bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity as a health problem
Authors: Rossner Stefan
Published: July 2011

Obesity is defined as an excess of body fat that is sufficient to adversely affect health. The prevalence of obesity has been difficult to study because many countries have had their own specific criteria for the classification of different degrees of overweight. However, during the 1990s, the body mass index (weight in kg/height in metres squared), or BMI, became a universally accepted measure of the degree of overweight and now identical limits are recommended. The most frequently accepted classification of overweight and obesity in adults by the WHO is shown in Table 12.1.1.1 (1).

In many community studies in affluent societies this scheme has been simplified and cut-off points of 25 and 30 kg/m2 are used for descriptive purposes of overweight and obesity. Both the prevalence of very low BMI (below 18.5 kg/m2) and very high BMI (40 kg/m2 or higher) are usually low, in the order of 1–2% or less. There are some indications that the limits used to designate obesity or overweight in Asian populations may be lowered by several units of BMI; this would greatly affect estimates of the prevalence of obesity. In countries such as China and India with each over a billion inhabitants, small changes in the criteria for overweight or obesity potentially increase the world estimate of obesity by several hundred million (currently estimates are about 250 million worldwide).

The distribution of abdominal fat should be considered for an accurate classification of overweight and obesity with respect to the health risks (Table 12.1.1.2). Traditionally this has been indicated by a relatively high waist-to-hip circumference ratio; however, the waist circumference alone may be a better and simpler measure of abdominal fatness (2). In 1998 the National Institutes of Health adopted the BMI classification and combined this with limits for waist measurement (3). This classification proposes that the combination of overweight (BMI between 25 and 30 kg/m2) and moderate obesity (BMI between 30 and 35 kg/m2) with a large waist circumference (greater than or equal to 102 cm in men or greater than or equal to 88 cm in women) carries additional risk (3).
Genetics of obesity
Authors: Clément Karine
Published: July 2011

Obesity is characterized by high phenotype heterogeneity linked most notably to differences in the stages of weight evolution. Each stage in the development of human obesity (weight gain, weight maintenance, variable response to treatment, development of comorbidities) is probably associated with various molecular mechanisms which still need to be elucidated. In some rare cases, genetic mutations strongly influence the early and rapid development of severe obesity.
Assessment and management of severe obesity in adults
Authors: Farooqi I. Sadaf
Published: July 2011

Body weight is determined by an interaction between genetic, environmental, and psychosocial factors acting through the physiological mediators of energy intake and expenditure (1). By definition, obesity results from an imbalance between energy intake and energy expenditure and in any individual, excessive caloric intake or low energy expenditure, or both, may explain the development of obesity. A third factor, nutrient partitioning, a term reflecting the propensity to store excess energy as fat rather than lean tissue, may contribute.
Weight regulation: physiology and pathophysiology
Authors: Hameed Saira , Dhillo Waljit S.
Published: July 2011

Body weight in humans is regulated by highly complex interacting neuronal and endocrine pathways that serve to stimulate food intake and reduce energy expenditure during food deficiency and to inhibit feeding when nutrition is replete. These mechanisms are highly conserved between mammalian species and promote the storage of sufficient quantities of energy-dense triglycerides in adipose tissue, thereby permitting survival during the frequent periods of food deprivation that were encountered during evolution. However, in modern times the ready availability of energy-dense food and the reduced necessity for energy expenditure has resulted in the excess storage of adipose tissue and a prevalence of overweight and obesity that the WHO considers to be an ‘epidemic’ (1). Overweight and obesity cause major morbidity and mortality, which are greatly attenuated when even modest amounts of weight are lost. Over the past two decades molecular biology and genetic studies have delineated many of the signals and pathways of appetite and body weight regulation. The therapeutic manipulation of these targets in the treatment of obesity is currently underway.
Classification and diagnosis of diabetes mellitus
Authors: M.M. Alberti K. George , Zimmet Paul
Published: July 2011

Diabetes mellitus is a group of metabolic diseases of multiple aetiologies characterized by hyperglycaemia together with disturbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycaemia of diabetes is associated with microvascular damage affecting, particularly, eyes, kidneys, nerves, and heart, together with an increased risk of macrovascular disease (1).
Clinical features of type 1 diabetes mellitus
Authors: Amiel Stephanie A.
Published: July 2011

As described in Chapter 13.2.3, type 1 diabetes results from the destruction of the glucose-responsive, insulin-secreting β‎ cells of the pancreatic islets. Its principal clinical features reflect significant insulin deficiency. In general, the β‎ cell damage is immune mediated and other clinical features occur related to other autoimmune processes. Although typically considered to have a short prodrome, in research studies biochemical evidence of impaired glucose metabolism has been detected years before diagnosis, in the form of mild elevation of blood glucose. It is likely that the clinical symptoms only manifest when 90% or more of the β‎ cells are lost. The effects of insulin deficiency are enhanced at times of insulin resistance, which explains the apparent link between clinical onset of type 1 diabetes and acute stress, such as an intercurrent infection or other illness, or physiological changes in insulin resistance, such as during puberty.

The rate of β‎ cell loss is highly variable. It is probable that type 1 diabetes presenting in prepubertal childhood may reflect a more aggressive destructive process, while, at the other extreme, type 1 diabetes may present in adult life with a slow evolution to an absolute need for insulin replacement. The latter is called ‘latent adult onset diabetes’ (LADA), and confounds the clinical definition of type 1 diabetes—often used in recruiting type 1 patients to trials—of requirement for insulin replacement within a year of diagnosis. The diagnosis of type 1A diabetes, i.e. type 1 diabetes of proven autoimmune pathogenesis, may be made by finding evidence of the autoimmune process against β‎ cell antigens, with the presence of anti-islet cell antibodies—or, more accurately, anti-glutamic acid decarboxylase (GAD) or anti-islet-associated protein 2 (IA-2) antibodies—in the blood. Absence of such antibodies does not mean the diagnosis is not type 1, as the antibodies tend to disappear over time, perhaps with loss of the β‎ cell antigens to stimulate them, but their presence is usual in type 1 diabetes when there is at least some residual insulin-secretory capacity, which is usually the case when the question of diagnosis arises.
Pathophysiology of type 2 diabetes mellitus
Authors: Yki-Järvinen Hannele
Published: July 2011

Insulin resistance, largely caused by obesity and physical inactivity, both precedes and predicts type 2 diabetes. The insulin resistance preceding type 2 diabetes is commonly referred to as the metabolic syndrome. The latter condition consists of a cluster of risk factors, which are thought to be either causes or consequences of insulin resistance. The development of type 2 diabetes, overt hyperglycaemia, also requires the presence of a relative defect in insulin secretion. This defect appears, at least in part, genetically determined.

Insulin resistance can be defined as the inability of insulin to produce its usual biological actions at circulating concentrations that are effective in normal subjects. This chapter is focused on defining and characterizing defects in insulin action and in insulin and glucagon secretion in patients with type 2 diabetes, and the effects that these defects have on the body. The causes of insulin resistance in different tissues is also discussed.

Hepatic insulin resistance and metabolic syndrome can be linked to atherosclerosis and cardiovascular disease, the main cause of the excess mortality in type 2 diabetes, by increased very-low-density lipoprotein production which leads to the generation of small, dense, and atherogenic LDL particles. Insulin resistance is also seen in adipose tissue and skeletal muscle, altering glucose and fatty acid handling in these tissues and the liver. The hepatic manifestation of insulin resistance in type 2 diabetes is nonalcoholic fatty liver disease (NAFLD). NFALD is defined as excess fat in the liver which is not due to excess alcohol use, and can lead to hepatic inflammation and even cirrhosis.

There are defects in both insulin and glucagon secretion in type 2 diabetes, the exact cause of which remains speculative. Whilst family history and genetic factors appear to play a significant role in determining the susceptibility to overt type 2 diabetes, the only certain aspect of its aetiology and pathogenesis is that its incidence can very significantly be reduced by increasing physical activity and avoiding obesity.
Epidemiology of type 2 diabetes mellitus
Authors: Wild Sarah , Price Jackie
Published: July 2011

Diabetes mellitus represents a group of metabolic disorders characterized by hyperglycaemia, which may or may not be associated with symptoms. The chronic hyperglycaemia of diabetes results from defects in insulin secretion, insulin action, or both, and is associated with long-term organ damage, particularly in the eyes, kidneys, nerves, heart, and blood vessels. Patients with type 2 diabetes have a higher prevalence of obesity (particularly abdominal obesity), hypertension, and lipid disorders, as well as an increased risk of macrovascular disease in coronary, peripheral, and cerebral arterial circulations, than people without diabetes. Microvascular complications of diabetes include retinopathy, which can lead to loss of vision, nephropathy (leading to renal failure), neuropathy (with an increased risk of foot ulcers, amputations, and foot deformations), and autonomic neuropathy, causing cardiovascular, gastrointestinal, genitourinary, and sexual dysfunction. Diabetes may have a serious emotional and social impact on affected individuals and their families, and has major economic implications for society as a whole in both developed and developing countries.
Monogenic forms of diabetes resulting from β‎ cell dysfunction
Authors: Besser Rachel , Hattersley Andrew
Published: July 2011

Monogenic diabetes refers to diabetes resulting from mutations in a single gene. This chapter discusses monogenic disorders causing β‎ cell dysfunction, which accounts for the majority of cases of monogenic diabetes.

Patients can usually be divided into three clinical categories: maturity-onset diabetes of the young (MODY), which is dominantly inherited familial diabetes; neonatal diabetes, diagnosed under the age of 6 months; and monogenic diabetes syndromes, which are characterized by multiple nonpancreatic features. In each clinical category, there are several aetiological genes that usually result in a discrete clinical phenotype.
Clinical features, lifestyle management, and glycaemic targets in type 2 diabetes mellitus
Authors: Matthews David , Ayyagari Usha , Dyson Pamela
Published: July 2011

Type 2 diabetes—previously named ‘maturity-onset diabetes’ or ‘non-insulin-dependent diabetes mellitus’—was, in the past, generally diagnosed in individuals over the age of 40 years old, but, with the modern epidemic, is found in increasing numbers in younger people, including teenagers and children. It is strongly associated with overweight and obese individuals, and tends to run in families. This feature may be environmental, since being overweight also runs in families, but there are specific genes for obesity (1). Type 2 diabetes that occurs in younger individuals with a very strong family history of early-onset diabetes may be the autosomally dominant ‘maturity-onset diabetes of the young’ (MODY) (see Chapter 13.3.4).

In an environment where there is a pandemic of diabetes, one should maintain a very high level of suspicion of diabetes in those who are overweight—in the USA, the prevalence of type 2 diabetes is running at 8% of the population, and, in South India and Sri Lanka, at up to 18% in urban communities (2).
Pharmacological therapy of hyperglycaemia in type 2 diabetes mellitus
Authors: Bailey Clifford J. , Davies Melanie J.
Published: July 2011

The management of type 2 diabetes is complex, due to the diverse, variable, and progressive nature of its pathogenesis, clinical complications, and societal impact (Box 13.4.2.1). Care plans need to be individualized, flexible, and realistic, with provision for patient education and empowerment to enable optimal benefit from the guidance and interventions offered by health care professionals. Relief of acute symptoms and attention to long-term complications and co-morbidities often preoccupy and sometimes overwhelm the treatment process. However, early and sustained remediation of endocrine and metabolic disturbances, plus containment of modifiable cardiovascular risk factors, prevent the onset and limit the severity of chronic pathology. Glycaemic control is a crucial part of the treatment process, and serves as the conventional indicator of metabolic status. This chapter will focus on the treatment of hyperglycaemia, and, particularly, the role of pharmacological therapies.
The world pandemic of diabetes
Authors: Unwin Nigel
Published: July 2011

A pandemic refers to a disease that is rapidly increasing in frequency across many populations, over a wide geographical area (1). Put another way, it refers to the situation in which epidemics of the disease are occurring simultaneously in many countries. This is the case for diabetes, which has the dubious distinction of being one of the few chronic non-communicable diseases known to be increasing in all countries from which data are available, irrespective of the level of economic development (2). This is mirrored by a pandemic of people who are overweight or obese (3), the major risk factors for type 2 diabetes.

This chapter focuses on diabetes in adults (aged 20 years old and above), of which 85% to more than 95%, depending on the population, have type 2 diabetes (2, 4), which is thus the main contributor to the growing burden of diabetes. However, it is worth noting that, in children (<15 years old), the incidence of type 1 diabetes is also increasing, particularly in the youngest age groups, across the vast majority of countries from which good data are available (5). The reasons for this increase are unclear, although various environmental risk factors have been implicated (5).

This chapter aims to do the following:

◆ provide an overview of the prevalence and trends in diabetes in adults across the world and its contribution to mortality

◆ describe the broad determinants that underlie the increasing trends in diabetes in adults

◆ provide an introduction to variations by ethnicity in the prevalence of type 2 diabetes
Diabetes in the South Asian diaspora
Authors: Bellary Srikanth , Khunti Kamlesh , Barnett Anthony H.
Published: July 2011

Increased labour demands in Europe following the Second World War led to a migration of workers from the Indian subcontinent to many parts of Europe. A further wave of migration occurred in the 1960s and 1970s because of political turmoil in East Africa. More recently, technological progress and the need for skilled labour has resulted in migration to different parts of the world, including the USA and Canada. The term ‘South Asian’ broadly refers to people of Indian, Pakistani, and Bangladeshi origin, but those from Sri Lanka and Nepal are commonly also included. Although there is considerable heterogeneity between these subgroups, they share many sociocultural factors.
Management of type 1 diabetes mellitus
Authors: Heller Simon R.
Published: July 2011

Almost 90 years after the discovery of insulin, people with type 1 diabetes still use subcutaneous insulin to manage their condition. Such treatment is life saving, preventing early death from ketoacidosis, relieving symptoms, and reversing most of the pathophysiological features within a few weeks of diagnosis. Yet people with diabetes still die prematurely from long-term complications, and the quality of the lives of others is blighted by impaired vision, amputation, renal replacement therapy, or recurrent hypoglycaemia. Despite the clear demonstration that tight glycaemic control can delay, and perhaps prevent, both micro- and macro-vascular disease, the limitations of current therapy prevent most from achieving these levels of blood glucose control. There is now a realistic, albeit distant, prospect of a revolution in treatment, involving either cell therapy (see Chapters 13.10 and 13.11) or closed-loop technology combining continuous glucose sensing and insulin-infusion pumps (see Chapter 13.4.9.2). However, for the foreseeable future, the responsibility of the diabetes professional is to assist individuals with type 1 diabetes to achieve both an optimum level of blood glucose and quality of life with best use of available methods.
Type 1 and type 2 diabetes mellitus in children
Authors: Matyka Krystyna A.
Published: July 2011

The global incidence of type 1 diabetes mellitus in childhood is increasing, with the greatest rise occurring in younger children (under five years of age). Data suggest that the annual rise is of the order of 3% and that changes in incidence figures are also occurring in those countries that have traditionally had low incidence rates of type 1 diabetes. Data collated for the IDF Diabetes Atlas suggest that one-quarter of all children with type 1 diabetes reside in Southeast Asia and more than a fifth are from Europe. However, data ascertainment from developing countries in sub-Saharan Africa and South America can be poor, so these figures may be misleading. Table 13.4.7.1 summarizes the data from 2007 examining incidence and prevalence by region (where available) (1).

The reasons for the increasing prevalence of childhood diabetes are unclear. Improvements in diagnosis and management in developing countries may account for some of the increasing prevalence in these parts of the world. Some studies also suggest that the rise in type 1 diabetes may reflect the rise in childhood obesity, and that type 1 and type 2 diabetes may represent points on a spectrum of disease: the so-called ‘accelerator hypothesis’. Type 2 diabetes is also becoming common in children, associated with increasing rates of obesity and physical inertia. Whatever the causes, the challenges of the management of diabetes in children and young people are significant. Audit data highlight significant problems, with many children experiencing poor glycaemic control (2). This chapter aims to explore the special considerations of diabetes in the young.
Glucose monitoring
Authors: Pickup John C.
Published: July 2011

Blood glucose concentrations are measured in diabetes to detect hyper- and hypo-glycaemia. Health care professionals need this information to diagnose diabetes, or states of impaired glucose tolerance, to adjust therapy and correct hyper- and hypo-glycaemia in established diabetes, to interpret signs and symptoms in patients (e.g. is confusion due to hypoglycaemia or another cause?), and to assess the risk of tissue complications developing in the future (the severity and duration of hyperglycaemia is clearly related to microvascular disease). The patient with diabetes measures blood glucose concentrations to take corrective action with food and insulin, to maintain good control, to check the safety of everyday activities (e.g. not driving when hypoglycaemic), to assess the

impact of events and lifestyle and on control (exercise, diet, illness, psychological stress), and to ensure a good quality of life and the ‘peace of mind’ that knowledge of the blood glucose concentration gives.

Glucose monitoring has traditionally been performed by intermittent sampling of blood glucose concentrations, either in hospital or by the patient testing their own blood glucose concentrations at home using finger-prick capillary blood samples applied to reagent strips and inserted into portable glucose meters – self-monitoring of blood glucose (SMBG). In addition, in the last decade or so, continuous glucose monitoring (CGM) has entered clinical practice as a supplement to SMBG, albeit with limited uptake at present. CGM is based on the implantation of needle-type glucose sensors, or microdialysis probes, into the subcutaneous tissue for measurement of interstitial glucose concentrations.
Hyperglycaemic crises in adult patients with diabetes mellitus
Authors: Kitabchi Abbas E. , Nyenwe Ebenezer
Published: July 2011

Diabetic ketoacidosis (DKA) and hyperosmolar nonketotic state (HONK; also referred to, in the USA, as hyperglycaemic hyperosmolar state) are the two most serious, potentially fatal acute metabolic complications of diabetes mellitus. In the USA, the annual incidence rate for DKA ranges from 4.6 to 8 episodes per 1000 patients with diabetes of all ages, and 13.4 per 1000 patients in subjects younger than 30 years old (1). The incidence rate in the USA is comparable to the rates in Europe, with estimates of 13.6 per 1000 patients with type 1 diabetes in the UK (2), and 14.9 per 1000 patients with type 1 diabetes in Sweden (3). In the USA, hospitalization for DKA has risen by more than 30% in the last decade, with DKA accounting for approximately 1 35 000 hospital admissions in 2006 (4). The incidence of HONK is difficult to determine because of the lack of population–based studies and the multiple combined illnesses often found in these patients. In general, it is estimated that the rate of hospital admissions due to HONK is lower than it is for DKA and HONK accounts for less than 1% of all primary diabetic admissions (5).

The mortality rate in patients with DKA has significantly decreased in experienced centres since the advent of low-dose insulin and appropriate fluid-/electrolyte-replacement protocols. Among adults with DKA in the USA, the overall mortality rate is less than 1% (4). A trend toward remarkable reduction in mortality from DKA has been reported in Europe as well, with one UK university recording no deaths among 46 patients who were admitted for DKA between 1997 and 1999 (2). The incidence and mortality of DKA remains high in developing countries, owing to socioeconomic factors. For instance, in Nairobi, Kenya, the incidence of DKA was about 80 per 1000 hospitalized diabetic patients in a study reported in 2005, and mortality rate was as high as 30% (6). The mortality rate of patients with HONK remains high even in the developed world, at approximately 11%. The prognosis of both conditions is substantially worsened with increased age, presence of coma, and hypotension (7). Despite threat to life, DKA is also expensive, with estimated annual direct and indirect cost of 2 billion US dollars (8).
Management of the inpatient with diabetes mellitus
Authors: McNally Paul G. , Hammersley Maggie Sinclair
Published: July 2011

Little attention has focused on aspects of diabetes care and glucose control of patients admitted to hospital. The majority of patients are admitted due to an unrelated general medical or surgical disorder and glucose control is often ignored, with the primary condition taking precedence. Their care is often delegated to nonspecialists and, as a consequence, standards of care vary and length of stay is often longer than age-matched patients without diabetes (1–3). A national survey of inpatient services in the UK in 2005–2006 identified substantial gaps in service provision for inpatient diabetes care; one-third of UK acute hospitals reported that they did not have diabetes management guidelines for day surgery, endoscopy, barium studies, or diabetes-related foot problems (4). Also, in many UK hospitals up to one-third of patients were not routinely managed by the diabetes specialist team and only 50% of acute hospitals in the UK had a diabetes inpatient specialist nurse in post (4).
Diabetes management in surgery
Authors: Hall Andrew P. , Davies Melanie J.
Published: July 2011

Diabetes mellitus is a common condition in the general population, and particularly so among hospital inpatients. Complications associated with diabetes mellitus further increase its incidence in surgical patients, particularly those requiring vascular, renal, or ophthalmic procedures.

Patients with diabetes have a higher rate of morbidity and mortality associated with surgery. This includes cardiovascular and renal complications, infection, and impaired wound healing. The process of surgery, a controlled form of trauma, provokes a metabolic response due to the release of cytokines and stress-associated hormones. These agents promote a catabolic state that includes increased insulin resistance. The resulting hyperglycaemia leads to overflow of substrates in the mitochondria and the generation of excess free oxygen radicals, which can be toxic to the cell. It should, therefore, be possible to reduce these effects by avoiding or attenuating the stress response and/or counteracting its metabolic effects. The stress response is proportional to the degree of tissue trauma. Insulin administration and normoglycaemia have been shown to reverse catabolic changes and improve wound healing and skin grafting, and also to reduce the incidence of infective complications.

Additionally, the stress response may be, in part, attenuated by the choice of anaesthetic technique. Neuraxial (spinal and epidural local anaesthetic) analgesia can reduce sympathetic nervous system tone and adrenal output. Additionally, much ophthalmic surgery is now performed with local anaesthesia techniques. Such approaches avoid the more prolonged starvation and cardiorespiratory risks associated with general anaesthesia.
Diabetes management in pregnancy
Authors: McCance David R.
Published: July 2011

Although the outlook for the woman with diabetes has greatly improved since the discovery of insulin, the goal of the St. Vincent Declaration (1989) that the outcome of diabetic pregnancy should approximate that of nondiabetic pregnancy has still not been realized. In the mid 1990s, a number of regional UK centres reported a four-fold to ten-fold increase in congenital malformations and three- to five-fold increase in perinatal mortality, compared with the background population. A general increase in the prevalence of type 2 diabetes is being translated into the pregnancy context and outcomes appear similar to those of type 1 diabetes. The problem of pregnancy planning and other key demographic and pregnancy-related features were highlighted in a major UK Confidential

Enquiry into Maternal and Child Health (CEMACH) during 2002–2003, which has provided a largely unrivalled source of reference (1). While the relevance of overt hyperglycaemia to maternal and perinatal outcomes is now clearly established, the significance of minor degrees of hyperglycaemia for maternal/fetal outcome has been the subject of much controversy and dogma. The lack of a robust evidence base is reflected in the lack of consensus among published guidelines (2).

Despite these limitations, the outcome of pregnancy for most women with diabetes is good, and this undoubtedly reflects improved obstetric surveillance and better management of maternal hyperglycaemia over the last several decades. The aim is, through education and maternal empowerment, to optimize blood glucose control both before and during pregnancy, so that pregnancy may proceed as normally as possible and result in the birth of a normal baby at near term.

The last few years have seen the publication of a number of landmark observational studies and randomized trials (3–8), which have the potential to alter the diagnostic and therapeutic landscape considerably. Some guidance for the management of diabetes in pregnancy has recently been published (9, 10).
Diabetic retinopathy
Authors: Guly Catherine M. , MacKinnon Jane R. , Forrester John V.
Published: July 2011

Blindness is one of the most feared complications of diabetes and although only a small proportion of people with diabetes will become legally blind, a larger number will have significantly impaired vision affecting their daily life. They may have concerns ranging from difficulty reading the telephone directory to loss of their driving licence and hence, restricted independence. The main issues in diabetic retinopathy are identification of those at risk of visually threatening eye disease, addressing modifiable risk factors, and institution of appropriate treatment. All diabetic patients should have access to an effective screening programme. Laser photocoagulation of the retina remains the cornerstone of treatment of sight-threatening diabetic retinopathy, but over the last few years a number of new therapies have been tried and show promise in preventing visual loss from diabetic retinopathy. This chapter will discuss the epidemiology of diabetic retinopathy and the characteristic clinical features and will give an outline of practical management.
Mechanisms of macrovascular disease in diabetes
Authors: Grant Peter J. , Kearney Mark T.
Published: July 2011

The virtual epidemic of diabetes that has appeared over the last couple of decades has highlighted the influence of Western lifestyles and obesity on the development of glucose intolerance and associated cardiovascular disease. Two important hypotheses need consideration in contemplating the strong clinical links that exist between diabetes and cardiovascular disease.

◆ The thrifty genotype hypothesis proposed that the development of insulin resistance was an innate biochemical mechanism that acted to conserve energy in times of food shortage as obesity becomes chronic, as in modern life, insulin resistance would lead to the development of type 2 diabetes, thus introducing the concept of exposure as an important pathogenic factor.

◆ The common soil hypothesis argued that diabetes and cardiovascular disease are the same condition underpinned by common genetic and environmental factors.

One of the great advances in understanding in the past 20 years has been the observation that insulin resistance is associated with inflammatory and atherothrombotic risk factor clustering to provide a risk ‘mirror’ for the changes observed in the vulnerable atheromatous plaque. This brings together the thrifty and the common soil hypotheses and indicates that physiological fluctuations in weight and insulin resistance seen in relation to variation in food availability become pathological with chronic exposure leading to both type 2 diabetes and cardiovascular disease. As insulin resistance cycles to type 2 diabetes, hyperglycaemia has further detrimental effects on vascular disease through the generation of reactive oxygen species, glycation of longlasting proteins, and direct effects of glucose. Epidemiological studies demonstrate a marked increase in vascular outcomes as individuals move from euglycaemic insulin resistance to type 2 diabetes to reflect this increased risk. Finally, the development of microvascular renal disease amplifies vascular risk further and the combination of hyperglycaemia and renal disease provides a common pathway for increased cardiovascular risk in both type 1 and type 2 diabetes.
Prediction models for cardiovascular disease in diabetes mellitus
Authors: Adler Amanda I. , Griffin Simon
Published: July 2011

Throughout the history of medicine, physicians have diagnosed and treated patients relying on their complaints and symptoms. Today, to gauge a patient’s risk of future ill health, physicians rely in addition on patient characteristics expressed as numerical values from physical and laboratory measurements, and from family and past medical histories. Risk scores represent examples of mathematical equations that utilize this information to model reality. Although sometimes not recognized as such, models currently aid in the everyday care of patients with diabetes and include, for example, simple models for adiposity (e.g. body mass index), more complex models for glomerular function, and even more complex algorithms to calculate dosages for continuous subcutaneous insulin based on levels of blood glucose, insulin sensitivity, exercise, diet, and more.

Calculators such as the Framingham or United Kingdom Prospective Diabetes Study (UKPDS) risk equations are increasingly being used to predict the occurrence of cardiovascular disease (CVD) and death. Among the complications of diabetes, CVD, comprising cerebrovascular, coronary, and depending on the definition, peripheral arterial disease, occurs most frequently and generates the highest costs. Cardiovascular risk scores provide a numerical estimate of the risk of future CVD and death from CVD, conditional on the presence of a number of factors.
Diabetic dyslipidaemia
Authors: Betteridge John
Published: July 2011

Management of dyslipidaemia is an integral part of the multifactorial approach to cardiovascular disease (CVD) prevention in people with diabetes. In this chapter the pathogenesis of lipid and lipoprotein disorders in diabetes and their relationship to CVD risk will be discussed together with a practical approach to diagnosis and management.
The diabetic foot
Authors: Edmonds Michael , Foster Alethea.
Published: July 2011

At some time in their life, 15% of people with diabetes develop foot ulcers, which are highly susceptible to infection. This may spread rapidly leading to overwhelming tissue destruction and amputation: indeed, 85% of amputations are preceded by an ulcer and there is an amputation in a person with diabetes every 30 seconds throughout the world (1). Evidence-based protocols for diabetic foot ulcers have been developed (2), and diabetic foot programmes that have promoted a multidisciplinary approach to heal foot ulcers with aggressive management of infection and ischaemia have achieved a substantial decrease in amputation rates (3, 4). Furthermore, a reduction in amputations has been reported nationwide in diabetic patients throughout the Netherlands (5). Recently, a decrease in major amputation incidence has been reported in diabetic as well as in nondiabetic patients in Helsinki (6). These reports have stressed the importance of early recognition of the ‘at-risk’ foot, the prompt institution of preventive measures, and the provision of rapid and intensive treatment of foot infection and also evascularization in multidisciplinary foot clinics. Such measures can reduce the number of amputations in diabetic patients.

Systematic reviews on prevention and treatment have been carried out, e.g. see Eldor et al. (7), and national guidelines have recently been formulated (8, 9). An International Consensus developed in 1999 was re-launched in revised form as an interactive DVD (10, 11) in 2007.

This chapter outlines a simple classification of the diabetic foot into the neuropathic and neuroischaemic foot. It then describes a simple staging system of the natural history of the diabetic foot and a treatment plan for each stage. Successful management of the diabetic foot needs the expertise of a multidisciplinary team which should include physician, podiatrist, nurse, orthotist, radiologist, and surgeon working closely together, within the focus of a diabetic foot clinic.
Diabetes mellitus and psychotic disease
Authors: Newcomer John W.
Published: July 2011

In 2006, investigators compiled data from the public mental health systems of eight states in the USA and compared life expectancy for patients with a major mental illness with general population values. Focusing on states with outpatient as well as inpatient data, this study indicated that individuals with a major mental illness have a mean age at death that is 25–30 years earlier than that observed in the general population over the same years in the same states (1). In this study, ‘major mental illness’ included affective disorders such as major depression and bipolar disorder, attention deficit/hyperactivity disorders, schizophrenia, and schizoaffective disorders. Importantly, these data indicated that the leading cause of death in the mentally ill is coronary heart disease (CHD) and when death due to stroke or cerebrovascular disease is included in a category of cardiovascular disease (CVD), they account for more than 35% of deaths in this population. Suicide, by contrast, was responsible for fewer than 5% of deaths overall. Such observations have led to growing clinical interest in the cardiovascular and metabolic risk factors that contribute to the major causes of morbidity and mortality in patients with psychotic disease, as exemplified by schizophrenia.
The informatics of diabetes management
Authors: New John P. , Buchan Iain E.
Published: July 2011

Informatics is the science of information, the practice of information processing, and the engineering of information systems (1). An early informatics driver in diabetes was the St Vincent Declaration (2), which promoted continuous quality improvement, requiring high-quality information on diabetes, its treatment, and outcomes. This led to the establishment of diabetes registers, compensating for the underdevelopment of clinical information systems. Now, electronic health records are more advanced and the common mobile phone has more computing power than the desktop computer of 20 years ago. Perhaps more important for diabetes care, information and communications technologies are now interwoven with the fabric of society, informing not only our individual behaviours but affecting our interactions with one another.
Treatment of diabetes (Type I) through transplantation
Authors: Srinivasan Parthi
Published: July 2011

Type 1 diabetes mellitus (T1DM) is an autoimmune disease associated with selected genetic HLA alleles, which results in the permanent destruction of beta cells of the pancreatic islets of Langerhans, with subsequent insulinopenia and hyperglycaemia (1). Meta-analysis indicates that high birth weight and increased early weight gain may be risk factors for type 1 diabetes (2). The clinical state leads to significant increase in premature mortality and morbidity, including through accelerated atherosclerosis, cardiac autonomic neuropathy, and possibly intrinsic cardiomyopathy (3). Intensive exogenous insulin therapy can be effective in preventing the progression of such morbidity, but carries with it a three- to six- fold increase in risk of life threatening hypoglycaemia (see Chapter 13.4.8). Clinicians seeking an alternative therapy or even potential cure of T1DM through replacement of the destroyed pancreatic beta cells conducted the first whole organ pancreas transplant (PT) in Minneapolis in 1966. Although now accepted as effective treatment for T1DM, PT involves major surgery, with its attendant complications. Recognition of this led, in the early nineties, to trials of islet allograft transplantation (IT), as this limits the transplant procedure to the islets. Representing only 2% of the whole organ, they are the only part of it that is abnormal in T1DM. Shapiro’s report in 2000 of consistent insulin independence without major surgery led to a worldwide increase in clinical IT (4). We herein discuss the two options in brief, pose our opinions and conclude with some thought to a few future novel therapies for the disease.
Diabetes mellitus and transplantation
Authors: Paul Riley , O’Grady John
Published: July 2011

Diabetes mellitus is a common and significant complication of solid organ transplantation, affecting approximately 20% of transplant recipients (1). However, reported incidences vary widely due to a combination of varying historical definitions, whether diabetes is transient or sustained, and the profile of risk factors, including the immunosuppressive regimens used.

The development of the entity of ‘new-onset diabetes after transplantation’ (NODAT) is gaining attention, as it can be associated with early microvascular complications (2) and an increase in cardiovascular risk (3–5). Cardiovascular disease is the most common cause of post-transplant death in some series (6). NODAT is also associated with an increased risk of infection, graft failure, and patient mortality (1, 3, 4, 7, 8). NODAT and pre-existing diabetes mellitus have also been associated with more aggressive disease recurrence after liver transplantation, particularly of hepatitis C (9).

Because of the above, considerable effort has been focused on identifying and reducing an individual’s risk of NODAT; establishing effective screening to allow early diagnosis and early intervention to prevent or delay the development of severe complications. In addition, the increased flexibility in immunosuppression regimens as a consequence of the wider range of drugs available is allowing the individualization of therapy that may be directed at reducing the risk of NODAT.

The wide ranges quoted for the incidence of NODAT preclude meaningful comparison between the different solid organs. However, liver transplantation is notable because of the very high incidence of transient impairment of glycaemic control immediately after implantation of the graft (resistant hyperglycaemia may be an indicator of poor early function), which is not considered to represent NODAT unless it persists beyond 2 weeks after transplantation. In addition, some people with pre-existing diabetes receiving liver transplants buck the trend and exhibit significant reductions in insulin requirements after liver transplantation, presumably due to increased tissue sensitivity.
The neurohypophysis
Authors: Ball Stephen G.
Published: July 2011

The neurohypophysis is a complex neurohumoral system with a key role in body fluid homoeostasis and reproductive function. This chapter will concentrate on the physiology and pathophysiology of the two hormones made by the neurohypophysis, vasopressin and oxytocin, outlining the roles of both hormones together with the molecular, cellular, and anatomical basis of their regulation and function.
Histopathology of pituitary tumours
Authors: Horvath Eva , Kovacs Kalman
Published: July 2011

The human pituitary gland consists of two major components: the adenohypophysis comprising the hormone producing cells of the pars anterior, pars intermedia, and pars tuberalis, and the neurohypophysis, also called pars nervosa or posterior lobe (1). In contrast to most mammalian species, the human gland has no anatomically distinct pars intermedia (2). The exclusively proopiomelanocortin (POMC)-producing cells of the pars intermedia are sandwiched between the anterior and posterior lobes in the majority of mammals, whereas in the human they are incorporated within the pars anterior, thereby constituting the pars distalis (3). The pars tuberalis is a minor upward extension of the adenohypophysis attached to the exterior of the lower pituitary stalk. In this chapter we deal only with adenohypophyseal tumours.

Histologically, the adenohypophysis consists of a central median (or mucoid) wedge flanked by the two lateral wings. The hormone-producing cell types are distributed in an uneven, but characteristic manner. The cells are arranged within evenly sized acini surrounded by a delicate but well-defined reticulin fibre network giving the pituitary its distinct architecture (4). In the center of the acini is the long-neglected pituitary follicle composed of the agranular nonendocrine folliculo-stellate cells (5).
Pituitary assessment strategy
Authors: Drake W. M. , Trainer P. J.
Published: July 2011

The optimum methods of testing anterior and posterior pituitary function and the interpretation of the results are subjects of continuing debate. The syndromes associated with and consequences of hypo- and hyperpituitarism, and the diagnosis and treatment of diabetes insipidus are all discussed elsewhere in this book. The intention of this chapter is to describe the physiological basis and evidence in favour of the various available tests of anterior pituitary function, discuss the limitations of using artificial assessments on which to base patient management decisions and, ultimately, endeavour to produce a rational approach to the investigation of suspected hypopituitarism.
Hypopituitarism: replacement of adrenal, thyroid, and gonadal axes
Authors: Howlett Trevor A.
Published: July 2011

Hormone replacement of anterior pituitary hormone deficiency is one of the most frequent clinical interventions in pituitary disease, yet is an area which has rarely been the subject of rigorous scientific evaluation. Even in an era of ‘evidence-based’ medicine, recommendations for patient management are frequently based predominantly on clinical experience, consensus guidelines and occasional retrospective reviews rather than on controlled, prospective clinical trials. Within these limitations, this chapter will attempt to give a balanced view on current best management of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) and gonadotropin deficiency.
Adult growth hormone deficiency
Authors: Aragon-Alonso Aurora , Sherlock Mark , Toogood Andrew A.
Published: July 2011

It has been known for many years that growth hormone is essential for normal linear growth, but over the past few years, with the advent of recombinant human growth hormone therapy, the importance of growth hormone during adult life has been described in detail. The growth hormone peptide was first isolated from bovine pituitaries in the 1940s (1), but was found to be species specific and inactive in humans. In 1956, growth hormone was extracted from human cadaveric pituitary tissue (2) and a year later was administered to a 13-year-old boy with hypopituitarism, resulting in an increased growth velocity (3). The first report suggesting growth hormone could have beneficial actions in adulthood was published in 1962 in which a 35-year-old woman with hypopituitarism reported increased vigour, ambition, and wellbeing after 2 months treatment with cadaveric growth hormone (4). However, the limited supply of pituitary-derived growth hormone confined its use to the treatment of children with severe growth failure caused by proven growth hormone deficiency (GHD). In 1985, the association of cadaveric growth hormone treatment with Creutzfeldt–Jakob disease led to its withdrawal from use worldwide (5). Since then, all growth hormone in clinical use has been produced using recombinant DNA technology.

The first placebo-controlled trials of growth hormone replacement therapy in adults with GHD were published in 1989 (6, 7). These and subsequent studies have led to the recognition of adult GHD as a specific clinical syndrome and the impact of GHD and replacement therapy in adults with GHD has been studied in detail.