Type 2 diabetes as a disease of ectopic fat?

Sattar, N. and Gill, J. (2014) Type 2 diabetes as a disease of ectopic fat? BMC Medicine, 12, 123. (doi: 10.1186/s12916-014-0123-4) (PMID:25159817) (PMCID:PMC4143560)

Abstract

Background: Although obesity and diabetes commonly co-exist, the evidence base to support obesity as the major driver of type 2 diabetes mellitus (T2DM), and the mechanisms by which this occurs, are now better appreciated.<p></p> Discussion: This review briefly examines several sources of evidence – epidemiological, genetic, molecular, and clinical trial – to support obesity being a causal risk factor for T2DM. It also summarises the ectopic fat hypothesis for this condition, and lists several pieces of evidence to support this concept, extending from rare conditions and drug effects to sex- and ethnicity-related differences in T2DM prevalence. Ectopic liver fat is the best-studied example of ectopic fat, but more research on pancreatic fat as a potential cause of β-cell dysfunction seems warranted. This ectopic fat concept, in turn, broadly fits with the observation that individuals of similar ages can develop diabetes at markedly different body mass indexes (BMIs). Those with risk factors leading to more rapid ectopic fat gain – for example, men (compared with women), certain ethnicities, and potentially those with a family history of diabetes, as well as others with genes linked to a reduced subcutaneous adiposity – are more likely to develop diabetes at a younger age and/or lower BMI than those without.<p></p> Summary: Obesity is the major risk factor for T2DM and appears to drive tissue insulin resistance in part via gain of ectopic fat, with the best-studied organ being the liver. However, ectopic fat in the pancreas may contribute to β-cell dysfunction. In line with this observation, rapid resolution of diabetes linked to a preferential and rapid reduction in liver fat has been noted with significant caloric reduction. Whether these observations can help develop better cost-effective and sustainable lifestyle /medical interventions in patients with T2DM requires further study.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gill, Professor Jason and Sattar, Professor Naveed
• Authors: Sattar, N., and Gill, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: BMC Medicine
• Publisher: BioMed Central
• ISSN: 1741-7015
• ISSN (Online): 1741-7015
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in BMC Medicine 12(123)
• Publisher Policy: Reproduced under a Creative Commons License