Ectopic Fat Deposition and Diabetes Mellitus

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Ectopic Fat Deposition and Diabetes Mellitus

Benedicte Gaborit, Anne Dutour

To cite this version:

Benedicte Gaborit, Anne Dutour. Ectopic Fat Deposition and Diabetes Mellitus. Journal of the American College of Cardiology, Elsevier, 2016, 68 (23), pp.2594 - 2595. �10.1016/j.jacc.2016.07.788�.

�hal-01478844�

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Dr. Zhu and colleagues also note the different situ- ations in which the vasovagal reflex can occur, and suggest matching work and life environments between the placebo andfludrocortisone groups. Although an interesting and insightful comment, this might not be practical. Rather, given how often in their daily affairs patients are subjected to orthostatic stress, the question might be why the reflex is provoked only occa- sionally rather than several times daily.

Both questions raise the issue of a more individu- alized approach to patients, and we suspect that just such an approach is the key to the successful treatment of vasovagal syncope (2). For this, we thank Dr. Zhu and colleagues.

*Robert Sheldon, MD, PhD for the POST 2 Investigators

*Libin Cardiovascular Institute of Alberta University of Calgary

3280 Hospital Drive NW Calgary, Alberta T2N 4Z6 Canada

E-mail:sheldon@ucalgary.ca

http://dx.doi.org/10.1016/j.jacc.2016.09.938

Please note: The Prevention of Syncope Trial II was supported by an Open Competition Operating Grant from the Canadian Institutes for Health Research, Ottawa, Canada, and a donation of placebo from Shire Pharmaceuticals, Saint- Laurent, Quebec, Canada. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data;

preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

R E F E R E N C E S

1.Sheldon R, Raj SR, Rose MS, et al., for the POST 2 Investigators.

Fludrocortisone for the prevention of vasovagal syncope: a randomized, placebo-controlled trial. J Am Coll Cardiol 2016;68:1–9.

2.Kelley JM, Lembo AJ, Ablon JS, et al. Patient and practitioner inﬂuences on the placebo effect in irritable bowel syndrome. Psychosom Med 2009;71:789–97.

Ectopic Fat Deposition and Diabetes Mellitus

We read with interest the paper by Levelt et al.(1)in a recent issue of the Journal, which deciphered the parameters that give rise to ectopic fat deposition in insulin-resistant states, such as type 2 diabetes (T2D).

One of the strengths of this study is the use of multiparametric cardiovascular and liver magnetic resonance imaging (MRI), and proton and phosphorus magnetic resonance spectroscopy, allowing a com- parison of epicardial adipose tissue (EAT), myocardial and hepatic triglyceride content, hepatic ﬁbroin- ﬂammatory changes, but also cardiac function and energetics between lean healthy and lean and obese subjects with T2D. One of the study limitations is that epicardial fat volume was not measured in lean

healthy subjects, so that the increase in EAT was only validated in 33 subjects with T2D without control subjects. However, MRI was performed in all subjects, and one could expect that the authors assessed EAT with MRI. Indeed, MRI offers excellent spatial resolution; it is now recognized to be the gold standard for adipose tissue imaging and superior to computed tomography in separating epicardial from pericardial fat, the latter of which has different vascularization and developmental origin from EAT. Moreover, it is also the only imaging modality in which volumetric quantification of EAT has been validated ex vivo(2). In this setting of body fat distribution, the different ectopic fat depots need to be distinguished, and we tend to disagree with the concept of EAT as a proxy for visceral fat. Visceral fat refers to visceral abdominal adipose tissue and cannot be replaced by EAT, as visceral abdominal adipose tissue flexibility to weight loss,“beiging”(brown in white adipose tissue) molecular features, has been shown to be different from EAT (3,4). Levelt et al.(1) evaluated different ectopic fat depots in lean healthy and lean and obese subjects with T2D. Nevertheless, the presence of a body mass index<25 kg/m²at diabetes mellitus diagnosis, with the current obesity epidemic, raises a question regarding the type of diabetes. Do these lean diabetic patients have non–type 2, secondary, or monogenic forms of diabetes? Did the authors elimi- nate latent autoimmune diabetes in adults, in which the progression of ß cell failure is slow? Among patients with phenotypic type 2 diabetes, latent autoimmune diabetes in adults occurs in 10% of individuals older than age 35 years (5). Further studies are needed to determine to what extent hyperglycemia drives specific ectopic fat deposition.

*Bénédicte Gaborit, MD, PhD Anne Dutour, MD, PhD

*Inserm U1062 Inra U1260

Aix Marseille Université, Faculté de Médecine 27 boulevard Jean Moulin

13385 Marseille Cedex 05 France

E-mail:benedicte.gaborit@ap-hm.fr

Please note: Both authors have reported that they have no relationships rele- vant to the contents of this paper to disclose.

R E F E R E N C E S

1.Levelt E, Pavlides M, Banerjee R, et al. Ectopic and visceral fat deposition in lean and obese patients with type 2 diabetes. J Am Coll Cardiol 2016;68:53–63.

2.Nelson AJ, Worthley MI, Psaltis PJ, et al. Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume.

J Cardiovasc Magn Reson 2009;11:15.

Letters J A C C V O L . 6 8 , N O . 2 3 , 2 0 1 6

D E C E M B E R 1 3 , 2 0 1 6 : 2 5 8 8–9 5 2594

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3.Sacks HS, Fain JN, Bahouth SW, et al. Adult epicardial fat exhibits beige features. J Clin Endocrinol Metab 2013;98:E1448–55.

4.Gaborit B, Jacquier A, Kober F, et al. Effects of bariatric surgery on cardiac ectopic fat: lesser decrease in epicardial fat compared to visceral fat loss and no change in myocardial triglyceride content. J Am Coll Cardiol 2012;60:

1381–9.

5.Schwartz SS, Epstein S, Corkey BE, Grant SFA, Gavin JR, Aguilar RB. The time is right for a new classiﬁcation system for diabetes: rationale and im- plications of theb-cell-centric classiﬁcation schema. Diabetes Care 2016;39:

179–86.

REPLY:Ectopic Fat Deposition and Diabetes Mellitus

We thank Drs. Gaborit and Dutour for their interest in our paper(1). We acknowledge the lack of assessment of epicardial adipose tissue (EAT) volumes in healthy control subjects, which was due to concerns regarding unnecessary ionizing radiation exposure with coronary computed tomographic angiography.

We agree that magnetic resonance imaging (MRI) is highly suitable for adipose tissue imaging. Dark blood prepared, T1-weighted, multislice turbo spin-echo pulse sequence with a water suppression pre-pulse is an established MRI technique for reliable volumetric measurement of EAT volumes(2). Fat quanti- ﬁcation on the basis of steady-state free precession cine imaging (i.e., the magnetic resonance images available to us) is unreliable in our experience.

However, the addition of the established technique for assessment of EAT volumes would have extended scanning time for our participants to an unacceptable length. Acquiring multiparametric cardiovascular and liver magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy protocol demanded a long scanning duration. Therefore, computed tomographic angiography, already part of the study protocol to rule out significant coronary artery stenosis, was used for EAT volume quantification, which allowed imaging of the coronary arteries and assessment of EAT volumes without additional scan time. This is a typical example of the challenge to find the balance between the desirable and the practical, regarding the amount of information we can obtain in a clinical MRI research study.

We also agree with Gaborit and Dutour that different fat depots need to be distinguished. EAT shares many of the pathophysiological properties of other visceral fat deposits and is widely considered by the scientiﬁc community to be a proxy of visceral fat;

accordingly, we followed the nomenclature set out by experts(3).

Regarding the differential diagnosis of type 2 diabetes (T2D) in lean patients, we hypothesized that body mass index (BMI) is not a reliable measure of

excess fat deposition, and assessing body composi- tion, therefore, is more important in patients with T2D than simple metrics of obesity. Consequently, there is increasing recognition of “normal weight obese” subjects (i.e., with increased ectopic and visceral adiposity but normal BMI) who are prone to the same risks of the metabolic syndrome (4). Our study supports that view by showing that, despite a normal BMI, patients diagnosed with T2D according to World Health Organization criteria had evidence of ectopic adiposity. We have not ruled out the possi- bility of the rare condition of latent autoimmune diabetes in adults (LADA). Although LADA patients do not necessarily require insulin during the initial period following diagnosis of diabetes, ultimately the majority develop insulin dependency, usually within 6 years, due to severe impairment inb-cell function (5). Mean diabetes duration in lean patients with T2D in our study was 6.14.7 years; the majority of these patients were treated successfully on oral antidia- betic agents or diet control(1), whereas insulin ther- apy is the treatment of choice for LADA(5), making the presence of LADA unlikely. Finally, 20% of the lean patients with T2D were of South Asian origin, and there is strong evidence to suggest that South Asians are more insulin resistant than Caucasians, even at lower BMI.

Eylem Levelt, MBBS, DPhil

*Stefan Neubauer, MD

*University of Oxford Centre for Clinical Magnetic Resonance Research

John Radcliffe Hospital Headley Way

Oxford OX3 9DU United Kingdom

E-mail:stefan.neubauer@cardiov.ox.ac.uk

Please note: Both authors have reported that they have no relationships rele- vant to the contents of this paper to disclose.

R E F E R E N C E S

1.Levelt E, Pavlides M, Banerjee R, et al. Ectopic and visceral fat deposition in lean and obese patients with type 2 diabetes. J Am Coll Cardiol 2016;68:

53–63.

2.Flüchter S, Haghi D, Dinter D, et al. Volumetric assessment of epicardial adipose tissue with cardiovascular magnetic resonance imaging. Obesity 2007;15:870–8.

3.Bertaso AG, Bertol D, Duncan BB, Foppa M. Epicardial fat: deﬁnition, measurements and systematic review of main outcomes. Arq Bras Cardiol 2013;101:e18–28.

4.Fitzgibbons TP, Czech MP. Epicardial and perivascular adipose tissues and their inﬂuence on cardiovascular disease: basic mechanisms and clinical as- sociations. J Am Heart Assoc 2014;3:e000582.

5.Stenström G, Gottsäter A, Bakhtadze E, Berger B, Sundkvist G. Latent autoimmune diabetes in adults. Diabetes 2005;54:S68.

J A C C V O L . 6 8 , N O . 2 3 , 2 0 1 6 Letters

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