Gut microbiota's causative relationship with peripheral artery disease: a Mendelian randomization study.

Introduction: The relationship between gut microbiota and peripheral artery disease (PAD) remains understudied. While traditional risk factors like smoking and hyperlipidemia are well-understood, our study aims to determine the potential causative association of gut microbiota with PAD using Mendelian Randomization. Methods: Data from the International MiBioGen Consortium and the FinnGen research project were used to study 211 bacterial taxa. Instrumental variables, comprising 2079 SNPs, were selected based on significance levels and linkage disequilibrium. Analyses were conducted utilizing the inverse-variance weighted (IVW) method and other statistical MR techniques to mitigate biases, processed in R (v4.3.1) with the TwosampleMR package. Results: Three bacterial taxa, namely genus Coprococcus2, RuminococcaceaeUCG004, and RuminococcaceaeUCG010, emerged as protective factors against PAD. In contrast, family. FamilyXI and the genus Lachnoclostridium and LachnospiraceaeUCG001 were identified as risk factors. Conclusion: Our findings hint at a causative association between certain gut microbiota and PAD, introducing new avenues for understanding PAD's etiology and developing effective treatments. The observed associations now warrant further validation in varied populations and detailed exploration at finer taxonomic levels.

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.

Intraoperative application of intelligent, responsive, self-assembling hydrogel rectifies oxygen and energy metabolism in traumatically injured brain.

In managing severe traumatic brain injury (TBI), emergency surgery involving the removal of damaged brain tissue and intracerebral hemorrhage is a priority. Secondary brain injury caused by oxidative stress and energy metabolic disorders, triggered by both primary mechanical brain damage and surgical insult, is also a determining factor in the prognosis of TBI. Unfortunately, the effectiveness of traditional postoperative intravenous neuroprotective agents therapy is often limited by the lack of targeting, timeliness, and side effects when neuroprotective agents systemically delivered. Here, we have developed injectable, intelligent, self-assembling hydrogels (P-RT/2DG) that can achieve precise treatment through intraoperative application to the target area. P-RT/2DG hydrogels were prepared by integrating a reactive oxygen species (ROS)-responsive thioketal linker (RT) into polyethylene glycol. By scavenging ROS and releasing 2-deoxyglucose (2DG) during degradation, these hydrogels functioned both in antioxidation and energy metabolism to inhibit the vicious cycle of post-TBI ROS-lactate which provoked secondary injury. In vitro and in vivo tests confirmed the absence of systemic side effects and the neuroprotective function of P-RT/2DG hydrogels in reducing edema, nerve cell apoptosis, neuroinflammation, and maintaining the blood-brain barrier. Our study thus provides a potential treatment strategy with novel hydrogels in TBI.

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.

CSF 14-3-3 zeta(ζ) isoform is associated with tau pathology and cognitive decline in Alzheimer's disease.

14-3-3 is a family of conserved proteins that consist of seven isoforms which are highly expressed in the brain, and 14-3-3 zeta(ζ) is one of the isoforms encoded by the YWHAZ gene. Previous studies demonstrated that 14-3-3ζ is deposited in the neurofibrillary tangles of Alzheimer's disease (AD) brains, and that 14-3-3ζ interacts with tau from the purified neurofibrillary tangles of AD brain extract. The present study examined the cerebrospinal fluid (CSF) 14-3-3ζ levels of 719 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively normal (CN) participants, patients with mild cognitive impairment (MCI) and patients with AD dementia, and aimed to identify whether CSF 14-3-3ζ is associated with tau pathology. CSF 14-3-3ζ levels were increased in AD, and particularly elevated among tau pathology positive individuals. CSF 14-3-3ζ levels were associated with CSF phosphorylated tau 181 (p-tau) (r = 0.741, P < 0.001) and plasma p-tau (r = 0.293, P < 0.001), which are fluid biomarkers of tau pathology, and could predict tau pathology positive status with high accuracy (area under the receiver operating characteristic curve [AUC], 0.891). CSF 14-3-3ζ levels were also correlated to synaptic biomarker CSF GAP-43 (r = 0.609, P < 0.001) and neuroinflammatory biomarker CSF sTREM-2 (r = 0.507, P < 0.001). High CSF 14-3-3ζ levels at baseline were associated with progressive decline of cognitive function and neuroimaging findings during follow up. In conclusion, this study suggests that CSF 14-3-3ζ is a potential biomarker of AD that may be useful in clinical practice.

CSF 14-3-3ß is associated with progressive cognitive decline in Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder characterized pathologically by amyloid-beta plaques, tau tangles and neuronal loss. In clinical practice, the 14-3-3 isoform beta (ß) is a biomarker that aids in the diagnosis of sporadic Creutzfeldt-Jakob disease. Recently, a proteomics study found increased CSF 14-3-3ß levels in Alzheimer's disease patients, suggesting a potential link between CSF 14-3-3ß and Alzheimer's disease. Our present study aimed to further investigate the role of CSF 14-3-3ß in Alzheimer's disease by analysing the data of 719 participants with available CSF 14-3-3ß measurements from the Alzheimer's Disease Neuroimaging Initiative. Higher CSF 14-3-3ß levels were observed in the mild cognitive impairment group compared to the cognitively normal group, with the highest CSF 14-3-3ß levels in the Alzheimer's disease dementia group. This study also found significant associations between CSF 14-3-3ß levels and CSF biomarkers of p-tau, t-tau, pTau/Aß42 ratios and GAP-43, as well as other Alzheimer's disease biomarkers such as Aß-PET. An early increase in CSF 14-3-3ß levels was observed prior to Aß-PET-positive status, and CSF 14-3-3ß levels continued to rise after crossing the Aß-PET positivity threshold before reaching a plateau. The diagnostic accuracy of CSF 14-3-3ß (area under the receiver operating characteristic curve = 0.819) was moderate compared to other established Alzheimer's disease biomarkers in distinguishing cognitively normal Aß pathology-negative individuals from Alzheimer's disease Aß pathology-positive individuals. Higher baseline CSF 14-3-3ß levels were associated with accelerated cognitive decline, reduced hippocampus volumes and declining fluorodeoxyglucose-PET values over a 4-year follow-up period. Patients with mild cognitive impairment and high CSF 14-3-3ß levels at baseline had a significantly increased risk [hazard ratio = 2.894 (1.599-5.238), P < 0.001] of progression to Alzheimer's disease dementia during follow-up. These findings indicate that CSF 14-3-3ß may be a potential biomarker for Alzheimer's disease and could provide a more comprehensive understanding of the underlying pathological changes of Alzheimer's disease, as well as aid in the diagnosis and monitoring of disease progression.

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.

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.

An independently validated nomogram for individualised estimation of short-term mortality risk among patients with severe traumatic brain injury: a modelling analysis of the CENTER-TBI China Registry Study.

Background: Severe traumatic brain injury (sTBI) is extremely disabling and associated with high mortality. Early detection of patients at risk of short-term (≤14 days after injury) death and provision of timely treatment is critical. This study aimed to establish and independently validate a nomogram to estimate individualised short-term mortality for sTBI based on large-scale data from China. Methods: The data were from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China registry (between Dec 22, 2014, and Aug 1, 2017; registered at ClinicalTrials.gov, NCT02210221). This analysis included information of eligible patients with diagnosed sTBI from 52 centres (2631 cases). 1808 cases from 36 centres were enrolled in the training group (used to construct the nomogram) and 823 cases from 16 centres were enrolled in the validation group. Multivariate logistic regression was used to identify independent predictors of short-term mortality and establish the nomogram. The discrimination of the nomogram was evaluated using area under the receiver operating characteristic curves (AUC) and concordance indexes (C-index), the calibration was evaluated using calibration curves and Hosmer-Lemeshow tests (H-L tests). Decision curve analysis (DCA) was used to evaluate the net benefit of the model for patients. Findings: In the training group, multivariate logistic regression demonstrated that age (odds ratio [OR] 1.013, 95% confidence interval [CI] 1.003-1.022), Glasgow Coma Scale score (OR 33.997, 95% CI 14.657-78.856), Injury Severity Score (OR 1.020, 95% CI 1.009-1.032), abnormal pupil status (OR 1.738, 95% CI 1.178-2.565), midline shift (OR 2.266, 95% CI 1.378-3.727), and pre-hospital intubation (OR 2.059, 95% CI 1.472-2.879) were independent predictors for short-term death in patients with sTBI. A nomogram was built using the logistic regression prediction model. The AUC and C-index were 0.859 (95% CI 0.837-0.880). The calibration curve of the nomogram was close to the ideal reference line, and the H-L test p value was 0.504. DCA curve demonstrated significantly better net benefit with the model. Application of the nomogram in external validation group still showed good discrimination (AUC and C-index were 0.856, 95% CI 0.827-0.886), calibration, and clinical usefulness. Interpretation: A nomogram was developed for predicting the occurrence of short-term (≤14 days after injury) death in patients with sTBI. This can provide clinicians with an effective and accurate tool for the early prediction and timely management of sTBI, as well as support clinical decision-making around the withdrawal of life-sustaining therapy. This nomogram is based on Chinese large-scale data and is especially relevant to low- and middle-income countries. Funding: Shanghai Academic Research Leader (21XD1422400), Shanghai Medical and Health Development Foundation (20224Z0012).

Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis.

AIMS/HYPOTHESIS: The clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect. METHODS: All participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions. RESULTS: A total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD. CONCLUSIONS/INTERPRETATION: At least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.

Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET)/Computed Tomography Features of Atypical Teratoid/Rhabdoid Tumors: Case Series and Review.

Purpose: The purpose of this article is to explore the clinical and neuroradiologic properties of atypical teratoid/rhabdoid tumors. Methods: Data from 6 pediatric patients with atypical teratoid/rhabdoid tumors, which mainly contained the features of magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), was retrospectively analyzed. Follow-up was conducted in all patients through clinic services and/or telephone consultation. Results: The patients included 4 males and 2 females, aged from 3.2 to 83.1 months at the initial diagnosis. All patients had MRI scans. Two patients underwent 18F-fluorodeoxyglucose PET/CT scintigraphy preoperatively and 4 postoperatively. All primary lesions were located in the cranial cavity and the average diameter of lesions was 37.2 mm. Cerebrospinal fluid spread on enhanced T1-weighted images were found in 2 patients. Multiple metastases were found on MRI and PET/CT scans, which were located at cranial cavity, spinal cord, lung and lymph node. The primary and metastatic lesions showed evident uptake of 18F-fluorodeoxyglucose. Two patients underwent total tumor removal, and 4 patients underwent subtotal removal. None of the patients received shunt surgery. Follow-up was performed in all 6 patients. One patient survived event-free 38.4 months after resection. The mean overall survival of the remaining 5 patients was 5.1 months. Conclusion: We identified specific PET/CT and MRI features that can facilitate the recognition of atypical teratoid/rhabdoid tumors prior to biopsy.

CSF GAP-43 as a biomarker of synaptic dysfunction is associated with tau pathology in Alzheimer's disease.

To test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) concentration is elevated in Alzheimer's disease (AD) dementia and its associations with other hallmarks of AD, we examined the CSF GAP-43 measurements of 787 participants (245 cognitively normal (CN), 415 individuals with mild cognitive impairment (MCI) and 127 individuals with AD dementia) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Associations were investigated between CSF GAP-43 and clinical diagnosis, Aß/tau/neurodegeneration (AT(N)) status, CSF and blood biomarkers of AD, cognitive measurements and brain neuroimaging findings. CSF GAP-43 levels were increased in patients with AD dementia (mean, 6331.05 pg/ml) compared with the CN (mean, 5001.05 pg/ml) and MCI (mean, 5118.8 pg/ml) (P < 0.001) groups. CSF GAP-43 correlated with CSF phosphorylated tau 181(p-tau) (r = 0.768, P < 0.001), and had high diagnostic accuracy in differentiating tau positive status vs. tau negative status (area under the receiver operating characteristic curve, 0.8606). CSF GAP-43 was particularly elevated among individuals with tau positive status. High CSF GAP-43 was associated with longitudinal deterioration of cognitive scores and brain neuroimaging findings. CSF GAP-43 was associated with a clinical diagnosis of AD dementia and with an individual's tau status, cognitive measurements and findings from neuroimaging. This study implies that CSF GAP-43 as a biomarker of synaptic dysfunction could predict the disease progression of AD patients.

Intrapancreatic, Liver, and Skeletal Muscle Fat Depositions in First Attack of Acute Pancreatitis Versus Health.

INTRODUCTION: Increased intrapancreatic fat deposition (IPFD) has emerged as a harbinger of pancreatic cancer and chronic pancreatitis. Although it is well recognized that diseases of the exocrine pancreas often lie on a continuum (with acute pancreatitis preceding the development of chronic pancreatitis and/or pancreatic cancer), whether increased IPFD predisposes to acute pancreatitis is unknown. This study aimed to compare fat depositions in the pancreas (as well as the liver and skeletal muscle) between individuals who developed first attack of acute pancreatitis and healthy individuals. METHODS: This was a matched case-control study nested into population-based cohort. MRI on a single 3 T scanner was used to quantify intrapancreatic, liver, and skeletal muscle fat depositions using the same protocols in all study participants. Binary logistic regression with adjustment for body mass index and other possible confounders was performed. RESULTS: Fifty individuals with first attack of nonnecrotizing acute pancreatitis comprised the case group and 100 healthy individuals comprised the control group. A 1% increase in IPFD (but not the other fat depositions) was significantly associated with a more than 30% higher chance of developing first attack of acute pancreatitis, consistently in both the unadjusted ( P = 0.004) and all adjusted models. Furthermore, a 1% increase in IPFD (but not the other fat depositions) was significantly associated with up to a 27% higher chance of developing first attack of acute pancreatitis in individuals with normotriglyceridemia, consistently in both the unadjusted ( P = 0.030) and all adjusted models. DISCUSSION: Increased IPFD may predispose to the development of acute pancreatitis. This opens up opportunities for reducing the burden of acute pancreatitis by means of primary prevention.

Direct Current Electric Field Coordinates the Migration of BV2 Microglia via ERK/GSK3ß/Cofilin Signaling Pathway.

Direct current electric field (DCEF) steers the migration of various neural cells. Microglia, as macrophage of the central nervous system (CNS), however, have not been reported to engage in electrotaxis. Here, we applied electric fields to an in vitro environment and found directional migration of BV2 microglia toward the cathode, in a DCEF strength-dependent manner. Transcriptome analysis then revealed significant changes in the mitogen-activated protein kinase cascades. In terms of mechanism, DCEF coordinated microglia movement by regulating the ERK/GSK3ß/cofilin signaling pathway, and PMA (protein kinase C activator) reversed cell migration through intervention of the ERK/GSK3ß/cofilin axis. Meanwhile, LiCl (GSK3ß inhibitor) showed similar functions to PMA in the electrotaxis of microglia. Furthermore, pharmacological and genetic suppression of GSK3ß or cofilin also modulated microglia directional migration under DCEF. Collectively, we discovered the electrotaxis of BV2 microglia and the essential role of the ERK/GSK3ß/cofilin axis in regulating cell migration via modulation of F-actin redistribution. This research highlights new insight toward mediating BV2 directional migration and provides potential direction for novel therapeutic strategies of CNS diseases.

Fat Distribution Within the Pancreas According to Diabetes Status and Insulin Traits.

A growing body of evidence suggests that intrapancreatic fat is associated with diabetes, but whether distribution of intrapancreatic fat across the regions of the pancreas has a pathophysiologic role is unknown. The aim of this study was to investigate the differences in intrapancreatic fat deposition between the head, body, and tail of the pancreas, as well as the relationship between regional intrapancreatic fat deposition and diabetes status and insulin traits. A total of 368 adults from the general population underwent MRI on a 3 Tesla scanner, and intrapancreatic fat was manually quantified in duplicate. Statistical models included adjustment for age, sex, ethnicity, BMI, and liver fat. Intrapancreatic fat deposition in the head, body, and tail of the pancreas did not differ significantly in adjusted models in either the overall cohort or the three subgroups based on diabetes status. HOMA of insulin resistance and fasting insulin were significantly positively associated with fat in the tail and body of the pancreas. There was no significant association between regional intrapancreatic fat and HOMA of ß-cell function. The association of increased intrapancreatic fat deposition in the tail and body regions with increased insulin resistance may have an important role in the early identification of patients at risk for developing insulin resistance and diseases that stem from it.

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.