Dysregulated lipid storage and its relationship with insulin resistance and cardiovascular risk factors in non-obese Asian patients with type 2 diabetes

References

• Kashima S, Inoue K, Matsumoto M, et al. Prevalence and characteristics of non-obese diabetes in Japanese men and women: the Yuport Medical Checkup Center Study. J Diabetes. 2015;7:523–530. doi:10.1111/1753-0407.12213.
   PubMed Web of Science ®Google Scholar
• Aekplakorn W. Prevalence, treatment, and control of metabolic risk factors by BMI status in Thai adults: National Health Examination Survey III. Asia Pac J Pub Health. 2011;23:298–306. doi:10.1177/1010539509340690.
   PubMed Web of Science ®Google Scholar
• Huxley R, James WPT, Barzi F, et al. Ethnic comparisons of the cross-sectional relationships between measures of body size with diabetes and hypertension. Obes Rev. 2008;9(Suppl 1):53–61. doi:10.1111/j.1467-789X.2007.00439.x.
   PubMedGoogle Scholar
• Chan WB, Tong PCY, Chow CC, et al. The associations of body mass index, C-peptide and metabolic status in Chinese type 2 diabetic patients. Diabet Med. 2004;21:349–353. doi:10.1111/j.1464-5491.2004.01158.x.
   PubMed Web of Science ®Google Scholar
• Chan JCN, Malik V, Jia W, et al. Diabetes in Asia. Epidemiology, risk factors and pathophysiology Lancet. 2009;301:2129–2140.
   Google Scholar
• Yokoyama H, Emoto M, Fujiwara S, et al. Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment in normal range weight and moderately obese type 2 diabetic patients. Diabetes Care. 2003;26:2426–2432. doi:10.2337/diacare.26.8.2426.
   PubMed Web of Science ®Google Scholar
• Kim D-J, Lee M-S, Kim K-W, et al. Insulin secretory dysfunction and insulin resistance in the pathogenesis of Korean type 2 diabetes mellitus. Metabolism. 2001;50:590–593. doi:10.1053/meta.2001.22558.
   PubMed Web of Science ®Google Scholar
• Rosalind Marita A, Sarkar JA, Rane S. Type 2 diabetes in non-obese Indian subjects is associated with reduced leptin levels: Study from Mumbai, Western India. Mol Cell Biochem. 2005;275:143–151. doi:10.1007/s11010-005-1204-7.
   PubMed Web of Science ®Google Scholar
• WHO, IASO. IOTF. The Asia Pacific perspective: Redefining obesity and its treatment. Melbourne: International Diabetes Institute; 2000.
   Google Scholar
• Wronska A, Kmiec Z. Structural and biochemical characteristics of various white adipose tissue depots. Acta Physiol. 2012;205:194–208. doi:10.1111/j.1748-1716.2012.02409.x.
   PubMed Web of Science ®Google Scholar
• Nazare J-A, Smith JD, Borel J-L, et al. Ethnic influences on the relations between abdominal subcutaneous and visceral adiposity, liver fat and cardiometabolic risk profile: the International Study of Prediction of Intra-abdominal Adiposity and Its Relationships With Cardiometabolic Risk/Intra-abdominal Adiposity. Am J Clin Nutr. 2012;96:714–726. doi:10.3945/ajcn.112.035758.
   PubMed Web of Science ®Google Scholar
• Jang Y, Lee JH, Cho EY, et al. Differences in body fat distribution and antioxidant status in Korean men with cardiovascular disease with or without diabetes. Am J Clin Nutr. 2001;73:68–74.
   PubMed Web of Science ®Google Scholar
• Misra A, Anoop S, Gulati S, et al. Body fay patterning, hepatic fat and pancreatic volume of non-obese Asian Indians with type 2 diabetes in North India: a case-control study. PLoS ONE. 2015;10:e0140447. doi:10.1371/journal.pone.0140447.
   PubMed Web of Science ®Google Scholar
• Bu J, Feng Q, Ran J, et al. Visceral fat mass is always, but adipokines (adiponectin and resistin) are diversely associated with insulin resistance in Chinese type 2 diabetic and normoglycemic subjects. Diabetes Res Clin Pract. 2012;96:163–169. doi:10.1016/j.diabres.2011.12.014.
   PubMed Web of Science ®Google Scholar
• Jung SH, Ha KH, Kim DJ. Visceral fat mass has stronger associations with diabetes and prediabetes than other anthropometric obesity indicators among Korean adults. Yonsei Med J. 2016;57:674–680. doi:10.3349/ymj.2016.57.3.674.
   PubMed Web of Science ®Google Scholar
• Boyko EJ, Fujimoto WY, Leonetti DL, et al. Visceral adiposity and risk of type 2 diabetes. A prospective study among Japanese Americans Diabetes Care. 2000;23:465–471.
   Google Scholar
• Kim C-H, Kim H-K, Kim E-H, et al. Impact of body mass index in predictive ability of body fat distribution for type 2 diabetes risk in Koreans. Diabetic Med. 2012;29:1395–8. doi:10.1111/j.1464-5491.2012.03661.x.
   PubMed Web of Science ®Google Scholar
• Rattarasarn C, Leelawattana R, Soonthornpun S, et al. Regional abdominal fat distribution in lean and obese Thai type 2 diabetic women: Relationships with insulin sensitivity and cardiovascular risk factors. Metabolism. 2003;52:1444–1447. doi:10.1016/S0026-0495(03)00257-9.
   PubMed Web of Science ®Google Scholar
• Rattarasarn C, Leelawattana R, Soonthornpun S, et al. Relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai men and women. Diabetes Res Clin Pract. 2003;60:87–94. doi:10.1016/S0168-8227(03)00017-2.
   PubMed Web of Science ®Google Scholar
• Indulekha K, Anjana RM, Surendar J, et al. Association of visceral and subcutaneous fat with glucose intolerance, insulin resistance, adipocytokines and inflammatory markers in Asian Indians(CURES-113). Clin Biochem. 2011;44:281–7. doi:10.1016/j.clinbiochem.2010.12.015.
   PubMed Web of Science ®Google Scholar
• Tang L, Zhang F, Tong N. The association of visceral adipose tissue and subcutaneous adipose tissue with metabolic risk factors in a large population of Chinese adults. Clin Endocrinol. 2016;85:46–53. doi:10.1111/cen.13013.
   PubMed Web of Science ®Google Scholar
• Tatsumi Y, Nakao YM, Masuda I, et al. Risk for metabolic diseases in normal weight individuals with visceral fat accumulation: A cross-sectional study in Japan. BMI Open. 2017;7:e013831. doi:10.1136/bmjopen-2016-013831.
   PubMed Web of Science ®Google Scholar
• Fukuda S, Hirata A, Nishizawa H, et al. Systemic arteriosclerosis and eating behavior in Japanese patients with visceral fat accumulation. Cardiovasc Diabetol. 2015;14:8. doi:10.1186/s12933-015-0174-7.
   PubMed Web of Science ®Google Scholar
• Matsushita Y, Nakagawa T, Yamamoto S, et al. Effect of longitudinal changes in visceral fat area and other anthropometric indices to the changes in metabolic risk factors in Japanese men. The Hitachi Health Study Diabetes Care. 2012;35:1129–43.
   Web of Science ®Google Scholar
• Cleal L, Aldea T, Chau Y-Y. Fifty shades of white: Understanding heterogeneity in white adipose stem cells. Adipocyte. 2017;6:205–216. doi:10.1080/21623945.2017.1372871.
   PubMed Web of Science ®Google Scholar
• Andersson DP, Arner E, Hogling DE, et al. Abdominal subcutaneous adipose tissue cellularity in men and women. Int J Obes. 2017;41:1564–1569. doi:10.1038/ijo.2017.148.
   Web of Science ®Google Scholar
• Dahlman I, Ryden M, Brodin D, et al. Numerous genes in loci associated with body fat distribution are linked to adipose function. Diabetes. 2016;65:433–437. doi:10.2337/db15-0828.
   PubMed Web of Science ®Google Scholar
• Sato S, Demura S, Nakai M. Storage capacity of subcutaneous fat in Japanese adults. Eur J Clin Nutr. 2015;69:933–938. doi:10.1038/ejcn.2014.292.
   PubMed Web of Science ®Google Scholar
• Arner P, Bernard S, Salehpour M, et al. Dynamics of human adipose lipid turnover in health and metabolic disease. Nature. 2011;478:110–113. doi:10.1038/nature10426.
   PubMed Web of Science ®Google Scholar
• Lafontan M. Adipose tissue and adipocyte dysregulation. Diabetes Metab. 2014;40:16–28. doi:10.1016/j.diabet.2013.08.002.
   PubMed Web of Science ®Google Scholar
• Sniderman AD, Bhopal R, Prabhakaran D, et al. Whu might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Int J Eptdemiol. 2007;36:220–225. doi:10.1093/ije/dyl245.
   PubMed Web of Science ®Google Scholar
• Tchoukalova YD, Koutsari C, Karpyak MV, et al. Subcutaneous adipocyte size and body fat distribution. Am J Clin Nutr. 2008;87:56–63.
   PubMed Web of Science ®Google Scholar
• Monolopoulos KN, Karpe F, Frayn KN. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes. 2010;34:949–959. doi:10.1038/ijo.2009.286.
   Web of Science ®Google Scholar
• Karpe F, Pinnick KE. Biology of upper-body and lower-body adipose tissue- Link to whole-body phenotype. Nature Rev Endocrinol. 2015;11:90–100. doi:10.1038/nrendo.2014.185.
   PubMed Web of Science ®Google Scholar
• Todorcevic M, Hilton C, McNeil C, et al. A cellular model for the investigation of depot specific human adipocyte biology. Adipocyte. 2017;6:40–55. doi:10.1080/21623945.2016.1277052.
   PubMed Web of Science ®Google Scholar
• Reilly SM, Satiel AR. Adapting to obesity with adipose tissue inflammation. Nature Rev Endocrinol. 2017;13:633–643. doi:10.1038/nrendo.2017.90.
   PubMed Web of Science ®Google Scholar
• Ryden M, Arner P. Cardiovascular risk score is linked to subcutaneous adipocyte size and lipid metabolism. J Intern Med. 2017;282:220–228. doi:10.1111/joim.12641.
   PubMed Web of Science ®Google Scholar
• Soccio RE, Chen ER, Lazar MA. Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes. Cell Metab. 2014;20:573–591. doi:10.1016/j.cmet.2014.08.005.
   PubMed Web of Science ®Google Scholar
• Fryan KN. Adipose tissue as a buffer for daily lipid flux. Diabetologia. 2002;45:1201–1210. doi:10.1007/s00125-002-0873-y.
   PubMed Web of Science ®Google Scholar
• Pellegrinelli V, Carobbio S, Vidal-Puig A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia. 2016;59:1075–1088. doi:10.1007/s00125-016-3933-4.
   PubMed Web of Science ®Google Scholar
• Thomas D, Apovian C. Macrophage functions in lean and obese adipose tissues. Metabolism. 2017;72:120–143. doi:10.1016/j.metabol.2017.04.005.
   PubMed Web of Science ®Google Scholar
• Schleinitz D, Bottcher Y, Bluher M, et al. The genetics of fat distribution. Diabetologia. 2014;57:1276–1286. doi:10.1007/s00125-014-3214-z.
   PubMed Web of Science ®Google Scholar
• Gesta S, Bluher M, Yamamoto Y, et al. Evidences for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci U S A. 2006;103:6676–6681. doi:10.1073/pnas.0601752103.
   PubMed Web of Science ®Google Scholar
• Chu AY, Deng X, Fisher VA, et al. Multi-ethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation. Nat Genet. 2017;49:125–130. doi:10.1038/ng.3738.
   PubMed Web of Science ®Google Scholar
• Shungin D, Winkler TW, Croteau-Chonka DC, et al. New genetic loci link adipose tissue and insulin biology to body fat distribution. Nature. 2015;518:187–196. doi:10.1038/nature14132.
   PubMed Web of Science ®Google Scholar
• Alligier M, Gabert L, Meugnier E, et al. Visceral fat accumulation during lipid overfeeding is related to subcutaneous adipose tissue characteristics in healthy men. J Clin Endocrinol Metab. 2013;98:802–810. doi:10.1210/jc.2012-3289.
   PubMed Web of Science ®Google Scholar
• Anand SS, TarnopolskyMA, Rashid S, et al. Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: The Molecular Study of Health and risk in Ethnic Groups (mol-SHARE). PLoS One. 2011;6: e22112. doi:10.1371/journal.pone.0022112.
   PubMed Web of Science ®Google Scholar
• Chandalia M, Lin P, Seenivasan T, et al. Insulin resistance and body fat distribution in South Asian men compared with Caucasian men. PLoS ONE. 2007;2:e812. doi:10.1371/journal.pone.0000812.
   PubMed Web of Science ®Google Scholar
• Meena VP, Seenu V, Sharma MC, et al. Relationship of adipocyte size and metabolic risk factors in Asian Indians. PLoS ONE. 2014;9:e108421. doi:10.1371/journal.pone.0108421.
   PubMed Web of Science ®Google Scholar
• Kohli S, Lear SA. Differences in subcutaneous abdominal adiposity regions in four ethnic groups. Obesity. 2013;21:2288–2295. doi:10.1002/oby.20102.
   PubMed Web of Science ®Google Scholar
• Khoo CM, Leow MK, Sadananthan SA, et al. Body fat partitioning does not explain the interethnic variation in insulin sensitivity among Asian ethnicity: the Singapore adults metabolism study. Diabetes. 2014;63:1093–1102. doi:10.2337/db13-1483.
   PubMed Web of Science ®Google Scholar
• Acosta JR, Douagi I, Andersson DP, et al. Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes. Diabetologia. 2016;59:560–570. doi:10.1007/s00125-015-3810-6.
   PubMed Web of Science ®Google Scholar
• Hammarstedt A, Graham TE, Kahn BB. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells. Diabetology Metab Syndr. 2012;4:42. doi:10.1186/1758-5996-4-42.
   PubMed Web of Science ®Google Scholar
• Henninger AMJ, Eliasson B, Jenndahl LE, et al. Adipocyte hypertrophy, inflammation and fibrosis characterize subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes. PLos One. 2014;9(8): e105260. doi:10.1371/journal.pone.0105262.
   Web of Science ®Google Scholar
• McLaughlin T, Lamendola C, Coghlan N, et al. Subcutaneous adipose cell size and distribution: Relationship to insulin resistance and body fat. Obesity. 2014;22:673–680. doi:10.1002/oby.20209.
   PubMed Web of Science ®Google Scholar
• Liu C-J. Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese. J Gastroenterol Hepatol. 2012;27:1555–1560. doi:10.1111/j.1440-1746.2012.07222.x.
   PubMed Web of Science ®Google Scholar
• Das K, Das K, Mukherjee PS, et al. Nonobese population in a developing country had a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology. 2010;51:1593–1602. doi:10.1002/hep.23567.
   PubMed Web of Science ®Google Scholar
• Ha Y, Seo N, Shim JH, et al. Intimate association of visceral obesitywith non-alcoholic fatty liver disease in healthy Asians: A case-control study. J Gastroenterol Hepatol. 2015;30:1666–1672. doi:10.1111/jgh.12996.
   PubMed Web of Science ®Google Scholar
• Kabir M, Catalano KJ, Ananthnarayan S, et al. Molecular evidence supporting the portal theory: a causative link between visceral adiposity and insulin resistance. Am J Physiol Endocrinol Metab. 2005;288:E454–E461. doi:10.1152/ajpendo.00203.2004.
   PubMed Web of Science ®Google Scholar
• Kato K, Takamura T, Takeshita Y, et al. Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease. PloS ONE. 2014;9:e92170. doi:10.1371/journal.pone.0092170.
   PubMed Web of Science ®Google Scholar
• Perry RJ, Samuel VT, Petersen KF, et al. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature. 2014;510:84–91. doi:10.1038/nature13478.
   PubMed Web of Science ®Google Scholar
• Takeno K, Tamura Y, Kawaguchi M, et al. Relation between insulin sensitivity and metabolic abnormalities in Japanese men with BMI of 23–25 kg/m2. J Clin Endocrinol Metab. 2016;101:3676–3684. doi:10.1210/jc.2016-1650.
   PubMed Web of Science ®Google Scholar
• Sharma R, Sinha S, Danishad KA, et al. Investigation of hepatic gluconeogenesis pathway in non-diabetic Asian Indians with non-alcoholic fatty liver disease using in vivo (31P) phosphorus magnetic resonance spectroscopy. Atherosclerosis. 2009;203:291–297. doi:10.1016/j.atherosclerosis.2008.06.016.
   PubMed Web of Science ®Google Scholar
• Furukawa Y, Tamura Y, Takeno K, et al. Impaired peripheral insulin sensitivity in non-obese Japanese with type 2 diabetes mellitus and fatty liver. J Diabetes Invest 2017 [Aug 24]; doi:10:1111/jdi12731.
   Web of Science ®Google Scholar
• Hwang J-H, Stein DT, Barzilai N, et al. Increased intrahepatic triglycerides associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies. Am J Physiol Endocrinol Metab. 2007;293:E1663–E1669. doi:10.1152/ajpendo.00590.2006.
   PubMed Web of Science ®Google Scholar
• Gastaldelli A, Cusi K, Pettiti M, et al. Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology. 2007;133:496–506. doi:10.1053/j.gastro.2007.04.068.
   PubMed Web of Science ®Google Scholar
• Petersen KF, Dufour S, Savage DB, et al. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci USA. 2007;104:12587–12594. doi:10.1073/pnas.0705408104.
   PubMed Web of Science ®Google Scholar
• Rabol R, Petersen KF, Dufour S, et al. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci USA. 2011;108:13705–13709. doi:10.1073/pnas.1110105108.
   PubMed Web of Science ®Google Scholar
• Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-kB. Nat Med. 2005;11:183–190. doi:10.1038/nm1166.
   PubMed Web of Science ®Google Scholar
• Jaganathan R, Ravindran R, Dhanasekaran S. Emerging role of adipocytokines in type 2 diabetes as mediators of insulin resistance and cardiovascular disease. Can J Diabetes. 2017; [Dec 8]; doi:10.1016/j.jcjd.2017.10.040.
   PubMed Web of Science ®Google Scholar
• Akash MSH, Rehman K, Liaqat A. Tumor necrosis factor-alpha: Role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2018;119:105–110. doi:10.1002/jcb.26174.
   PubMed Web of Science ®Google Scholar
• Rehman K, Akash MSH, Liaqat A, et al. Role of interleukin-6 in development of insulin resistance and type 2 diabetes mellitus. Crit Rev Eukaryot Gene Expr. 2017;27:229–236. doi:10.1615/CritRevEukaryotGeneExpr.2017019712.
   PubMed Web of Science ®Google Scholar
• Fizelova M, Jauhiainen R, Kangas AJ, et al. Differential associations of inflammatory markers with insulin sensitivity and secretion: The prospective METSIM Study. J Clin Endocrinol Metab. 2017;102:3600–3609. doi:10.1210/jc.2017-01057.
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Rodella S, et al. NASH predicts plasma inflammatory biomarkers independently of visceral fat in men. Obesity. 2008;16:1394–1399. doi:10.1038/oby.2008.64.
   PubMed Web of Science ®Google Scholar
• Kitessa SM, Abeywardena MY. Lipid-induced insulin resistance in skeletal muscle: The chase for the culprit goes from total intramuscular fat to lipid intermediates, and finally to species of lipid intermediates. Nutrients. 2016;8:466. doi:10.3390/nu8080466.
   PubMed Web of Science ®Google Scholar
• Jacob S, Machann J, Rett K, et al. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes. 1999;48:1113–1119. doi:10.2337/diabetes.48.5.1113.
   PubMed Web of Science ®Google Scholar
• Perseghin G, Scifo P, De Cobelli F, et al. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans. A 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes. 1999;48:1600–1606. doi:10.2337/diabetes.48.8.1600.
   PubMed Web of Science ®Google Scholar
• Lattuada G, Costantino F, Caumo A, et al. Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocelllar lipid content in offspring of type 2 diabetic patients. Diabetologia. 2005;48:741–747. doi:10.1007/s00125-005-1686-6.
   PubMed Web of Science ®Google Scholar
• Misra A, Sinha S, Kumar M, et al. Proton magnetic resonance spectroscopy study of soleus muscle in non-obese healthy and type 2 diabetic Asian Northern Indian male: high intramyocellular lipid content correlates with excess body fat and abdominal obesity. Diabet Med. 2003;20:361–367. doi:10.1046/j.1464-5491.2003.00932.x.
   PubMed Web of Science ®Google Scholar
• Gemmink A, Goodpaster BH, Schrauwen P, et al. Intramyocellular lipid droplets and insulin sensitivity, the human perspective. Mol Cell Biol Lipids. 2017;1862:1242–1249. doi:10.1016/j.bbalip.2017.07.010.
   Google Scholar
• Bergman BC, Perreault L, Strauss A, et al. Intramuscular triglyceride synthesis- importance in partitioning muscle lipids in humans. Am J Physiol Endocrinol Metab 2017 [Oct 3]; DOI:. 10:1152.
   Google Scholar
• De Feyter HM, van den Broek NM, Praet SF, et al. Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction. Eur J Endocrinol. 2008;158:643–653. doi:10.1530/EJE-07-0756.
   PubMed Web of Science ®Google Scholar
• Lai N, Kummitha C, Hoppel C. Defects in skeletal muscle subsarcolemmal mitochondria in a non-obese model of type 2 diabetes mellitus. PLoS One. 2017;12:e0183978. doi:10.1371/journal.pone.0183978.
   PubMed Web of Science ®Google Scholar
• Callahan ZJ, Oxendine MJ, Schaeffer PJ. Intramuscular triglyceride content precedes impaired glucose metabolism without evidences for mitochondrial dysfunction during early development of a diabetic phenotype. Appl Physiol Nutr Metab. 2017;42:963–972.
   PubMed Web of Science ®Google Scholar
• Chaurasia B, Summers SA. Ceramides-lipotoxic inducers of metabolic disorders. Trend Endocrinol Metab. 2015;26:538–550. doi:10.1139/apnm-2016-0685. doi:10.1016/j.tem.2015.07.006.
   PubMed Web of Science ®Google Scholar
• Brons C, Grunnet LG. Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander? Eur J Endocrinol. 2017;176:R67.–R78. doi:10.1530/EJE-16-0488.
   PubMed Web of Science ®Google Scholar
• Lingvay I, Esser V, Legendre JL, et al. Noninvasive quantification of pancreatic fat in humans. J Clin Endocrinol Metab. 2009;94:4070–4076. doi:10.1210/jc.2009-0584.
   PubMed Web of Science ®Google Scholar
• Begovatz P, Koliaki C, Weber K, et al. Pancreatic adipose tissue infiltration, parenchymal steatosis and beta cell function in humans. Diabetologia. 2015;58:1646–1655. doi:10.1007/s00125-015-3544-5.
   PubMed Web of Science ®Google Scholar
• Ma J, Song Z, Yan F. Detection of hepatic and pancreatic fat infiltration in type II diabetes mellitus patients with IDEAL-Quant using 3.0T MR: comparison with single-voxel proton spectroscopy. Chin Med J. 2014;127:3548–3552.
   PubMed Web of Science ®Google Scholar
• Kim MK, Chun HJ, Park JH, et al. The association between ectopic fat in the pancreas and subclinical atherosclerosis in type 2 diabetes. Diabetes Res Clin Pract. 2014;106:590–596. doi:10.1016/j.diabres.2014.09.005.
   PubMedGoogle Scholar
• Singh RG, Yoon HD, Wu LM, et al. Ectopic fat accumulation in the pancreas and its clinical relevance: A systemic review, meta-analysis and meta-regression. Metabolism. 2017;69:1–13. doi:10.1016/j.metabol.2016.12.012.
   PubMed Web of Science ®Google Scholar
• Zhou J, Li M-L, Zhang D-D, et al. The correlation between pancreatic steatosis and a metabolic syndrome in a Chinese population. Pancreatology. 2016;16:578–583. doi:10.1016/j.pan.2016.03.008.
   PubMed Web of Science ®Google Scholar
• Wang CY, Ou HY, Chen MF, et al. Enigmatic ectopic fat: prevalence of nonalcoholic fatty pancreas disease and its associated factors in a Chinese population. J Am Heart Assoc. 2014;3:e000297. doi:10.1161/JAHA.113.000297.
   PubMed Web of Science ®Google Scholar
• Lesmana CRA, Pakasi LS, Inggriani S, et al. Prevalence of non-alcoholic fatty pancreas disease (NAFPD) and its risk factors among adult medical check-up patients in a private hospital: a large cross sectional study. BMC Gastroenterol. 2015;15:174. doi:10.1186/s12876-015-0404-1.
   PubMed Web of Science ®Google Scholar
• Tushuizen ME, Bunck MC, Pouwels PJ, et al. Pancreatic fat content and β cell function in men with and without type 2 diabetes. Diabetes Care. 2007;30:2916–2921. doi:10.2337/dc07-0326.
   PubMed Web of Science ®Google Scholar
• van der ijl NJ, Goossens GH, Moors CCM, et al. ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on β-cell function in individuals with impaired glucose metabolism. J Clin Endocrinol Metab. 2011;96:459–467. doi:10.1210/jc.2010-1722.
   PubMed Web of Science ®Google Scholar
• Saisho Y, Butler AE, Meier JJ, et al. Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type 2 diabetes. Clin Anat. 2007;20:933–942. doi:10.1002/ca.20543.
   PubMed Web of Science ®Google Scholar
• Murakami R, Saisho Y, Watanabe Y, et al. Pancreatic fat and β cell mass in human with and without diabetes: An analysis in the Japanese population. J Clin Endocrinol Metab. 2017;102:3251–3260. doi:10.1210/jc.2017-00828.
   PubMed Web of Science ®Google Scholar
• Yamazaki H, Tsuboya T, Katanuma A, et al. Lack of independent association between fatty pancreas and incidence of type 2 diabetes: 5-year Japanese cohort study. Diabetes Care. 2016;39:1677–1683. doi:10.2337/dc16-0074.
   PubMed Web of Science ®Google Scholar
• Guglielmi V, Sbraccia P. Type 2 diabetes: does pancreatic fat really matter? Diabetes Metab Res Rev. 2017; [Oct 5]: doi:10.1002/dmrr.2955.
   Web of Science ®Google Scholar
• Dubois M, Kerr-Conte J, Gmyr V, et al. Non-esterified fatty acids are deleterious for human pancreatic islet function at physiologic glucose concentration. Diabetologia. 2004;47:463–469. doi:10.1007/s00125-004-1347-1.
   PubMed Web of Science ®Google Scholar
• Goh TT, Mason TM, Gupta N, et al. Lipid-induced beta-cell dysfunction in vivo in models of progressive beta-cell failure. Am J Physiol Endocrinol Metab. 2007;292:E549–E560. doi:10.1152/ajpendo.00255.2006.
   PubMed Web of Science ®Google Scholar
• Wicklow BA, Griffith AT, Dumontet JN, et al. Pancreatic lipid content is not associated with beta cell dysfunction in youth-onset type 2 diabetes. Can J Diabetes. 2015;39:398–404. doi:10.1016/j.jcjd.2015.04.001.
   PubMed Web of Science ®Google Scholar