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      The relationship between pancreas steatosis and the risk of metabolic syndrome and insulin resistance in Chinese adolescents with concurrent obesity and non‐alcoholic fatty liver disease

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          Summary

          Background

          The incidence of childhood obesity and associated comorbidities are on an increasing trend worldwide. More than 340 million children and adolescents aged between 5 and 19 years old were overweight or had obesity in 2016, from which over 124 million children and adolescents (6% of girls and 8% of boys) had obesity.

          Objective

          To describe the relationship between pancreas steatosis, body fat and the risk of metabolic syndrome, insulin resistance in Hong Kong Chinese adolescents with both obesity and non‐alcoholic fatty liver disease (NAFLD).

          Methods

          Fifty two adolescents with obesity and NAFLD were analysed (14‐18 years), stratified into fatty and non‐fatty pancreas groups using chemical shift encoded MRI‐pancreas proton density fat fraction 5%. Pancreatic, abdominal subcutaneous adipose tissue (SAT)/visceral adipose tissue (VAT) volumes, biochemical and anthropometric parameters were measured. Mann‐Whitney U test, multiple linear/binary logistic regression analyses and odds ratios were used.

          Results

          Fifty percent had fatty pancreas, 38% had metabolic syndrome and 81% had insulin resistance. Liver proton density fat fraction (PDFF) and VAT were independent predictors of insulin resistance ( P = .006, .016). Pancreas and liver PDFF were both independent predictors of beta cells dysfunction ( P = .015, .050) and metabolic syndrome ( P = .021, .041). Presence of fatty pancreas in obesity was associated with insulin resistance (OR = 1.58, 95% CI = 0.39‐6.4) and metabolic syndrome (OR = 1.70, 95% CI = 0.53‐5.5).

          Conclusion

          A significant causal relationship exists between fatty pancreas, fatty liver, body fat and the risk of developing metabolic syndrome and insulin resistance.

          Key Points

          • Fatty pancreas is a common finding in adolescents with obesity, with a prevalence rate of 50% in this study cohort.

          • Liver PDFF and VAT are independent predictors of insulin resistance while pancreas PDFF and liver PDFF are independent predictors of both beta cells dysfunction and metabolic syndrome.

          • Presence of fatty pancreas at imaging should not be considered as a benign finding but rather as an imaging biomarker of emerging pancreatic metabolic and endocrine dysfunction.

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          Most cited references37

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          Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

          Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.
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            Pancreatic fat content and beta-cell function in men with and without type 2 diabetes.

            Insulin resistance, associated with increased lipolysis, results in a high exposure of nonadipose tissue to lipids. Experimental data indicate that fatty infiltration of pancreatic islets may also contribute to beta-cell dysfunction, but whether this occurs in humans in vivo is unknown. Using proton magnetic resonance spectroscopy and oral glucose tolerance tests, we studied the association of pancreatic lipid accumulation in vivo and various aspects of beta-cell function in 12 insulin-naive type 2 diabetic and 24 age- and BMI-matched nondiabetic men. Patients versus control subjects had higher A1C, fasting plasma glucose, and insulin and triglyceride levels and lower HDL cholesterol, but similar waist circumference. Median (interquartile range) pancreatic fat content in patients and control subjects was 20.4% (13.4-43.6) and 9.7% (7.0-20.2), respectively (P = 0.032). Pancreatic fat correlated negatively with beta-cell function parameters, including the insulinogenic index adjusted for insulin resistance, early glucose-stimulated insulin secretion, beta-cell glucose sensitivity, and rate sensitivity (all P < 0.05), but not potentiation. However, these associations were significantly affected by the diabetic state, such that a significant association of pancreatic fat with beta-cell dysfunction was only present in the nondiabetic group (all P < 0.01), suggesting that once diabetes occurs, factors additional to pancreatic fat account for further beta-cell function decline. In control subjects, the association of pancreatic fat and beta-cell function remained significant after correction for BMI, fasting plasma glucose, and triglycerides (P = 0.006). These findings indicate that pancreatic lipid content may contribute to beta-cell dysfunction and possibly to the subsequent development of type 2 diabetes in susceptible humans.
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              Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots.

              Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the "culprits" were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount. Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties. Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance. There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear. Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.
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                Author and article information

                Contributors
                winniechu@cuhk.edu.hk
                Journal
                Pediatr Obes
                Pediatr Obes
                10.1111/(ISSN)2047-6310
                IJPO
                Pediatric Obesity
                John Wiley & Sons, Inc. (Chichester, UK )
                2047-6302
                2047-6310
                29 April 2020
                September 2020
                : 15
                : 9 ( doiID: 10.1111/ijpo.v15.9 )
                : e12653
                Affiliations
                [ 1 ] Department of Imaging and Interventional Radiology The Chinese University of Hong Kong Hong Kong China
                [ 2 ] Department of Paediatrics The Chinese University of Hong Kong Hong Kong China
                [ 3 ] Russell H. Morgan Department of Radiology and Radiological Science The Johns Hopkins University School of Medicine Baltimore Maryland USA
                [ 4 ] Department of Paediatrics and Adolescent Medicine The University of Hong Kong Hong Kong China
                [ 5 ] Department of Clinical Oncology The Chinese University of Hong Kong Hong Kong China
                Author notes
                [*] [* ] Correspondence

                Winnie C. W. Chu, Department of Imaging & Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Room 27026, Hong Kong SAR, China.

                Department of Imaging & Interventional Radiology, G/F, Treatment Block & Children Wards, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.

                Email: winniechu@ 123456cuhk.edu.hk

                Author information
                https://orcid.org/0000-0002-4744-1714
                https://orcid.org/0000-0003-4962-4132
                Article
                IJPO12653
                10.1111/ijpo.12653
                7507143
                32351030
                f2c954bd-1b89-4db0-b633-0799529944c2
                © 2020 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 October 2019
                : 17 March 2020
                : 17 April 2020
                Page count
                Figures: 4, Tables: 3, Pages: 11, Words: 8147
                Funding
                Funded by: Direct Grant for Research
                Award ID: 2014.1.065
                Funded by: Health and Medical Research Fund, Food and Health Bureau
                Award ID: 11122981
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                September 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:22.09.2020

                fatty liver,insulin resistance,magnetic resonance imaging,metabolic syndrome,pancreas

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