Оглавление
Richard I. G. Holt. Essential Endocrinology and Diabetes
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Essential Endocrinology and Diabetes
Preface
The authors
Further reading
List of abbreviations
CHAPTER 1 Overview of endocrinology. Key topics
Learning objectives
Box 1.1 The endocrine and nervous systems are the two main communication systems in the body
A brief history of endocrinology and diabetes
Box 1.2 Some landmarks in endocrinology over the last century or so
Box 1.3 The ‘Endocrine Postulates’: Edward Doisy, St Louis University School of Medicine, USA, 1936
The role of hormones
Classification of hormones
Peptide hormones
Box 1.4 Major hormone groups
Amino acid derivatives
Steroid hormones
Control systems regulating hormone production
Simple control
Negative feedback
Positive feedback
Box 1.5 Endocrine cycles
Inhibitory control
Endocrine rhythms
Endocrine disorders
Key points
CHAPTER 2 Basic cell biology and hormone synthesis. Key topics
Learning objectives
Box 2.1 The structure of DNA
Chromosomes, mitosis and meiosis
Synthesizing a peptide or protein hormone. Gene transcription and its regulation
Translation into protein
Box 2.2 Genetic, genomic and epigenetic abnormalities that can result in endocrinopathy
Post‐translational modification of peptides
Box 2.3 Role of post‐translational modifications
Storage and secretion of peptide hormones
Synthesizing a hormone derived from amino acids or cholesterol
Enzyme action and cascades
Synthesizing hormones derived from amino acids
Box 2.4 Hormones derived from tyrosine
Synthesizing hormones derived from cholesterol
Box 2.5 Hormones derived from cholesterol
Nomenclature of steroidogenic pathways
Storage of steroid hormones
Hormone transport
Key points
CHAPTER 3 Molecular basis of hormone action. Key topics
Learning objectives
Cell‐surface receptors
Binding of hormone to receptor
Signal transduction
Box 3.1 Some basic facts about hormone receptors
Box 3.2 Binding characteristics of hormone receptors
Box 3.3 Categories of cell‐surface receptors
Tyrosine kinase receptors
Receptors with intrinsic tyrosine kinase activity
Insulin signalling pathways
Box 3.4 Defects in the insulin signalling pathways and ‘insulin resistance’ syndromes
Receptors that recruit tyrosine kinase activity
Growth hormone and prolactin signalling pathways – the Janus family of tyrosine kinases
Box 3.5 One of the major targets of GH signalling is the IGF‐I gene
G‐protein–coupled receptors
Box 3.6 Defects in growth hormone signalling pathways and growth hormone resistance syndromes
Box 3.7 Sub‐families of Gα protein subunits
Second messenger pathways. Cyclic adenosine monophosphate
Diacylglycerol and Ca 2+
Box 3.8 Defects in the G‐protein–coupled receptor/G‐protein signalling pathways
Nuclear receptors
Target cell conversion of hormones destined for nuclear receptors
Nuclear localization, DNA binding and transcriptional activation
Orphan nuclear receptors and variant nuclear receptors
Endocrine transcription factors
Key points
CHAPTER 4 Investigations in endocrinology and diabetes. Key topics
Learning objectives
Pre‐analytical requirements for accurate endocrine testing
Laboratory assay platforms
Immunoassays
Box 4.1 Pre‐analytical requirements for accurate endocrine testing. Patient preparation:
Sample Collection. Blood samples
Urine
Sample Handling
Immunometric assays – the sandwich assays
Immunoassays – the competitive‐binding assays
Analytical methods linked to mass spectrometry
Enzymatic assays
Reference ranges
Static and dynamic testing
Box 4.2 Dynamic investigation in endocrinology
Cell and molecular biology as diagnostic tools. Karyotype
Fluorescence in situ hybridization
Genome‐wide microarray‐based technology
Diagnosing mutations in single genes by polymerase chain reaction and sequencing
Imaging in endocrinology. Ultrasound
Computed tomography and magnetic resonance imaging
Nuclear medicine and uptake marker scans
Positron emission tomography (PET)
Key points
CHAPTER 5 The hypothalamus and pituitary gland. Key topics
Learning objectives
To recap
Cross‐reference
Embryology and anatomy
Pituitary tumours. Pituitary tumours as space‐occupying lesions
Non‐functioning adenomas
Box 5.1 Pituitary tumours
Genetics of pituitary tumours
Case history 5.1
Box 5.2 Summary of non‐pharmacological treatment of pituitary tumours
Treating pituitary tumours
The hypothalamus
The hypothalamic–anterior pituitary hormone axes
The anterior pituitary hormones. Growth hormone
Effects
Metabolic actions. Intermediate metabolism
Energy expenditure
Anabolic actions
Box 5.3 Growth hormone excess: a constellation of signs and symptoms caused by bony and soft tissue overgrowth, and metabolic disturbance
Sodium and water homeostasis
Mechanism of action of GH and IGFs
Growth hormone regulation. Input from the hypothalamus and higher brain centres
Box 5.4 Assessing the GH–IGF‐I axis
Ghrelin
Input from other hypothalamic–anterior pituitary–end‐organ axes
Neuronal control
Nutritional control
Exercise
Clinical disorders. Growth hormone excess – acromegaly and gigantism
Symptoms and signs
Investigation and diagnosis
Treatment
Case history 5.2
Growth hormone deficiency
Investigation and diagnosis
Treatment
Box 5.6 Symptoms and signs of growth hormone deficiency
Box 5.7 Clinical benefits of GH replacement in people with GH deficiency
Prolactin
Effects and mechanism of action
Regulation of production
Case history 5.3
Clinical disorders. Hyperprolactinaemia
Symptoms and signs
Investigation and diagnosis
Box 5.8 Cause of hyperprolactinaemia
Treatment
Hypoprolactinaemia
Adrenocorticotrophic hormone
Effects and mechanism of action
Regulation of production
Clinical disorders. Excess ACTH and Cushing disease
Excess ACTH as a result of adrenocortical insufficiency
ACTH deficiency
Thyroid‐stimulating hormone
Effects and mechanism of action
Regulation of production
Clinical disorders. Excess TSH
TSH deficiency
Gonadotrophins – luteinizing hormone and follicle‐stimulating hormone
Effects and mechanism of action
Regulation of production
Clinical disorders. Excess gonadotrophins
Deficiency of the gonadotrophins
Box 5.9 Hypogonadotrophic hypogonadism
Hypopituitarism
Box 5.10 Causes of hypopituitarism
Case history 5.4
Hormones of the posterior pituitary
Vasopressin
Effects and mechanism of action
Box 5.11 Summary of vasopressin biology
Regulation of production
Clinical disorders. Syndrome of inappropriate antidiuresis
Box 5.12 Regulation of vasopressin
Case history 5.5
Box 5.13 Excess vasopressin/SIAD
Symptoms and signs
Investigation, diagnosis and treatment
Diabetes insipidus
Symptoms and signs
Investigation and diagnosis
Box 5.14 Causes of diabetes insipidus
Treatment
Case history 5.6
Oxytocin
Effects and mechanism of action
Regulation of production
Clinical disorders
Key points
Answers to case histories. Case history 5.1
Case history 5.2
Case history 5.3
Case history 5.4
Case history 5.5
Case history 5.6
CHAPTER 6 The adrenal gland. Key topics
Learning objectives
To recap
Cross‐reference
The adrenal cortex. Embryology and anatomy
Box 6.1 Clinical consequences of the embryology of the adrenal gland
Box 6.2 Zones of the adult adrenal cortex and their steroid hormone secretion
Biochemistry by zones
Function and regulation of the hormones
Box 6.3 Adrenocortical steroidogenesis can be summarized into a few key steps
Cortisol
Regulation of cortisol biosynthesis and secretion – the hypothalamic–pituitary–adrenal axis
Box 6.4 Important cortisol metabolism takes place in peripheral tissues and target cells
Functions. Intermediary metabolism
Box 6.5 Cortisol, like glucagon, epinephrine and growth hormone, can be thought of as antagonistic to insulin (Figure 11.11)
Skin, muscle and bone
Salt and water homeostasis and blood pressure
Growth and development
Lactation
Central nervous system and psyche
Anti‐inflammatory effects
Aldosterone
Box 6.6 Aldosterone is the body’s major mineralocorticoid
Regulation of aldosterone secretion
Sex steroid precursors
Clinical disorders of the adrenal cortex
Hypoadrenalism
Primary hypoadrenalism – Addison disease
Symptoms and signs
Investigation
Box 6.7 Causes of primary hypoadrenalism
Case history 6.1
Box 6.8 Symptoms and signs of hypoadrenalism
Box 6.9 A testing regimen for inadequate cortisol secretion
Treatment
Secondary hypoadrenalism
Hyperadrenalism
Box 6.10 Glucocorticoid replacement
Glucocorticoid excess – ‘Cushing syndrome’
Symptoms and signs
Diagnosis. Identifying glucocorticoid excess
Box 6.11 Symptoms and signs of Cushing syndrome
Case history 6.2
Box 6.12 Pseudo‐Cushing syndrome
Box 6.13 Causes of Cushing syndrome
Diagnosing the cause and site of glucocorticoid excess
Treatment
Primary mineralocorticoid excess – Conn syndrome
Symptoms and signs
Box 6.14 Think of unusual causes of hypertension, especially in younger patients
Case history 6.3
Box 6.15 Causes of hypokalaemia
Diagnosis
Treatment
Tumours involving the zona reticularis
Other tumours of the adrenal cortex. Adrenocortical carcinoma
Incidentalomas
Congenital adrenal hyperplasia
Box 6.16 A pragmatic approach to adrenal incidentalomas?
Case history 6.4
Case history 6.5
The adrenal medulla
Embryology and anatomy
Catecholamine biosynthesis and metabolism
Physiology
Clinical disorders
Phaeochromocytoma and paraganglioma (PPGL)
Case history 6.6
Symptoms and signs
Diagnosis
Box 6.17 The triad of classical symptoms in phaeochromocytoma
Treatment
Follow‐up including the identification of germline mutations
Key points
Answers to case histories. Case history 6.1
Case history 6.2
Case history 6.3
Case history 6.4
Case history 6.5
Case history 6.6
CHAPTER 7 Reproductive endocrinology. Key topics
Learning objectives
To recap
Cross‐reference
Embryology of the reproductive organs
Sex determination
Box 7.1 The early development of biological sex
Sexual differentiation
Box 7.2 Differentiation of the internal genitalia
Differences in sex development
Box 7.3 Differences of sex development
Box 7.4 Diagnosing differences in sex development
Box 7.5 Some of the contentious issues in the management of differences of sex development
Chromosomal abnormalities
SRY gene abnormalities
Androgen insensitivity syndrome
Enzymes in the biosynthetic pathway to testosterone. 5‐alpha reductase deficiency
Congenital Adrenal Hyperplasia
The male reproductive system. Morphology and function of the testis
Spermatogenesis
Box 7.6 The testis has two important functions
Box 7.7 Semen analysis (WHO standards)
Androgen biosynthesis, secretion and metabolism
Box 7.8 Major functions of the gonadotrophins
Regulation of testicular function – the hypothalamic–anterior pituitary – testicular axis
Phases of testicular function and reproductive development after birth
Neonatal life and childhood
Puberty
Adulthood and old age
Box 7.9 The effects of rising androgens in boys at puberty
Case history 7.2
Clinical disorders. Hypogonadism
Box 7.10 Clinical features of male hypogonadism
Symptoms and signs
Box 7.11 Causes of male primary hypogonadism/testicular failure
Investigation and diagnosis
Box 7.12 Distinguishing primary and secondary or tertiary male hypogonadism
Treatment
Testicular tumours
Box 7.13 Testicular tumours of germ cell origin
Gynaecomastia
The female reproductive system
Ovarian morphology and function
Follicle development, ovulation and early embryogenesis
Formation of the corpus luteum
Ovarian steroidogenesis and the hypothalamic–anterior pituitary–ovarian axis: the menstrual cycle
Box 7.14 Ovarian hormone action and measurement during the menstrual cycle
The follicular phase: the control of follicle development
Ovulation
The luteal phase: the hormonal milieu for maintaining an early pregnancy
Cyclical effects on the uterus and vagina
Phases of ovarian function and reproductive development after birth. Neonatal life and childhood
Puberty
Menopause
Box 7.15 Symptoms of the menopause
The endocrinology of pregnancy
Fertilization and implantation
Endocrine changes during pregnancy, parturition and lactation
Box 7.16 Local environmental factors for early embryo growth and implantation
Box 7.17 Endocrine alterations during pregnancy, parturition and lactation
Clinical disorders. Amenorrhoea
Box 7.18 Amenorrhoea
Amenorrhoea with absent oestrogen. Symptoms and signs
Investigation and diagnosis
Case history 7.3
Treatment
Box 7.19 When to choose the combined oral contraceptive pill or hormone replacement therapy
Amenorrhoea with endogenous oestrogen production
Box 7.20 Clinical features of Turner syndrome
Polycystic ovary syndrome
Symptoms and signs
Box 7.21 Management of Turner syndrome
Case history 7.4
Investigation and diagnosis
Treatment
Other female reproductive endocrinology referrals. Hirsuitism and male‐pattern balding
Galactorrhoea
Case history 7.5
Case history 7.6
Hormone‐dependent gynaecological disorders
Pubertal disorders
Precocious puberty
Delayed puberty
Subfertility
Male factor treatment
Female factor treatment
Box 7.22 Delayed puberty: defined as >2 standard deviations above mean age
Case history 7.7
Key points
Answers to case histories. Case history 7.1
Case history 7.2
Case history 7.3
Case history 7.4
Case history 7.5
Case history 7.6
Case history 7.7
CHAPTER 8 The thyroid gland. Key topics
Learning objectives
To recap
Cross‐reference
Embryology
Box 8.1 Clinical consequences of abnormal thyroid development
Anatomy and vasculature
Box 8.2 The thyroid gland
Thyroid hormone biosynthesis
Uptake of iodide from the blood
The synthesis of thyroglobulin
Iodination of thyroglobulin
The production of thyroid hormone
Box 8.3 Iodine deficiency
Box 8.4 Antithyroid drugs that suppress the synthesis and secretion of thyroid hormones
The secretion of thyroid hormone
Regulation of secretion
Circulating thyroid hormones
Box 8.5 Activities and features of the follicular cells increased by TSH
Box 8.6 Circulating thyroid hormones
Metabolism of thyroid hormones: conversion of T4 to T3 or rT3
Function of thyroid hormones
Thyroid function tests
Clinical disorders
Hypothyroidism
Primary hypothyroidism
Box 8.7 Causes of hypothyroidism
Box 8.8 Organ‐specific autoimmune diseases with shared predisposition
Symptoms and signs
Box 8.9 Symptoms, signs and features of hypothyroidism
Case history 8.1
Investigation and diagnosis
Overt hypothyroidism
Subclinical hypothyroidism
Normal thyroid function
Treatment. Overt hypothyroidism
Subclinical hypothyroidism
Monitoring
Box 8.10 Myxoedema coma: very severe hypothyroidism
Secondary hypothyroidism
Hyperthyroidism
Box 8.11 Causes of Hyperthyroidism
Graves disease
Symptoms and Signs
Investigation and diagnosis
Box 8.12 Symptoms and signs of thyrotoxicosis plus features associated with Graves disease
Treatment
Case history 8.2
Antithyroid drugs
Box 8.13 Clinical assessment of the thyroid and thyroid hormone status
Surgery
Radioiodine
Graves disease in pregnancy
Thyroid eye disease (Graves orbitopathy)
Case history 8.3
Amiodarone‐associated thyroid disease
Toxic adenoma
Box 8.14 Amiodarone affects the thyroid gland and thyroid function tests
Case history 8.4
Thyrotoxic crisis “thyroid storm’
Single thyroid nodules and multinodular goitre
Box 8.15 Approach to diagnosing thyroid malignancy
Case history 8.5
Thyroid cancer
Case history 8.6
Key points
Answers to case histories. Case history 8.1
Case history 8.2
Case history 8.3
Case history 8.4
Case history 8.5
Case history 8.6
CHAPTER 9 Calcium and metabolic bone disorders. Key topics
Learning objectives
To recap
Cross‐reference
Calcium
Box 9.1 Key facts about calcium
Box 9.2 Concentration of calcium in different locations in the body
Case history 9.1
Dietary intake of calcium
Box 9.3 Foods that are rich in calcium and/or vitamin D
Hormones that regulate calcium
Vitamin D
Synthesis and inactivation of active vitamin D
Box 9.4 Hormones that regulate serum calcium
Box 9.5 Why vitamin D is a hormone
Regulation of vitamin D synthesis
Function of vitamin D
Box 9.6 Osteoblasts and osteoclasts
Parathyroid glands and parathyroid hormone
Synthesis of parathyroid hormone
Regulation of parathyroid hormone production
Function of parathyroid hormone
Parathyroid hormone‐related peptide
Calcitonin
Clinical disorders of calcium homeostasis
Hypocalcaemia
Box 9.7 Causes of hypocalcaemia
Box 9.8 Causes of hypoparathyroidism
Case history 9.2
Case history 9.3
Box 9.9 Symptoms and signs of hypocalcaemia
Symptoms and signs
Investigation and diagnosis
Treatment
Hypercalcaemia
Box 9.10 Causes of hypercalcaemia
Primary hyperparathyroidism
Malignancy
Box 9.11 Primary tumours commonly associated with hypercalcaemia
Drugs and dietary causes
Familial benign hypercalcaemia
Case history 9.4
Other Causes
Symptoms and signs
Box 9.12 Symptoms and signs of hypercalcaemia
Investigation and diagnosis
Treatment
Box 9.13 Investigating hypercalcaemia
Box 9.14 Emergency management of hypercalcaemia
Bone health and metabolic bone disease. Bone and its composition
Cell types in bone
Box 9.16 The two types of bone
Box 9.17 What is collagen?
Bone growth and remodelling during life
Clinical conditions of bone metabolism. Osteoporosis
Symptoms and signs
Investigation and diagnosis
Box 9.18 Risk factors for osteoporosis
Malignancy
Case history 9.5
Treatment
Anti‐resorptive Drugs
Anabolic drugs
Monitoring
Vitamin D deficiency, osteomalacia and rickets
Box 9.19 Groups at risk of vitamin D deficiency
Case history 9.6
Box 9.20 Secondary causes of rickets and osteomalacia
Symptoms and signs
Investigation and diagnosis
Treatment
Key points
Answers to case histories. Case history 9.1
Case history 9.2
Case history 9.3
Case history 9.4
Case history 9.5
Case history 9.6
CHAPTER 10 Pancreatic and gastrointestinal endocrinology and endocrine neoplasia. Key topics
Learning objectives
To recap
Cross‐reference
Pancreatic endocrinology
Cell types and hormones of the pancreatic islet
Insulin
Glucagon, somatostatin, pancreatic polypeptide and Ghrelin
Clinical disorders of insulin and the other islet hormones
Insulinoma and its differential diagnosis
Symptoms and signs
Differential diagnosis
Box 10.1 Differential diagnosis of hypoglycaemia
Case history 10.1
Case history 10.2
Investigation and diagnosis
Treatment
Other types of islet cell tumour
Box 10.2 Pancreatic and gastrointestinal hormone‐secreting tumours
Gastrointestinal endocrinology and associated clinical conditions
Gastrin
Gastrinomas and Zollinger–Ellison syndrome
Case history 10.3
Vasoactive intestinal polypeptide
VIPomas and Verner–Morrison syndrome
Glucagon‐like peptide‐1 and glucose‐dependent insulinotropic peptide
Cholecystokinin, secretin and motilin
Carcinoid syndrome
Symptoms and signs
Box 10.3 Clinical features of carcinoid syndrome
Case history 10.4
Investigation and diagnosis
Treatment
Endocrine tumour predisposition syndromes
Box 10.4 Warning signs for neoplasia syndromes
Box 10.5 Four types of tumour‐promoting mutation
Multiple endocrine neoplasia
MEN‐1
Familial isolated hyperparathyroidism
MEN‐2
Familial medullary thyroid cancer
MEN‐3
MEN‐4
Case history 10.5
Other endocrine tumour predisposition syndromes. Familial phaeochromocytoma/paraganglioma syndromes
McCune–Albright syndrome
Carney complex
Tumours with ectopic hormone production
Case history 10.6
Hormone‐sensitive tumours
Prostate cancer
Box 10.6 Endocrine treatments of prostate cancer
Breast cancer
Box 10.7 Endocrine treatments of breast cancer
Other tumours relevant to endocrinology. Ovarian cancer
Endometrial cancer
Testicular cancer
Key points
Answers to case histories. Case history 10.1
Case history 10.2
Case history 10.3
Case history 10.4
Case history 10.5
Case history 10.6
CHAPTER 11 Overview of diabetes. Key topics
Learning objectives
To recap
Cross‐reference
Case history 11.1
Case history 11.2
Box 11.1 A brief history of diabetes
A brief history of diabetes and its classification
Case history 11.3
Classification of diabetes
Box 11.2 Classification of diabetes
Diagnosis of diabetes
Box 11.3 How a glucose tolerance test is performed
Box 11.4 What is glycated haemoglobin?
Insulin
Box 11.5 Limitations of HbA1c
Secretion
Case history 11.4
Action
Effects on intermediate metabolism
Glucose metabolism
Lipid metabolism
Protein metabolism
Glucagon
Key points
Answers to case histories. Case history 11.1
Case history 11.2
Case history 11.3
Case history 11.4
CHAPTER 12 Type 1 diabetes. Key topics
Learning objectives
To recap
Cross‐reference
What is type 1 diabetes?
Epidemiology
Box 12.1 What is autoimmunity?
Box 12.2 Genetic and acquired factors that can affect pancreatic β ‐cell function leading to a presentation of diabetes that is similar to autoimmune type 1 diabetes
Box 12.3 The difference between monogenic and polygenic disorders
Pathogenesis
Case history 12.1
Aetiology
Genetic factors
Box 12.4 What are HLA molecules?
Environmental factors
Clinical features
Symptoms related to the osmotic effect of the hyperglycaemia
Box 12.5 Presenting features of type 1 diabetes
Symptoms related to the failure of anabolism
Diabetic ketoacidosis
Diagnosis
Management of type 1 diabetes
Box 12.6 Definition of pathognomonic
Insulin
Types of insulin. Mealtime (prandial) insulin
Box 12.7 Disadvantages of subcutaneous insulin administration compared with endogenous insulin production from the pancreas
Basal insulin
Insulin regimens
Injection sites and technology
Case history 12.2
Lipohypertrophy and lipoatrophy
Box 12.8 Six steps to safer insulin prescribing
Monitoring diabetes control
Box 12.9 Methods of monitoring glycaemic control
Capillary blood glucose monitoring
Case history 12.3
Continuous glucose monitoring
Integrated measures of glycaemic control
Diabetes self‐management education
Box 12.10 Features of a structured diabetes self‐education programme
Diet
Exercise
Box 12.11 Dietary advice for people with type 1 diabetes
Acute metabolic emergencies. Hypoglycaemia
Physiological response to hypoglycaemia
Box 12.12 Consequences of hypoglycaemia
Case history 12.4
Box 12.13 Causes of hypoglycaemia
Symptoms and signs
Treatment
Diabetic ketoacidosis
Case history 12.5
Case history 12.6
Biochemistry
Hyperglycaemia – the ‘diabetic’ part of diabetic ketoacidosis
Hyperketonaemia – the ‘keto’ part of diabetic ketoacidosis
Acidosis – the ‘acidosis’ part of diabetic ketoacidosis
Diagnosis
Box 12.14 Clinical features of diabetic ketoacidosis
Box 12.15 Diagnosis of diabetic ketoacidosis
Management
Fluid and electrolyte administration
Box 12.16 Typical fluid and electrolytes losses in diabetic ketoacidosis
Box 12.17 Crystalloids and colloids
Insulin replacement
Sodium bicarbonate and phosphate
Transfer to subcutaneous insulin
Complications
Box 12.18 Complications of diabetic ketoacidosis
Key points
Answers to case histories. Case history 12.1
Case history 12.2
Case history 12.3
Case history 12.4
Case history 12.5
Case history 12.6
Note
CHAPTER 13 Type 2 diabetes. Key topics
Learning objectives
To recap
Cross‐reference
Epidemiology
Risk factors for type 2 diabetes
Genetic predisposition
Ageing
Intrauterine environment
Obesity
Physical inactivity
Box 13.1 Epigenetics
Diet
Depression
Emerging risk factors
Pathophysiology
Box 13.2 What are insulin sensitivity, insulin responsiveness and insulin resistance?
Insulin resistance
Box 13.3 Consequences of insulin resistance
Box 13.4 Potential mechanisms of insulin resistance (review Figure 3.6)
Box 13.5 Mitochondria and diabetes
β‐Cell dysfunction
Hyperglucagonaemia
Abnormal incretin hormone secretion
Increased glucose reabsorption by the kidney
Brain – neurotransmitters and neural control of metabolism
The microbiome
Prognosis
Clinical features
Hyperosmolar hyperglycaemic state
Prevention of diabetes
Box 13.6 Precipitating causes of hyperosmolar hyperglycaemic state
Case history 13.1
Box 13.7 Measures to reduce the incidence of type 2 diabetes
Box 13.8 Screening for diabetes and those at risk of diabetes. Who should have a risk assessment for diabetes?
How should a risk assessment for diabetes be performed?
Box 13.9 Strategies to support lifestyle change to prevent diabetes
Screening for diabetes
Management of type 2 diabetes
Glycaemic targets
Diet
Box 13.10 Factors to consider when discussing glycaemic targets
Case history 13.2
Physical activity
Oral glucose‐lowering agents
Biguanides – Metformin
Mode of action
Clinical use
Adverse effects
Sulfonylureas
Mode of action
Clinical use
Adverse effects
Meglitinides or post‐prandial insulin releasers
Mode of action
Clinical use
Adverse effects
Thiazolidinediones or ‘glitazones’
Mode of action
Box 13.11 What is the Randle cycle?
Clinical use
Side‐effects
DPP‐4 inhibitors or ‘gliptins’
Mode of action
Box 13.12 DPP‐4 inhibitors currently available in Europe and the USA
Clinical use
Adverse effects
Sodium–glucose co‐transporter 2 inhibitors
Case history 13.3
Box 13.13 SGLT‐2 inhibitors currently available in Europe and the USA
Mode of action
Clinical use
Case history 13.4
Adverse effects
Alpha‐glucosidase inhibitors
Mode of action
Clinical use
Adverse effects
Quick‐release bromocriptine
Mode of action
Clinical use
Adverse effects
Colesevelam
Mode of action
Clinical use
Adverse effects
Injectable glucose‐lowering agents. GLP‐1 receptor agonists
Mode of action
Clinical use
Adverse effects
Case history 13.5
Case history 13.6
Insulin
Amylin analogues
Mode of action
Clinical use
Adverse effects
Which drug and when?
Key points
Answers to case histories. Case history 13.1
Case history 13.2
Case history 13.3
Case history 13.4
Case history 13.5
Case history 13.6
CHAPTER 14 Complications of diabetes. Key topics
Learning objectives
To recap
Cross‐reference
Introduction
Microvascular complications
Pathology of microvascular complications
Pathogenesis of microvascular complications
Hyperglycaemia
Box 14.1 Why do microvascular complications occur?
Formation of advanced glycation end products (AGE)
Increased flux of glucose through the sorbitol – polyol pathway
Activation of the hexosamine pathway
Haemodynamic factors
The renin‐angiotensin system
Growth factors and cytokines
The growth hormone – insulin‐like growth factor axis
Innate immune system
Genetics
Clinical features of microvascular complications. Diabetes‐related eye disease
Box 14.2 Ways in which diabetes can affect the eye
Case history 14.1
Natural history of diabetic retinopathy. Early changes without vision loss
Transition to sight‐threatening retinopathy
Sight‐threatening retinopathy
Maculopathy
Screening for retinopathy
Box 14.3 Indications and urgency for referral to an ophthalmologist
Management of retinopathy. Medical management
Intra‐vitreal injectable therapy. VEGF inhibitors
Corticosteroids
Laser photocoagulation
Surgery
Onset of blindness
Diabetes‐related kidney disease
Box 14.4 Ways in which diabetes can affect the kidney
Classical diabetic nephropathy
Non‐classical diabetes‐related kidney disease
Screening and diagnosis of diabetic nephropathy
Box 14.5 Estimated glomerular filtration rate (eGFR)
Management of diabetic nephropathy
Case history 14.2
Neuropathy
Box 14.6 Classification of diabetic neuropathy
Hyperglycaemic neuropathy
Distal symmetrical neuropathy
Pressure palsies
Mononeuropathies and radiculopathies
Management of painful diabetic neuropathy
Autonomic neuropathy
The diabetic foot
Box 14.7 Symptoms and signs of autonomic neuropathy
Case history 14.3
Pathogenesis of diabetic foot ulcers
Box 14.8 Cause of diabetic foot ulcers
Screening for foot disease
Box 14.9 Sites to be tested with monofilament
Management of diabetic foot ulcers
Charcot arthropathy
Acute onset
Bony destruction
Stabilization
Genitourinary and sexual problems of diabetes. Male problems
Case history 14.4
Female problems
Atherosclerotic cardiovascular disease. Epidemiology
Pathogenesis
Box 14.10 Mechanisms leading to accelerated atherosclerosis in people with diabetes
Glycaemia
Other cardiovascular risk factors
Management of cardiovascular disease
Case history 14.5
Heart failure. Epidemiology
Case history 14.6
Clinical features
Management
Box 14.11 Symptoms and signs of heart failure
Cancer
Non‐alcoholic fatty liver disease
Gastro‐intestinal tract
Bone and Joint
Skin disorders
Acanthosis nigricans
Box 14.12 Ways in which diabetes can affect the skin
Necrobiosis lipoidica diabeticorum
Psychological and psychiatric sequelae of diabetes
Adjustment disorders
Diabetes distress
Fear of hypoglycaemia
Depression
Eating disorders
Case history 14.7
Box 14.13 Simple screening questions that can be used to identify people with depression
Cognitive dysfunction
Diabetes and pregnancy
Effect of diabetes on pregnancy
Effect of pregnancy on diabetes
Management of the diabetic pregnancy. Pre‐existing diabetes
Pre‐conception care
Antenatal care
Birth
Postnatal care
Gestational diabetes
Box 14.14 Major risk factors for gestational diabetes
Social sequelae of diabetes
Driving
Employment
Box 14.15 Advice to reduce the risk of a road traffic accident
Organization of diabetes care
Box 14.16 Issues to consider during the diabetes consultation
Key points
Answers to case histories. Case history 14.1
Case history 14.2
Case history 14.3
Case history 14.4
Case history 14.5
Case history 14.6
Case history 14.7
CHAPTER 15 Obesity. Key topics
Learning objectives
To recap
Cross reference
Introduction
What is obesity?
Box 15.1 How to calculate body mass index?
Box 15.2 The World Health Organization definitions of underweight, overweight and obesity in adults
Box 15.3 Percentage body fat in men and women
The health and social consequences of overweight and obesity
Regulation of body weight
Hypothalamic control of body weight
Signals from the gastrointestinal tract
Long‐term control of fat mass — the role of leptin
Hedonistic control of eating behaviour
The causes of obesity
Genetic factors
Environmental changes
Dietary intake
Total energy intake
Changes in eating behaviour
Dietary macronutrients
Case history 15.1
Energy expenditure
Box 15.4 Examples of technological advances that have reduced physical activity
Box 15.5 UK Government recommendations for physical activity
Case history 15.2
Medical causes of obesity
Prevention of obesity
Management of the individual with obesity
Clinical assessment of obesity
History
Examination
Investigations
Lifestyle interventions
Dietary strategies
Box 15.6 Eating and activity objectives in weight management programmes
Physical activity
Behavioural change techniques
Drugs
Orlistat. Mode of action
Clinical use
Adverse effects
Liraglutide. Mode of action
Clinical use
Adverse effects
Naltrexone/bupropion. Mode of action
Clinical use
Adverse effects
Phentermine/topiramate
Other drugs
Bariatric surgery
Organization of obesity services
Case history 15.3
Conclusions
Key points
Answers to case histories. Case history 15.1
Case history 15.2
Case history 15.3
Index
WILEY END USER LICENSE AGREEMENT
