Diabetes Mellitus Type 1 - Article Example

Diabetes Mellitus Type – 1 Introduction: Insulin is a hormone that is produced in the pancreas. Insulin is responsible for regulating the amount of glucose present in the blood. Ingestion, digestion and absorption of food lead to increased blood sugar levels, which acts as a trigger for the secretion of insulin. Insulin helps in transferring sugar from the blood into the cells, where it is converted into energy. When insulin is not produced in the pancreas or there is insufficient secretion of insulin, glucose or sugar levels in the blood get elevated. “Diabetes Mellitus is a metabolic disorder in which the body has a deficiency of and/or resistance to insulin”. (1). The Endocrine Pancreas: The pancreas consists of two functionally different organs, namely the exocrine pancreas and the endocrine pancreas. The exocrine pancreas is associated with the digestive system being a major digestive gland of the body. The endocrine pancreas remains the source for insulin, glucagon, somatostatin and pancreatic polypeptide in the human body. The endocrine pancreas is made up of 0.7 to one million small endocrine glands, called the islets of Langerhans, which are scattered within the glandular substance of the endocrine pancreas. Between 1-1.5% of the total mass of the pancreas is made up by the islets of Langerhans, which weighs about one to two grams in a normal human adult. In the islets of Langerhans four cell types have been identified and have been named as A, B, D and PP cell types. The distribution of these cell types is not uniform throughout the pancreas and each have a function of their own. The A cells produce glucagon, proglucagon, and glucagon-like peptides. The B cells produce Insulin, C peptide, proinsulin, amylin and aminobutyric acid (GABA). The D cells produce somastatin and the PP cells produce pancreatic polypeptide. Insulin is a protein. It is made up of fifty-one amino acids that are found in two peptide chains. The A chain has twenty-one amino acids and the B chain thirty amino acids. The two chains are linked by means of two disulfide bridges. The molecular weight of insulin is 5808. On a daily basis in a normal human adult the pancreas secrete forty to fifty units of insulin. Glucose is the most effective stimulant for insulin secretion by the pancreas. Ingestion of food results in the increase in peripheral insulin concentration within eight to ten minutes. Peak concentration of insulin in peripheral blood occurs between thirty to forty-five minutes of the ingestion of food. This results in a quick drop in the postprandial plasma glucose concentrations and return to baseline levels in about two hours of ingestion of food in a normal human. This occurrence results from the major function of insulin to encourage the storage of ingested nutrients. Secreted insulin reaches the liver via the blood stream, where it promotes anabolism and inhibits catabolism. The promotion of anabolism in the liver by insulin is through the promotion of glycogen synthesis and storage and the inhibition of glycogen breakdown. Insulation also enhances protein and triglyceride synthesis and the formation of VLDL by the liver. The inhibition of catabolism by insulin is through its action to reverse catabolic events of the post-absorptive stage in inhibiting hepatic glycogenolysis, ketogenosis and gluconeogenosis. In the muscles insulin promotes protein synthesis through the increased amino acid transport supported by the stimulation of ribosomal protein synthesis. Insulin also promotes glycogen synthesis for replacing the glycogen stores used up by activity of the muscles. This is done by enhancing glucose transport into the muscle cell, encouraging the activity of glucose synthase and reducing the activity of glycogen phosphorylase. In the human body fat in the form of triglyceride is the most efficient means of storing energy. Triglyceride storage in adipocytes is promoted through several mechanisms of insulin action. Insulin causes the production of lipoprotein lipase in adipose tissues, which results in the hydrolysis of triglycerides from the circulating lipoproteins. Insulin enhances glucose transportation into fat cells, thereby increasing the availability of alpha-glycerol-phosphate, which is essential for the esterification of free fatty acids into triglycerides. Through the inhibiting action on intracellular lipase, insulin inhibits intracellular lipolysis of stored triglyceride. This reduction in fatty acid flux to the liver is believed to be the key regulatory component in the action of insulin in reducing hepatic gluconeogenesis and ketogenesis. (2) Epidemiology and Differential Diagnosis of Diabetes Mellitus Type 1: Type 1 diabetes mellitus accounts for almost one-fourth of all diabetic cases. The onset of symptoms of hyperglycaemia is sudden. Nearly ninety percent of Type 1 diabetes is seen in patients below the age of thirty-five, which led to the earlier name of ‘juvenile-onset diabetes’. Type 1 diabetes mellitus appears to be the result of an infection or toxic environmental attack on genetically predisposed individuals. In such cases the aggressive immune system destroys the B cells of the islets of Langerhans in the process of overcoming the invasive agent. The general life time risk for type 1 diabetes mellitus in a population is only 0.4%, but increases to two percent if the female parent has it, six percent if the male parent has it or a sibling has it, while there is a risk of thirty-six percent in monozygotic twins. Genetic disposition is found to be responsible for nearly a third of all type I diabetes. Various regions of the human genome are associated with the development of type 1 diabetes. The most common however, are the major histo-compatibility complex (MHC) antigens or human leukocyte antigens (HLA). In the United Kingdom more than ninety percent of type 1 diabetes patients are found to have HLA-DR3, DR4 or both. (3). The challenge of diagnosing type 1 diabetes lies in differentiating it from type-2 diabetes mellitus. Low age factor and the presence of lipolysis and ketoacidosis are indicative of type 1 diabetes. However measurements of diabetes-related antibodies like, islet cell antibodies, anti-glutamic acid decarboxylase (GAD) antibodies, and anti-tyrosine phosphatase antibodies, C-peptide and insulin levels in individuals provides greater clarity for differential diagnosis. (4) Pathophysiology of Type 1 Diabetes Mellitus: A relative or absolute insulin deficiency at key cell sites results in hyperglycaemia. In type 1 diabetes mellitus hyperglycaemia is a reflection of the state of almost complete insulin deficiency due to the destruction of the B cells in the Islets of Langerhans. This state can be confirmed through insulin or C-peptide assays. A very small percentage of individuals with type 1 diabetes continue to release a small quantity of insulin as all the B cells in the islets of Langerhans have been destroyed. This release continues for a period of up to three years from the time of diagnosis, when all secretion stops. Death is a rare possibility within the first few weeks of type 1 diabetes. The islets of Langerhans in such individuals are normally enlarged and degranulated. During the course of the disease, the islets of Langerhans become individually smaller and are reduced in numbers and demonstrate evidence of a lymphocytic infiltrate. This is representative of the hallmark of the thyrogastric immune group of disorders. There also arises the question of concomitant glucagons deficiency in type 1 diabetes. There is evidence to show that glucagon secretion is elevated when diabetes remains uncontrolled, which acts to potentate hyperglycaemia. . Normalisation of glucose levels in the blood invariably causes a reduction in plasma glucogen levels. Insulin insufficiency in type 1 diabetes if untreated could lead to coma and death. Insufficient control of hyperglycaemia in type diabetes could lead to long-term vascular and neurological complications typical of continued state of hyperglycaemia, which could lead to morbidity and mortality associated with these complications (5). Conclusion: Type 1 diabetes mellitus is less common than type 2 diabetes mellitus. It is associated with the destruction of the capacity of the islets of Langerhans to produce the essential hormone insulin. Lack of sufficient insulin in the blood leads to hyperglycaemia and the consequences of complications associated with elevated blood sugar levels. Literary References 1. L. Jerreat, Diabetes for Nurses, Whurr Publishers Ltd., London, 1999, p. 3. 2. F.S. Greenspan & D.G. Gardner, Basic & Clinical Endocrinology, seventh edition, Lange Medical Books/McGraw-Hill, New York, 2004, p. 658-669. 3. H.E. Turner & J.A.H. Wass, OXFORD HANDBOOK OF ENDOCRINOLOGY AND DIABETES, OXFORD UNIVERSITY PRESS, Oxford, 2004, p. 804. 4. R.P. Hoffman, ‘Practical management of type 1 diabetes mellitus in adolescent patients: challenges and goals’, Treatments in endocrinology, vol. 3, no. 1, 2004, pp. 27-39. 5. J.F. Laycock & P.H. Wise. Essential Endocrinology, third edition, OXFORD UNIVERSITY PRESS, Oxford, 1996, p. 293-296. Read More