Diabetes Mellitus - Term Paper Example

? Diabetes mellitus Diabetes Mellitus Introduction Diabetes mellitus is an endocrine disorder associated with hyperglycemia or increased glucose levels in the blood. There are various types of diabetes depending on different etiologies that contributes in the underlying pathogenesis of the disease. Insulin is an important hormone that plays a key role in metabolism and storage of glucose in a human body. Therefore, the main causes of increased blood glucose level include a decline in insulin levels, decrease sensitivity towards insulin, increase production or decreased metabolism of glucose. Increase in blood glucose level can have variable effects on the body depending upon the quantitative rise of glucose. Diabetes can cause multi-organ dysfunction with severe impairment in quality of life. Therefore, it contribute as a major disease that burden not only the individual that is affected but also to the health care system (Winter & Maria, 2002). Which ethnic group is more prone the development of pre diabetes and diagnosed diabetes? Which ethnic groups naturally have high insulin levels which increases the susceptibility of the individuals to the development of diabetes? Methodology I have consulted a number of textbooks for the compilation of this research paper. In order to ensure that only authentic and up to date information is written in this paper, I have chosen books written by renowned authors. The utilization of famous textbooks ensure that the information is authentic. Classification of Diabetes Mellitus Diabetes can be classified into many ways but the most common two types include type 1 and type 2 diabetes mellitus. Type 1 is also known as insulin dependent diabetes mellitus (IDMM) and type 2 as Insulin Independent Diabetes Mellitus for the reasons explained in the pathogenesis section. Gestational Diabetes Mellitus (GDM) and Maturity Onset Diabetes of the Young (MODY) are other important types of DM. Analysis and Discussion The incidence rate of Diabetes Mellitus is on the rise and its prevalence has increased markedly over the past two decades. As mentioned in the 2004 statistical report of World Health Organization (WHO) and International diabetes federation, by the year 2030 more than 360 million people will have diabetes. The statistical data also show that the prevalence of type 2 diabetes is rising at a greater rate than the others because of the more sedentary life style of the present generation and increase in obesity which is a leading risk factor for the type 2 DM. According to the Centre for Disease Control and Prevention (CDC), more than 7% of the American population had Diabetes in 2005, which is about 20.8 million. (Fauci and Tinsley, 2008). The following figure (Fig 1) represents the geographical distribution of diabetes as of 2000 and also the predicted values for 2030. It is evident from this distribution that Asian region has the highest prevalence of diabetes with America and Europe head to head for the second place. The expected rise in the prevalence of diabetes in the year 2030 is very significant and if the risk factors are not reduced or no steps are taken to change the lifestyle of the current population than it is expected that diabetes will put a heavy burden on the world health system (Poretsky, 2002). Source: Epidemiology of Diabetes Mellitus, Ekoe?, 2008. The above table shows the prevalence of diabetes mellitus in some Latin-American country. It shows the percentage of total population suffering from diabetes. An important point to remember regarding the incidence rate and prevalence of diabetes is that most of the cases, about 30%, are not reported and are not included in the survey due to certain limitations. So the actual prevalence of diabetes can be more than discussed by these statistical data. Diagnosis According to the American Diabetes Association, the following are the criteria for diagnosis of diabetes mellitus. Symptoms of diabetes plus random blood glucose concentration 11.1 mmol/L (200 mg/dL) or Fasting plasma glucose 7.0 mmol/L (126 mg/dL) or Two-hour plasma glucose 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test. Random blood glucose is measured randomly at any instant, whereas, fasting blood glucose is measured after an overnight fast. Fasting blood glucose is also considered as most reliable test for diabetes especially in patients with no associated signs and symptoms. Another important test is Hb A1C test that can evaluate the blood glucose control of a patient over the past few months. Insulin To understand the pathophysiology of diabetes mellitus as a disease it is important to first understand the most crucial hormone that is associated with glucose metabolism. Insulin is a hormone that is secreted from the pancreas, more specifically from the beta cells. Its synthesis and secretion is stimulated by elevated blood glucose level evident right after the meal. Insulin has various functions in the body mostly related to glucose storage. In simple terms, it increases the permeability of glucose in the target organs enhancing its uptake. As almost all cells can use glucose as a fuel source, it is readily taken by most tissues in the presence of glucose. This partly contributes in reducing the blood glucose level. Moreover, insulin induces glycogenesis in the liver. Glucose can only be stored in the form of glycogen and this process of converting glucose in a storage form is called glycogenesis. This conversion of glucose into glycogen further normalizes the glucose level in blood. Lastly, insulin inhibits Gluconeogenesis, a process of forming new glucose molecule in the liver. All these actions of insulin ensure that blood glucose is maintained at the baseline normal levels. (Fauci and Tinsley, 2008) Type 1 diabetes As mentioned before, this type of diabetes is called insulin dependent diabetes because it is caused by the deficiency of insulin in the body. The functions of insulin discussed above are crucial to maintain blood glucose. So its absence will ultimately raise the glucose levels in the blood (Niewoehner, 2004). Pathogenesis Insulin is produced by beta cells of the pancreas, so their destruction can lead to insulin deficiency. There are many factors that contribute to the pathogenesis of this destruction of beta cells. Important among those factors are genetic, environmental and immunological factors. Although, most of the patients with type 1 diabetes have autoimmune destruction of beta cells, some may not have any evidence of immunological markers (Alt, 2009). This highlights that other unknown mechanisms can also lead to type 1 DM. It is important to remember that most of these patients are born with normal beta cells which are fully functional but due to certain genetic factors they develop autoimmunity against these cells leading to their gradual destruction. Infections and environmental factors are important stimulants that trigger this autoimmune destruction. This process of beta cell destruction is gradual and its pace varies in individuals. Therefore, decline in insulin is also gradual with some patients presenting with symptoms early in the age, first decade, while others may not have significant loss of insulin function till the second or third decade of life. Twin studies have shown significant genetic association in the development of diabetes mellitus with concordance rate of 30-70%. HLA DR 3 and HLA DR 4 are the most common haplotypes associated with type 1 diabetes mellitus (LeRoith et al, 2004). Apart from genetic component, many environmental factors have been proposed to be associated but none of them is a confirmed as a definite cause. These environmental factors include certain pathogens such as rubella and coxsackie virus. (Fauci and Tinsley, 2008) Type 2 diabetes mellitus Unlike type 1, insulin independent type is not caused by insulin deficiency but rather due of its lack of ability to perform intrinsic activity at a receptor level. Type 2 also has a strong genetic association with twin concordance rate of 70-90% which is significantly higher than the type 1 DM. Pathogenesis Insulin resistance is an important underlying factor that contributes to type 2 DM. But, it also eventually leads to impaired secretion of insulin from the pancreas. Other important processes include excessive production of glucose by liver, via gluconeogenesis, and abnormal fat metabolism. All these factors build up to give the actual picture of this disease. Earlier in the disease resistance to insulin results in hyperglycemia but it is initially compensated by increase in the insulin production by the beta cells. But this overload of work output exhaust these cells over the years, leading to decline in their function and ultimately decreasing the insulin levels in the body. The inability of insulin to act on liver results in overproduction of new glucose further deteriorating the issue and leading to even higher level of hyperglycemia. Abnormal mobilization of fatty acids in liver as a result of insulin resistance can also lead to non alcoholic fatty liver disease. (Fauci and Tinsley, 2008) Risk Factors for Type 2 Diabetes Mellitus: Following is a summary of important risk factors associated with the development of type 2 diabetes mellitus. Family history of diabetes (i.e., parent or sibling with type 2 diabetes) Obesity (BMI 25 kg/m2) Habitual physical inactivity Race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander) Previously identified IFG or IGT History of GDM or delivery of baby >4 kg (>9 lb) Hypertension (blood pressure 140/90 mmHg) HDL cholesterol level 250 mg/dL (2.82 mmol/L) Polycystic ovary syndrome or acanthosis nigricans History of vascular disease Acute complications of Diabetes Mellitus: The two important acute complications associated with DM are Diabetic Ketoacidosis and hyperosmolar state or HHS. Diabetic ketoacidosis is associated with type 1 DM because of complete absence of insulin; whereas, HHS is hallmark of type 2 diabetes. Diabetic Ketoacidosis The main underlying cause of diabetic ketoacidosis is the absolute absence of insulin as evident in type 1 diabetes mellitus. The counter hormones such as glucagon, growth hormones and cortisol are elevated or their actions are pronounced in the absence of insulin. These hormones are further responsible for promoting gluconeogenesis and ketone body formation. These ketones exist as acids (ketoacids) at the physiological pH and bicarbonate ions are used to neutralize them. This consumption of bicarbonate ions further decrease the pH leading to metabolic alkalosis. (Fauci and Tinsley, 2008). Following figure shows the clinical signs and symptoms of patient with DKA. Source: (Harrison’s principle of medicine, Fauci and Tinsley, 2008) After confirming the diagnosis of diabetic ketoacidosis, it is important to treat the underlying acidosis. pH monitoring should be done with regular interval to ensure the progression of acidosis. Hyperglycemic hyperosmolar state Hyperglycemic hyperosmolar state or HHS is commonly seen in type 2 patients which presents with lethargy and mental confusion or sometimes with coma. The pathogenesis is similar to DKA with the exception that no ketone bodies are formed most likely because insulin deficiency is relative and not absolute (Fauci and Tinsley, 2008). The following table compares both DKA and HHS. DKA HHS Glucose,a mmol/L (mg/dL) 13.9–33.3 (250–600) 33.3–66.6 (600–1200) Sodium, meq/L 125–135 135–145 Potassiuma Normal to Normal Magnesiuma Normalb Normal Chloridea Normal Normal Phosphatea Normal Creatinine Slightly Moderately Osmolality (mOsm/mL) 300–320 330–380 Plasma ketonesa ++++ +/– Serum bicarbonate,a meq/L 7.3 Arterial PCO2,a mmHg 20–30 Normal Anion gapa[Na - (Cl + HCO3)] Normal to slightly Table 338-4 Laboratory Values in Diabetic Ketoacidosis (DKA) and Hyperglycemic Hyperosmolar State (HHS) (Representative Ranges at Presentation) aLarge changes occur during treatment of DKA. bAlthough plasma levels may be normal or high at presentation, total-body stores are usually depleted. Source: (Harrison’s principle of medicine, Fauci and Tinsley, 2008) Chronic Complications of Diabetes Diabetes is a chronic disease and complications that result from this chronic elevation of blood glucose is what makes this disease a burden on patient and health care system. Following is a list of most important long term manifestation of uncontrolled diabetes mellitus. Microvascular Eye disease Retinopathy (nonproliferative/proliferative) Macular edema Neuropathy Sensory and motor (mono- and polyneuropathy) Autonomic Nephropathy Macrovascular Coronary artery disease Peripheral arterial disease Cerebrovascular disease Other Gastrointestinal (gastroparesis, diarrhea) Genitourinary (uropathy/sexual dysfunction) Dermatologic Infectious Cataracts Glaucoma Periodontal disease Source: Harrison’s principle of medicine, Fauci and Tinsley, 2008 Prevention and Management Reducing the risk factors associated with the development of diabetes, especially type 2 can significantly prevent the incidence rate of diabetes in a population. Most important risk factor such as obesity is dependent on life style modification and, therefore, requires education about the disease. Diabetes is not a disease as long as blood glucose is maintained at in a narrow base line range by the patient. Therefore, the main aim in the management of diabetic patient is to prevent high surge of glucose level, either by medications or lifestyle modification. (Guthrie & Richard, 2008). For type 1 diabetes insulin is the drug of choice, derived from animal source or recombinant DNA technology. Type 2 patients can get glycemic control by certain drugs that can potentiate the effect of insulin on the target receptors decreasing its resistance. Conclusion The prevalence of diabetes is highest amongst the Asian countries. The identified reasons for the high incidence of diabetes amongst these countries are their lifestyle. In addition it has been observed that individuals belonging to these countries are naturally prone to insulin resistance because of high circulating levels of insulin. In order to control diabetes in Asia, Lifestyle modifications are a prerequisite. The lifestyle modifications needed and integral reasons for the increased susceptibility of Asians to diabetes are potential topics for future research. References Winter, W. E., Signorino, M. R., & American Association for Clinical Chemistry. (2002).Diabetes mellitus: Pathophysiology, etiologies, complications, management, and laboratory evaluation : special topics in diagnostic testing. Washington, DC: AACC Press. Ekoe?, J.-M. (2008). The epidemiology of diabetes mellitus. Chichester, UK: Wiley-Blackwell.. Niewoehner, C. B. (1998). Endocrine pathophysiology. Madison, Conn: Fence Creek Pub. Guthrie, D. W., & Guthrie, R. A. (2008). Management of diabetes mellitus: A guide to the pattern approach. New York: Springer Pub. Co. Alt, F. W. (2009). Immunopathogenesis of type 1 diabetes mellitus. London: Academic. Poretsky, L. (2002). Principles of diabetes mellitus. Boston: Kluwer Academic Publishers.. LeRoith, D., Taylor, S. I., & Olefsky, J. M. (2004). Diabetes mellitus: A fundamental and clinical text. Philadelphia: Lippincott Williams & Wilkins. Fauci, A. S. (2008). Harrison's principles of internal medicine. New York: McGraw-Hill Medical. Read More