Clinical Chemistry - Chapter 3: Carbohydrate Part 2 PDF

Al- Balqa' Applied University (BAU) Zarqa University College Dept. Of Allied Medical Sciences Clinical Chemistry Chapter 3: Carbohydrate part 2: Normal and abnormal carbohydrate metabolism By : Dr Laila Alsawalha Revision : Insulin action The integration...

Al- Balqa' Applied University (BAU) Zarqa University College Dept. Of Allied Medical Sciences Clinical Chemistry Chapter 3: Carbohydrate part 2: Normal and abnormal carbohydrate metabolism By : Dr Laila Alsawalha Revision : Insulin action The integration of energy metabolism is controlled primarily by the actions of two peptide hormones: insulin and glucagon  GLUCAGON Glucagon is a polypeptide hormone secreted by the α- cells of the pancreatic islets of Langerhans. Glucagon, along with epinephrine, cortisol, and growth hormone. Most importantly, glucagon acts to maintain blood glucose levels by activation of hepatic glycogenolysis and gluconeogenesis. 4 A. Stimulation of glucagon secretion The α-cells is responsive to a variety of stimuli that signal actual or potential hypoglycemia. Glucagon secretion is increased by: 1. Low blood glucose: During an overnight or prolonged fast, elevated glucagon levels prevent hypoglycemia 5 2. Amino acids: Amino acids derived from a meal containing protein stimulate the release of both glucagon and insulin. The glucagon effectively prevents hypoglycemia that would otherwise occur as a result of increased insulin secretion that occurs after a protein meal. 6 Inhibition of glucagon secretion Glucagon secretion is significantly decreased by elevated blood glucose and by insulin. Both substances are increased following ingestion of glucose or a carbohydrate-rich meal 7 Metabolic effects of glucagon 1. Effects on carbohydrate metabolism: The intravenous administration of glucagon leads to an immediate rise in blood glucose. This results from an increase in the breakdown of liver (not muscle) glycogen and an increase in gluconeogenesis. 8 9 2. Effects on lipid metabolism: Glucagon activates lipolysis in adipose tissue. The free fatty acids released are taken up by liver and oxidized to acetyl coenzyme A, which is used in ketone body synthesis. 10 3. Effects on protein metabolism: Glucagon increases uptake of amino acids by the liver, resulting in increased availability of carbon skeletons for gluconeogenesis. As a consequence, plasma levels of amino acids are decreased. 11 12 13 3. Epinephrine: - It is a neuroendocrine catecholamine that is synthesized by the adrenal medulla, it is released in response to a decrease in glucose below a certain concentration Epinephrine is the ‘fight or flight’ hormone that increases the blood supply to liver and muscles Glycogenolysis and gluconeogenesis are stimulated in the liver in response to epinephrine, in addition, glucose utilization is limited by the partial inhibition of insulin release 4. Cortisol It is a glucocorticoid hormone of the adrenal cortex, extended elevations of cortisol result in an increase in gluconeogenesis and insulin antagonism which results in hyperglycemia 14 5. Growth hormone ( somatotropin) -Is an anterior pituitary hormone that antagonizes insulin action, prolonged elevations of growth hormone will result in a hyperglycemic state -It stimulates gluconeogenesis, enhances lipolysis and antagonizes insulin-stimulated glucose uptake 6. Thyroxine - It is an amino acid derivative that is secreted by the thyroid gland, its effect on glucose metabolism and control is minimal, however, it is capable of promoting glycogenolysis and deleting the liver of glycogen - It is also able of increasing the rate of absorption of glucose from the gut Alterations in carbohydrates metabolism Humans can have both hyper or hypoglycemic states, hyperglycemic states are more prevalent. The expected glucose concentration in plasma is dependent on the time and contents of the subject’s last meal After an overnight fast, the plasma glucose concentration is normally between 70-110 mg/dl. The expected overall range for random glucose in non-fasting individuals is 70-150 mg/dl Diagnosis of hyperglycemia depends on the observation of glucose concentrations beyond a certain recommended concentration and under defined conditions It must be noted that transient hyperglycemic states can be caused by a number of physiologic and endocrine changes and the diagnosis of diabetes mellitus is not always absolute Diabetes Mellitus ❖ Diabetes mellitus is actually a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Therefore, the ADA/World Health Organization (WHO) guidelines recommend the following categories of diabetes: Type 1 diabetes Type 2 diabetes Other specific types of diabetes Gestational diabetes mellitus (GDM)  Classification of DM Type 1 diabetes mellitus (insulin-dependent diabetes mellitus) - Cause: Destruction of beta cells of pancreatic islets - Consequence: Absolute deficit of insulin - Present during childhood and adolescence - Insulin therapy is essential A- subtype: induced by autoimmunity processes. B- subtype: idiopathic diabetes mellitus. There is also LADA (Latent autoimmune diabetes of adults), sometime called slow-onset type 1 diabetes 18 Type 2: Diabetes mellitus(T2DM) It is the most common form of diabetes, this disease is characterized by insulin insensitivity at target tissues Most patients acquire the disease after age 40, but it may occur in younger people Genetic factors may play a greater role in this disease than in IDDM. Concordance rates for NIDDM in identical twins are 100% Environmental factors, such as diet, may play an important role in the development of NIDDM. Obesity, especially of the abdominal viscera is common in individuals with NIDDM Changes in the normal substrate concentrations delivered to the liver, adipose tissues, and skeletal muscles are thought to affect the normal functioning of insulin receptors. This in turn may decrease the number of glucose transporters that are delivered to the cell surface, thereby decreasing the delivery of glucose into the cell It is known that restriction of caloric intake and weight loss are often sufficient to control NIDDM Pathogenesis of type 2 DM: - 1- Insulin resistance: - Insulin resistance is defined as a decreased biological response to normal concentrations of insulin. It is found in both obese, nondiabetic individuals and in patients with type 2 diabetes - The insulin resistance syndrome ( also known as syndrome X or the metabolic syndrome) is a constellation of associated clinical and laboratory findings consisting of: 1- insulin resistance, 2- hyperinsulinemia, 3- obesity, 4- dyslipidemia ( high TG and low HDL cholesterol), 5- hypertension Insulin Resistance( metabolic syndrome MetS) The metabolic syndrome is diagnosed if an individual meets 3 or more of the following criteria: 1. Abdominal obesity: waist circumference greater than 35 inches ( women) or 40 inches ( men) 2. Triglyceride greater than 150 mg/dl 3. HDL-cholesterol less than 50 mg/dl ( women) or less than 40 mg/dl ( men) 4. Blood pressure greater than or equal to 130/85 mm Hg 5. Fasting plasma glucose greater than or equal to 110 mg/dl Individuals with this syndrome are at increased risk for cardiovascular disease 2- Loss of beta cells: The increased β cell demand induced by insulin resistance is associated with a progressive loss of β cell function that is necessary for the development of fasting hyperglycemia The major defect is a loss of glucose-induced insulin release that is termed selective glucose unresponsiveness  3- Environment: Environmental factors such as diet and exercise are important determinants in the pathogenesis of type 2 diabetes All obese people, even those with normal carbohydrate tolerance have hyperinsulinemia and are insulin resistant Other factors as family history of type 2 diabetes, the duration of obesity and the distribution of fat are also important  Chapter1-Carbohydrates Type 1 diabetes Type 2 diabetes Synonyms IDDM,juvenile onset NIDDM, adult onset Age of onset Usually 40 years Ketosis common rare Body weight Non obese obese Prevalence 0.5% 6-10% Genetics HLA associated Non-HLA associated Circulating islet cell 50-85%