Human Insulin

For 60 years after its discovery, insulin for therapeutic use was obtained from the pancreata of cattle and pigs. With the development of recombinant DNA technology it was possible to 'genetically engineer' molecules and insulin was the first protein to be made in this way, becoming available for the treatment of humans in the 1980s. Several of the existing animal insulin formulations were withdrawn, principally for commercial reasons, and human insulin rapidly became the most commonly...

References

Abraira C, Colwell JA, Nuttall FQ, Sawin CT, Nagel NJ, Comstock JP et al., the VA CSDM Group (1995). Veterans Affairs Cooperative Study on glycemic control and complications in Type II Diabetes (VA CSDM). Diabetes Care 18 1113-23. Ahren B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A (2004). Inhibition of dipetidyl-peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. Journal of Clinical Endocrinology and Metabolism 89 2078-84....

Structural Changes of the Brain in Diabetes

Hypertension and hyperlipidaemia are common in diabetes and cerebrovascular disease is a recognised macrovascular complication. Atheromatous cerebral artery occlusion involving major vessels, embolism from cervical arteries, and lacunar strokes are more extensive and occur at an earlier age in diabetic patients compared with the non-diabetic population (McCall, 1992 Mankovsky and Ziegler, 2004). It is uncertain whether microvascular disease affects the brain. Following the death of a group of...

Glycaemic Control

Insulin requirements vary with age and are approximately 0.5-1 U kg day before puberty and 1.5-2 U kg day during adolescence, reflecting the insulin resistance that is present during this period of rapid growth and development Dunger, 1992 . Despite numerous developments in terms of novel insulin preparations and modes of delivery, people with type 1 diabetes still experience varying states of insulin deficiency or excess that are difficult to control and predict. This is probably most evident...

Frequency of Mild Symptomatic Hypoglycaemia

The features of several studies that have examined the frequency of mild hypoglycaemia, either prospectively or retrospectively, in adults with type 1 diabetes are shown in Table 3.1. Rates of mild hypoglycaemia vary substantially, ranging from 8 to 160 episodes per patient per year. However, it is extremely difficult to make direct comparisons between individual studies because of differences in methodology and patient characteristics. Two retrospective studies by a Danish group...

Normal Glucose Counterregulation

Normal Glucose Counterregulation

Under normal circumstances, the brain uses glucose as its predominant fuel and is almost completely dependent upon a continuous supply of glucose from the peripheral circulation to maintain normal function. Consequently, to protect the delivery of glucose to the brain, a hierarchy of counterregulatory responses Figure 6.4 are activated as peripheral blood glucose falls below normal Mitrakou et al., 1991 . The main components of this system of normal i.e. non-diabetic glucose counterregulation,...

Definition Of Hypoglycaemia In Childhood

The definition of hypoglycaemia in childhood has been extremely controversial. It has been suggested that children can tolerate lower levels of blood glucose, especially as the developing brain can use alternative substrates for cerebral metabolism. This has been supported by the clinical finding that some children with diabetes appear to be 'normal' when their blood glucose concentrations are low as demonstrated by home blood glucose monitoring. However, difficulties arise as young children...

Recreation

Strenuous and protracted exercise is not confined to sport and may occur during recreational activities, such as prolonged and vigorous dancing. These social events may also involve the consumption of alcohol, another potential cause of promoting and protracting hypoglycaemia. Some 'recreational' drugs such as amphetamines have been associated with promoting frenetic behaviour and increased metabolic rate, which may then induce hypoglycaemia in people treated with insulin Jenks and Watkinson,...

The Somogyi Phenomenon The Concept Of Rebound Hyperglycaemia

Counterregulatory Hormones Diabetes

In the late 1930s, a Hungarian biochemist, Michael Somogyi, working in St Louis, USA, suggested that nocturnal hypoglycaemia might provoke rebound hyperglycaemia on the following morning, and he supported his hypothesis with a demonstration that reducing evening doses of insulin led to a reduction in fasting urinary glycosuria Somogyi, 1959 . He proposed that nocturnal hypoglycaemia provokes a counterregulatory response with rises in plasma epinephrine, cortisol and growth hormone resulting in...

Glucagon

As in adults the glucagon response during hypoglycaemia is lost in children with diabetes Amiel et al., 1987 Jones et al., 1991 Ross et al., 2005 . This is also the case in toddlers, aged 18-57 months old, who have a very short duration of diabetes Brambilla et al., 1987 . This means that individuals with diabetes are more reliant on adequate epinephrine responses to correct hypoglycaemia. The majority of studies suggest that children have exaggerated epinephrine responses to hypoglycaemia,...

Risks Of Death From Hypoglycaemia

The risk factors that are commonly cited as increasing the risk of death from hypoglycaemia are often anecdotal, and may owe more to the prejudices of individual clinicians than to scientific evidence. Those suggested are detailed in Box 12.1 and include alcohol abuse and or inebriation Arky et al., 1968 Kalimo and Olsson, 1980 Critchley et al., 1984 MacCuish, 1993 , psychiatric illness or personality disorder Shenfield et al., 1980 Tunbridge, 1981 , self-neglect Tunbridge, 1981 , resistance to...

Pathogenesis Of Impaired Awareness Of Hypoglycaemia

The mechanisms underlying impaired awareness of hypoglycaemia are not known and may be multifactorial. Possible mechanisms are listed in Box 7.2. Box 7.2 Impaired awareness of hypoglycaemia possible mechanisms CNS adaptation Chronic exposure to low blood glucose glucose clamp 2.9mmol l for 56 hours in non-diabetic subjects insulinoma in non-diabetic patients strict glycaemic control in diabetic patients Recurrent transient exposure to low blood glucose antecedent hypoglycaemia CNS...

Normal Glucose Homeostasis

Liver Homeostasis

Humans evolved as hunter-gatherers and, unlike people today, did not consume regular meals. Mechanisms therefore evolved for the body to store food when it was in abundance, and to use these stores to provide an adequate supply of energy, in particular in the form of glucose when food was scarce. Cahill 1971 originally described the 'rules of the metabolic game' which humans had to follow to ensure their survival. These rules were modified by Tattersall personal communication and are as follows...

Biochemical Definitions of Hypoglycaemia

At first glance, it would seem sensible to employ a biochemical definition of hypogly-caemia, specifying a given blood glucose concentration, below which hypoglycaemia would be deemed to occur. However, it is not possible to provide such a precise biochemical criterion for the diagnosis of hypoglycaemia Service, 1995 . As blood glucose concentrations Hypoglycaemia in Clinical Diabetes, 2nd Edition. Edited by B.M. Frier and M. Fisher 2007 John Wiley amp Sons, Ltd decline, a hierarchy of events...

From Symptom Perception to Action

People with diabetes are better at estimating their blood glucose in natural, everyday situations, as opposed to clinical laboratory settings Cox et al., 1985 . In some ways this is surprising as natural hypoglycaemia often occurs at a time when it is unexpected. In this situation, attention toward symptoms will not be as actively directed toward detection as in the laboratory setting where it is usually anticipated. Furthermore, hypoglycaemia in everyday life occurs on the background of other...

Metabolic Changes During Pregnancy

Fundamental changes occur in maternal metabolism and physiology during pregnancy. Over 280 days the mother's weight increases on average by 12.5 kg. The main increase in weight occurs in the second half of pregnancy and is caused by the growth of the conceptus, the enlargement of maternal organs, maternal storage of fat and protein and an increase in maternal blood volume and interstitial fluid. An increase in the basal metabolic rate results in the need for increased energy intake. In addition...

Contributors

Lawrence Professor of Diabetes, Department of Medicine, King's College Hospital, Bessemer Road, London, SE5 9PJ e-mail stephanie.amiel kcl.ac.uk Professor Ian J. Deary, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ e-mail ian.deary ed.ac.uk Dr Miles Fisher, Consultant Physician, Glasgow Royal Infirmary, Glasgow, G4 0SF e-mail Professor Brian M. Frier, Consultant Physician, Department of Diabetes, Royal Infirmary, 51...

Effect of Hypoglycaemia on Cerebral Blood Flow and Structure

Diagram Hypoglycaemia

Hypoglycaemia promotes a redistribution of regional cerebral blood flow Tallroth et al., 1992 MacLeod et al., 1994 Kennan et al., 2005 which may encourage localised neuronal ischaemia, particularly if the cerebral macro- or microcirculation is already compromised in subjects with type 1 diabetes. Using techniques such as Single Photon Emission Tomography, the blood flow to the frontal lobes has been shown to be increased during acute hypoglycaemia in non-diabetic subjects Tallroth et al., 1992...

Effects Of Glucose Deprivation On Central Nervous System Metabolism

The brain constitutes only 2 of body weight, but consumes 20 of the body's oxygen and receives 15 of its cardiac output Sokaloff, 1989 . It is almost totally dependent on carbohydrate as a fuel and since it cannot store or synthesise glucose, depends on a continuous supply from circulating blood. The brain contains the enzymes needed to metabolise fuels other than glucose such as lactate, ketones and amino acids, but under physiological conditions their use is limited by insufficient quantities...

Diabetes Mcq Hyperglycemia

Amiel SA, Simonson DC, Sherwin RS, Lauriano AA, Tamborlane WV 1987 . Exaggerated epinephrine responses to hypoglycemia in normal and insulin-dependent diabetic children. Journal of Pediatrics 110 832-7. Amiel S 1991 . Glucose counter-regulation in health and disease current concepts in hypoglycaemia recognition and response. Quarterly Journal of Medicine 293 707-27. Banarer S, Cryer PE 2003 . Sleep-related hypoglycemia-associated autonomic failure in type 1 diabetes reduced awakening from sleep...

Problems of Establishing the Cause of Death at Postmortem

In attempting to establish a post-mortem diagnosis of hypoglycaemia, the pathologist needs to perform biochemical tests, examine the brain for evidence of hypoglycaemic brain damage, and exclude any other possible cause of death Tattersall and Gale, 1993 . Carbohydrate metabolism continues after death, and post-mortem changes in blood glucose can cause difficulties in confirming a hypoglycaemic death forensically. The continuing breakdown of glycogen glycogenolysis increases the blood glucose...

Introduction

Diabetes mellitus is one of the most common medical conditions affecting women during their reproductive years. A successful outcome of diabetic pregnancy can usually be anticipated with current management strategies, although an adverse outcome is still more common than in the non-diabetic population Casson et al., 1997 Penney et al., 2003a Evers et al., 2004 Jensen et al., 2004 Confidential Enquiry into Maternal and Child Health, 2005 . Meticulous control of blood glucose before conception...

Signs And Symptoms Of Hypoglycaemia Daytime Hypoglycaemia

The classical symptoms of hypoglycaemia, as described in adults Chapter 2 , are classified into three distinct groups autonomic, neuroglycopenic and non-specific Deary et al., 1993 . In adults the sympathoadrenal response during hypoglycaemia is primarily responsible for the classical autonomic symptoms which alert the individual to the falling glucose Table 9.2 Summary of studies examining prevalence of severe hypoglycaemia since the Diabetes Control and Complications trial in 1993 Bognetti et...

Classifying Symptoms of Hypoglycaemia

Until now the symptoms of hypoglycaemia have been treated as a homogeneous whole. Can these symptoms be divided into different groups Hypoglycaemia has effects on more than one part of the body, and the symptoms of hypoglycaemia reflect this. First, the direct effects of a low blood glucose concentration on the brain - especially the cerebral cortex - cause neuroglycopenic symptoms. Second, autonomic symptoms result from activation of parts of the autonomic nervous system. Finally, there may be...