ContextComplications of atherosclerosis cause most morbidity and mortality
in patients with diabetes mellitus. Despite the frequency and severity of
disease, proven medical therapy remains incompletely understood and underused.ObjectiveTo review the epidemiology, pathophysiology, and medical and invasive
treatment of atherosclerosis in patients with diabetes mellitus.Data SourcesUsing the index terms diabetes mellitus, myocardial infarction, peripheral vascular
diseases, cerebrovascular accident, endothelium, vascular smooth muscle, platelets, thrombosis, cholesterol, hypertension, hyperglycemia, insulin, angioplasty, and coronary artery bypass, we
searched the MEDLINE and EMBASE databases from 1976 to 2001. Additional data
sources included bibliographies of identified articles and preliminary data
presented at recent cardiology conferences.Study SelectionWe selected original investigations and reviews of the epidemiology,
pathophysiology, and therapy of atherosclerosis in diabetes. We selected randomized,
double-blind, controlled studies, when available, to support therapeutic recommendations.
Criteria for data inclusion (168 of 396) included publication in a peer-reviewed
journal or presentation at a national cardiovascular society–sponsored
meeting.Data ExtractionData quality was determined by publication in peer-reviewed literature.
Data extraction was performed by one of the authors.Data SynthesisDiabetes mellitus markedly increases the risk of myocardial infarction,
stroke, amputation, and death. The metabolic abnormalities caused by diabetes
induce vascular dysfunction that predisposes this patient population to atherosclerosis.
Blood pressure control, lipid-lowering therapy, angiotensin-converting enzyme
inhibition, and antiplatelet drugs significantly reduce the risk of cardiovascular
events. Although diabetic patients undergo revascularization procedures because
of acute coronary syndromes or critical limb ischemia, the outcomes are less
favorable than in nondiabetic cohorts.ConclusionsSince most patients with diabetes die from complications of atherosclerosis,
they should receive intensive preventive interventions proven to reduce their
cardiovascular risk.

Diabetes and atherosclerosis: epidemiology, pathophysiology, and management.

Diabetes mellitus affects approximately 100 million persons worldwide.1 Five to ten percent have type 1 (formerly known as insulin-dependent) and 90% to 95% have type 2 (non–insulin-dependent) diabetes mellitus. It is likely that the incidence of type 2 diabetes will rise as a consequence of lifestyle patterns contributing to obesity.2 Cardiovascular physicians are encountering many of these patients because vascular diseases are the principal causes of death and disability in people with diabetes. The macrovascular manifestations include atherosclerosis and medial calcification. The microvascular consequences, retinopathy and nephropathy, are major causes of blindness and end-stage renal failure. Physicians must be cognizant of the salient features of diabetic vascular disease in order to treat these patients most effectively. The present review will focus on the relationship of diabetes mellitus and atherosclerotic vascular disease, highlighting pathophysiology and molecular mechanisms (Part I) and clinical manifestations and management strategies (Part II).

Abnormalities in endothelial and vascular smooth muscle cell function, as well as a propensity to thrombosis, contribute to atherosclerosis and its complications. Endothelial cells, because of their strategic anatomic position between the circulating blood and the vessel wall, regulate vascular function and structure. In normal endothelial cells, biologically active substances are synthesized and released to maintain vascular homeostasis, ensuring adequate blood flow and nutrient delivery while preventing thrombosis and leukocyte diapedesis.3 Among the important molecules synthesized by the endothelial cell is nitric oxide (NO), which is constitutively produced by endothelial NO synthase (eNOS) through a 5-electron oxidation of the guanidine-nitrogen terminal of l-arginine.4 The bioavailability of NO represents a key marker in vascular health. NO causes vasodilation by activating guanylyl cyclase on subjacent vascular smooth muscle cells.4 In addition, NO protects the blood vessel from endogenous injury—ie, atherosclerosis—by mediating molecular signals that prevent platelet and leukocyte interaction with …

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Diabetes and Vascular Disease Pathophysiology, Clinical Consequences, and Medical Therapy: Part I

Guidelines and Expert Consensus documents aim to present management and recommendations based on all of the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient, suffering from a specific condition, taking into account not only the impact on outcome, but also the risk benefit ratio of a particular diagnostic or therapeutic procedure. The ESC recommendations for guidelines production can be found on the ESC website†.

In brief, the ESC appoints experts in the field to carry out a comprehensive and critical evaluation of the use of diagnostic and therapeutic procedures and to assess the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined below. Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. If necessary, the document is revised once more to be finally approved by the Committee for Practice Guidelines and selected members of the Board of the ESC.

The ESC Committee for Practice Guidelines ( CPG ) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have, which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.

 
| Classes of recommendations |
|:-------------------------- | ------------------------------------------------------------------------------------------------------------------------ |
| Class I | Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective |
| Class II | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment or procedure |
|  Class IIa | Weight of evidence/opinion is in favour of usefulness/efficacy |
|  Class IIb | Usefulness/efficacy is less well established by evidence/opinion |
| Class III | Evidence or general agreement that the treatment or procedure is not useful/effective and, in some cases, may be harmful |

Diabetes and cardiovascular diseases (CVD) often appear …

/pdf/guidelines-on-diabetes-pre-diabetes-and-cardiovascular-4j63bs7fb2.pdf

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).

2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

New data on the epidemiology of peripheral artery disease (PAD) are available, and they should be integrated with previous data. We provide an updated, integrated overview of the epidemiology of PAD, a focused literature review was conducted on the epidemiology of PAD. The PAD results were grouped into symptoms, diagnosis, prevalence, and incidence both in the United States and globally, risk factors, progression, coprevalence with other atherosclerotic disease, and association with incident cardiovascular morbidity and mortality. The most common symptom of PAD is intermittent claudication, but noninvasive measures, such as the ankle-brachial index, show that asymptomatic PAD is several times more common in the population than intermittent claudication. PAD prevalence and incidence are both sharply age-related, rising >10% among patients in their 60s and 70s. With aging of the global population, it seems likely that PAD will be increasingly common in the future. Prevalence seems to be higher among men than women for more severe or symptomatic disease. The major risk factors for PAD are similar to those for coronary and cerebrovascular disease, with some differences in the relative importance of factors. Smoking is a particularly strong risk factor for PAD, as is diabetes mellitus, and several newer risk markers have shown independent associations with PAD. PAD is strongly associated with concomitant coronary and cerebrovascular diseases. After adjustment for known cardiovascular disease risk factors, PAD is associated with an increased risk of incident coronary and cerebrovascular disease morbidity and mortality.

Epidemiology of Peripheral Artery Disease

OBJECTIVE —The aim of this study was to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both groups of patients. RESEARCH DESIGN AND METHODS —Randomly selected lower-extremity angiograms were examined according to the Bollinger system. Patient demographics and medical history were recorded and case notes were examined to determine which patients later underwent a revascularization procedure or amputation and which patients had died. RESULTS —A total of 136 arteriograms obtained between 1992 and 1996 were analyzed. The age (mean ± SD) of the patients was 64.7 ± 10.8 years. Diabetic patients (43%) and nondiabetic patients were of similar age (63.9 ± 10.4 vs. 65.3 ± 11.1 years, P = 0.43), with a similar history of smoking (81.0 vs. 76.9%, P = 0.26), ischemic heart disease (41.4 vs. 37.2%, P = 0.54), and hypercholesterolemia (24.4 vs. 30.8%, P = 0.48). However, there were a greater proportion of hypertensive patients in the diabetic group (63.8 vs. 39.7%, P = 0.006). Diabetic patients had greater severity of arterial disease in the profunda femoris and all arterial segments below the knee ( P = 0.02). A greater number of amputations occurred in the diabetic group: diabetic patients were five times more likely to have an amputation (41.4 vs. 11.5%, odds ratio [OR] 5.4, P P = 0.002), and diabetic patients who died were younger at presentation than nondiabetic patients (64.7 ± 11.4 vs. 71.1 ± 8.7 years, P = 0.04). CONCLUSIONS —In patients with peripheral arterial disease, diabetic patients have worse arterial disease and a poorer outcome than nondiabetic patients.

https://care.diabetesjournals.org/content/diacare/24/8/1433.full.pdf

Nicholas Chalmers

Papers

Peripheral arterial disease in diabetic and nondiabetic patients: A comparison of severity and outcome