Ectopic fat accumulation in the pancreas and its clinical relevance: A systematic review, meta-analysis, and meta-regression

Singh, Ruma G.; Yoon, Harry D.; Wu, Landy M.; Lu, Jun; Plank, Lindsay D.; Petrov, Maxim S.

doi:10.1016/j.metabol.2016.12.012

Cited by 193 publications

(175 citation statements)

References 48 publications

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“…In particular, excess abdominal adiposity has been implicated in development of type 2 diabetes. Emerging research also shows that intra‐pancreatic fat deposition (IFD) is associated with a twofold increased risk of type 2 diabetes . Individuals with type 2 diabetes are known to have altered insulin sensitivity and insulin secretion .…”

Section: Introductionmentioning

confidence: 99%

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

Singh

Nguyen

DeSouza

et al. 2018

Diabetes Obesity Metabolism

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

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Section: Introductionmentioning

confidence: 99%

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

Singh

Nguyen

DeSouza

et al. 2018

Diabetes Obesity Metabolism

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“…Fatty pancreas (FP) is increasingly recognized as an important clinical entity, owing to its association with metabolic co‐morbidities. The presence of FP is associated with at least 2‐fold increased risk of type 2 diabetes mellitus (T2D), metabolic syndrome, and hypertension . Importantly, accumulation of pancreatic fat in individuals with T2D increases with time .…”

Section: Introductionmentioning

confidence: 99%

Ectopic fat accumulation in the pancreas and its biomarkers: A systematic review and meta‐analysis

Singh

Yoon

Poppitt

et al. 2017

Diabetes Metabolism Res

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Presence of fat in the pancreas increases the risk of metabolic co-morbidities. Detection and quantification of pancreatic fat is not a routine clinical practice, at least in part because of need to use expensive imaging techniques. We aimed to systematically review common markers of pancreatic fat in blood and to investigate differences in these markers associated with fatty pancreas. The search was conducted in 3 databases (EMBASE, Scopus, and MEDLINE). Studies in humans were eligible for inclusion if they reported on biological markers and percentage of pancreatic fat or fatty pancreas prevalence. Data were pooled for correlation and effect size meta-analysis. A total of 17 studies including 11 967 individuals were eligible for meta-analysis. Markers of lipid metabolism, including circulating triglycerides (r = 0.38 [95% confidence interval (CI) 0.31, 0.46]) and high-density lipoprotein cholesterol (r = -0.33 [95% CI -0.35, -0.31]), and markers of glucose metabolism, including glycated haemoglobin (r = 0.39 [95% CI 0.30, 0.48], insulin (r = 0.38 [95% CI 0.33, 0.43]), and homeostasis model assessment-insulin resistance (r = 0.37 [95% CI 0.30, 0.44], yielded the best correlations with percentage of pancreatic fat. Further, effect size analysis showed large and medium effects for the above markers of lipid and glucose metabolism. Circulating levels of triglycerides and glycated haemoglobin appear to be the best currently available markers of pancreatic fat. The approach of non-invasive and accurate detection of pancreatic fat by blood analysis should be further explored in the future, by investigating other potential biological markers of pancreatic fat.

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“…Human adipose tissue depots have been identified as a major site of pro-calcitonin mRNA with recent studies reporting calcitonin secretion from adipocytes in obese individuals with associated insulin resistance (15,16). Increasing body of evidence shows that abdominal adiposity is also involved in metabolic dysregulations following an episode of acute pancreatitis (17)(18)(19). Further, elevated amylin levels have been reported in patients with chronic alcoholic pancreatitis and abnormal glucose metabolism (13), with similar findings reported in a study involving patients with acute pancreatitis that found a significant correlation between amylin and abnormal glucose metabolism (20,21).…”

Section: Introductionmentioning

confidence: 99%

Calcitonin gene-related peptide: neuroendocrine communication between the pancreas, gut, and brain in regulation of blood glucose

et al. 2017

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Background: Calcitonin gene-related peptide (CGRP), a ubiquitous neuropeptide, plays a diverse and intricate role in chronic low-grade inflammation, including conditions such as obesity, type 2 diabetes, and diabetes of the exocrine pancreas. Diabetes of exocrine pancreas is characterised by chronic hyperglycemia and is associated with persistent low-grade inflammation and altered secretion of certain pancreatic and gut hormones. While CGRP may regulate glucose homeostasis and the secretion of pancreatic and gut hormones, its role in chronic hyperglycemia after acute pancreatitis (CHAP) is not known. The aim of this study was to investigate the association between CGRP and CHAP.Methods: Fasting blood samples were collected to measure insulin, HbA1c, CGRP, amylin, C-peptide, glucagon, pancreatic polypeptide (PP), somatostatin, gastric inhibitory peptide, glicentin, glucagon-like peptide-1 and 2, and oxyntomodulin. Modified Poisson regression analysis and linear regression analyses were conducted. Five statistical models were used to adjust for demographic, metabolic, and pancreatitisrelated risk factors.Results: A total of 83 patients were recruited. CGRP was significantly associated with CHAP in all five models (P-trend <0.005). Further, it was significantly associated with oxyntomodulin (P<0.005) and glucagon (P<0.030). Oxyntomodulin and glucagon independently contributed 9.7% and 7%, respectively, to circulating CGRP variance. Other pancreatic and gut hormones were not significantly associated with CGRP.Conclusions: CGRP is involved in regulation of blood glucose in individuals after acute pancreatitis. This may have translational implications in prevention and treatment of diabetes of the exocrine pancreas.

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Ectopic fat accumulation in the pancreas and its clinical relevance: A systematic review, meta-analysis, and meta-regression

Cited by 193 publications

References 48 publications

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

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

Ectopic fat accumulation in the pancreas and its biomarkers: A systematic review and meta‐analysis

Calcitonin gene-related peptide: neuroendocrine communication between the pancreas, gut, and brain in regulation of blood glucose

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