Scanner-referenced T1 (srT1) is a method for measuring pancreas T1 relaxation time. The purpose of this multi-centre study is 2-fold: (1) to evaluate the repeatability of manual ROI-based analysis of srT1, (2) to validate a semi-automated measurement method with an automatic quality control (QC) module to identify likely discrepancies between automated and manual measurements.

Pancreatic MRI scans from a scan-rescan cohort (46 subjects) were used to evaluate the repeatability of manual analysis. Seven hundred and eight scans from a longitudinal multi-centre study of 466 subjects were divided into training, internal validation (IV), and external validation (EV) cohorts. A semi-automated method for measuring srT1 using machine learning is proposed and compared against manual analysis on the validation cohorts with and without automated QC.

Inter-operator agreement between manual ROI-based method and semi-automated method had low bias (3.8 ms or 0.5%) and limits of agreement [-36.6, 44.1] ms. There was good agreement between the 2 methods without automated QC (IV: 3.2 [-47.1, 53.5] ms, EV: -0.5 [-35.2, 34.2] ms). After QC, agreement on the IV set improved, was unchanged in the EV set, and the agreement in both was within inter-operator bounds (IV: -0.04 [-33.4, 33.3] ms, EV: -1.9 [-37.6, 33.7] ms). The semi-automated method improved scan-rescan agreement versus manual analysis (manual: 8.2 [-49.7, 66] ms, automated: 6.7 [-46.7, 60.1] ms).

The semi-automated method for characterization of standardized pancreatic T1 using MRI has the potential to decrease analysis time while maintaining accuracy and improving scan-rescan agreement.

We provide intra-operator, inter-operator, and scan-rescan agreement values for manual measurement of srT1, a standardized biomarker for measuring pancreas fibro-inflammation. Applying a semi-automated measurement method improves scan-rescan agreement and agrees well with manual measurements, while reducing human effort. Adding automated QC can improve agreement between manual and automated measurements.

We describe a method for semi-automated, standardized measurement of pancreatic T1 (srT1), which includes automated quality control. Measurements show good agreement with manual ROI-based analysis, with comparable consistency to inter-operator performance.

Fat deposition in the pancreas is implicated in beta cell dysfunction and the progress of type 2 diabetes. However, there is limited evidence to confirm the correlation and explore how pancreatic fat links with beta cell dysfunction in human type 2 diabetes. This study aimed to examine the spatial relationship between pancreatic fat and islets in human pancreases.

Histological analysis of pancreatic specimens from 50 organ donors (15 with type 2 diabetes, 35 without) assessed pancreatic fat content variation among individuals with diabetes and its correlation with estimated beta cell mass and cell distribution within islets. Bioinformatic analysis of single-cell RNA-seq of 11 type 2 diabetic donors (from the Human Pancreatic Analysis Project database) explored the impact of high pancreatic fat content on beta cell gene expression and cell fate. Validation of bioinformatic results was performed with the above diabetic pancreases.

Pancreatic fat content was higher in individuals with type 2 diabetes (10.24% [3.29-13.89%] vs 0.74% [0.34-5.11%], p<0.001), negatively correlated with estimated beta cell mass (r=-0.675, p=0.006) and positively with alpha-to-beta cell ratio (r=0.608, p=0.016). Enrichment analysis indicated that in diabetic donors with higher pancreatic fat content, the expression of ALDH1A3, beta cell dedifferentiation marker, in both alpha and beta cells was significantly increased, and in beta cells, the expression of NPY decreased. Pseudotime analysis revealed beta cell dedifferentiation and transdifferentiation towards alpha cells in diabetic donors with higher pancreatic fat content, with decreased expression of genes related to beta cell maturation and function, including INSM1, MafA and NPY. Concurrently, pathways related to inflammation and immune response were activated. Histologically, pancreatic fat content correlated positively with the percentage of beta cells positive for aldehyde dehydrogenase 1 family member A3 (ALDH1A3) within the islets (r=0.594, p=0.020) and the ALDH1A3 positivity rate in beta cells (r=0.615, p=0.015). And the number of T cells adjacent to adipocytes was related to the distribution pattern of adipocytes and the dedifferentiation phenotype in islets.

Higher pancreatic fat content was accompanied by increased beta cell dedifferentiation in the individuals with diabetes. Clusters of adipocytes significantly contribute to higher pancreatic fat content and immune cell recruitment. Overall, the interactions among adipocytes, immune cells and beta cells in the pancreas microenvironment might contribute to beta cell failure and dedifferentiation in type 2 diabetes.

Fatty pancreas disease (FPD) is characterized by abnormal fat accumulation in pancreatic tissue and is often associated with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). While its pathophysiology and impact on pancreatic functions have been explored, the interplay between FPD, glycemic control, and exocrine dysfunction in T2DM remains inadequately defined. This study aimed to evaluate the presence of FPD, the factors affecting it, and its relationship with endocrine and exocrine pancreatic functions in newly diagnosed T2DM.

A total of 126 individuals were included in the study, comprising 63 newly diagnosed T2DM patients and 63 healthy controls matched for age, sex, body mass index and body fat distribution. Body composition, biochemical parameters (glucose, insulin, C-peptide, HbA1c), fecal elastase levels, and pancreatic/hepatic steatosis grades (evaluated using ultrasonography) were assessed.

Newly diagnosed T2DM patients presented significantly higher hepatic steatosis grades (p = 0.018) and lower fecal elastase levels (p < 0.001) compared to controls. Pancreatic exocrine insufficiency was more prevalent in the T2DM group (p < 0,001). A positive correlation was observed between the FPD grade, hepatic steatosis grade, and hepatic fat fraction. A negative and statistically significant correlation (p < 0.05) was observed between FPD grade and fecal elastase level (r = -0.264). HbA1c levels demonstrated a nonlinear (inverse U-shaped) relationship with FPD, peaking at 9.8% and declining thereafter, while showing a continuous negative relationship with fecal elastase levels. HbA1c predicted low fecal elastase (< 200 μg/g) with a cutoff value of 7.4%. Patients with HbA1c levels > 9.8% presented with reduced FPD alongside persistent exocrine insufficiency.

Fatty pancreas disease is closely associated with hepatic steatosis, glycemic control, and exocrine pancreatic dysfunction in newly diagnosed T2DM patients. The interplay between FPD, glycemic control, and exocrine dysfunction highlights the need for comprehensive metabolic assessments in this population.

To investigate the causal relationship between various lipid-modifying drugs and new-onset diabetes, as well as the mediators contributing to this relationship.

Mediation Mendelian randomization was performed to investigate the causal effect of lipid-modifying drug targets on type 2 diabetes (T2D) outcomes and the proportion of this association that is mediated through ectopic fat accumulation traits. Specific sets of variants in or near genes that encode 11 lipid-modifying drug targets (LDLR, HMGCR, NPC1L1, PCSK9, APOB, ABCG5/ABCG8, LPL, PPARA, ANGPTL3, APOC3, and CETP; for expansion of gene symbols, use search tool at www.genenames.org) were extracted. Random effects inverse variance weighted were performed to evaluate the causal effects among outcomes. Mediation analyses were performed to identify the mediators of the association between lipid-modifying drugs and T2D. The study was conducted from November 10, 2023, to April 2, 2024 RESULTS: The genetic mimicry of HMGCR and APOB inhibition was associated with an increased T2D risk, whereas the genetic mimicry of LPL enhancement was linked to a lower T2D risk. Gluteofemoral adipose tissue volume was a mediator for explaining 9.52% (P=.002), 16.90% (P=.03), and 10.50% (P=.003) of the total effect of HMGCR, APOB, and LPL on T2D susceptibility, respectively. Liver fat was a mediator for explaining 21.12% (P=.005), 12.28% (P=.03), and 9.84% (P=.005) of the total effect of HMGCR, APOB, and LPL on T2D susceptibility, respectively.

Our findings support the hypothesis that liver fat and gluteofemoral adipose tissue play a mediating role in the prodiabetic effects of HMGCR and APOB inhibition, as well as in the antidiabetic effects of LPL enhancement.

Objectives: This study aimed to compare the pancreatic volume between beta-thalassemia major (β-TM) and beta-thalassemia intermedia (β-TI) patients and between thalassemia patients and healthy subjects and to determine the predictors of pancreatic volume and its association with glucose metabolism in β-TM and β-TI patients. Methods: We considered 145 β-TM patients and 19 β-TI patients enrolled in the E-MIOT project and 20 healthy subjects. The pancreatic volume and pancreatic and hepatic iron levels were quantified by magnetic resonance imaging. Results: The pancreatic volume indexed by body surface area (PVI) was significantly lower in both β-TI and β-TM patients compared to healthy subjects and in β-TM patients compared to β-TI patients. The only independent determinants of PVI were pancreatic iron in β-TM and hepatic iron in β-TI. In β-TM, there was an association between alterations of glucose metabolism and PVI, and PVI was a comparable predictor of altered glucose metabolism compared to pancreatic iron. Only one β-TI patient had an altered glucose metabolism and showed a reduced PVI and pancreatic iron overload. Conclusions: Thalassemia syndromes are characterized by a reduced pancreatic volume, associated with iron levels. In β-TM, the pancreatic volume and iron deposition are associated with the development and progression of alterations of glucose metabolism.

Background/Objectives: It has been shown that the use of statins in patients with type 2 diabetes mellitus (T2DM) worsens hyperglycemia and hemoglobin A1c levels but may help in the preservation of pancreatic β-cell function. The potential role of a high pancreatic fat fraction (PFF) in this process has not yet been clarified. This study aimed to investigate whether the liver fat fraction (LFF) and PFF in T2DM patients is affected by statin therapy. Methods: This cross-sectional study involved a total of 140 T2DM patients, including both those who were receiving (n = 70) and those who were not receiving (n = 70) statin therapy. The mapping of the LFF and PFF utilizing the IDEAL-IQ sequence was conducted in magnetic resonance imaging. Results: In T2DM patients who used statins, the median PFF was higher compared to those who did not use statins (8.4 vs. 6.2%, p = 0.021), while the median LFF was found to be similar (8.4 vs. 8.9, p = 0.572). Variations in PFF were associated with the use of various statins (non-statin group: 6.2 vs. atovastatin: 8.7 vs. rosuvastatin: 3.2 vs. pitavastatin: 9.2, p = 0.004). The multivariable regression analysis indicated that insulin usage decreased log(LFF) by a factor of 0.16-fold (ꞵ ± SE = -0.16 ± 0.05, p = 0.010), and rosuvastatin usage reduced log(PFF) by 0.16-fold (ꞵ ± SE = -0.16 ± 0.07, p = 0.025), irrespective of other risk factors. Furthermore, the use of atorvastatin (ꞵ ± SE = 0.17 ± 0.06, p = 0.011) and pitavastatin (ꞵ ± SE = 0.19 ± 0.07, p = 0.008) were independently associated with an increase in log(PFF). Conclusions: In patients with T2DM, statin use did not show a significant effect on the liver fat fraction, but it caused differences in the pancreatic fat fraction. The observation of a lower pancreatic fat fraction in patients taking a rosuvastatin and atorvastatin dose of 40 mg/day suggests that different types and doses of statins may have varying effects on pancreatic fat accumulation.

We assessed the impact of a 3-year change-percent in adiposity measures on regression and pre-diabetes (Pre-DM) progression among Iranian adults.

Three-year change-percent in body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and visceral adiposity index (VAI) were calculated for 1458 Pre-DM subjects (mean age of 53.0 ± 13.7, 46.8% men), participated in the third examination of the Tehran Lipid and Glucose Study (2006-2008). Multinomial logistic regression models were used to estimate relative risk ratios (RRRs) of the outcomes [i.e., regression to normal glucose regulation (NGR), persistence in Pre-DM, and progression to newly diagnosed type 2 diabetes (T2D)] across 3-year change categories of adiposity measures (i.e., ≥ 5% decrease, 0-5% decrease, increase).

Over nine years of follow-up, 37.7 and 39.0% returned to NGR and progressed to T2D, respectively. Decreased BW (0-5 and ≥ 5%) was associated with regression to NGR (RRRs = 1.44, 95% CIs = 1.05-1.98, and 2.64, 1.63-4.28, respectively). Decreased BMI and WC ≥ 5% were also associated with regression to NGR (RRRs = 1.63, 95% CI = 1.01-2.64; 1.69, 1.20-2.37, respectively). Changes in WHR and VAI were not associated with Pre-DM regression or progression. Pre-DM subjects with ≥ 5% BW loss had a constant FSG level overtime and a lower overall mean of FSG (116 vs. 111 and 112 mg/dL, P = 0.023 and 0.009, respectively) and 2 h-SG (154 vs. 165 and 168 mg/dL) compared to those had 0-5% BW loss or BW gain.

Short-term management of adiposity measures increases the regression probability to NGR. Targeting BW loss seems a more potent predictor of Pre-DM reversion among the adiposity measures.

Adipose tissue accumulation around non-adipose tissues is associated with obesity and metabolic disease. One relatively unstudied depot is peripancreatic adipose tissue (PAT) that accumulates in obesity and insulin resistance and may impact beta cell function. Pancreatic lipid accumulation and PAT content are negatively related to metabolic outcomes in humans, but these studies are limited by the inability to pursue mechanisms.

We obtained PAT from human donors through the Human Pancreas Analysis Program to evaluate differences in paracrine signaling compared to subcutaneous adipose tissue (SAT), as well as effects of the PAT secretome on aortic vasodilation, human islet insulin secretion, and gene transcription using RNAseq.

PAT had greater secretion of IFN-γ and most inflammatory eicosanoids compared to SAT. Secretion of adipokines negatively related to metabolic health were also increased in PAT compared to SAT. We found no overall effects of PAT compared to SAT on human islet insulin secretion, however, insulin secretion was suppressed after PAT exposure from men compared to women. Vasodilation was significantly dampened by PAT conditioned media, an effect explained almost completely by PAT from men and not women. Islets treated with PAT showed selective changes in lipid metabolism pathways while SAT altered cellular signaling and growth. RNAseq analysis showed changes in islet gene transcription impacted by PAT compared to SAT, with the biggest changes found between PAT based on sex.

The PAT secretome is metabolically negative compared to SAT, and impacts islet insulin secretion, blood flow, and gene transcription in a sex dependent manner.

We investigated the association of a 3-year change in body weight (BW) and regression to normal glucose regulation (NGR) among different phenotypes of pre-diabetes (Pre-DM), i.e., isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG) and combined IFG-IGT.

1458 Pre-DM subjects (iIFG = 618, iIGT = 462, and IFG-IGT = 378) were assessed for 3-year change-percent in BW (2006-2008 to 2009-2011) and then followed up to 2015-2017, within the national cohort of Tehran Lipid and Glucose Study (TLGS). Binary logistic regression models were used to estimate the probability (odds ratio, ORs) of regression to NGR across categories of 3-year BW change (i.e., ≥5% BW loss, <5% BW loss, BW gain) in different phenotypes of Pre-DM.

The mean age of the participants was 53.0 ± 13.7, and 46.8% were men. Over a median of 6 years of follow-up, the rate of regression to normoglycemia was 50.6, 43.2, and 12.7% in iIGT, iIFG, and combined IFG-IGT, respectively. The baseline-adjusted mean of 3-year BW change was not significantly different across Pre-DM phenotypes (0.68 ± 0.19, 0.32 ± 0.22, and 0.23 ± 0.24 kg, in iIFG, iIGT, and IFG-IGT). Three-year BW loss ≥5% was associated with a greater NGR probability in iIGT than other phenotypes (OR = 4.29 vs. 3.90 and 2.84 in IFG-IGT and iIFG, respectively). A modest reduction (<5% of initial BW) resulted in an increased chance of Pre-DM regression among subjects with iIGT (OR = 1.61, 95% CI = 1.03-2.52) but not iIFG or IFG-IGT phenotypes.

Short-term intensive BW loss (≥5% of initial BW) increased NGR probability in all Pre-DM phenotypes, with an order of iIGT > combined IFG-IGT > iIFG. Only iIGT takes advantage of moderate BW loss (<5% of initial BW) to increase the chance of Pre-DM regression.

Non-alcoholic fatty pancreatic disease (NAFPD), also known as pancreatic steatosis, is a benign condition characterized by deposition of lipids in the pancreas and is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, aging, and absence of heavy alcohol intake or infection. Similar to nonalcoholic fatty liver disease, NAFPD is a phenotypic entity that includes fat buildup in the pancreas, pancreatic inflammation, and subsequent fibrosis. The extent to which pancreatic fat infiltration is clinically important remains unclear. Despite these clinical associations, most of the clinical effects of NAFPD are not known. NAFPD may be identified by transabdominal and elastography ultrasound, computed tomography scan, or magnetic resonance imaging modalities, but a confirmatory diagnosis can only be made through tissue histology. In addition to complications such as acute and chronic pancreatitis, NAFPD may progress to pancreatic ductal adenocarcinoma. However, further research is required to fully understand the associations, pathophysiology, and effects of NAFPD. This review provides a narrative synthesis of the current literature on the epidemiology, pathophysiology, complications, diagnostic and imaging tools, and management of NAFPD.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [18F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted.

This work proposes a method for automatic standardized assessment of bone marrow volume and spatial distribution of the proton density fat fraction (PDFF) in vertebral bodies. Intra- and interindividual variability in size and shape of vertebral bodies is a challenge for comparable interindividual evaluation and monitoring of changes in the composition and distribution of bone marrow due to aging and/or intervention. Based on deep learning image segmentation, bone marrow PDFF of single vertebral bodies is mapped to a cylindrical template and corrected for the inclination with respect to the horizontal plane. The proposed technique was applied and tested in a cohort of 60 healthy (30 males, 30 females) individuals. Obtained bone marrow volumes and mean PDFF values are comparable to former manual and (semi-)automatic approaches. Moreover, the proposed method allows shape-independent characterization of the spatial PDFF distribution inside vertebral bodies.

Diabetes mellitus presents a global health challenge characterized by dysregulated glucose metabolism and insulin resistance. Pancreas dysfunction contributes to the development and progression of diabetes. Cross-sectional imaging modalities have provided new insight into the structural and functional alterations of the pancreas in individuals with diabetes. This review summarizes MRI and CT studies that characterize pancreas alterations in both type 1 and type 2 diabetes and discusses future applications of these techniques.

Intra-pancreatic fat deposition (IPFD) is suspected to be associated with various medical conditions. This study aimed to assess pancreatic fat content in lean and obese individuals, characterize obese individuals with and without IPFD, and explore the underlying mechanisms.

Sixty-two obese individuals without diabetes and 35 lean controls underwent magnetic resonance imaging (MRI) using proton density fat fraction (PDFF) maps to evaluate pancreatic and hepatic fat content, and visceral adipose tissue (VAT) content. Pancreatic fibrosis was explored by T1 relaxation time and MR elastography (MRE) measurements. Associations between pancreatic fat, measures of obesity and metabolic syndrome were examined using uni- and multivariate regression analyses.

Pancreatic PDFF was higher in obese than in lean controls (median 8.0%, interquartile range (6.1;13.3) % vs 2.6(1.7;3.9)%, p < 0.001). Obese individuals with IPFD (PDFF ≥6.2%) had higher waist circumference (114.0 ± 12.5 cm vs 105.2 ± 8.7 cm, p = 0.007) and VAT (224.9(142.1; 316.1) cm2 vs 168.2(103.4; 195.3) cm2, p < 0.001) than those without. In univariate analysis, pancreatic PDFF in obese individuals correlated with BMI (r = 0.27, p = 0.03), waist circumference (r = 0.44, p < 0.001), VAT (r = 0.37, p = 0.004), hepatic PDFF (r = 0.25, p = 0.046) and diastolic blood pressure (r = 0.32, p = 0.01). However, in multivariate analysis, only VAT was associated to pancreatic fat content. MRI measures of pancreatic fibrosis indicated no evident fibrosis in relation to increased pancreatic fat content.

Pancreatic fat content was increased in obese individuals compared with lean controls and predominantly correlated with the amount of visceral adipose tissue. Pancreatic fat content was not clearly linked to measures of pancreatic fibrosis.

Non-alcoholic fatty pancreas disease (NAFPD) can be detected using various imaging techniques, but accurately measuring the amount of fat in the pancreas remains difficult. Fatty acid binding protein-1 (FABP-1) is a marker specific to certain tissues and can aid in diagnosing NAFPD. However, this study aimed to investigate the prevalence of NAFPD among obese and non-obese people with and without diabetes mellitus (DM). Additionally, it aimed to evaluate the associated risk factors for NAFPD and the utility of the FABP-1 level as a simple, non-invasive biomarker for diagnosing NAFPD.

This study is a prospective cross-sectional study.

Ninety-five patients were enrolled in the study, comprising 35 males and 60 females, with a mean age of 44 years and a standard deviation (SD) of 11 years. However, 26.3 % were morbidly obese, 22.1 % were severely obese, 31.6 % were obese, 12.6 % were overweight, and 7.4 % were normal. Additionally, 35.8 % had diabetes mellitus, while 26.3 % of patients had hypertension. Regarding the ultrasonographic findings, 94.7 % of the patients had fatty liver, with the majority (41.1 %) classified as grade II, followed by 38.9 % classified as grade I, and 14.7 % classified as grade III fatty liver. Among these patients, 78.9 % had fatty pancreas, with 38.9 % classified as grade II, 31.6 % classified as grade I, and 8.4 % classified as grade III fatty pancreas. The median FABP-1 level among patients with fatty pancreas was 3.3 ng/ml, which exhibited a significant fair negative correlation with total bilirubin and a fair, positive correlation with alkaline phosphatase and portal vein diameter. A statistically substantial distinction was observed between the levels of AFABP-1 and the presence or grading of the fatty pancreas (p-value = 0.048 and < 0.001, respectively). Using multivariate analysis, FABP-1 was the only significant predictor of a fatty pancreas. The receiver operating characteristic (ROC) curve analysis indicated that at a cut-off point of FABP-1 of ≤ 3.7, it had a sensitivity of 58 %, specificity of 80 %, positive predictive value (PPV) of 96.6 %, negative predictive value (NPV) of 17 %, and an area under the curve (AUC) of 0.77.

NAFPD is becoming an increasingly significant challenge. FABP-1 can potentially be a straightforward and non-invasive predictor of the fatty pancreas.

Individuals with obesity may develop intrapancreatic fat deposition (IPFD) and fatty pancreas disease (FPD). Whether this causes inflammation and fibrosis and leads to pancreatic dysfunction is less established than for liver damage in metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, the interrelations of FPD and MASLD are poorly understood. Therefore, we aimed to assess IPFD and fibro-inflammation in relation to pancreatic function and liver disease severity in individuals with MASLD.

Seventy-six participants from the Amsterdam MASLD-MASH cohort (ANCHOR) study underwent liver biopsy and multiparametric MRI of the liver and pancreas, consisting of proton-density fat fraction sequences, T1 mapping and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).

The prevalence of FPD was 37.3%. There was a clear correlation between pancreatic T1 relaxation time, which indicates fibro-inflammation, and parameters of glycemic dysregulation, namely HbA1c (R = 0.59; p <0.001), fasting glucose (R = 0.51; p <0.001) and the presence of type 2 diabetes (mean 802.0 ms vs. 733.6 ms; p <0.05). In contrast, there was no relation between IPFD and hepatic fat content (R = 0.03; p = 0.80). Pancreatic IVIM diffusion (IVIM-D) was lower in advanced liver fibrosis (p <0.05) and pancreatic perfusion (IVIM-f), reflecting vessel density, inversely correlated to histological MASLD activity (p <0.05).

Consistent relations exist between pancreatic fibro-inflammation on MRI and endocrine function in individuals with MASLD. However, despite shared dysmetabolic drivers, our study suggests IPFD is a separate pathophysiological process from MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and 68% of people with type 2 diabetes have MASLD. However, fat infiltration and inflammation in the pancreas are understudied in individuals with MASLD. In this cross-sectional MRI study, we found no relationship between fat accumulation in the pancreas and liver in a cohort of patients with MASLD. However, our results show that inflammatory and fibrotic processes in the pancreas may be interrelated to features of type 2 diabetes and to the severity of liver disease in patients with MASLD. Overall, the results suggest that pancreatic endocrine dysfunction in individuals with MASLD may be more related to glucotoxicity than to lipotoxicity.

NTR7191 (Dutch Trial Register).

High amount of fat in the pancreas is linked to poor functioning of β-cells and raises the risk of type 2 diabetes. Here we report the putative role of a circulatory glycoprotein Fetuin-A, a known obesity marker, in promoting lipid accumulation in β-cells and its association with Fatty acid translocase/CD36 for lipid storage culminate in β-cell dysfunction. Additionally, this work reveals regulation of CD36 via Nrf2, a key regulator of oxidative stress, and reduction of lipid accumulation by suppression of Nrf2 that restores β-cell function. Palmitate (0.50 mM) and Fetuin-A (100 μg/mL) exposure showed high levels of intracellular lipid in MIN6 (mouse insulinoma cells) with a concomitant decrease in insulin secretion. This also increased the expression of important lipogenic factors, like CD36, PGC1α, PPARγ, and SREBP1. Flow cytometry analysis of CD36 membrane localization has been corroborated with an increased accumulation of lipids as indicated by Oil-Red-O staining. Immunoblotting and immunofluorescence of Nrf2 indicated its high expression in palmitate-fetuin-A incubation and translocation in the nucleus. Suppression of Nrf2 by siRNA showed a reduced expression of lipogenic genes, ablation of lipid droplets, decrease in the number of apoptotic cells, and restoration of insulin secretion with a corresponding increase of Pdx1, BETA2, and Ins1 gene expression. Our study thus suggested an important aspect of lipid accumulation in the pancreatic β-cells contributing to β-cell dysfunction and demonstrated the role of Fetuin-A in CD36 expression, with a possible way of restoring β-cell function by targeting Nrf2.

Patients with adrenal incidentaloma (AI) are at increased risk of impaired glucose metabolism, which is known to be associated with pancreatosteatosis (PS). We aimed to investigate the risk of developing dysglycemia for patients with non-functioning AI (NFAI) versus those without, and whether the presence of PS predicts future dysglycemia in patients with NFAI.

In 80 patients with NFAI and 127 controls matched for age, sex, and body mass index, changes in fasting plasma glucose (FPG) and hemoglobin A1c(HbA1c) were evaluated at 2 years. PS was evaluated with data obtained from non-contrast abdominal computed tomography (CT) performed at the initial evaluation.

Mean FPG levels increased significantly after 2 years in both groups (P < 0.001, for both), albeit significantly higher among patients than the controls (P = 0.002). The increases in HbA1c and FPG levels were significantly higher among patients with PS than without PS, in the adenoma group (p < 0.001, P = 0.00, respectively). The change in Hba1c levels was associated with the presence of PS in patients with NFAI (p < 0.001).

Our findings suggest that the presence of PS may provide significant information in predicting newly developed dysglycemia in patients with NFAI.

Non-Alcoholic Fatty Pancreas disease (NAFPD), characterized by fat accumulation in pancreatic tissue, is an emerging clinical entity. However, the clinical associations, the underlying molecular drivers, and the pathophysiological mechanisms of NAFPD have not yet been characterized in detail. The NAFPD spectrum not only includes infiltration and accumulation of fat within and between pancreatic cells but also involves several inflammatory processes, dysregulation of physiological metabolic pathways, and hormonal defects. A deeper understanding of the underlying molecular mechanisms is key to correlate NAFPD with clinical entities including non-alcoholic fatty liver disease, metabolic syndrome, diabetes mellitus, atherosclerosis, as well as pancreatic cancer and pancreatitis. The aim of this review is to examine the pathophysiological mechanisms of NAFPD and to assess the possible causative/predictive risk factors of NAFPD-related clinical syndromes.

The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance.

A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction.

Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively).

MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders.

Background  The most crucial step in the management of type 2 diabetes is identifying its pathogenesis and progression. Fat accumulation in the pancreas and decreased parenchymal volume can influence pancreatic function due to insulin resistance or β-cell dysfunction. This study aims to find out the difference in pancreatic volume and fat content by using contrast-enhanced computed tomography (CECT) between normal subjects and patients with different durations of type 2 diabetes mellitus (T2DM). Methods  This was a cross-sectional study. Patients who underwent CECT abdomen for the evaluation of conditions other than pancreatic origin were included. The study group was divided into three subgroups according to the duration of diabetes as <5 years, 5 to 10 years, and >10 years. In total, 40 nondiabetic controls were included. Pancreatic fat volume and parenchymal volume were measured in cm 3 using CECT. Correlation between pancreatic parenchymal and fat volume with the duration of T2DM as well as with levels of hemoglobin A1c, random blood sugar, serum triglyceride, low-density lipoproteins, and high-density lipoproteins was done. Results  T2DM patients had significantly ( p  < 0.001) lower pancreatic parenchymal volume (mean value of 57.08 ± 8.26 cm 3 in diabetics and 72.23 ± 3.41 cm 3 in controls) and higher pancreatic fat volume (mean value of 3.08 ± 1.90 cm 3 in diabetics and 0.67 ± 0.27cm 3 in controls) as compared to nondiabetic controls. In patients with T2DM, as the duration of T2DM increased, pancreatic parenchymal volume decreased and pancreatic fat volume increased. Conclusion  Reduction in pancreatic volume and fat deposition may have a role in the onset and progression of diabetes. Determining the pancreatic volume and fat content would be useful for identifying high-risk patients and determining the pathogenesis of the development of diabetes.

The propensity to develop type 2 diabetes (T2D) is known to have both environmental and hereditary components. In those with a genetic predisposition to T2D, it is widely believed that elevated concentrations of circulatory long-chain fatty acids (LC-FFA) significantly contribute towards the demise of insulin-producing pancreatic β-cells - the fundamental feature of the development of T2D. Over 25 years of research support that LC-FFA are deleterious to β-cells, through a process termed lipotoxicity. However, the work underpinning the theory of β-cell lipotoxicity is mostly based on rodent studies. Doubts have been raised as to whether lipotoxicity also occurs in humans. In this review, we examine the evidence, both in vivo and in vitro, for the pathogenic effects of LC-FFA on β-cell viability and function in humans, highlighting key species differences. In this way, we aim to uncover the role of lipotoxicity in the human pathogenesis of T2D and motivate the need for species-specific understanding.

In the UK, populations of Black African and Caribbean (BAC) ethnicity suffer higher rates of cardiometabolic disease than White Europeans (WE). Obesity, leading to increased visceral adipose tissue (VAT) and intrahepatic lipid (IHL), has long been associated with cardiometabolic risk, driving insulin resistance and defective fatty acid/lipoprotein metabolism. These defects are compounded by a state of chronic low-grade inflammation, driven by dysfunctional adipose tissue. Emerging evidence has highlighted associations between central complement system components and adipose tissue, fatty acid metabolism and inflammation; it may therefore sit at the intersection of various cardiometabolic disease risk factors. However, increasing evidence suggests an ethnic divergence in pathophysiology, whereby current theories fail to explain the high rates of cardiometabolic disease in BAC populations. Lower fasting and postprandial TAG has been reported in BAC, alongside lower VAT and IHL deposition, which are paradoxical to the high rates of cardiometabolic disease exhibited by this ethnic group. Furthermore, BAC have been shown to exhibit a more anti-inflammatory profile, with lower TNF-α and greater IL-10. In contrast, recent evidence has revealed greater complement activation in BAC compared to WE, suggesting its dysregulation may play a greater role in the high rates of cardiometabolic disease experienced by this population. This review outlines the current theories of how obesity is proposed to drive cardiometabolic disease, before discussing evidence for ethnic differences in disease pathophysiology between BAC and WE populations.

To assess the association of ectopic fat deposition in the liver and pancreas quantified by Dixon magnetic resonance imaging (MRI) with insulin sensitivity and β-cell function in patients with central obesity.

A cross-sectional study of 143 patients with central obesity with normal glucose tolerance (NGT), prediabetes (PreD), and untreated type 2 diabetes mellitus (T2DM) was conducted between December 2019 and March 2022. All participants underwent routine medical history taking, anthropometric measurements, and laboratory tests, including a standard glucose tolerance test to quantify insulin sensitivity and β-cell function. The fat content in the liver and pancreas was measured with MRI using the six-point Dixon technique.

Patients with T2DM and PreD had a higher liver fat fraction (LFF) than those with NGT, while those with T2DM had a higher pancreatic fat fraction (PFF) than those with PreD and NGT. LFF was positively correlated with homeostatic model assessment of insulin resistance (HOMA-IR), while PFF was negatively correlated with homeostatic model assessment of insulin secretion (HOMA-β). Furthermore, using a structured equation model, we found LFF and PFF to be positively associated with glycosylated hemoglobin via HOMA-IR and HOMA-β, respectively.

In patients with central obesity, the effects of LFF and PFF on glucose metabolism. were associated with HOMA-IR and HOMA-β, respectively. Ectopic fat storage in the liver and pancreas quantified by MR Dixon imaging potentially plays a notable role in the onset ofT2DM.

We highlight the potential role of ectopic fat deposition in the liver and pancreas in the development of type 2 diabetes in patients with central obesity, providing valuable insights into the pathogenesis of the disease and potential targets for intervention.

• Ectopic fat deposition in the liver and pancreas is associated with T2DM. • T2DM and prediabetes patients had higher liver and pancreatic fat fractions than normal individuals. • The results provide valuable insights into pathogenesis of T2DM and potential targets for intervention.

There have been few reports about the longitudinal changes in pancreas volume (PV) or pancreatic steatosis (PS) in response to obesity. In this longitudinal analysis using health check-up data, we explored changes in PV, PS and glucose metabolic indices that occurred after weight gain in Japanese without diabetes.

Clinical data on 37 Japanese subjects with a ≥1 kg/m² increase in body mass index between two health check-ups and without diabetes were collected. PV, pancreas attenuation (PA) and splenic attenuation (SA) were evaluated using computed tomography (CT) images. The pancreas area was outlined by hand in multiple images with slice thickness of 2 mm, and the PV was computed by summing these areas. PS was defined as the difference between SA and PA (SA-PA). Medical records were collected, including findings on immunoreactive insulin (IRI), homeostasis model assessment of insulin resistance (HOMA-R) and beta cell function (HOMA-β). Paired t-test and Spearman's correlation coefficient were used in the analyses.

The median follow-up period was 21.1 months and the mean BMI was increased from 25.5 ± 3.3 kg/m² to 27.0 ± 3.3 kg/m². PV (53.5 ± 15.9 cm³ vs. 56.2 ± 16.4 cm³) and SA-PA (8.7 ± 9.1 HU vs. 13.6 ± 10.9 HU) increased significantly after weight gain (both, P < 0.001). There were significant increases of IRI and HOMA-R with the weight gain (both, P < 0.05), whereas HOMA-β exhibited only a nonsignificant trend of increase (55.4％ (41.5-65.5) vs. 56.8％ (46.2-83.7), P = 0.07).

Both PV and PS were increased longitudinally with weight gain in Japanese without diabetes.

Overstimulation of pancreatic β-cells can lead to dysfunction and death, prior to the clinical manifestations of type 2 diabetes (T2D). The excessive consumption of carbohydrates induces metabolic alterations that can affect the functions of the β-cells and cause their death. We analyzed the role of p53 in pancreatic β cell death in carbohydrate-supplemented Sprague Dawley rats. For four months, the animals received drinking water containing either 40% sucrose or 40% fructose. The glucose tolerance test was performed at week 15. Apoptosis was assessed with the TUNEL assay (TdT-mediated dUTP-nick end-labeling). Bax, p53, and insulin were assessed by Western blotting, immunofluorescence, and real-time quantitative PCR. Insulin, triacylglycerol, and serum glucose and fatty acids in pancreatic tissue were measured. Carbohydrate consumption promotes apoptosis and mobilization of p53 from the cytosol to rat pancreatic β-cell mitochondria before blood glucose rises. An increase in p53, miR-34a, and Bax mRNA was also detected (P < 0.001) in the sucrose group. As well as hypertriglyceridemia, hyperinsulinemia, glucose intolerance, insulin resistance, visceral fat accumulation, and increased pancreatic fatty acids in the sucrose group. Carbohydrate consumption increases p53 and its mobilization into β-cell mitochondria and coincides with the increased rate of apoptosis, which occurs before serum glucose levels rise.

Type 2 diabetes disparities in the USA persist in both the prevalence of disease and diabetes-related complications. We conducted a literature review related to diabetes prevention, management, and complications across racial and ethnic groups in the USA. The objective of this review is to summarise the current understanding of diabetes disparities by examining differences between and within racial and ethnic groups and among young people (aged <18 years). We also examine the pathophysiology of diabetes as it relates to race and ethnic differences. We use a conceptual framework built on the socioecological model to categorise the causes of diabetes disparities across the lifespan looking at factors in five domains of health behaviours and social norms, public awareness, structural racism, economic development, and access to high-quality care. The range of disparities in diabetes prevalence and management in the USA calls for a community-engaged and multidisciplinary approach that must involve community partners, researchers, practitioners, health system administrators, and policy makers. We offer recommendations for each of these groups to help to promote equity in diabetes prevention and care in the USA.

The purpose of this study was to assess the performance of quantitative computed tomography (CT) imaging for detecting pancreatic fatty infiltration, using the results of histopathological analysis as reference.

Sixty patients who underwent pancreatic surgery for a pancreatic tumor between 2016 and 2019 were retrospectively included. There were 33 women and 27 men with a mean age of 56 ± 12 (SD) years (age range: 18-79 years). Patients with dilatation of the main pancreatic duct, chronic pancreatitis, or preoperative treatment were excluded to prevent any bias in the radiological-pathological correlation. Pancreatic fatty infiltration was recorded at pathology. Pancreatic surface lobularity, pancreatic attenuation, visceral fat area, and subcutaneous fat area were derived from preoperative CT images. The performance for the prediction of fatty infiltration was assessed using area under receiver operating characteristic curve (AUC) and backward binary logistic regression analysis. Results were validated in a separate cohort of 34 patients (17 women; mean age, 50 ± 14 [SD] years; age range: 18-73).

A total of 28/60 (47%) and 17/34 (50%) patients had pancreatic fatty infiltration in the derivation and validation cohorts, respectively. In the derivation cohort, patients with pancreatic fatty infiltration had a significantly higher PSL (P < 0.001) and a lower pancreatic attenuation on both precontrast and portal venous phase images (P = 0.011 and 0.003, respectively), and higher subcutaneous fat area and visceral fat area (P = 0.010 and 0.007, respectively). Multivariable analysis identified pancreatic surface lobularity > 7.6 and pancreatic attenuation on portal venous phase images < 83.5 Hounsfield units as independently associated with fatty infiltration. The combination of these variables resulted in an AUC of 0.85 (95% CI: 0.74-0.95) and 0.83 (95% CI: 0.67-0.99) in the derivation and validation cohorts, respectively.

CT-based quantitative imaging accurately predicts pancreatic fatty infiltration.

Abnormal lipid metabolism is known to increases the risk for metabolic diseases, such as type 2 diabetes mellitus(T2DM). The relationship between baseline ratio of triglyceride to HDL cholesterol (TG/HDL-C) and T2DM in Japanese adults was investigated in this study. Our secondary analysis included 8419 male and 7034 female Japanese subjects who were free of diabetes at baseline. The correlation between baseline TG/HDL-C and T2DM was analyzed by a proportional risk regression model, the nonlinear correlation between baseline TG/HDL-C and T2DM was analyzed by a generalized additive model (GAM), and the threshold effect analysis was performed by a segmented regression model. We conducted subgroup analyses in different populations. During the median 5.39 years follow-up, 373 participants, 286 males and 87 females, developed diabetes mellitus. After full adjustment for confounders, the baseline TG/HDL-C ratio positively correlated with the risk of diabetes (hazard ratio 1.19, 95% confidence interval 1.09-1.3), and smoothed curve fitting and two-stage linear regression analysis revealed a J-shaped relationship between baseline TG/HDL-C and T2DM. The inflection point for baseline TG/HDL-C was 0.35. baseline TG/HDL-C > 0.35 was positively associated with the development of T2DM (hazard ratio 1.2, 95% confidence interval 1.10-1.31). Subgroup analysis showed no significant differences in the effect between TG/HDL-C and T2DM in different populations. A J-shaped relationship was observed between baseline TG/HDL-C and T2DM risk in the Japanese population. When TG/HDL-C was higher than 0.35, there was a positive relationship between baseline TG/HDL-C and the incidence of diabetes mellitus.

To investigate the clinical value of measuring pancreatic fat fraction using dual-energy computed tomography (DECT) in association with type 2 diabetes mellitus (T2DM).

This retrospective study included patients who underwent abdominal DECT between September 2021 and July 2022. The fat fractions in the head, body, and tail of the pancreas were calculated using fat maps generated from unenhanced DECT images, and CT values were measured at the same locations. The intraclass correlation coefficient (ICC) was used to analyze the reproducibility of measurements from two observers. Diagnostic performance was assessed using receiver operating characteristic curves.

Seventy-eight patients, including 45 T2DM patients and 33 controls, were enrolled. The fat fractions of the pancreas were significantly higher in the T2DM group than in the control group (pancreatic head: 8.4 ± 6.3 % vs 5.1 ± 3.9 %; pancreatic body: 4.8 ± 4.0 % vs 2.7 ± 3.9 %; and pancreatic tail: 5.3 ± 3.2 % vs 2.7 ± 2.9 %, all p < 0.05). And the CT values of the pancreas were significantly lower in the T2DM group than in the control group (pancreatic head: 41.1 ± 8.5 HU vs 45.7 ± 4.6 HU; pancreatic body: 44.4 ± 5.0 HU vs 47.4 ± 3.7 HU; and pancreatic tail: 44.5 ± 5.0 HU vs 47.6 ± 3.2 HU, all p < 0.05). The fat fraction of the pancreatic tail was the best indicator for distinguishing T2DM patients from the controls (area under the curve: 0.716 (95 % CI: 0.601, 0.832), sensitivity: 64.4 % (95 % CI: 48.7 %, 77.7 %), and specificity: 78.8 % (95 % CI: 60.6 %, 90.4 %)).

The DECT fat fractions of the pancreas could be a valuable additional parameter in the detection of T2DM.

Diabetes mellitus is a prevalent, life-threatening, and costly medical illness. Type 2 diabetes is defined by insulin resistance caused by persistent hyperglycemia, and it is frequently diagnosed by tests such as fasting blood glucose levels of more than 7.0 mmol/L or HbA1c values of more than 6.5%. Pathogenesis and development of type 2 diabetes mellitus are clearly varied, with genetic and environmental factors both leading to it. The attainment of glycated hemoglobin (HbA1c) levels below the diagnostic level and maintaining it for a minimum of six months without pharmacotherapy, is described as diabetes remission. Diagnosis is a two-part procedure. To begin, the diagnosis of diabetes must be confirmed, and then the type of diabetes must be determined. Even in patients who succeeded to maintain remission, follow-up with the physician and regular tests should be done to prevent any expected diabetes complications.

Intrapancreatic fat deposition (IPFD) usually occurs in individuals with type 2 diabetes mellitus (T2DM), but its physiopathological influence remains controversial. The present study aimed to investigate IPFD and its associations with various aspects of glucose and lipid metabolism in individuals with newly diagnosed T2DM.

A total of 100 individuals were included, consisting of 80 patients with newly diagnosed T2DM and 20 age- and sex-matched healthy controls. Then, we assessed IPFD using magnetic resonance imaging (MRI) and various parameters of glucose and lipid metabolism.

Individuals with newly diagnosed T2DM had a significantly higher IPFD (median: 12.34%; IQR, 9.19-16.60%) compared with healthy controls (median: 6.35%; IQR, 5.12-8.96%) (p < 0.001). In individuals with newly diagnosed T2DM, IPFD was significantly associated with FINS and HOMA-IR in unadjusted model (β = 0.239, p=0.022; β = 0.578, p=0.007, respectively) and adjusted model for age and sex (β = 0.241, p=0.022; β = 0.535, p=0.014, respectively), but these associations vanished after adjustment for age, sex, and BMI. The OR of lower HDL-C for the prevalence of high IPFD was 4.22 (95% CI, 1.41 to 12.69; p=0.010) after adjustment for age, sex, BMI, and HbA1c.

Lower HDL-C was an independent predictor for a high degree of IPFD.

To investigate the application value of 3T MRI qDixon-WIP technique in the quantitative measurement of pancreatic fat content in patients with type 2 diabetes mellitus (T2DM).

The 3T MRI qDixon-WIP sequence was used to scan the livers and the pancreas of 47 T2DM patients (experimental group) and 48 healthy volunteers (control group). Pancreatic fat fraction (PFF), hepatic fat fraction (HFF), Body mass index (BMI) ratio of pancreatic volume to body surface area (PVI) were measured. Total cholesterol (TC), subcutaneous fat area (SA), triglyceride (TG), abdominal visceral fat area (VA), high density lipoprotein (HDL-c), fasting blood glucose (FPC) and low-density lipoprotein (LDL-c) were collected. The relationship between the experimental group and the control group and between PFF and other indicators was compared. The differences of PFF between the control group and different disease course subgroups were also explored.

There was no significant difference in BMI between the experimental group and the control group (P=0.231). PVI, SA, VA, PFF and HFF had statistical differences (P<0.05). In the experimental group, PFF was highly positively correlated with HFF (r=0.964, P<0.001), it was moderately positively correlated with TG and abdominal fat area (r=0.676, 0.591, P<0.001), and it was weakly positively correlated with subcutaneous fat area (r=0.321, P=0.033). And it had no correlation with FPC, PVI, HDL-c, TC and LDL-c (P>0.05). There were statistical differences in PFF between the control group and the patients with different course of T2DM (P<0.05). There was no significant difference in PFF between T2DM patients with a disease course ≤1 year and those with a disease course <5 years (P>0.05). There were significant differences in PFF between the groups with a disease course of 1-5 years and those with a disease course of more than 5 years (P<0.001).

PVI of T2DM patients is lower than normal, but SA, VA, PFF, HFF are higher than normal. The degree of pancreatic fat accumulation in T2DM patients with long disease course was higher than that in patients with short disease course. The qDixon-WIP sequence can provide an important reference for clinical quantitative evaluation of fat content in T2DM patients.

While there is an emerging role of pancreatic fat in the aetiology of type 2 diabetes mellitus (T2DM), its impact on the associated decrease in insulin secretion remains controversial. We aimed to determine whether pancreatic fat negatively affects β-cell function and insulin secretion in women with overweight or obesity but without T2DM.

20 women, with normo- or dysglycaemia based on fasting plasma glucose levels, and low (< 4.5%) vs high (≥ 4.5%) magnetic resonance (MR) quantified pancreatic fat, completed a 1-hr intravenous glucose tolerance test (ivGTT) which included two consecutive 30-min square-wave steps of hyperglycaemia generated by using 25% dextrose. Plasma glucose, insulin and C-peptide were measured, and insulin secretion rate (ISR) calculated using regularisation deconvolution method from C-peptide kinetics. Repeated measures linear mixed models, adjusted for ethnicity and baseline analyte concentrations, were used to compare changes during the ivGTT between high and low percentage pancreatic fat (PPF) groups.

No ethnic differences in anthropomorphic variables, body composition, visceral adipose tissue (MR-VAT) or PPF were measured and hence data were combined. Nine women (47%) were identified as having high PPF values. PPF was significantly associated with baseline C-peptide (p = 0.04) and ISR (p = 0.04) in all. During the 1-hr ivGTT, plasma glucose (p<0.0001), insulin (p<0.0001) and ISR (p = 0.02) increased significantly from baseline in both high and low PPF groups but did not differ between the two groups at any given time during the test (PPF x time, p > 0.05). Notably, the incremental areas under the curves for both first and second phase ISR were 0.04 units lower in the high than low PPF groups, but this was not significant (p > 0.05).

In women with overweight or obesity but without T2DM, PPF did not modify β-cell function as determined by ivGTT-assessed ISR. However, the salient feature in biphasic insulin secretion in those with ≥4.5% PPF may be of clinical importance, particularly in early stages of dysglycaemia may warrant further investigation.

Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired β-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD.

Decreased pancreatic volume, increased pancreatic fat mass, and serrated pancreatic margins are characteristic morphological changes of the pancreas in subjects with type 2 diabetes mellitus. This retrospective study aimed to clarify the clinical significance of pancreatic morphological changes in subjects with type 2 diabetes mellitus who underwent abdominal magnetic resonance imaging. The mean age and HbA1c value were 59.1 ± 16.3 years old and 8.9 ± 2.3%, respectively. Pancreatic body mass corrected for body surface area (BSA) in subjects with diabetes mellitus was lower compared to those in normal glucose tolerance (49.4 ± 15.3 cm³ vs. 60.9 ± 7.8 cm³), although it did not reach a statistic significance. There was a negative correlation between BSA-corrected pancreatic volume and age, duration of diabetes, glycoalbumin, mean and max IMT, and there was a positive correlation between BSA-corrected pancreatic volume and HOMA2-β. Serration of the pancreatic limbus was more often observed in subjects with diabetes mellitus compared to those in normal glucose tolerance (74.1% vs. 14.3%). Subjects with serrated changes were older and had higher HbA1c, and visceral fat area was significantly larger in subjects with serrated changes. BSA-corrected pancreatic volume in subjects with serrated changes was significantly smaller, and mean IMT was significantly thicker in subjects with serrulation. Furthermore, advanced diabetic retinopathy and diabetic nephropathy were more often observed in subjects with serrated changes. Taken together, decreased BSA-corrected pancreatic volume and serrated changes were associated with the progression of vascular complications in subjects with type 2 diabetes mellitus.