Type-2 diabetes and coronary heart disease: common physiopathology, viewed from autoimmunity

Abstract

Two highly prevalent diseases, Type-2 diabetes mellitus and coronary heart disease (CHD), share risk factors. Excess levels of LDL-cholesterol have been overemphasized to uniformly encompass the development of CHD, and the origin of insulin resistance underlying Type-2 diabetes has not been fully elucidated. Autoimmune response has been recognized to be responsible only of a small minority of diabetes. The increasing trend in the worldwide prevalence of diabetes and the risk factors for both diseases are reviewed, the independent mediation for CHD of (central) adiposity in both diseases and the ‘hypertriglyceridemic waist’ phenotype are outlined. Evidence is described that serum lipoprotein (Lp)(a) concentrations, not only in excess, but also in apparently ‘reduced’ levels, as a result of autoimmune response, underlie both disorders and are closely related to insulin resistance.

Keywords::

• autoimmune activation
• coronary heart disease
• primary prevention
• proinflammatory state
• statin therapy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Both Type 2 diabetes and coronary heart disease commonly have a substrate of proinflammatory state, dysfunction of high-density lipoprotein and its apolipoproteins, as well as of autoimmune activation.

• Autoimmune activation is usually mediated by damaged epitopes of excess lipoprotein (a) or other plasma proteins.

• The concomitant partial escape of the damaged protein from current immunoassay methods manifests in ‘reduced’ concentrations.

• ‘Hypertriglyceridemic waist’ phenotype is the hallmark of this clinical constellation associated with high cardiometabolic risk.

• Hypertriglyceridemic waist, more prominent and frequently observed in females, is promoted by discontinuance of smoking that inhibits autoimmune responses, and long-term use of some drugs may trigger aggravation of autoimmune processes.

Notes