

Associations of pancreas fat content and size with markers of iron metabolism.

OBJECTIVE: To comprehensively investigate the associations of pancreas fat content and size with circulating markers of iron metabolism. METHODS: A total of 116 individuals underwent magnetic resonance imaging and spectroscopy on a 3.0 Tesla scanner, exclusively for the purpose of the COSMOS research programme. Intra-pancreatic fat deposition, total pancreas volume, liver fat content, visceral and subcutaneous fat volumes were quantified. Plasma levels of hepcidin and ferritin were measured. Multiple linear regression analysis was conducted, adjusting for body mass index, age, and sex. RESULTS: Total intra-pancreatic fat deposition was inversely associated with hepcidin (ß = -0.54, 95 % confidence interval -1.02 to -0.07) whereas total pancreas volume was not associated with hepcidin (ß = 0.36, 95 % confidence interval -7.12 to 7.84) in the most adjusted model. Neither total intra-pancreatic fat deposition (ß = -0.03, 95 % confidence interval -0.39 to 0.33) nor total pancreas volume (ß = -1.02, 95 % confidence interval -6.67 to 4.63) was associated with ferritin in the most adjusted model. Subcutaneous fat, visceral fat, and liver fat were not associated with hepcidin. Subcutaneous fat was inversely associated with ferritin (ß = -0.06, 95 % CI -0.11 to -0.01) whereas visceral fat (ß = 0.05, 95 % CI -0.01 to 0.14) and liver fat (ß = 0.09, 95 % CI -0.04 to 0.34) were not associated with ferritin in the most adjusted model. CONCLUSIONS: Increased intra-pancreatic fat deposition, but not other fat depots, is associated with reduced circulating levels of hepcidin. Deranged iron metabolism may play a role in the pathogenesis of fatty change of the pancreas.

Comprehensive analysis of dyslipidemia states associated with fat in the pancreas.

BACKGROUND: The global burden of cardiovascular diseases continues to rise, and it is increasingly acknowledged that guidelines based on traditional risk factors fail to identify a substantial fraction of people who develop cardiovascular diseases. Fat in the pancreas could be one of the unappreciated risk factors. This study aimed to investigate the associations of dyslipidemia states with fat in the pancreas. METHODS: All participants underwent magnetic resonance imaging on the same 3.0 T scanner for quantification of fat in the pancreas, analyzed as both binary (i.e., fatty change of the pancreas) and continuous (i.e., intra-pancreatic fat deposition) variables. Statistical analyses were adjusted for body mass index, glycated hemoglobin, fasting insulin, ethnicity, age, and sex. RESULTS: There were 346 participants studied. On most adjusted analyses, high-density lipoprotein cholesterol dyslipidemia was significantly associated with both fatty change of the pancreas (p = 0.010) and intra-pancreatic fat deposition (p = 0.008). Neither low-density lipoprotein cholesterol dyslipidemia nor triglyceride dyslipidemia were significantly associated with fatty change of the pancreas and intra-pancreatic fat deposition. The absence of any dyslipidemia was inversely associated with both fatty change of the pancreas (p = 0.016) and intra-pancreatic fat deposition (p < 0.001). CONCLUSIONS: Dyslipidemias are uncoupled when it comes to the relationship with fat in the pancreas, with only high-density lipoprotein cholesterol dyslipidemia having a consistent and strong link with it. The residual cardiovascular diseases risk may be attributed to fatty change of the pancreas.

Relationships between intra-pancreatic fat deposition and lifestyle factors: a cross-sectional study.

Aims: The excess deposition of intra-pancreatic fat deposition (IPFD) has been reported to be associated with type 2 diabetes, chronic pancreatitis, and pancreatic ductal adenocarcinoma. In the current study, we aimed to identify a relationship between lifestyle factors and IPFD. Materials and methods: 99 patients admitted to the Osaka University Hospital who had undergone abdominal computed tomography were selected. We evaluated the mean computed tomography values of the pancreas and spleen and then calculated IPFD score. Multiple regression analyses were used to assess the associations between IPFD score and lifestyle factors. Results: Fast eating speed, late-night eating, and early morning awakening were significantly associated with a high IPFD score after adjusting for age, sex, diabetes status and Body Mass Index (p=0.04, 0.01, 0.01, respectively). Conclusion: The current study has elucidated the significant associations of fast eating speed, late-night eating, and early morning awakening with IPFD.

Intra-pancreatic fat deposition across the pancreatitis spectrum and the influence of gut hormones.

BACKGROUND AND AIMS: Acute pancreatitis (AP) and chronic pancreatitis (CP) often represent parts of the spectrum of disease. While growing evidence indicates that intra-pancreatic fat deposition (IPFD) plays an important role in the pathogenesis of pancreatitis, no study of living individuals has investigated IPFD in both AP and CP. Further, the associations between IPFD and gut hormones remain to be elucidated. The aims were to investigate the associations of IPFD with AP, CP, and health; and to study whether gut hormones affect these associations. METHODS: Magnetic resonance imaging on the same 3.0 Tesla scanner was used to determine IPFD in 201 study participants. These participants were arranged into the health, AP, and CP groups. Gut hormones (ghrelin, glucagon-like peptide-1, gastric inhibitory peptide, peptide YY, and oxyntomodulin) were measured in blood, both after an 8-hour overnight fasting and after ingestion of a standardised mixed meal. A series of linear regression analyses was run, accounting for age, sex, ethnicity, body mass index, glycated haemoglobin, and triglycerides. RESULTS: Both the AP group and CP group had significantly higher IPFD in comparison with the health group, consistently across all models (p for trend 0.027 in the most adjusted model). Ghrelin in the fasted state had a significant positive association with IPFD in the AP group (but not the CP or health group), consistently across all models (p = 0.019 in the most adjusted model). None of the studied gut hormones in the postprandial state was significantly associated with IPFD. CONCLUSION: Fat deposition in the pancreas is similarly high in individuals with AP and those with CP. The gut-brain axis, and more specifically overexpression of ghrelin, may contribute to increased IPFD in individuals with AP.

Associations between Intra-Pancreatic Fat Deposition, Pancreas Size, and Pancreatic Enzymes in Health and after an Attack of Acute Pancreatitis.

INTRODUCTION: Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the exocrine pancreas has never been explored in this setting. The aim was to investigate the associations between intra-pancreatic fat deposition (IPFD), pancreas size, and pancreatic enzymes. METHODS: This cross-sectional study recruited individuals with a history of acute pancreatitis and healthy controls. All participants underwent 3T magnetic resonance imaging, from which IPFD, total pancreas volume (TPV), and pancreas diameters (across the head, body, and tail) were measured independently by 2 raters in a blinded fashion. Circulating levels of pancreatic amylase, pancreatic lipase, and chymotrypsin were measured in a fasted state. A series of linear regression analyses was conducted, accounting for possible confounders. RESULTS: A total of 108 individuals with pancreatitis and 60 healthy controls were studied. There was a statistically significant difference in IPFD (p < 0.001), but not in TPV (p = 0.389), between the groups. In the post-pancreatitis group, IPFD was significantly inversely associated with pancreas tail diameter (ß = -0.736, p = 0.036 in the most adjusted model). In the control group, IPFD was significantly inversely associated with TPV (ß = -3.557, p = 0.026 in the most adjusted model). Levels of pancreatic amylase were significantly directly associated with pancreas tail diameter in the post-pancreatitis group (ß = 3.891, p = 0.042 in the most adjusted model), whereas levels of pancreatic lipase were significantly inversely associated with TPV in the control group (ß = -10.533, p = 0.024 in the most adjusted model). CONCLUSION: Increased IPFD in individuals after an attack of pancreatitis is associated with reduced pancreas tail diameter, which is in turn associated with reduced circulating levels of pancreatic amylase. The relationship between IPFD and the exocrine pancreas warrants further investigations.

The impact of ethnicity and intra-pancreatic fat on the postprandial metabolome response to whey protein in overweight Asian Chinese and European Caucasian women with prediabetes.

The "Thin on the Outside Fat on the Inside" TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow's milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0 g (water control), 12.5 g (low protein, LP) and 50 g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T0-240mins) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort's WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models' discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.

A Systematic Review of Intra-pancreatic Fat Deposition and Pancreatic Carcinogenesis.

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.