Contemporary treatment strategies for Type 2 diabetes-related macrovascular disease

Abstract

Type 2 diabetes mellitus poses a major challenge to healthcare providers in the coming years as its prevalence increases across the globe. The disease doubles the risk of cardiovascular morbidity and mortality, with 70% of sufferers dying from a cardiac cause. Large clinical trials of current glucose-lowering therapies for Type 2 diabetes have shown no benefit in reducing the risk of macrovascular events. Blood pressure control, angiotensin-converting enzyme inhibitor therapy and improvement of dyslipidemia with statins have proven benefit in reducing cardiovascular risk in Type 2 diabetes. A growing understanding of the importance of pathological processes including endothelial dysfunction, abnormal growth factor biology, oxidative stress, dysregulation of adipokines and deficient vascular repair and regeneration in insulin-resistant states promises new treatments to combat the problem.

Keywords::

• cardiovascular
• endothelial dysfunction
• growth factor
• insulin resistance
• macrovascular
• oxidative stress
• prediabetes
• progenitor cell
• Type 2 diabetes
• vascular repair

Financial & competing interests disclosure

This work was supported by the University of Leeds, UK and the British Heart Foundation. AMN Walker and RM Cubbon are supported by grants from the British Heart Foundation and MT Kearney is a British Heart Foundation Professor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Intensive glucose control has little if any benefit in reducing cardiovascular risk in Type 2 diabetes, and may indeed be harmful.

• Blood pressure control with a target systolic blood pressure of 140 mmHg reduces cardiovascular morbidity and mortality in patients with Type 2 diabetes, but current evidence does not support the use of a lower target.

• Weight loss can achieve remission from both the metabolic syndrome and Type 2 diabetes. Further research is needed to examine the effects of both pharmacological and surgical weight loss on cardiovascular outcomes over long-term follow-up.

• Statins reduce major coronary events in Type 2 diabetes patients by around 20% when used for both primary and secondary prevention.

• Renin–angiotensin system inhibition reduces cardiovascular risk in Type 2 diabetes over and above its antihypertensive effects. As such, angiotensin-converting enzyme inhibitors should be used as first-line treatment for hypertension in patients with the disease.

• Pathological processes such as oxidative stress, abnormal growth factor signaling and impaired vascular repair and regeneration are important contributors to cardiovascular risk in insulin-resistant states. Further work to characterize these processes promises new therapeutic targets to reduce macrovascular events in Type 2 diabetes.