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.

Fateful fat: Intra-pancreatic lipids cause pancreatic cancer.

In a Mendelian randomization and prospective cohort study,1 intra-pancreatic fat increases the risk of pancreatic cancer. This provides persuasive human evidence of causal relation between lipids and cancer in the pancreas, which confirms a prediction of the PANDORA hypothesis.

The Pharmacological Landscape for Fatty Change of the Pancreas.

The quest for medications to reduce intra-pancreatic fat deposition is now quarter a century old. While no specific medication has been approved for the treatment of fatty change of the pancreas, drug repurposing shows promise in reducing the burden of the most common disorder of the pancreas. This leading article outlines the 12 classes of medications that have been investigated to date with a view to reducing intra-pancreatic fat deposition. Information is presented hierarchically-from preclinical studies to retrospective findings in humans to prospective interventional studies to randomised controlled trials. This lays the grounds for shepherding the most propitious drugs into medical practice through well-designed basic science studies and adequately powered randomised controlled trials.

Epidemiology of post-pancreatitis diabetes mellitus: insights from the COSMOS program.

INTRODUCTION: Post-pancreatitis diabetes mellitus (PPDM) has long been recognized as one of the most challenging sub-types of diabetes to manage. Part of the problem is that the earlier literature on epidemiology of PPDM was confusing because of the presence of selection bias. AREAS COVERED: A concerted series of population-based nationwide studies on PPDM from New Zealand has recently been published as part of the COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatic diseaseS) program and is the main focus of the present article. EXPERT OPINION: The foundational knowledge on epidemiology of PPDM generated by the COSMOS program is generalizable to the population at large. It brings the field closer to a comprehensive narrative of risk factors, burden, mortality, and morbidity outcomes of PPDM. In producing new knowledge on epidemiology of PPDM, it will be important to adhere to the guidelines on identification of PPDM in population-based datasets advanced in the present article.

Dietary Fibre for the Prevention of Post-Pancreatitis Diabetes Mellitus: A Review of the Literature and Future Research Directions.

Post-pancreatitis diabetes mellitus-the most common sequela of pancreatitis-leads to poorer glycaemic control compared with type 2 diabetes. Because post-pancreatitis diabetes mellitus is an exemplar of secondary diabetes (with a clear underlying cause), much post-pancreatitis diabetes mellitus is preventable or treatable early. Earlier literature established the important role of dietary fibre in reducing plasma glucose in individuals with type 2 diabetes. The present review benchmarks available evidence on the role of habitual dietary fibre intake in pancreatitis and post-pancreatitis diabetes mellitus. It also paves the way for future research on the use of dietary fibre in the post-pancreatitis setting.

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.

Response to lowering plasma glucose is characterised by decreased oxyntomodulin: Results from a randomised controlled trial.

BACKGROUND: With the prevalence of diabetes reaching an epidemic level, there is a growing interest in the investigation of its remission. Proglucagon-derived peptides (PGDP) have been shown to have a glucose-regulating effect. However, whether they play a role in diabetes remission remains poorly understood. AIM: To investigate changes in plasma levels of PGDP in glycaemic responders versus non-responders. METHODS: The study was a randomised placebo-controlled trial comprising 18 adults with prediabetes (registered at www. CLINICALTRIALS: gov as NCT03889210). Following an overnight fast, participants consumed ketone ß-hydroxybutyrate (KEßHB)-supplemented beverage and placebo beverage in crossover manner. Serial blood samples were collected from baseline to 150 min at 30-min intervals. The endpoints were changes in glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, glucagon, and major proglucagon fragment (MPGF). Participants were stratified into the 'responders' and 'non-responders' subgroups based on their glycaemic changes following the ingestion of KEßHB. The area under the curve (AUC) was calculated to estimate the accumulated changes in the studied PGDP and compared using paired-t test between the KEßHB and placebo beverages. RESULTS: Responders had a significantly greater reduction in plasma glucose compared with non-responders following acute ketosis (p < 0.001). The AUC0-150 for oxyntomodulin was significantly lower following the KEßHB beverage compared with the placebo (p = 0.045) in responders, but not in non-responders (p = 0.512). No significant differences in AUCs0-150 were found for GLP-1, glicentin, glucagon, and MPGF in either responders or non-responders. CONCLUSION: Oxyntomodulin is involved in lowering plasma glucose and may play an important role in diabetes remission.

Effect of Acute Nutritional Ketosis on Circulating Levels of Growth Differentiation Factor 15: Findings from a Cross-Over Randomised Controlled Trial.

Exogenous supplementation with ketone beverages has been shown to reduce plasma glucose levels during acute nutritional ketosis. It remains to be investigated whether growth differentiation factor 15 (GDF-15)-an anorexigenic hormone-is involved in this process. The aim was to investigate the effect of a ketone ester beverage delivering ß-hydroxybutyrate (KEßHB) on plasma levels of GDF-15, as well as assess the influence of eating behaviour on it. The study was a randomised controlled trial (registered at clinicaltrials.gov as NCT03889210). Individuals were given a KEßHB beverage or placebo in a cross-over fashion. Blood samples were collected at baseline, 30, 60, 90, 120, and 150 min after ingestion. Eating behaviour was assessed using the three-factor eating questionnaire. GDF-15 levels were not significantly different (p = 0.503) after the KEßHB beverage compared with the placebo. This finding remained consistent across the cognitive restraint, emotional eating, and uncontrolled eating domains. Changes in the anorexigenic hormone GDF-15, irrespective of eating behaviour, do not appear to play a major role in the glucose-lowering effect of exogenous ketones.

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.