Adiposopathy, Diabetes Mellitus, and Primary Prevention of Atherosclerotic Coronary Artery Disease: Treating “Sick Fat” Through Improving Fat Function with Antidiabetes Therapies

Both obesity and type 2 diabetes mellitus (DM) are worldwide epidemics, an association that is neither incidental nor coincidental. Adipose tissue is as an active endocrine and immune organ whose dysfunction (adiposopathy or “sick fat”) is promoted by excessive caloric balance in genetically and environmentally susceptible patients. The resultant adiposopathic responses directly and indirectly contribute to pathologies leading to hyperglycemia, high blood pressure, and dyslipidemia—all major cardiovascular risk factors—as well as to cardiovascular disease (CVD) itself. Toward the goal of primary prevention of CVD among DM patients, clinical trial outcomes evidence support the use of antihypertensive agents, lipid-altering drugs, and antiplatelet agents. Some of the most proactive measures to reduce the onset of cardiovascular risk factors and potentially prevent the onset of DM are early and aggressive nutritional, physical activity, and lifestyle interventions. Such measures improve the functionality of adipose tissue, reduce adiposopathic responses, and thus improve glycemic, blood pressure, and lipid parameters—all of which would be expected to reduce CVD risk. Finally, if nutritional, physical activity, and lifestyle interventions are not successful, and if DM pharmacologic therapies are indicated, then the choice of anti-DM medications should take into consideration the effects of such agents on adipose tissue function and dysfunction, which in turn, affects major CVD risk factors and CVD.