Adipokines Adiponectin

There is considerable interest in the relationship between the adipocyte-derived protein adiponectin in both type 2 diabetes and CHD. Adiponectin is a 244-amino-acid protein that, despite being solely derived from adipose tissue, is paradoxically reduced in obesity (Greenberg and Obin, 2006). Circulating adiponectin levels, ranging from 0.5 to 30 g ml in humans, are reportedly around 1000-fold higher than circulating levels of other hormones such as insulin and leptin. Prospective...

Dyslipidaemia and Type Diabetes

With increasing obesity, in particular visceral obesity, fat cells become enlarged and apparently less responsive to insulin, i.e. insulin resistant (Frayn, 2001). Some investigators argue that adipocyte sensitivity to insulin is maintained until well after other organs become insulin resistant but such work generally derives from studies on subcutaneous tissues rather than the generally accepted more relevant visceral Figure 2.3 The relevance of insulin action extends beyond skeletal muscle,...

Metabolic Syndrome as a Link between Insulin Resistance and CVD

Metabolic syndrome refers to a constellation of risk factors that is apparently associated with risk for both CVD and type 2 diabetes (Figure 2.7). Although a clustering of risk factors had been recognized as early as the 1920s, Gerald Reaven's Banting lecture in 1988 (Reaven, 1988) disseminated the concept to a wider audience and stimulated considerable further research. Reaven linked 'upstream' insulin resistance to a 'downstream' clustering of risk factors potentially responsible for the...

Nonpharmacological interventions

Lifestyle intervention inspires a sense of well-being, may be less expensive than pharmacological interventions and has no known harmful effects. In impaired glucose tolerance, progression to diabetes can be prevented or postponed by lifestyle modifications, such as dietary manipulation and physical activity (Pan etal., 1997 Tuomilehto etal., 2001) (see also Chapter 10). A variety of lifestyle modifications reduce blood pressure and the incidence of hypertension (Ebrahim and Smith, 1998 He...

Prevalence of the metabolic syndrome

As is the case for the diagnosis of diabetes, the application of different diagnostic criteria for the metabolic syndrome results in differing figures of prevalence and the identification of different individuals. It is still too early to see how the new IDF definition of the metabolic syndrome will fare, but application of the NCEP ATPIII and WHO diagnostic criteria to individuals aged > 20 years in the National Health and Nutritional Examination Survey (NHANES) cohort resulted in an...

Risk factors for PAD in patients with diabetes Table

The high PAD risk in patients with diabetes is due to the complex interplay between the various haemodynamic and metabolic components of the metabolic syndrome. Diabetes is no longer considered to be a disease confined to hyperglycaemia but rather part of a syndrome comprising various risk factors, all of which confer an increased risk of atherosclerosis and cardiovascular events (see also Chapter 2). Hence, although the diagnosis and symptoms of diabetes are still defined by hyperglycaemia,...

Risk of Cardiovascular Disease in Prediabetes

The American Diabetes Association (ADA) has recently introduced the term pre-diabetes in an attempt to simplify what has become an increasingly confusing literature on impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) (see also Chapter 11). In fact, pre-diabetes was introduced as an official term nearly 40 years ago, although with an entirely different definition (World Health Organization, 1965), and some may argue that it may be a misleading label for some subjects with...

Screening for Prediabetes

There are several good reasons why measurement of blood glucose can be used as an effective screening tool. Firstly, as described above, it can be helpful in predicting risk for two important and common diseases, T2D and CVD, and screening for pre-diabetes will inevitably identify a group of individuals with asymptomatic T2D. Secondly, the mechanisms by which hyperglycaemia is involved in the pathophysiology of these diseases are increasingly well understood, ensuring that the screening test is...

Summary and Conclusions

We are currently in the midst of a global epidemic of type 2 diabetes, which may well reverse the downward trend in CVD mortality seen in recent decades. The epidemic is being driven by the increasing prevalence of 'unhealthy lifestyle' involving a combination of obesity, physical inactivity and a diet high in saturated fat and refined carbohydrate. While established diabetes has long been regarded as an important cardiovascular risk factor, and hyperglycaemia has been shown to promote vascular...

The metabolic syndrome and cardiovascular risk

The DECODE study group have undertaken similar studies in the metabolic syndrome in an attempt to clarify its prevalence and also to define its relationship with cardiovascular mortality. Using a modification of the WHO definition of the metabolic syndrome and excluding patients with diabetes, the non-diabetic adult prevalence of metabolic syndrome in Europeans was found to be 15.7 in males and 14.2 in females. Over a median follow-up of 8.8 years the hazard ratio for all-cause and...

Hyperglycaemia and PAD

There is a positive correlation between hyperglycaemia and the risk of developing PAD (Figure 8.1). In the UK Prospective Diabetes Study (UKPDS), for example, a PVD 8 17 12 8 8 8 All 681 676 443 285 158 155 PVD 8 17 12 8 8 8 All 681 676 443 285 158 155 Mean systolic blood presssure (mmHg) Figure 8.1 Odds ratio for HbAlc (A) and SBP (B) by category adjusted for age, HDL cholesterol, previous cardiovascular disease, smoking, retinopathy, and peripheral sensory neuropathy in 61 patients with...

Hospitalisation due to CHF in patients with both diabetes and CHF

Patients with both diabetes and CHF are frequently hospitalised due to CHF. In the BEST trial, diabetes was an independent predictor of hospitalisation due to CHF (relative risk 1.16 (1.02-1.32), P 0.027) (Domanski etal., 2003). In the RESOLVD study, diabetes was again an independent predictor of CHF hospitalisation (Suskin etal., 2000). 5.7 CHRONIC HEART FAILURE, ABNORMALITIES OF INSULIN AND GLUCOSE METABOLISM 103 In the placebo arm of MERIT-HF, patients with diabetes had a 76 (38-126 , P <...

Poststroke hyperglycaemia PSH

In any given population of acute stroke patients it has been estimated that 8-20 will have a past history of diabetes, with a further 6-42 having previously unrecognised diabetes prior to the acute event (Riddle and Hart, 1982 Oppenheimer etal., 1985 Gray etal., 1987 Kiers etal., 1992). Variations in the populations studied, the criteria applied for the diagnosis of diabetes and the use of blood fructosamine and glycosylated haemoglobin as indirect diagnoses of diabetes have contributed to such...

Clopidogrel

The efficacy of clopidogrel in addition to aspirin for the prevention of cardiovascular death, MI or stroke, in the setting of ACS (non-ST-segment elevation), was tested in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study (Yusuf etal., 2001). Patients were eligible for enrollment in this multicentre trial if they presented within 24 h after the onset of ischaemic chest pain, and had either electrocordiograph (ECG) evidence of ischaemia or elevation of cardiac...

Correction of dyslipidaemia

Lipid lowering has a moderately favourable effect (Fried etal., 2001 Sica and Gehr, 2002). Treatment with atorvastatin in addition to a regimen including ACE inhibitor or angiotensin receptor blocker reduces proteinuria and the rate of progression of kidney disease in patients with chronic kidney disease, proteinuria and hypercholesterolaemia (Bianchi etal., 2003). Although not all patients had diabetes, the benefit might be extrapolated to that population. Intensive strategies to control blood...

Novel agents in the treatment of type diabetes

Following many years of having little therapeutic choice in the treatment of type 2 diabetes, it appears that there are an increasing number of agents that will become available to treat hyperglycaemia in the very near future. While the development of PPAR agents that act at the delta and alpha as well as the gamma receptors has faltered, new agents that increase insulin secretion via the incretin system, which is based in the stomach and small intestine, seem to offer safe and efficacious...

List of Contributors

Colin Berry Department of Cardiology, Western Infirmary, Glasgow G11 6NT, UK Stephen J. Cleland Department of Medicine, Stobhill Hospital, 133 Balornock Rd, Glasgow G21 3UT, UK Alistair Cormack Department of Cardiology, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK Richard Donnelly The Medical School, Derby City General Hospital, Uttoxeter Road, Derby DE22 3DT, UK Miles Fisher Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK Christopher S. Gray Department of...

Stents for Coronary Artery Disease in Diabetes

Adjunctive devices, such as stents, and novel antithrombotic therapies were generally not used in the clinical trials described above. Early cohort studies derived from a non-randomised setting demonstrated that restenosis rates at 6 months after single-vessel balloon angioplasty, as measured by quantitative coronary angiography, were twice as high in diabetic patients 63 compared with non-diabetic patients due to higher rates of late lumen loss and late vessel occlusion, but no differences...

Reni nangi otensi n system i nhi biti on i n pati ents with di abetes and PAD

Recent trials have highlighted the benefits of agents that block the renin-angiotensin -system in reducing cardiovascular events independent of their effects on blood pressure lowering. The HOPE study showed that long-term treatment with ramipril compared to placebo as add-on to other cardiovascular therapies confers significant reductions in morbidity and mortality among patients with CHD and asymptomatic patients with diabetes plus one other risk factor who do not have left ventricular...

Nature of Coronary Heart Disease in Diabetes

Case-control studies have demonstrated that diabetic patients with angiographically normal coronary arteries have smaller calibre coronary arteries than non-diabetic control subjects Mosseri etal., 1998 . Diabetes is an aetiological factor for the pathogenesis of coronary heart disease CHD and an adverse prognostic marker Kip etal., 1996 . Diabetic patients with coronary disease have a higher prevalence of other risk factors for CHD, and related vascular co-morbidity Kip etal., 1996 .When CHD...

Chapter

Acute Catheterisation and Urgent Intervention Triage Strategy Clopidogrel as Adjunctive Reperfusion Therapy - Thrombolysis in Myocardial Infarction 28 Clopidogrel and Metoprolol in Myocardial Infarction Trial Clopidogrel in Unstable Angina to Prevent Recurrent Events Danish Trial in Acute Myocardial Infarction Danish Trial in Acute Myocardial Infarction 2 Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Enhanced Suppression of the Platelet IIb IIIa Receptor with Integrilin Therapy...

Intermittent claudication

The term claudication is derived from the Latin word for limping. In the Framingham Study, diabetes was associated with two- to threefold excess risk of intermittent claudication for both sexes Brand etal., 1989 . Diabetics with intermittent claudication were at especially high risk for cardiovascular events. Claudicants present with a history of exercise-induced pain in the leg, typically affecting the calves, thighs or buttocks, depending on the location of occlusive arterial disease in the...

Riddle Mc Hart J. Hyperglycemia Recognised And Unrecognised As A Risk Factor For Stroke And Transient Ischemic Attacks.

Adams HP, Bendixen B, Kapelle J etal. 1993 . Classification of subtypes of acute ischaemic stroke. Stroke 24 35-41. Adler A, Stratton IM, Neil HAW, Yudkin JS, Matthews DR, Cull CA etal. 2000 . Association of systolic blood pressure with macrovascular and microvascular complications of type-2 diabetes UKPDS 36 prospective observational study. British Medical Journal 321 412-9. Albers GW, Caplan LR, Easton JD, Fayad PB, Mohr JP, Saver JL, Sherman DG for the TIA Working Group 2002 . Transient...

How do abnormalities of glucose and insulin metabolism affect the SNS and reninangiotensinaldosterone system RAAS

There is some experimental evidence suggesting that neurohormonal systems are activated by diabetes and or insulin resistance, but this has not been demonstrated in patients with CHF. Hyperinsulinaemia increases circulating levels of norepinephrine and angiotensin II in normal volunteers Anderson etal., 1991 Reaven etal., 1996 Scherrer and Sartori, 1997 . Insulin resistance enhances the pressor response to angiotensin II in hypertensive patients Gaboury etal., 1994 . Infusion of FFAs in rats...

Rest pain and critical ischaemia

When PAD worsens, there is insufficient blood to supply the tissues of the leg even at rest and this often presents as continuous pain in the most distal part, namely the forefoot. Nerve ischaemia, manifesting as nocturnal rest pain and a form of neuritis, often precedes the onset of rest pain. It occurs at night when perfusion of the extremities is reduced. Patients often gain relief by hanging their foot over the side of the bed or walking for a few steps. This increases cardiac output,...

Risk factors for amputation

Studies have looked at various risk factors that contribute to lower extremity amputation in patients with diabetes. Poor glycaemic control is a major factor in the development of lower extremity amputation Lehto etal., 1996 and seems to be Diabetic Cardiolog Editors Miles Fisher and John J. McMurray 2007 John Wiley amp Sons, Ltd. ISBN 978-0-470-86204-9 more strongly associated with PAD than coronary artery disease Adler etal., 2002 . High HbAlc and high fasting plasma glucose are associated...

Management of Glycaemia The Digami studies

The metabolic consequences of acute coronary syndromes include the release of epinephrine, glucagon and other counter-regulatory hormones. These antagonise the effects of insulin, and cause further worsening of insulin resistance. In the myocardium this insulin resistance favours the utilisation of free fatty acids, which may have a deleterious effect on myocardial function. In non-diabetic subjects, this may cause temporary hyperglycaemia, sometimes called 'stress hyperglycaemia', that...

References

ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group 2002 . Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic. The antihypertensive and lipid-lowering treatment to prevent heart attack trial ALLHAT . Journal of American Medical Association 288 2981-97. Beckman JA, Creager MA, Libby P 2002 . Diabetes and atherosclerosis. Epidemiology, pathophysiology, and management. Journal of...

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Abaci A, Oguzhan A, Kahraman S, Eryol NK, Unal S, Arinc H, Ergin A 1999 . Effect of diabetes mellitus on formation of coronary collateral vessels. Circulation 99 2239-42. Abizaid A, Kornowski R, Mintz GS, Hong MK, Abizaid AS, Mehran R etal. 1998 . The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation. Journal of the American College of Cardiology 32 584-9. Abizaid A, Costa MA, Centemero M, Abizaid AS, Legrand VMG, Limet RV etal. 2001 ....