Insulin (pancreas/type II diabetes) - Essay Example

of the of the Concerned Health Sciences and Medicine 2 May Insulin pancreas type II diabetes Introduction Globally, 346 million people suffer from diabetes and World Health Organisation (WHO) estimates that mortality rates due to diabetes will double between 2005 and 2030 (WHO 2011). In England, the prevalence of diabetes in 2009/10 was determined to be 4.3 per cent (NHS 2011). Diabetes mellitus (DM) type 2 is a lifestyle linked metabolic disorder, with multiple aetiologies, in which the main abnormality is chronic hyperglycaemia. Hyperglycaemia can result from defective secretion of insulin, insulin action or both (WHO 2006; ADA 2012). Chronically elevated blood glucose levels lead to various metabolic disturbances, organ damage and clinico-pathological manifestations related to nerves, heart, blood vessels, kidneys and eyes. Also, uncontrolled diabetes mellitus type 2 can present with acute hyperglycaemic emergencies such as diabetic ketoacidosis and hyperglycaemic hyperosmolar nonketotic state both of which can be life threatening (Longmore et al 2010). Insulin and pancreas The pancreas is an organ located in the epigastric and left hypochondrium regions of the abdomen. It has both endocrine and exogenous functions (Snell 2008). Exocrine function of the gland is to produce secretions rich in hydrolyzing enzymes which aid in the digestion of food. One of its most important endocrine functions is the production of insulin and glucagon from richly perfused clusters of cells called islets of Langerhans scattered across pancreatic tissue (Snell 2008). Twenty per cent of these cells are ? cells which produce glucagon and more than 50% cells are ? cells which secrete insulin (Barrett et al 2010). Insulin is one of the numerous endocrine hormones produced in the body. It is a polypeptide molecule composed of two amino acid chains which are linked by disulfide bridges (Barrett et al 2010, p. 316). It is secreted as a preprohormone, which yields a proinsulin, which is then further cleaved to release insulin and c- peptide, an inactive moiety (Barrett et al 2010, p. 316). Insulin exerts its actions by binding to insulin receptors and has a short half life of 5 minutes in the circulation (Barrett et al 2010). It is the principal anabolic hormone of the body and is involved in storage of carbohydrates, proteins and fats. Some of its actions are rapid such as decreasing plasma glucose levels, whereas, others are delayed like prompting protein synthesis and lipogenesis which take place over a period of minutes to hours (Barrett et al 2010, p. 318). In the fed state, rise in glucose levels causes insulin levels to rise. Insulin, in turn, leads to utilisation or storage of glucose and storage of amino acids and fatty acids into proteins and fats, respectively (Harvey & Ferrier 2011). Glucose homeostasis Blood glucose level is primarily regulated by the hormone insulin whose main action is to decrease it to < 5.5 mmol/l. This action is carried out by increasing the entry of glucose in the peripheral tissues. In muscles and adipose tissues, this is achieved by increasing the number of glucose transporters (GLUT 4) across the cell membrane and thereby, increasing facilitated diffusion of glucose into the cells. In liver cells, increased entry of glucose is achieved by maintaining low levels of free intracellular glucose by induction of enzyme glucokinase via insulin insensitive GLUT 2 receptors (Harvey & Ferrier 2011, p. 323). Glucagon is a linear polypeptide with primarily glycogenolytic and gluconeogenic actions. Glucagon is the principal catabolic hormone, with actions reciprocal to those of insulin on intermediary metabolic activities. It has proteolytic, lipolytic and ketogenic activity (Barrett et al 2010, p. 328). Physiologically, plasma glucose levels are tightly regulated by alternate actions of theses hormones. Increased glucose entry in ? cells of pancreas stimulates insulin production and in turn, lowers plasma glucose. On the other hand, when glucose levels drop, for example in starvation, glucagon levels are increased favouring energy mobilization (Harvey & Ferrier 2011, pp. 322-326). Pathophysiology of type 2 diabetes The fundamental abnormality in diabetes mellitus is a decrease in the effects of insulin at a cellular level. In type 2 diabetes, insulin levels may be normal or decreased. However, it is dysregulated and its action on the peripheral tissues such as skeletal muscle and liver is reduced and this phenomenon is termed as insulin resistance (Barrett et al 2010). Insulin resistance is predominantly seen in individuals with obesity, increased abdominal fat and waist to hip ratio and, as a part of the metabolic syndrome (Grundy et al 2004). Owing to decreased insulin action, there is decreased entry of glucose in the peripheral tissues and they cannot take up glucose for utilization. Moreover, unopposed action of glucagon leads to an increased output of glucose from the liver. These are the two key mechanisms which result in hyperglycaemia (Harvey & Ferrier 2011). Consecutively, chronic hyperglycaemia leads to urinary excretion of excess glucose as the renal capacity for reabsorption of glucose is overwhelmed. This causes osmotic diuresis and electrolyte disturbances which is the explanation for clinical symptoms of polydipsia and polyuria (Harvey & Ferrier 2011, p. 347). Additionally, lack of insulin produces an intracellular deficiency of glucose owing to decreased uptake. Proteins and fats are instead utilized for energy production, setting off a cycle of metabolic abnormalities such as protein depletion, increased free fatty acids, cholesterol and lipaemia, and ketoacidosis (Barrett et al 2010). A state of carbohydrate intolerance which presents in pregnancy for the first time is known as gestational diabetes mellitus (GDM). This disorder is characterized by increased insulin resistance which is caused by placental hormones, as is evident by rapid resolution of diabetes with termination of pregnancy (Perkins et al 2007; Di Cianni et al 2003). In a normal pregnancy, this increased resistance is countered by ? cell hypertrophy and an increased secretion of insulin. However, in GDM, this compensatory response fails to occur (Perkins et al 2007; Di Cianni et al 2003). Diagnosis of type 2 diabetes Fundamentally, diabetes can be classified into two broad categories. Diabetes which arises from an absolute deficiency of insulin in the body is called type 1 diabetes. Diabetes in which there is relative lack of insulin in the body combined with an inherent resistance to the actions of insulin is classified as type 2 diabetes. Earlier classifications based on insulin requirement (insulin dependent diabetes mellitus and non-insulin dependent diabetes mellitus) as well as age of onset of disease are no longer used. Diagnostic criteria for diabetes were proposed by WHO in 2006 and are still widely followed. According to these, diabetes is diagnosed when fasting plasma glucose levels are more than or equal to 7.0mmol/l (126mg/dl), and plasma glucose level 2 hrs post prandial are more than or equal to 11.1mmol/l (200mg/dl). Desirable fasting plasma glucose is less than 6.1 mmol/l (110mg/dl) and 2-hr plasma glucose is less than 7.8mmol/l (140mg/dl). Fasting plasma glucose level between 6.1 to 6.9mmol/l (110mg/dl and 125mg/dl) is called Impaired Fasting Glucose (IFG). 2-hr plasma glucose between 7.8 and 11.1mmol/l (140mg/dl and 200mg/dl) in the presence of normal fasting plasma glucose ( 25% risk of developing type 2 DM over the next 5 years (ADA 2012). Latest recommendations from WHO also provide HbA1c as a diagnostic test for diabetes with a value of 6.5% as the cut point, with strict standards and criteria defined for its measurement (WHO 2011). American Diabetes Association (ADA) has also updated the criteria for diagnosis of diabetes. These include a HbA1c level more than 6.5% OR fasting plasma glucose ? 126 mg/dl (7.0 mmol/l) OR 2-h plasma glucose ? 200 mg/dl (11.1mmol/l) after 75 g glucose load OR random plasma glucose ? 200 mg/dl (11.1mmol/l) in the presence of symptoms of hyperglycaemia (ADA 2012). In GDM, either fasting plasma glucose is ? 92mg/dl (5.1mmol/l) or glucose values at 24-28 weeks of gestation after 75 gram glucose load are abnormal. They are ? 180mg/dl after 1 hour and ? 153mg/dl after 2 hours (ADA 2012). Treatment Treatment of type 2 diabetes focuses on decreasing insulin resistance and exogenous supplementation of insulin to make up for the deficiency. Non-pharmacological approach to reduce insulin resistance entails restricted calorie intake, weight reduction, physical activity and exercise (NICE 2008). All of these have been reported to increase the sensitivity of cells to actions of insulin and even decrease the requirement of exogenous insulin. Pharmacologically, insulin resistance can be targeted by two classes of oral hypoglycaemic agents. Biguanides and thiazolidinediones (insulin sensitizers) have been shown to reduce insulin resistance and decrease hepatic glucose output, and thereby, give rise to improved glucose metabolism and lower blood glucose levels (Grundy et al 2004; Saltiel & Olefsky 1996). Other oral glucose lowering medications include insulin secretagogues and ?-glucosidase inhibitors. Endogenous insulin secretion is enhanced by insulin secretagogues such as sulfonylureas and meglitinides. Post-prandial glucose levels are lowered by ?- glucosidase inhibitors which delay the digestion of carbohydrates in the gut (Finkel et al 2009) To begin with, insulin resistance can be countered with oral hypoglycaemic agents but, in long standing untreated diabetes mellitus type 2, exogenous insulin is eventually required to surmount this problem of insulin resistance and relative deficiency. Various preparations of recombinant insulin and its modifications are available with varying onset and duration of action. They are prescribed and tailored on an individual basis (Longmore et al 2010). Conclusion Physiologically, plasma glucose levels are precisely regulated by complex interaction of two principal endocrine hormones, insulin and glucagon, both of which are secreted by islets of Langerhans located in the pancreas. In type 2 diabetes, relative deficiency of insulin in the body tilts the balance in favour of the catabolic hormone glucagon which instigates hyperglycaemia, proteolysis, lipolysis and ketogenesis. It is a metabolic disorder of multiple aetiologies, characterized by chronic hyperglycaemia with abnormalities in carbohydrate, protein and fat metabolism. Epidemiologically, diabetes mellitus type 2 is a disease with significant socioeconomic repercussions. Diabetes is diagnosed according to the criteria for plasma glucose levels as defined by WHO and ADA. Treatment of this disease aims at decreasing insulin resistance, enhancing insulin secretion and exogenous insulin supplementation. References American Diabetes Association 2012, ‘Diagnosis and Classification of Diabetes Mellitus’, Diabetes Care, vol. 35, pp. 64-71 Barrett, KE, Barman, SM, Boitano, S & Brooks, HL 2010, Ganong’s Review of Medical Physiology, 23rd edn, Mc Graw Hill Lange, New York, pp. 315-330 Di Cianni, G, Miccoli, R, Volpe, L, Lencioni, C, Del Prato, S 2003, ‘Intermediate metabolism in normal pregnancy and in gestational diabetes’, Diabetes/Metabolism Research and Reviews, vol. 19, pp. 259–270. Finkel R, Clark, MA, Champe, PC & Cubeddu,LX 2009, Lippincott's Illustrated Reviews: Pharmacology, 4th edn, Lippincott Williams & Wilkins, Philadelphia, pp. 285-97 Grundy, SM, Brewer, BH Jr, Cleeman, JI, Smith, SC Jr & Lenfant, C 2004,‘Definition of Metabolic Syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition’, Circulation, vol. 109, no. 3, pp. 433-38, viewed 2 May 2012, Harvey, RA & Ferrier, RD 2011, Lippincott's Illustrated Reviews: Biochemistry, Lippincott Williams & Wilkins, Philadelphia, pp. 337-47. Longmore, M, Wilkinson, IB, Davidson, EH, Foulkes, A & Mafi, AR 2010, Oxford Handbook of Clinical Medicine, 8TH edn, Oxford University Press, New York, pp. 198-201 National Institute for Health and Clinical Excellence 2008, Type 2 diabetes The management of type 2 diabetes, National Institute For Health And Clinical Excellence, London, viewed 2 May 2012, NHS Information Centre, Prescribing and Primary Care Services 2011, Prescribing for Diabetes in England: 2005/6 to 2010/11, viewed 2 May2012, Perkins, JM, Dunn, JP & Jagasia, SM 2007, ‘Perspectives in Gestational Diabetes Mellitus: A Review of Screening, Diagnosis, and Treatment’, Clinical Diabetes, vol. 25, no. 2, pp. 57-62 Saltiel, AR & Olefsky, JM 1996, ‘Thiazolidinediones in the treatment of insulin resistance and type II diabetes’, Diabetes, vol. 45, no. 12, pp. 1661-69 Snell, RS 2008, Clinical Anatomy by Regions, 8th edn, Lippincott Williams & Wilkins, Philadelphia, pp. 256-7. 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