Future anti-inflammatory metabolic and cardiovascular management of Type 2 diabetes mellitus

Abstract

Although vascular inflammation is now accepted as a principal agent of atherosclerotic cardiovascular disease, much less is known concerning the dysmetabolic roles of low-grade chronic inflammatory events that often accompany obesity, insulin resistance and the metabolic syndrome or syndrome X. However, it is becoming apparent that current insulin-sensitising antihyperglycaemic therapy, represented by the biguanide metformin and the thiazolidionediones (TZD) pioglitazone and rosiglitazone, may exert powerful adjunctive anti-inflammatory actions with the potential to modify not only dysmetabolic cardiovascular disease but also Type 2 diabetes mellitus (T2DM) incidence. Such anti-inflammatory attributes may be shared by a variety of diverse traditional cardiovascular therapies, including renin–angiotensin system inhibitors, oestrogen receptor modulators, β₁-adrenoceptor blockers, statins, fibrates and aspirin, as well as insulin itself. Recognising the relationships between inflammatory mediators and processes, and the pathophysiology of oxidative stress, vascular endothelial dysfunction, insulin resistance and pancreatic β-cell decompensation, is likely to introduce a new treatment paradigm in the management of syndrome X, T2DM and dysmetabolic cardiovascular disease. Such a paradigm, in addition to justifying the further development of anti-inflammatory TZD and nonTZD peroxisome proliferator-activated receptor-γ agonists, can also be expected to clinically target markers of systemic inflammation, cell adhesion molecule expression, mononucleocyte activation, reactive oxygen species generation, and intracellular redox-sensitive, pro-inflammatory transcription factor activation. Anti-inflammatory treatment modalities may therefore therapeutically exploit the common inflammatory basis of metabolic and cardiovascular disease.

• cardiovascular disease
• endothelial dysfunction
• inflammation
• insulin resistance
• nitric oxide (NO)
• oxidant stress
• syndrome X
• Type 2 diabetes mellitus