Cover -- Title page -- Copyright page -- Contents -- List of Contributors -- Preface -- 1: Normal Glucose Metabolism and Responses to Hypoglycaemia -- Normal Glucose Homeostasis -- Fasting (Figure 1.1a) -- Fed state (Figure 1.1b) -- Effects of Glucose Deprivation on Central Nervous System Metabolism -- Counterregulation During Hypoglycaemia -- Hormonal Changes During Hypoglycaemia -- Activation of the autonomic nervous system -- Neuroendocrine activation (Box 1.3) -- Physiological Responses -- Haemodynamic changes (Box 1.4) -- Changes in regional blood flow (Box 1.5 and Figure 1.6) -- Functional changes (Box 1.6) -- Conclusions -- Acknowledgement -- References -- 2: Symptoms of Hypoglycaemia and Effects on Mental Performance and Emotions -- Introduction -- Symptoms of Hypoglycaemia -- Identifying the symptoms -- The validity of symptom beliefs -- Classifying symptoms of hypoglycaemia -- Symptoms in children and older people -- From symptom perception to action -- Symptom generation -- Symptom detection -- Low blood glucose detection - symptom interpretation -- Symptom scoring systems -- Acute Hypoglycaemia and Cognitive Functioning -- Influences on the degree of, and threshold for, cognitive dysfunction -- Are the cognitive changes during acute hypoglycaemia important and valid? -- Acute Hypoglycaemia and Emotions -- Conclusions -- References -- 3: Counterregulatory Deficiencies in Diabetes -- Introduction -- Normal Glucose Counterregulation -- Age and Glucose Counterregulation -- Defective Hormonal Glucose Counterregulation -- Insulin -- Glucagon -- Catecholamines -- Cortisol and growth hormone -- Mechanisms of Counterregulatory Failure -- Systemic mediator -- Brain fuel transport -- Brain metabolism -- Hypoglycaemia tolerance -- Conclusions -- References -- 4: Frequency, Causes and Risk Factors for Hypoglycaemia in Type 1 Diabetes.

Introduction -- Definitions of Hypoglycaemia -- Biochemical definitions of hypoglycaemia -- Clinical definitions of hypoglycaemia -- Frequency of Hypoglycaemia -- Frequency of mild, symptomatic hypoglycaemia -- Causes of Hypoglycaemia -- Patient error -- Alcohol -- Exercise -- Risk Factors for Severe Hypoglycaemia -- Intensive insulin therapy -- Strict glycaemic control -- Genetic predisposition to hypoglycaemia -- Absent endogenous insulin secretion -- Dose and type of insulin -- Sleep -- Microvascular complications -- Social and psychological factors -- Endocrinopathies -- Other risk factors -- Causes and risk factors for hypoglycaemia: summary and conclusions -- Conclusions -- References -- 5: Nocturnal Hypoglycaemia -- Introduction -- Epidemiology - How Common is Nocturnal Hypoglycaemia? -- Causes of Nocturnal Hypoglycaemia -- The limitations of therapeutic insulin delivery -- Impaired counterregulatory responses to hypoglycaemia during nocturnal hypoglycaemia -- Supine posture -- Sleep -- Consequences of Nocturnal Hypoglycaemia -- Impaired awareness of hypoglycaemia -- The 'dead in bed' syndrome -- Neurological consequences of nocturnal hypoglycaemia on cerebral function -- Can Nocturnal Hypoglycaemia be Predicted? -- The Somogyi Phenomenon: The Myth of Rebound Hyperglycaemia -- Clinical Solutions (Box 5.3) -- Dietary measures -- Pharmaceutical interventions -- Timing and type of insulin, including insulin analogues -- Continuous Subcutaneous Insulin Infusion (CSII), Real-time Continuous Glucose Monitoring Systems (RT-CGMS) and closed loop insulin delivery -- Conclusions -- References -- 6: Impaired Awareness of Hypoglycaemia -- Introduction -- Normal Responses to Hypoglycaemia -- 'Awareness' of hypoglycaemia -- Impaired Awareness of Hypoglycaemia (IAH) -- Definition -- Classification and natural history -- Clinical identification.

Prevalence of Impaired Awareness of Hypoglycaemia -- Frequency of associated severe hypoglycaemia -- Pathogenesis of Impaired Awareness of Hypoglycaemia -- Altered glycaemic threshold for initiation of symptoms -- Peripheral autonomic neuropathy -- Hypoglycaemia-associated autonomic failure -- Central nervous system adaptation to hypoglycaemia -- Antecedent (episodic) hypoglycaemia -- Neuroimaging studies -- Impaired Awareness of Hypoglycaemia and Long-Term Effect on Cognitive Function -- Human Insulin -- Treatment Strategies -- Conclusions -- References -- 7: Risks of Intensive Therapy -- Introduction -- The Need for Intensive Therapy -- Risks of Intensive Insulin Therapy -- Hypoglycaemia in Intensive Insulin Therapy -- Definition of Hypoglycaemia -- Contributors to Increased Risk of Severe Hypoglycaemia in Patients Undertaking Intensified Insulin Therapy -- The effects of intensified insulin therapy on risk of severe hypoglycaemia -- Other Risks of Intensified Insulin Therapy -- Weight gain -- Diabetic ketoacidosis and hyperinsulinaemia -- Patients Unsuitable for Strict Control -- Risks of intensive glycaemic therapy in people with type 2 diabetes -- Other risks of intensive therapy in type 2 diabetes -- Deciding when to use intensive therapy in diabetes -- Conclusions -- References -- 8: Management of Acute and Recurrent Hypoglycaemia -- Introduction -- Moderators of Hypoglycaemia Risk -- Alcohol and hypoglycaemia -- Monitoring for Hypoglycaemia -- Capillary blood glucose monitoring -- Continuous Glucose Monitoring (CGM) -- Management of Hypoglycaemia -- Acute hypoglycaemia -- Recurrent hypoglycaemia -- Structured education -- Insulin regimens -- CGM -- The artificial pancreas -- Pancreas transplantation -- Future Potential Therapeutic Approaches -- Amino acids -- Beta agonists -- Selective Serotonin Reuptake Inhibitors (SSRI) -- Theophylline.

Fructose -- Uncooked corn-starch -- Caffeine -- Conclusions -- References -- 9: Technology for Hypoglycaemia: CSII and CGM -- Introduction -- Insulin Pump Therapy -- Monitoring -- Continuous glucose monitoring -- Severe hypoglycaemia -- Cost and Reimbursement -- Insulin pump therapy -- Continuous glucose monitoring -- Future Expectations -- Conclusions -- References -- 10: Hypoglycaemia in Children with Diabetes -- Introduction -- Definition of Hypoglycaemia in Childhood -- Definition of hypoglycaemia in childhood diabetes -- Prevalence of Hypoglycaemia -- Nocturnal hypoglycaemia -- SIGNS AND SYMPTOMS OF HYPOGLYCAEMIA -- Daytime hypoglycaemia -- Nocturnal hypoglycaemia -- Impaired awareness of hypoglycaemia -- Risk Factors for Hypoglycaemia -- Glycaemic control -- Nocturnal insulin requirements -- Intensive insulin regimens -- Diet -- Physical activity -- Age -- Counterregulation in Childhood -- Effect of sleep stage on counterregulation -- Consequences of Hypoglycaemia -- Cognitive impairment -- Acute effects -- Long-term effects -- Hypoglycaemic hemiplegia -- Fear of hypoglycaemia -- Management of Hypoglycaemia -- Prevention -- Education -- Insulin regimen -- Continuous glucose monitoring systems -- Diet -- Exercise -- Conclusions -- References -- 11: Hypoglycaemia During Pregnancy in Women with Pregestational Diabetes -- Introduction -- Frequency of Hypoglycaemia During Pregnancy -- Hormonal Counterregulation -- Beta Cell Function -- Risk Factors for Severe Hypoglycaemia During Pregnancy -- Maternal Consequences of Severe Hypoglycaemia -- Hypoglycaemia and Pregnancy Outcome -- Hypoglycaemia During Breastfeeding -- Prevention and Clinical Management -- Treatment -- References -- 12: Hypoglycaemia in Type 2 Diabetes and in Elderly People -- Introduction -- Pathophysiology of Hypoglycaemia -- The effects of ageing on the responses to hypoglycaemia.

The effects of type 2 diabetes on the responses to hypoglycaemia -- Moderators of hypoglycaemia in type 2 diabetes -- Frequency of Hypoglycaemia in Type 2 Diabetes -- Hypoglycaemia and oral antidiabetes agents -- Studies comparing hypoglycaemia secondary to insulin or oral antidiabetes agents -- Hypoglycaemia and insulin -- Hypoglycaemia and incretin mimetics -- Morbidity of Hypoglycaemia and Need for Emergency Treatment -- Conclusions -- References -- 13: Mortality, Cardiovascular Morbidity and Possible Effects of Hypoglycaemia on Diabetic Complications -- Introduction -- Deaths Directly Attributed to Hypoglycaemia -- Crude estimates of mortality secondary to hypoglycaemia -- Risk factors for death from hypoglycaemia -- Hypoglycaemia and Sudden Death in Type 1 Diabetes -- Dead-in-Bed Syndrome -- Risk Factors for Dead-in-Bed Syndrome -- Hypoglycaemia -- Autonomic neuropathy -- Mechanisms of Sudden Death -- Cardiac arrhythmia -- What do we say to patients? -- Hypoglycaemia as a Risk Factor for Increased All Cause and Cardiovascular Mortality -- Potential Mechanisms by Which Hypoglycaemia Can Increase Vascular Risk -- Hypoglycaemia and Microvascular Complications -- Hypoglycaemia and Macrovascular Complications -- Inflammation and atherogenesis -- Thrombosis -- Ischaemia -- Autonomic function -- Cardiac arrhythmias -- Conclusions -- References -- 14: Long-Term Effects of Hypoglycaemia on Cognitive Function in Diabetes -- Introduction -- Adults with Type 1 Diabetes -- Profound hypoglycaemia and brain dysfunction -- Recurrent episodes of moderate to severe hypoglycaemia -- Children and Adolescents with Type 1 Diabetes -- Profound hypoglycaemia and brain dysfunction -- Recurrent episodes of moderate to severe hypoglycaemia -- Animal Models of Recurrent Hypoglycaemia -- Recurrent Hypoglycaemia in Older Adults with Type 2 Diabetes -- Conclusions.

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