Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease

Abstract

Epidemiological studies have documented that insulin resistance and diabetes not only constitute metabolic abnormalities but also predispose to hypertension, vascular stiffness, and associated cardiovascular disease. Meanwhile, excessive arterial stiffness and impaired vasorelaxation, in turn, contribute to worsening insulin resistance and the development of diabetes. Molecular mechanisms promoting hypertension in diabetes include inappropriate activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, mitochondria dysfunction, excessive oxidative stress, and systemic inflammation. This review highlights recent studies which have uncovered new underlying mechanisms for the increased propensity for the development of hypertension in association with diabetes. These include enhanced activation of epithelial sodium channels, alterations in extracellular vesicles and their microRNAs, abnormal gut microbiota, and increased renal sodium-glucose cotransporter activity, which collectively predispose to hypertension in association with diabetes. This review also covers socioeconomic factors and currently recommended blood pressure targets and related treatment strategies in diabetic patients with hypertension.

Keywords: blood pressure; cardiovascular diseases; insulin resistance; obesity; vascular stiffness.

Figure 1.

Interaction of insulin resistance, diabetes, and hypertension in metabolic syndrome. Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), mitochondria dysfunction, oxidative stress, inflammation, abnormal release of extracellular vesicles (EVs) and related microRNAs (miRNAs), as well as dysregulation of gut microbiota, GLP-1 (glucagon-like peptide) and SGLT2 (sodium-glucose cotransporter 2), are involved in insulin resistance and type 2 diabetes-induced vascular stiffness and hypertension. CV indicates cardiovascular; EnNaC, endothelial epithelial sodium channel; and NO, nitric oxide.

Figure 2.

Proposed molecular mechanism in activated renin-angiotensin-aldosterone system (RAAS) and insulin resistance-related hypertension. Akt indicates protein kinase B; AT-1R, angiotensin type 1 receptor; EnNaC, endothelial epithelial sodium channel; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; MR, mineralocorticoid receptor; NO, nitric oxide; PI3K, phosphatidylinositide 3-kinase; and SGK-1, serum and glucocorticoid regulated kinase 1.