Diabetic Angiopathy, Part 2

There is an epidemic of diabetes, obesity, and cardiovascular/renal disease of global proportions. Prevention and treatment will require an in-depth understanding of the extremely complex pathophysiology of these syndromes and diseases. It is therefore timely and appropriate that two issues of Seminars in Vascular Medicine have been dedicated to the topic of diabetic angiopathy.

As guest editors, we are fortunate to have persuaded a number of leading authorities in the field to provide detailed discussions of current concepts and challenges. We have deliberately included experts from the disciplines of epidemiology, clinical medicine, and both clinical and experimental physiology, because we strongly feel that progress in this field will depend on integrating these different approaches.

The first issue dealt with the role of microvascular function in the pathogenesis of microangiopathy and insulin resistance; the role of early growth patterns and intrauterine programming in the causation of adult metabolic and vascular disease; the insulin resistance syndrome; diabetic dyslipidemia; inflammation and atherothrombosis in diabetes; the regulation of coagulation and fibrinolysis in diabetes; hyperhomocysteinemia; and diabetic nephropathy.

In this second issue, Amanda Adler summarizes the now impressive evidence in favor of strict blood pressure control in diabetes. John Yudkin discusses the determinants of high blood pressure in diabetes and emphasizes the clinical importance of a high pulse pressure and of its main cause, that is, an increased arterial stiffness. Jaap Deinum and Nish Chaturvedi explain that the renin-angiotensin system is involved not only in blood pressure regulation, but also in various other processes that are considered important in the pathogenesis of diabetic angiopathy and that may in part underlie the positive results obtained in trials of ACE inhibitors and angiotensin II-receptor antagonists. Jukka Westerbacka and Hannele Yki-Järvinen review the associations between insulin resistance and systolic hypertension and conclude that insulin resistance may directly contribute to arterial stiffness and thus systolic blood pressure. Hertzel Gerstein reviews the relationship of cardiovascular disease with elevated concentrations of glucose in the nondiabetic range and argues the need for major trials to determine whether, as for cholesterol and blood pressure, high-risk subjects might warrant glucose-lowering strategies even without having diabetes.

The association between poor metabolic control and the microvascular complications of diabetes is now well established, but the relationship between long-term metabolic control and the accelerated atherosclerosis of diabetes is as yet poorly defined. One mechanism by which elevated glucose levels may mediate vascular injury is through early and advanced glycation reactions affecting a wide variety of target molecules. The ``glycation hypothesis,'' the ``carbonyl stress hypothesis,'' and the ``oxidative stress hypothesis'' are complex interlinked concepts, which, in two separate chapters, are elegantly explained by Tim Lyons and by Casper Schalkwijk and coworkers.

John Chambers and Jaspal Kooner review the epidemic of cardiovascular disease and diabetes among Indian Asians and discuss the importance of conventional and novel risk factors. They make a strong case for the development of clinical strategies that identify Indian Asians at increased risk. Abel Thijs and Coen Stehouwer discuss the very contentious issue of whether postmenopausal women with diabetes are likely to benefit from hormone replacement therapy in terms of cardiovascular risk. They conclude that there is no basis for prescription of such therapy to diabetic women if the aim is to lower cardiovascular morbidity. On the other hand, there is also no reason not to prescribe hormone replacement to diabetic women to treat climacteric symptoms.

In the final chapter of this issue, Nicolaas Schaper and Marrigje Nabuurs-Franssen summarize our current knowledge of a clinical entity often frustratingly difficult to manage, namely, the diabetic foot.

We hope that you will enjoy reading these chapters, as we have, and that you will find them both practical and thought provoking.