Pancreatic triacylglycerol distribution in type 2 diabetes

Abstract

colleagues concluded that there was no fat in the parenchymal tissue of the pancreas, and hence local release of fatty acids could not influence endocrine function [1]. The authors describe intralobular fat within the pancreas as detected by spectroscopy but then concluded that there was no fat in the parenchyma of the pancreas. This conclusion relied upon magnetic resonance (MR) techniques. We draw attention to three serious errors in the MR methodology employed, and to the sound evidence for the existence of parenchymal fat.First, the imaging method used to measure parenchymal fat yielded negative percentages for pancreas parenchymal fat in approximately half of all individuals, the range of individual parenchymal fat appearing to be from −3% to +4%. Negative fat content of tissue is a concept of no biological validity. The lower limit of detection is stated by the authors as 2%, and from Fig. 2l in their paper it can be seen that this means the majority of their observations cannot yield what they themselves define as a meaningful result. There appears to be a problem of calibration at low fat fraction, possibly caused by the noise performance of fitting too many variables to a twopoint Dixon acquisition, rather than using three or more echoes. Although the authors claim that the technique used has been validated, their supporting reference 29 is an abstract that relates to the simpler matter of measuring liver fat content.Second, it is suggested that there is no fat in the parenchyma of the pancreas but that fat within the pancreas in type 2 diabetes is contained in thick bands of adipose tissue. We have thoroughly assessed over 100 pancreases of people with diabetes and 32 with normal glucose tolerance using our published three-point Dixon method [2]. As illustrated by six examples in our Fig. 1, fat is distributed at a low level throughout each pancreas, and localised very high concentrations of fat are rare within the organ. One of the advantages of the three-point Dixon technique is that it is possible to study smaller organs with precise knowledge of boundaries [3]. We have previously reported that the pancreas is 30% smaller in volume and has a more serrated border in type 2 diabetes compared with age-, weight-and sex-matched controls [4]. Care is indeed required in selecting regions of interest in which to quantify triacylglycerol in the parenchyma of the pancreas and this underscores the value of using an imagingbased method.Third, the authors state that they wanted to assess fat distribution in the pancreas in three supposedly different regions [1]. To do this they employed two very different methods, modified Dixon imaging and spectroscopy. This introduces differences related to the methods. Yet the assessment would more simply be carried out by use of a properly established three-point Dixon technique. Using this method, the region of * Roy Taylor

Pancreatic triacylglycerol distribution in type 2 diabetes. Reply to Hollingsworth K. G., Al Mrabeh A., Steven S. et al [letter]

“…The second issue raised by Hollingsworth et al is that we reported no fat within pancreatic parenchymal tissue, which contradicts their findings of a 3.3-6.2% fat fraction in the pancreas of type 2 diabetic humans [1]. In our paper, we stated that the MRI measurements revealed regions of parenchymal tissue void of any relevant lipid accumulation in all participants, which can be taken as evidence against a uniform pancreatic steatosis.…”

“…Thus, it is misleading for Hollingsworth et al to claim that we suggest that there is no fat within the pancreatic parenchymal tissue. The lower pancreas fat fraction reported by us [2] compared Hollingsworth et al [1] is probably due to the noise bias, which does not seem to be corrected for in their method [4].…”

“…To clarify the seemingly contradictory results between our publication [2] and those of Hollingsworth et al [1], we measured pancreas fat content in three non-diabetic and three type 2 diabetic volunteers with both the 2-point 3D mDIXON [2] and the 3-point 2D DIXON [4] Fig. 1.…”

“…To the Editor: We welcome the comments of Hollingsworth et al [1], as the role of pancreas fat content in type 2 diabetes has become a hotly debated issue with diverse non-invasive measurement techniques providing seemingly contradictory results [2]. Although several fat/water imaging techniques have been proposed for assessing pancreatic fat content, including 2-point or multi-echo DIXON [3,4] and fat-selective imaging techniques [5,6], there is still no consensus or agreement on what constitutes a valid clinical measurement technique for non-invasive assessment of pancreatic fat.…”

Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

“…The role of pancreatic steatosis in the pathogenesis of type 2 diabetes is currently under discussion and may depend on additional risk factors [1][2][3]. Fat accumulation in the pancreas is associated with reduced insulin secretion in glucose intolerant humans [4].…”