Treatment strategy for type 2 diabetes from the perspective of systemic vascular protection and insulin resistance

Abstract

This paper provides an update on the mechanisms of vascular impairment associated with insulin resistance and the pathogenesis of diabetic nephropathy and peripheral artery disease (PAD). It also considers the optimal treatment strategies for systemic vascular protection in light of recent findings. This area is of major clinical importance given the ongoing global epidemic of type 2 diabetes and the pivotal role played by insulin resistance in the mechanism of vascular impairment that manifests as macroangiopathy and microangiopathy. Timely diagnosis and intervention is critical in patients with systemic arteriosclerotic disease. Therefore, treatment strategies are aimed not only at targeting the presenting pathology, but also at reducing the risk of cardiovascular events. These efforts can help reduce the risk of both cardiovascular events and mortality. Treatment for PAD includes pharmacotherapy, endovascular treatment, and vascular reconstruction, along with exercise therapy. Because PAD can cause ischemia in the lower extremities, typical drug approaches include use of vasodilators and antiplatelet agents. Beraprost sodium and cilostazol are common choices in Japan, and their risks and benefits are discussed. Of note, beraprost has several therapeutic properties, including vascular endothelial protection, and antiplatelet and anti-inflammatory effects, in addition to vasodilatory activity. In patients with PAD, these activities improve the pathological process in the lower extremities and reduce the incidence of systemic vascular events. Recent preclinical findings indicate that beraprost improves not only ischemic extremities through its vasodilatory properties, but also reduces the insulin resistance which affects vascular endothelium. In this way, beraprost may contribute to an overall systemic vascular protective action. The use of agents, such as beraprost, which are capable of improving insulin resistance and resulting vascular endothelial function at an earlier disease stage, may ultimately contribute to increasing the life expectancy of patients with PAD.

Keywords: beraprost; insulin resistance; peripheral artery disease; protection; vascular.

Figure 1

Risk of disease aggravation with diabetes progression. Abbreviations: CKD, chronic kidney disease; MetS, metabolic syndrome.

Figure 2

Relationship between insulin resistance and PAD. Reena L, et al. Circulation. 2008;118:33–41. © 2008 Wolters Kluwer Health. Abbreviations: HOMA-IR, homeostatic model assessment of insulin resistance; PAD, peripheral artery disease.

Figure 3

Life expectancy in PAD patients. Diehm, et al. Circulation. 2009;120:2053–2061. © 2008 Wolters Kluwer Health. Abbreviation: PAD, peripheral artery disease.

Figure 4

Relationship between eGFR levels and PAD prevalence. Selvin E, et al. Eur Heart J. 2009;30:1918–1925. © 2010 SAGE Publications. Abbreviation: PAD, peripheral artery disease; eGFR, estimated glomerular filtration rate.

Figure 5

Relationship between CKD/PAD complication and cardiovascular death. Luo Y, et al. Vasc Med. 2010;15:107–112. © 2010 SAGE Publications. Abbreviations: CKD, chronic kidney disease; PAD, peripheral artery disease.

Figure 6

Insulin transfer from vascular endothelial cells to skeletal muscle. Kubota T, et al. Cell Metab. 2011;13:294–307. © 2011 Elsevier.

Figure 7

Development of vascular impairment in insulin-resistant state and treatment. Abbreviations: PAD, peripheral artery disease; ARB, angiotensin receptor blocker; ACEI, angiotensin converting enzyme inhibitor.