Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms

Abstract

Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes.

Figure 1

Vascular processes whereby diabetes and hypertension predispose to cardiovascular disease. Common risk factors promote diabetes and hypertension, which are associated with atherosclerosis, vascular inflammation, endothelial dysfunction, and structural remodelling, which lead to macrovascular and microvascular disease. Vascular damage and endothelial dysfunction is amplified when diabetes and hypertension coexist.

Figure 2

Putative mechanisms whereby diabetes and hypertension cause vascular disease. Immune cell activation and inflammation are mediated through oxidative stress. AGEs, advanced glycation end products; RAAS, renin-angiotensin-aldosterone system; RAGE, receptor AGE.