Clearly, the place where diabetes meets cardiovascular disease (CVD) is a broad interface. This wide expanse is obvious in terms of numbers, as encountered in waiting rooms, clinics, cardiac catheterization laboratories, and surgical suites around the world, where the deluge of patients with both diabetes and cardiovascular disease, or who have one disease and are at high risk for the other, is already apparent and on the increase. This large intersection is also apparent clinically, given the multitude of critical medical issues patients with diabetes and CVD present [1]. This cardiometabolic complexity is obvious from a therapeutic vantage point, given the number of relevant therapies that patients with these problems may need to be on and the expanding options for how to approach their concomitant hypertension, dyslipidemia, thrombogenicity, adiposity, and hyperglycemia [2,3]. Finally, this vast interface between vascular issues and diabetes is also manifest scientifically, in mechanisms, as we learn more about the intricate ways in which metabolism can influence inflammation, atherosclerosis, vascular responses, and myocardial function, and how these pathways may go awry [4].
This issue of Hot Topics in Cardiometabolic Disorders - by focusing on dipeptidyl peptidase-4 (DPP-4) and its inhibition in the treatment of diabetes - touches upon all these intermixed questions. Unmet therapeutic needs exist among patients with diabetes, and known DPP-4 inhibitors are among the latest options to emerge as part of a treatment strategy [5], representing therapeutics that many practitioners are just beginning to understand and utilize. The overlap between CVD and diabetes means that the impact of DPP-4 inhibitors on relevant clinical cardiometabolic issues must be considered. And, the fact remains that our appreciation of DPP-4 as well as incretin biology in general is relatively new, a valuable example of how basic science continues to provide new insights and therapeutic opportunities.
Drs. Gilbert and Pratley provide an authoritative review here of the clinical evidence and rationale behind DPP-4 inhibition as well as a thorough discussion of the pharmacology and action of specific DPP-4 inhibitors. This comprehensive analysis is of immense value, as is the perspective these experienced, expert diabetologists offer on how DPP-4 inhibitors might be placed among current anti-diabetic options. The erudite discussion provided by Gilbert and Pratley is well matched by the article by Dr. Vivian Fonseca, a renowned authority in diabetes and its cardiovascular issues. Dr. Fonseca takes on the question of the potential impact of DPP-4 inhibitors on CVD, an issue of relevance not just in terms of safety but also potential benefit.
Broad interfaces are difficult to navigate. But there is no doubt, that when it comes to the intersection of diabetes and cardiovascular disease, clinicians are being forced to maneuver through these issues every day. No doubt the discussions provided in this issue will prove helpful in understanding the relevant issues and continuing our efforts to meet this challenge.

 

REFERENCES

1. Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds K, He J. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med 2009;151:394-403.

2. Blonde L. Current antihyperglycemic treatment guidelines and algorithms for patients with type 2 diabetes mellitus. Am J Med 2010;123:S12-S18.

3. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009;53:S35-S42.

4. Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 2008;371:1800-1809.

5. Pei Z. From the bench to the bedside: dipeptidyl peptidase IV inhibitors, a new class of oral antihyperglycemic agents. Curr Opin Drug Discov Devel 2008;11:512-532.