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.

Remnant cholesterol, but not low-density lipoprotein cholesterol, is associated with intra-pancreatic fat deposition.

AIM: To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD). METHODS: All participants underwent abdominal magnetic resonance imaging on the same 3.0-Tesla scanner and IPFD was quantified. Blood samples were collected in the fasted state for analysis of lipid panel components. A series of linear regression analyses was conducted, adjusting for age, sex, ethnicity, body mass index, fasting plasma glucose, homeostatic model assessment of insulin resistance, and liver fat deposition. RESULTS: A total of 348 participants were included. Remnant cholesterol (P = 0.010) and triglyceride levels (P = 0.008) were positively, and high-density lipoprotein cholesterol level (P = 0.001) was negatively, associated with total IPFD in the most adjusted model. Low-density lipoprotein cholesterol and total cholesterol were not significantly associated with total IPFD. Of the lipid panel components investigated, remnant cholesterol explained the greatest proportion (9.9%) of the variance in total IPFD. CONCLUSION: Components of the lipid panel have different associations with IPFD. This may open up new opportunities for improving outcomes in people at high risk for cardiovascular diseases (who have normal low-density lipoprotein cholesterol) by reducing IPFD.

Dietary carbohydrate intake and insulin traits in individuals after acute pancreatitis: Effect modification by intra-pancreatic fat deposition.

OBJECTIVES: Current knowledge of the link between dietary carbohydrate intake and insulin regulation in individuals after an attack of pancreatitis is limited. We aimed to investigate the associations between dietary carbohydrate intake and insulin traits in post-pancreatitis versus healthy individuals, taking into account intrapancreatic fat deposition (IPFD). METHODS: All participants underwent magnetic resonance imaging (using the same protocol and 3T scanner) to quantify IPFD. Dietary carbohydrate intake was assessed using a validated 131-item food frequency questionnaire. Insulin, HOMA-IR, HOMA-ß were determined in the fasted state. Linear regression and effect modification analyses were conducted in unadjusted and adjusted models (accounting for age, sex, body mass index, daily energy intake, use of anti-diabetic medications, and recurrence of acute pancreatitis). RESULTS: The study included 111 post-pancreatitis individuals (categorized into low IPFD (n = 33), moderate IPFD (n = 40), high IPFD (n = 38)) and 47 healthy controls. In the high IPFD group, starch intake was negatively associated with fasting insulin and HOMA-ß in both the unadjusted (p < 0.001 both) and fully adjusted models (p < 0.001 both); and with HOMA-IR in the fully adjusted model (p < 0.001) only. Total sugar intake was positively associated with fasting insulin (p = 0.015) and HOMA-ß (p = 0.007) in the fully adjusted model but not associated with HOMA-IR. None of the above associations was statistically significant in the low IPFD, moderate IPFD, and healthy controls groups. The studied associations were more pronounced in the high IPFD group but not in the moderate IPFD or low IPFD groups (when compared with the healthy controls group). CONCLUSIONS: Dietary carbohydrate intake is differentially associated with insulin traits in individuals after an attack of pancreatitis and the associations are modified by IPFD. These findings will be helpful for the development of dietary guidelines specifically for individuals after an attack of pancreatitis.

Associations between intra-pancreatic fat deposition and circulating levels of cytokines.

While a plethora of studies have been conducted to investigate the associations between pro-inflammatory cytokines and obesity, the inter-relationship between pro-inflammatory cytokines and intra-pancreatic fat deposition (IPFD) has been poorly investigated. In the present study, circulating levels of C-C motif chemokine ligand 2 (CCL2), interleukin-6 (IL-6), leptin, and tumor necrosis factor-alpha (TNFα) were measured in 90 individuals after acute pancreatitis (AP) as well as 21 healthy non-obese individuals. Magnetic resonance imaging was used to quantify IPFD and visceral-to-subcutaneous fat volume ratio by two independent raters. Linear regression analyses were performed to investigate the associations between IPFD and each cytokine, adjusting for demographic, metabolic, and pancreatitis-related factors, as well as abdominal fat distribution. In healthy non-obese individuals, IPFD was not significantly associated with any of the studied cytokines in both the unadjusted and adjusted models. In individuals after AP, IPFD was significantly associated with leptin in the models adjusted for age and sex (ß = 0.063 [95% confidence interval: 0.007, 0.119], P = 0.026); age, sex, visceral-to-subcutaneous fat volume ratio, glycated hemoglobin, and pancreatitis-related factors (ß = 0.056 [95% confidence interval: 0.000, 0.111], P = 0.049). Also, IPFD was significantly associated with TNFα in the unadjusted model (ß = 0.102 [95% confidence interval: 0.002, 0.202], P = 0.045) and the model adjusted for age, sex, visceral-to-subcutaneous fat volume ratio, glycated hemoglobin, and pancreatitis-related factors (ß = 0.128 [95% confidence interval: 0.034, 0.223], P = 0.008). The associations between IPFD and IL-6, CCL2 were not statistically significant, in both the unadjusted and adjusted models. These findings indicate that leptin and TNFα are associated with IPFD independent of abdominal fat distribution and other covariates in individuals after AP. The role of IPFD in low-grade inflammation warrants further investigations.

Comprehensive analysis of body composition and insulin traits associated with intra-pancreatic fat deposition in healthy individuals and people with new-onset prediabetes/diabetes after acute pancreatitis.

Current knowledge of biomarkers of intra-pancreatic fat deposition (IFD) is limited. We aimed to analyse comprehensively body composition and insulin traits as biomarkers of IFD in healthy normoglycaemic individuals as well as in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP). A total of 29 healthy individuals and 34 individuals with NODAP took part in this cross-sectional study. The studied biomarkers belonged to the following domains: body composition (anthropometric and MRI-derived variables); indices of insulin secretion; indices of insulin sensitivity; incretins and related peptides; and pancreatitis-related factors. All MRI-derived variables (including IFD) were measured using ImageJ software. Univariate and step-wise regression analyses were conducted to determine variables that best explained variance in IFD. Visceral fat volume and oxyntomodulin were the best biomarkers of IFD in normoglycaemic healthy individuals, contributing to 64% variance. The Raynaud index was the best biomarker of IFD in individuals with NODAP, contributing to 20% variance. Longitudinal studies are warranted to investigate the cause and effect relationship between oxyntomodulin and IFD in healthy individuals, as well as insulin sensitivity and IFD in individuals with NODAP.

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.

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.

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.

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.

Relationship of Serum Bile Acids with Fat Deposition in the Pancreas, Liver, and Skeletal Muscle.

Introduction: Ectopic fat deposition is well appreciated as a key contributor to digestive and liver diseases. Bile acids have emerged as pleiotropic signalling molecules involved in numerous metabolic pathways. The aim was to study the associations of bile acids with ectopic fat deposition and lipid panel. Methods: A single 3.0 Tesla magnetic resonance imaging scanner was employed to measure fat deposition in the pancreas, liver, and skeletal muscle in 76 adults. Blood samples were drawn to determine total bile acids and lipid panel. Linear regression analyses were run, taking into account age, sex, body mass index, and other covariates. Results: The studied ectopic fat depots were not significantly associated with levels of total bile acids in serum. Total bile acids were significantly associated high-density lipoprotein cholesterol - consistently in both the unadjusted (p = 0.018) and all adjusted models (p = 0.012 in the most adjusted model). Low-density lipoprotein cholesterol, total cholesterol, and triglycerides were not significantly associated with total bile acids in both the unadjusted and all adjusted models. Conclusion: Fat deposition in the pancreas, liver, and skeletal muscle is not associated with circulating levels of total bile acids. High-density lipoprotein cholesterol is the only component of lipid panel that is associated with total bile acids.

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.

A fat fraction phantom for establishing new convolutional neural network to determine the pancreatic fat deposition.

The determination of fat fraction based on Magnetic Resonance Imaging (MRI) requires extremely accurate data reconstruction for the assessment of pancreatic fat accumulation in medical diagnostics and biological research. In this study, the signal model of the oil and water emulsion was created with a 3.0 T field strength. We examined the quantification of the fat fraction from phantom and the intrapancreatic fat fraction using the techniques of magnetic resonance spectroscopy (MRS) and Iterative Decomposition with Echo Asymmetry and Least-Squares estimate (IDEAL) in magnetic resonance imaging (MRI). Additionally, we contrasted expert manual pancreatic fat assessment with MRS and IDEAL pancreatic fat fraction quantification. There was a strong connection between the true fat volume fraction and the fat fraction from IDEAL and MRS (R2 = 0.99 and 0.99, respectively). For both phantom and in vivo measurements, Pearson's correlation and linear regression analysis were used. The findings of the in vivo assessment revealed a variable correlation between the pancreatic fat fraction MRI readings. We also used MR-opsy for manual pancreatic fat fraction segmentation since it read pancreatic fat fractions more accurately than IDEAL and MRS, which aided in the development of machine learning's ability to assess pancreatic fat automatically.

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.

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.

Intra-pancreatic fat deposition as a modifier of the relationship between habitual dietary fat intake and insulin resistance.

BACKGROUND: Insulin resistance is a well-known derangement after an attack of pancreatitis but the role of dietary fat intake and intra-pancreatic fat deposition (IPFD) in it is unknown. We aimed to investigate the relationship of dietary fat intake with markers of insulin resistance in individuals after acute pancreatitis, taking into account IPFD. METHODS: This was a cross-sectional study. The EPIC-Norfolk food frequency questionnaire was used to determine the habitual intake of saturated, monounsaturated, polyunsaturated fatty acids. The studied markers of insulin resistance were fasting insulin, HOMA-IR, and METS-IR. 3 T magnetic resonance imaging was used to quantify IPFD. Linear regression analysis, with adjustment for possible confounders, was performed. RESULTS: A total of 111 individuals after acute pancreatitis (33 low IPFD, 40 moderate IPFD, and 38 high IPFD) were included. In the high IPFD group, intake of monounsaturated fatty acids was inversely associated with both fasting insulin, and HOMA-IR, and METS-IR in the unadjusted (ß = -65.405, p < 0.001; ß = -15.762, p < 0.001; ß = -0.760, p = 0.041, respectively) and fully adjusted models (ß = -155.620, p < 0.001; ß = -34.656, p < 0.001, ß = -2.008, p = 0.018, respectively). Intake of polyunsaturated or saturated fatty acids did not have a consistently significant pattern of associations with the three markers of insulin resistance. None of the above associations was significant in the low IPFD and moderate IPFD groups. CONCLUSIONS: Habitual dietary fat intake is associated with insulin resistance only in individuals after an attack of pancreatitis who have high IPFD. These indviduals may benefit from a calorically balanced diet that is rich in monounsaturated fatty acids.

Pancreatic enzymes and abdominal adipose tissue distribution in new-onset prediabetes/diabetes after acute pancreatitis.

BACKGROUND: New-onset prediabetes/diabetes after acute pancreatitis (NODAP) is the most common sequela of pancreatitis, and it differs from type 2 prediabetes/diabetes mellitus (T2DM). AIM: To study the associations between circulating levels of pancreatic amylase, pancreatic lipase, chymotrypsin and fat phenotypes in NODAP, T2DM, and health. METHODS: Individuals with NODAP (n = 30), T2DM (n = 30), and sex-matched healthy individuals (n = 30) were included. Five fat phenotypes (intra-pancreatic fat, liver fat, skeletal muscle fat, visceral fat, and subcutaneous fat) were determined using the same magnetic resonance imaging protocol and scanner magnet strength for all participants. One-way analysis of covariance, linear regression analysis, and relative importance analysis were conducted. RESULTS: Intra-pancreatic fat deposition (IPFD) was higher in NODAP (9.4% ± 1.8%) and T2DM (9.8% ± 1.1%) compared with healthy controls (7.8% ± 1.9%) after adjusting for covariates (P = 0.003). Similar findings were observed in regards to visceral fat volume (P = 0.005), but not subcutaneous fat volume, liver fat, or skeletal muscle fat. Both IPFD (ß = -2.201, P = 0.023) and visceral fat volume (ß = -0.004, P = 0.028) were significantly associated with circulating levels of pancreatic amylase in NODAP, but not in T2DM or healthy individuals. Of the five fat phenotypes, IPFD explained the highest amount of variance in pancreatic amylase concentration (R 2 = 15.3% out of 41.2%). None of the phenotypes contributed meaningfully to the variance in pancreatic lipase or chymotrypsin. CONCLUSION: Both NODAP and T2DM are characterized by increased IPFD and visceral fat volume. However, only NODAP is characterized by significant inverse associations between the two fat phenotypes and pancreatic amylase.

Post-pancreatitis diabetes mellitus and excess intra-pancreatic fat deposition as harbingers of pancreatic cancer.

Progress in the fight against pancreatic cancer has been hampered by many factors. One of them is the inability to detect the disease early in overwhelming majority of patients. The present paper outlines a novel way in which progress could be accelerated. This includes a focus on two harbingers-post-pancreatitis diabetes mellitus and excess intra-pancreatic fat deposition-that converge at affecting the tumor macroenvironment and microenvironment specifically in the pancreas, not other organs. The two entities have the potential to be incorporated into future screening strategies with a view to early detecting of pancreatic cancer.

Abdominal fat distribution modulates the metabolic effects of exogenous ketones in individuals with new-onset prediabetes after acute pancreatitis: Results from a randomized placebo-controlled trial.

BACKGROUND AND AIMS: Exogenous ketone supplementation is emerging as a nutritional intervention that beneficially affects blood glucose control. We hypothesized that varying abdominal fat phenotypes play a role in the effect of exogenously induced ketosis. The aim was to investigate whether intra-abdominal fat distribution modulates the effect of exogenous ketones on glucoregulatory peptides in new-onset prediabetes. METHODS: Eighteen individuals with new-onset prediabetes after acute pancreatitis were randomized to receive a ketone monoester supplement or placebo in a crossover fashion. All participants underwent magnetic resonance imaging on a 3T scanner to determine their abdominal fat phenotypes. They were non-exclusively categorized as low adiposity or high adiposity phenotypes based on their abdominal and ectopic fat distribution (regardless of body mass index and waist circumference). Blood samples were analyzed for glucoregulatory peptides. Total area under the curve (AUC) over 150 min was calculated for each analyte. RESULTS: The total AUCs for insulin and C-peptide were significantly higher after ketone supplementation in individuals with high intra-pancreatic fat deposition, skeletal muscle fat deposition, and subcutaneous fat volume; and low visceral fat volume and intra-hepatic fat deposition. The total AUC for glucose-dependent insulinotropic peptide was significantly higher after ketone supplementation in individuals with high intra-pancreatic fat deposition, skeletal muscle fat deposition, subcutaneous fat volume, and visceral fat volume. The total AUC for glucagon-like peptide-1 was not associated with any adiposity phenotype. CONCLUSIONS: Individuals with high depositions of intra-pancreatic fat, skeletal muscle fat, subcutaneous fat may not achieve favorable outcomes of blood glucose control following ketone supplementation. Abdominal fat distribution is an important factor in the pathogenesis of new-onset prediabetes and it may influence the effectiveness of nutritional strategies designed for these individuals. REGISTERED UNDER CLINICALTRIALS. GOV IDENTIFIER NO: NCT03889210.

Evaluation of Ethnic Variations in Visceral, Subcutaneous, Intra-Pancreatic, and Intra-Hepatic Fat Depositions by Magnetic Resonance Imaging among New Zealanders.

Anthropometric indices, such as body mass index (BMI), waist circumference (WC), and waist to height ratio (WHtR), have limitations in accurately predicting the pathophysiology of diabetes mellitus, cardiovascular diseases, and metabolic syndrome due to ethnic differences in fat distribution. Recent studies showed that the visceral adipose tissue (VAT) deposition and fat content of internal organs, most notably intra-hepatic and intra-pancreatic fat, has emerged as a more important parameter. In this study, we aimed to assess the coordination between the traditional anthropometric indices and the various fat depositions within different ethnicities in New Zealand. We recruited 104 participants with different ethnic backgrounds, including New Zealand Europeans, Maori (the indigenous people of New Zealand), Pacific Islanders (PI), and Asians. Their weight, height, and WC were measured, and subcutaneous, visceral, intra-hepatic, and intra-pancreatic fat depositions were obtained by magnetic resonance imaging (MRI). The result showed VAT, but not subcutaneous adipose tissue (SAT) depositions at all levels were significantly varied among the three groups. BMI was associated best with L23SAT in NZ Europeans (30%) and L45VAT in Maori/PI (24.3%). WC and WHtR were correlated well with L45SAT in the total population (18.8% and 12.2%, respectively). Intra-pancreatic fat deposition had a positive Pearson relationship with NZ European BMI and Maori/PI WC, but no regression correlation with anthropometric indices. Conventional anthropometric indices did not correspond to the same fat depositions across different ethnic groups.