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A review of potential metabolic etiologies of the observed association between red meat consumption and development of type 2 diabetes mellitus

      Abstract

      Epidemiological studies suggest that red and processed meat consumption is related to an increased risk of type 2 diabetes. However, it is not clearly understood which components of red and processed meat contribute to this increased risk. This review examines potential mechanisms addressing the role of saturated fatty acid, sodium, advanced glycation end products (AGEs), nitrates/nitrites, heme iron, trimethylamine N-oxide (TMAO), branched amino acids (BCAAs) and endocrine disruptor chemicals (EDCs) in the development of type 2 diabetes based on data from published clinical trials and animal models. TMAO which is derived from dietary carnitine and choline by the action of bacterial enzymes followed by oxidation in the liver may be a strong candidate molecule mediating the risk of type 2 diabetes. BCAAs may induce insulin resistance via the mammalian target of rapamycin complex 1 (mTORC1) and ribosomal protein S6 kinase β 1 (S6k1)-associated pathways. The increased risk associated with processed meat compared with red meat suggests that there are interactions between the saturated fat, salt, and nitrates in processed meat and iron, AGEs and TMAO. Intervention studies are required to clarify potential mechanisms and explore interactions among components, in order to make firm recommendations on red and processed meat consumption.

      Abbreviations:

      AGEs (advanced glycation end products), TMAO (trimethylamine N-oxide), BCAAs (branched amino acids), EDCs (endocrine disrupting chemicals), mTORC1 (mammalian target of rapamycin complex 1), S6k1 (ribosomal protein S6 kinase β 1), T2DM (type 2 diabetes mellitus), CVD (cardiovascular disease), HR (hazard ratio), 95% CI (95% confidence interval), SFA (saturated fatty acid), BMI (body mass index), MUFA (monounsaturated fatty acid), PUFA (polyunsaturated fatty acid), FSIGT (frequently sampled intravenous glucose tolerance test), IRS-1 (insulin receptor substrate-1), PI3K (phosphatidylinositol 3-kinase), SF (saturated fat), RR (relative risk), OGTT (oral glucose tolerance test), HOMA (homeostatic model assessment), RAS (renin–angiotensin system), RAGE (receptor for AGE), NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells;-), AAS (α-amino adipic semi-aldehyde), GGS (γ-glutamic semi-aldehyde), VCAM-1 (vascular cell adhesion molecule 1), TNF-α (tumor necrosis factor-alpha), IL-1β (interleukin-1 beta), IL-6 (interleukin 6), CRP (C-reactive protein), ROS (reactive oxygen species), AGE-BSA (advanced glycation end product of bovine serum albumin), NO (nitric oxide), ATP (adenosine triphosphate), ICAM-1 (intercellular adhesion molecule 1), TBARS (thiobarbituric acid reactive substances), ONOO− (peroxynitrite), LDL (low-density lipoprotein), NOx (nitric oxide metabolic pathway products), Fe3+ (ferric), O2− (superoxide), Fe2+ (ferrous), O2 (oxygen), H2O2 (hydrogen peroxide), •OH (hydroxyl radicals, OH–, hydroxyl ion), GLUT4 (glucose transporter type 4), FFA (free fatty acid), HOMA-IR (homeostasis model assessment of insulin resistance), CHD (coronary heart disease), TMA (trimethylamine), HbA1c (glycated hemoglobin), IRS-2 (insulin receptor substrate 2), BPA (bisphenol A), DEHP (di-2-ethylhexyl phthalate), SML (specific migration limit), DBP (dibutyl phthalate), EFSA (the European Food Safety Authority), TDI (tolerable daily intake)

      Keywords

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