Diabetes (with a focus on type 2 diabetes in this section) is closely associated with hypertension. Diabetes significantly increases the risk of developing hypertension, and hypertension markedly raises the risk of cardiovascular and cerebrovascular events. Therefore, the comorbid management of hypertension and diabetes is particularly important for reducing cardiovascular disease risk.
Pathogenesis
The mechanisms are primarily related to overactivation of the renin-angiotensin-aldosterone system (RAAS), mitochondrial dysfunction, and chronic inflammation.
Overactivation of RAAS
Hyperglycemia and insulin resistance can trigger excessive activation of RAAS, leading to elevated levels of angiotensin II and aldosterone. This suppresses the downstream PI3K/Akt pathway of the insulin signaling cascade, inhibits eNOS activation, and reduces nitric oxide (NO) production, resulting in increased vascular resistance and elevated blood pressure.
Mitochondrial Dysfunction
Diabetes and insulin resistance are often accompanied by mitochondrial dysfunction, which reduces mitochondrial energy synthesis and causes endothelial cell dysfunction.
Elevated Chronic Inflammation
Excessive pro-inflammatory signaling mediated by Toll-like receptors (TLRs) can activate transcription factors such as NF-κB and c-Jun, promoting the release of inflammatory factors such as IL-6, TNF-α, VCAM-1, and MCP-1. This regulation of the insulin signaling pathway inhibits NO production and increases vascular stiffness.
Clinical Manifestations
Patients with diabetes and hypertension often present with multiple coexisting cardiometabolic risk factors, such as high-salt and high-fat diets, overweight or obesity, sedentary lifestyles, and sleep apnea.
Diagnosis and Differential Diagnosis
These can be seen in Hypertension and Diabetes.
Treatment
Blood Pressure Targets
Antihypertensive therapy can reduce composite cardiovascular endpoints (non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death) and slow the progression of proteinuria and retinopathy. Blood pressure control below 130/80 mmHg is recommended. For patients with long disease durations, advanced age, or frailty, blood pressure targets may be moderately relaxed.
RAAS inhibitors (including ACE inhibitors and ARBs) are preferred antihypertensive agents for diabetes patients, as they not only lower blood pressure but also improve insulin resistance, reduce visceral fat accumulation, and slow the progression of nephropathy.
For patients with higher baseline blood pressure or those who do not achieve target levels with monotherapy, a combination of RAAS inhibitors with calcium channel blockers or diuretics may be considered. For patients with elevated heart rates (resting heart rate > 80 beats per minute) or those with comorbid coronary artery disease or heart failure, beta-blockers may be added.
In addition to the above antihypertensive drugs, metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, and SGLT-2 inhibitors have demonstrated some degree of blood pressure-lowering effects and can be prioritized during glucose-lowering therapy.
Weight Loss Surgery
Metabolic surgery may exert antihypertensive effects through mechanisms such as weight reduction, improved insulin sensitivity, and decreased sympathetic nerve activity. For diabetes patients with severe obesity, metabolic surgery can be considered as a treatment option.