bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Physiology of Bodyweight Regulation
Authors: Coll Anthony P. 
Published: January 2022

Abstract
Mammalian body weight is highly regulated. An understanding of the processes governing body weight is closely relevant to clinical practice as disorders of energy homeostasis are common, cause significant morbidity and mortality and can be challenging to treat. Detailed clinical observation of extreme phenotypes, both human and model organism, coupled with significant advances in molecular biology have led to the identification of a host of endocrine pathways that control appetitive behaviour, body composition, and energy expenditure. Compelling data show the central nervous system, in particular regions such as the hypothalamus and brainstem, have primacy in sensing a multitude of humoral and neuronal signals from the periphery, integrating them into a coordinated output that aims to maintain weight in the face of a changing environment. This understanding not only gives a biological basis for interindividual variation in body weight, but has opened up new avenues for rational therapeutic interventions.
Metabolic Surgery
Authors: Rubino Francesco , Anastasiou Vivian , Ferraro Luca , Qanaq Dalal , Chamseddine Ghassan 
Published: January 2022

Abstract
Despite constantly evolving drugs, many patients with type 2 diabetes have suboptimal glycaemic control and excess illness and mortality. Widely adopted guidelines from the 2nd Diabetes Surgery Summit (DSS-II) recommend consideration of bariatric/metabolic surgery as a standard treatment option for patients with obese type II diabetes. Studies in animals and humans have shown that gastrointestinal operations can induce weight-independent effects on glucoregulatory physiology, while randomized trials have shown that surgery achieves better glycaemic control than lifestyle and available pharmaceutical interventions. The exact mechanisms of action of surgery remain unclear, but it provides compelling evidence for a critical role of the gastrointestinal system in glucose homeostasis. Further elucidation of the mechanisms of action of surgery and the role of the gut in metabolic regulation may identify novel targets for prevention and therapy of diabetes and obesity. To capitalize fully on this opportunity, however, addressing of common misperceptions and misconceptions that impede appropriate use of metabolic surgery will be required. This chapter reviews biological, clinical, and economic evidence supporting a surgical approach to type 2 diabetes and discusses current evidence-based indications.
Assessment of Obesity in Children
Authors: Farooqi I. Sadaf 
Published: January 2022

Abstract
It is becoming increasingly important for physicians to have a systematic approach to the assessment of children with severe obesity. While a small proportion of severely obese children have features associated with classical genetic obesity syndromes such as Prader–Willi syndrome, there is increasing recognition that genetic disorders can present as severe obesity alone without developmental delay, dysmorphology, or other clinical signs. The diagnosis of a genetic obesity syndrome is of value for families and may help both children and families deal with the social stigma around severe childhood obesity. The finding of a genetic cause for a patient’s obesity sometimes leads to specific therapy. Exome and genome sequencing have accelerated discovery of genes and mechanisms that explain a variety of previously unrecognized childhood obesity syndromes.
Lipoprotein Metabolism
Authors: Angelin Bo , Parini Paolo 
Published: January 2022

Abstract
Lipids are a heterogeneous group of substances with a myriad of structural and regulatory functions. The realization that changes in plasma lipids, particularly elevated cholesterol in apolipoprotein B-containing lipoproteins, are associated with an increased risk of cardiovascular disease has given great impetus to the study of factors regulating plasma lipid metabolism. With the use of increasingly refined methodology, understanding of normal plasma lipoprotein metabolism and its derangements in the face of genetic and/or environmental factors is continuously expanding. This chapter summarizes current concepts regarding normal plasma lipoprotein synthesis, transport, and interconversion in humans, forming a basis for subsequent discussions of pathogenesis, diagnosis, and treatment of dyslipidaemia.
Autoimmune Hypoglycaemia
Authors: Gorden Phillip , Malandrino Noemi 
Published: January 2022

Abstract
Insulin autoimmune syndrome and type B insulin resistance are rare causes of autoimmune hypoglycaemia. Insulin autoimmune syndrome is due to autoantibodies against endogenous insulin, and typically presents with episodes of postprandial hyperinsulinaemic hypoglycaemia. Type B insulin resistance is caused by autoantibodies against the insulin receptor, and may present with severe insulin resistance and hyperglycaemia, hypoglycaemia following a period of hyperglycaemia, or hypoglycaemia alone. The combination of clinical manifestations and positive insulin or insulin-receptor antibodies in the blood confirm the diagnosis of autoimmune hypoglycaemia. However, in rare cases, insulin treatment in patients with positive insulin antibodies and frequent episodes of hypoglycaemia can complicate the diagnosis of insulin autoimmune syndrome. In this chapter, the clinical characteristics, pathophysiology, diagnosis, and management of autoimmune hypoglycaemia syndromes will be described, and the challenges in identifying those insulin antibodies which may significantly affect insulin kinetics in insulin-treated diabetes discussed.
Physiology of Glucose Homeostasis
Authors: Persaud Shanta J. , Jones Peter M. 
Published: January 2022

Abstract
This chapter provides an overview of the physiological mechanisms underlying appropriate control of blood glucose levels. In particular, it focuses on the anatomy and cellular composition of islets of Langerhans; regulation of synthesis and storage of the anabolic hormone insulin in secretory granules of islet beta-cells; cellular mechanisms by which elevations in blood glucose levels stimulate insulin release from beta-cells by a process known as exocytosis; modulation of glucose-stimulated insulin secretion by hormones and neurotransmitters; and the physiological signal transduction pathways used by insulin to stimulate storage of fuels in adipose tissue, liver, and skeletal muscle. It also reviews the deleterious effects of chronic hyperglycaemia that are responsible for diabetic complications.
Pathogenesis
Authors: Bashir Ayat , Oram Richard A. , Wong F. Susan 
Published: January 2022

Abstract
Multiple genes encode susceptibility factors for the development of type 1 diabetes. These interact with environmental factors, the exact nature of which are, as yet unknown, and this leads to activation of autoimmune B and T lymphocytes. The pathogenesis of type 1 diabetes results from complex interactions between these immune cells and the insulin-producing beta-cells of the pancreatic islets of Langerhans, causing damage and destruction, ultimately leading to insufficient production of insulin. In this chapter, the evidence for autoimmunity will be discussed, and currently unanswered questions relating to pathogenesis of type 1 diabetes will be highlighted, among other important aspects.
Hypoglycaemia in the Treatment of Diabetes Mellitus
Authors: Amiel Stephanie A. 
Published: January 2022

Abstract
Hypoglycaemia (blood glucose concentration below the normal range) is a common and feared complication of exogenous insulin and insulin secretagogue treatments for diabetes. Severe hypoglycaemia is defined as an episode in which third-party intervention is required because of cognitive impairment secondary to the glucose lack. Even non-severe episodes can be unpleasant, as the body mounts a symptomatic stress response to the glucose fall. These protective, counterregulatory responses are impaired in diabetes, increasingly so with increasing diabetes duration, increasing the risk of severe hypoglycaemia. Much can be done to reduce individual risk of severe hypoglycaemia, starting with adjustment of medications and, for insulin users, structured education in how to use insulin flexibly; through use of technologies such as analogue insulins, insulin infusion, and continuous glucose monitoring, with β cell replacement a final step. Technological solutions should be accompanied by support for psychological issues of having diabetes and hypoglycaemia, which are challenging for patients and families. This chapter discusses the epidemiology of hypoglycaemia in diabetes, explores the pathogenesis of impaired awareness and severe hypoglycaemia and discusses the treatment pathway.
Psychological and Behavioural Aspects of Type 1 Diabetes Management
Authors: Hendrieckx Christel , Speight Jane 
Published: January 2022

Abstract
Type 1 diabetes is a demanding, complex lifelong condition. Optimal self-care involves repetitive behavioural tasks, undertaken ‘24/7’: administering multiple daily insulin doses, adjusted for food/activity and monitoring glucose levels to avoid hyper- and hypoglycaemia. This requires a comprehensive understanding of diabetes, as well as healthy coping, resilience, problem-solving, and risk reduction skills. It is unsurprising that many experience emotional distress as a consequence of living with type 1 diabetes, which impacts not only on their well-being but also on self-management and outcomes. Clinical guidelines acknowledge that diabetes affects both physical and emotional health. However, the misguided perception persists that the psychosocial care is separate from the diabetes care, and that it requires mental health specialists to assist. A paradigm shift is needed. Diabetes health professionals need to enhance their consultation skills to identify and address psychological needs, if they are to support people to live well with this challenging condition.
Management of the Inpatient with Diabetes Mellitus
Authors: Rayman Gerry 
Published: January 2022

Abstract
The previous edition of this textbook lamented on the general lack of interest in inpatient diabetes care. Since then there has been a significant change, partly brought about by increasing recognition of the significant financial burden of inpatient diabetes, increased lengths of stay, worryingly high levels of patient harms associated with poor control (both hyperglycaemia and hypoglycaemia), and poor patient experience. In England and Wales, the National Diabetes Inpatient Audit (NaDIA—vide infra), the world’s first national diabetes audit was partially instrumental in highlighting the levels of patient harms and patient dissatisfaction as well revealing the paucity of inpatient diabetes specialists. Additionally, recognizing the need to improve inpatient diabetes care the Joint British Diabetes Societies (JBDS) for inpatient care was formed to produce evidence and consensus based national guidelines to promote better care and reduce variation in practice. Similarly, in 2013, diabetes specialists in the United States formed a consortium for Planning Research in Inpatient Diabetes (PRIDE) to improve inpatient diabetes care. Thus, driven by evidence of suboptimal management and the associated high costs, inpatient diabetes care has now become a major focus for funders, hospital management, clinicians, and patients. The goal should be to ensure that the outcomes for people with diabetes admitted to hospital are no different from those without diabetes by prevention of inpatient hyperglycaemia, hypoglycaemia, and hospital acquired foot lesions and ensuring early and safe discharge.
Lipodystrophies and Severe Insulin Resistance Syndromes
Authors: Stears Anna , Savage David B. , O’Rahilly Stephen 
Published: January 2022

Abstract
Severe insulin resistance syndromes are rare disorders which may be inherited or acquired. They can be classified into three groups: (1) defects in insulin signalling (including insulin receptoropathies); (2) defects in adipocyte triglyceride storage (lipodystrophies); and (3) complex syndromes. All three groups are associated with clinical features including acanthosis nigricans, hyperandrogenism in women, and metabolic abnormalities including diabetes. Diabetes may be relatively resistant to standard therapies, and disabling hypoglycaemia may precede it. Lipodystrophies predispose to severe hypertriglyceridaemia which may be complicated by pancreatitis; therefore, management involves strict dietary calorie and fat restriction. Acquired insulin receptoropathies may be successfully be treated with immunosuppression. Accurate diagnosis is key so that appropriate management can be put into place and genetic counselling can be undertaken where required. Biochemical and genetic study of patients with rare syndromes of severe insulin resistance also provides insights into the pathogenesis of the insulin resistance associated with obesity and type 2 diabetes.
Macrovascular Disease in Type 1 Diabetes
Authors: Petrie John R. 
Published: January 2022

Abstract
Even young adults with type 1 diabetes are affected by accelerated atherosclerosis. This manifests as a premature onset of angina, myocardial infarction, stroke, congestive heart failure, peripheral vascular disease, or a combination of these. The development of subclinical renal disease (microalbuminuria) is an early marker of especially high risk. Current management focuses on prevention, aiming for: (i) intensive glucose control and smoking avoidance from diagnosis; and (ii) blood pressure and cholesterol control with longer disease duration. With the exception of the Epidemiology of Diabetes Interventions and Complications (EDIC) study, a post-randomization follow-up of the Diabetes Control and Complications Trial (DCCT), there are very few long-term data to guide cardiovascular risk management in type 1 diabetes. Current thresholds and targets for treatments are therefore largely extrapolated from type 2 diabetes, even although the underlying pathophysiology is very different.
Health Economics of Diabetes Care and Prevention
Authors: Clarke Philip , Lung Thomas 
Published: January 2022

Abstract
There is an ever-increasing demand for healthcare. While clinical studies determine an intervention’s efficacy or effectiveness, limited resources mean that choices need to be made when deciding which healthcare interventions should be funded. Health economics focuses on how to make these choices to fund healthcare interventions that will maximize health benefits. This chapter introduces the ideas of key drivers in healthcare costs and issues around sustainability of funding for diabetes-specific programmes. It will then focus on the concept and different types of economic evaluation, measuring quality-adjusted life-years, and its use in identifying diabetes interventions that provide value for money, providing specific examples.
Types of Treatment
Authors: Rastrelli Giulia , Maggi Mario , Corona Giovanni 
Published: January 2022

Abstract
Several therapeutic options are available in the treatment of adult hypogonadism, the choice of which depend on the clinical situation, availability/costs of medications, patient expectations, and preferences. The induction or restoration of both fertility and testosterone (T) production are potentially achievable, in patients with secondary hypogonadism, whereas only T substitution is effective when the testes are damaged (i.e. primary hypogonadism). When fertility is desired, the use of gonadotrophins in secondary hypogonadism is the most appropriate treatment allowing sperm production to be achieved in about 50% of cases. In all other patients, T substitution is the treatment of choice as it is cheaper and easier to administer when compared to gonadotropins. The use of transdermal T preparations and long-acting injectable T undecanoate are currently the most popular forms of the treatment worldwide. They generally achieve a high level of efficacy with limited side effects.
Endocrine and Local Regulation of Testicular Hormone and Sperm Production
Authors: Huhtaniemi Ilpo , Toppari Jorma 
Published: January 2022

Abstract
The testis has two main functions, that is, androgen production and spermatogenesis, and the key role in their endocrine regulation is played by the two pituitary gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates Leydig cells of testicular interstitial tissue in the production of testosterone (T). T, secreted into the peripheral circulation, regulates the function of an array of androgen-responsive non-gonadal target tissues. Within the testis, T regulates indirectly spermatogenesis through stimulation of Sertoli cells in the seminiferous tubules. FSH promotes spermatogenesis, also indirectly, through actions on Sertoli cells. A plethora of local paracrine signals and metabolites between Sertoli and germ cells underlie the intricate regulatory mechanisms of spermatogenesis. This chapter summarizes the main hormonal regulation of the testis, that is, the hypothalamic–pituitary–testicular axis, and the main events in the process of spermatogenesis and its regulation.
Clinical Evaluation
Authors: Anawalt Bradley D. 
Published: January 2022

Abstract
The evaluation of the man with suspected hypogonadism and/or infertility begins with a directed history and physical examination on specific elements that help to determine the likely onset and possible causes of the androgen deficiency or infertility. Determination of the onset and possible causes of androgen deficiency or infertility is essential for determination of a rational diagnostic evaluation. For example, in the adult man who has testes are very small (≤6 cc each) has prepubertal onset of male hypogonadism. Congenital causes of hypogonadism such as Klinefelter syndrome and Kallmann syndrome become much more likely as aetiologies whereas acquired causes such as sellar masses and metabolic disorders such as hemochromatosis more commonly present postpubertally (because they take time to progress to hypogonadism) or there are clues to the acquired causes such as major testicular or hypothalamic disease or surgery when they occur pre- or peripubertally. Finally, the history and physical examination is indispensable in determining the potential benefits and risks of therapy for man with suspected androgen deficiency or infertility. This chapter introduces the reader into the rationale approach history taking and the physical examination of the man with possible hypogonadism.
Klinefelter’s Syndrome
Authors: Gravholt Claus H. 
Published: January 2022

Abstract
Klinefelter syndrome (KS) is a frequent genetic condition caused by the presence of an extra X chromosome with the resultant karyotype being 47,XXY. The condition is in males and results in hypergonadotropic hypogonadism, small testis, and infertility, although recent research has shown that some KS males harbour sparse amounts of spermatocytes that can be retrieved by testicular sperm extraction. Other characteristics include cognitive impairment, dyslexia, tall stature, gynaecomastia, a range of medical conditions, including the metabolic syndrome, type 2 diabetes, hyperlipidaemia, cardiovascular disease, extragonadal germ cell tumours, and breast cancer. Although the estimated prevalence of KS is 150 per 100 000 liveborn males, diagnosis poses several problems. Most KS are only diagnosed during adulthood, and only about 10% are diagnosed during childhood and adolescence. Studies from different countries indicate that only 25–50% of the expected number are ever diagnosed. Mortality and morbidity are high and the socioeconomic status is low. Medical therapy is directed towards hypogonadism and consists of testosterone replacement therapy, although no formal randomized clinical trial has been conducted in KS, and the prevention of lifestyle diseases. Comprehensive multidisciplinary care needs to be in place throughout life in order also to alleviate the neurocognitive problems encountered by many with KS and facilitate extra scholastic help and speech therapy, etc. The genetic background for KS is not thoroughly understood, but recent developments show global epigenetic and RNA expression changes that are likely tied with the phenotype.
Aetiology
Authors: Matsumoto Alvin M. , Narla Radhika 
Published: January 2022

Abstract
Male hypogonadism is diagnosed in patients who have symptoms and signs of androgen deficiency, and repeatedly low serum testosterone concentrations and decreased sperm production. The aetiology of hypogonadism may be due to disorders of the testes (primary hypogonadism) or hypothalamus or pituitary gland (secondary hypogonadism), or combined disorders. Primary and secondary hypogonadism are distinguished by gonadotropin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) concentrations. Either primary or secondary hypogonadism may be caused by a structural or congenital disorder of the hypothalamic–pituitary–testicular (HPT) axis that is usually permanent and necessitates testosterone treatment (organic hypogonadism) or a disorder that results in suppressed function of an intact HPT axis that is potentially reversible with treatment of the etiologic condition or discontinuing the offending medication (functional hypogonadism). The benefits and risks of testosterone treatment in men who have functional hypogonadism have not been evaluated fully in randomized, double-blind, placebo-controlled trials, while managing the underlying conditions may reverse the hypogonadism and confer other health benefits. Given that clinical management of primary and secondary hypogonadism due to organic or functional aetiologies vary, it is important to evaluate and establish the aetiology of hypogonadism prior to initiating testosterone treatment.
Benefits of Testosterone Treatment
Authors: Basaria Shehzad , Gagliano-Jucá Thiago 
Published: January 2022

Abstract
Male hypogonadism is a clinical syndrome that results from failure to produce physiological concentrations of testosterone, normal concentrations of sperm, or both. Hypogonadism may result from disease or dysfunction of the testes (primary hypogonadism) or hypothalamic–pituitary unit (secondary hypogonadism). In young men with organic (classic) hypogonadism that results from diseases of the hypothalamus, pituitary, or testes, testosterone replacement therapy results in beneficial effects, which include induction and maintenance of secondary sexual characteristics, improvement in sexual function, increase in lean mass and improvement of bone mass and quality. In these young androgen-deficient men, testosterone therapy is generally safe and associated with few adverse effects. In contrast to the organic hypogonadism, the relatively low incidence of which has remained unchanged for decades, symptomatic older men with low circulating serum testosterone concentrations are increasingly being seen in clinical practice and commonly referred to as ‘late-onset’ or ‘age-related’ hypogonadism. This age-related decline in testosterone levels is generally small compared to men with organic hypogonadism. The evidence for clinical benefits of testosterone treatment in older men is limited and long-term risks (mainly prostate and cardiovascular) remain unknown. In this chapter, we will review efficacy of testosterone replacement therapy in men with organic hypogonadism as well as in men with age-related decline in testosterone.