Lecture 5: Assessing Laboratory Tests for Glucose Metabolism Disorders PDF

Assessing Laboratory Tests for Glucose Metabolism Disorders Pixabay.com 1. The Pancreas Made up of two parts: Exocrine pancreas Endocrine pancreas ▪ Alpha cells ▪ Beta cells ▪ Delta cells ▪ Alpha and beta cells regulate blood glucose levels...

Assessing Laboratory Tests for Glucose Metabolism Disorders Pixabay.com 1. The Pancreas Made up of two parts: Exocrine pancreas Endocrine pancreas ▪ Alpha cells ▪ Beta cells ▪ Delta cells ▪ Alpha and beta cells regulate blood glucose levels Pixabay.com 2. Major Sources of Fuel for Metabolism Glucose is a vital source of energy for various tissues and organs From diet From storage (glycogen breakdown) New synthesis (gluconeogenesis) Mostly in liver, less in kidneys Pixabay.com Triglycerides (from diet or storage) Fatty acids + glycerol Ketones (acetoacetate, hydroxybutyrate, and acetone) Play a role in glucose metabolism disorders 2.1 Glucose – a major energy source Major energy substrate Only utilizable source of energy for some tissues Body’s source of glucose Dietary Endogenous production (glycogenolysis and gluconeogenesis) All energy production in the cells begins with glycolysis Many tissues oxidize glucose completely to CO2 Other tissues metabolize glucose as far as lactate Converted to glucose in liver and kidneys (gluconeogenesis) 2.2 Glucose Homeostasis Excess of glucose Shortage of glucose Lipogenesis 3. Key Metabolic Processes Excess of glucose: Glycolysis Glucose pyruvate Glycogenesis Glucose Glycogen Lipogenesis Excess carbohydrates and dietary fat triglycerides (storage) Shortage of glucose: Gluconeogenesis Noncarbohydrate sources glucose Glycogenolysis Glycogen Glucose Lipolysis Lipid fatty acids + glycerol Ketogenesis Fatty acids (liver) Ketones Beta oxidation Fatty acids Acetyl-CoA 4. Regulation of Blood Glucose Concentration Fed state Dietary glucose and amino acid load - high Portal vein [glucose] high Increased Insulin Glucose is taken up and stored by: ▪ Liver glycogen; triglyceride ▪ Muscle glycogen ▪ Adipose tissue triglyceride 4. Regulation of Blood Glucose Concentration Fasting State Increase in glucagon, adrenaline, glucocorticoids and growth hormones Liver Muscle Adipose tissue https://www.austincc.edu/apreview/EmphasisItems/Glucose_regulation.html Glycolysis and gluconeogenesis/glycogenolysis are reciprocally controlled Activation of one pathway results in inhibition of the other 5. The Actions of Insulin 6. Disorders of Glucose Metabolism Diabetes Mellitus ▪ Inappropriate hyperglycemia due to absolute or relative insulin deficiency ❖Type 1 – 10% of all cases of diabetes Absolute lack of insulin Destruction of beta cells of pancreas Prone to develop ketosis Insulin replacement is essential Age onset ❖Type 2 Relative lack of insulin Insulin resistance of peripheral tissues Insulin level may be normal or high (hyperinsulinemia) https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes Usually not associated with ketosis Age onset ❖ Clinical Features of Diabetes Mellitus types 1 and 2 Type 1 Type 2 * *Human leukocyte antigen – genetic link between HLA genes and risk of diabetes ❖ Signs and Symptoms Clinical Features at Diagnosis Type 1 Type 2 In crisis at Dx often rarely Polyuria and thirst extreme moderate Weakness/fatigue extreme moderate Polyphagia with weight extreme none loss Asymptomatic never often 6. Disorders of Glucose Metabolism Other types of diabetes Or secondary diabetes Pancreatic disease Endocrine disease (e.g., Cushing’s syndrome) Drug therapy (e.g., corticosteroids) Gestational diabetes mellitus Carbohydrate intolerance during pregnancy Metabolic and hormonal changes 6% to 8% of pregnant women High risk for DM type 2 Screened through an oral glucose tolerance test Pixabay.com ❖ Diagnosis of Diabetes Mellitus It can be diagnosed by: Venous plasma glucose Fasting plasma glucose - fasting for 8-12 hours/ less variable results Random plasma glucose – more variable results Oral glucose tolerance test Used to assess individuals with signs or symptoms of diabetes with normal fasting plasma glucose or with prediabetes and during pregnancy Glycated hemoglobin (HbA1c) Consistent elevated glucose - binding to proteins The higher the blood glucose levels over time, the more glycation occurs Accompanied by symptoms (“3 Ps”) – or confirmed by repeat sampling on a different day ❖ Clinical practice Guidelines for diagnosis of Diabetes Mellitus (Diabetes Canada) Fasting plasma glucose (FPG) test FPG ≥7.0 mmol/L Random plasma glucose test Random PG ≥11.1 mmol/L Oral glucose tolerance test (OGTT) 2hPG in a 75 g OGTT ≥11.1 mmol/L Hemoglobin A1c (HbA1c) test (< 5.5%) A1C ≥6.5% (in adults) Symptoms of hyperglycemia If an individual exhibits classic symptoms of hyperglycemia and has a random plasma glucose level of 11.1 mmol/L (200 mg/dL) or higher, diabetes is diagnosed ❖ Monitoring of Diabetes Mellitus HbA1c has a more established role in monitoring glycemic control of diabetes Self-monitoring Point-of-care glucose meter Varying time is necessary Recommended for individuals with type-1 diabetes Individuals with type-2 diabetes treated with insulin Individuals with hypoglycemic episodes On oral medication that increase the risk of hypoglycemia (act on pancreas) Pregnant Individuals with Type 1 diabetes are advised to monitor ketones (blood and urine) if hyperglycemic or unwell 6. Disorders of Glucose Metabolism Diabetic Ketoacidosis (DKA) ▪ A feature of diabetes mellitus type 1 ▪ New diabetic or established diabetics with inadequate dose of insulin ▪ Commonly initiated by: omission of insulin, infection, myocardial infarction and trauma ▪ Glucagon, cortisol, epinephrine secretion further increases glucose levels ▪ Low intracellular [glucose] ❖ Diabetic Ketoacidosis - Development 1. Increased [glucose] 20-40 mmol/L (hyperglycemia) 2. Glycosuria (osmotic diuresis, dehydration) 3. Increased lipolysis overproduction of fatty acids 4. Conversion to ketones (ketonemia, metabolic acidosis, ketonuria) – “fruity” “acetone” breath smell 5. Severe metabolic acidosis, pH drops hyperventilation 6. Vomiting exacerbates fluid/electrolytes depletion ❖ Treatment of Diabetic Ketoacidosis Close clinical and biochemical monitoring are necessary Fluid replacement Restore ECF (blood pressure, glomerular function) Insulin Restore glucose metabolism Inhibit fatty acid breakdown to ketones Potassium Monitoring Initial apparently normal or high potassium levels – all have whole body potassium depletion May need to give K+ to restore intracellular losses (K+ shift) ❖ Diabetic Ketoacidosis - Laboratory Role Monitoring Glucose (monitored hourly at the bedside until less than 14 mmol/L) Ketones (plasma and urine) Blood gases (pH, pCO2, pO2, HCO3-) Electrolytes – (Na, K, Cl) Urea, creatinine Lipids Rapid turn around of results required Pixabay.com 6. Disorders of Glucose Metabolism Hyperosmolar Hyperglycemic State (HHS) A feature of type 2 diabetes Marked hyperglycemia (50 mmol/L) Osmotic diuresis No ketosis Slow onset Pixabay.com ▪ Elderly patients ▪ Stop eating/drinking ▪ Increased stress ▪ Increased [glucose] ▪ Osmotic diuresis ▪ Nausea, vomiting , dehydration, impaired consciousness ▪ Death rate 15% ❖ Hyperosmolar Hyperglycemia State- Treatment High glucose levels cause: Osmotic diuresis Severe water and electrolyte loss Dehydration Increased Na+ Coma Treatment Similar to that of DKA Fluid replacement Insulin if required in small doses Monitor K+ Pixabay.com 9. DKA vs HHS 6. Disorders of Glucose Metabolism Hypoglycemia Plasma glucose (< 2.5 mmol/L) ❖Clinical effects: Suppression of insulin secretion “fight-or-flight” response – lead to common symptoms E.g., Shaking, increased heartbeat, heavy breathing Stimulation of glucagon, cortisol and growth hormone Commonly self-treated (carbohydrate consumption) Severe hypoglycemia- decrease of glucose fuel to the brain Mental confusion, unconsciousness ❖ Hypoglycemia - Assessment Diagnosis depends on Whipple’s triad (3 criteria): Symptoms of hypoglycemia must be present Laboratory confirmation Symptoms must be relieved by glucose administration ❖If hypoglycemia is confirmed, insulin should be analyzed (during a symptomatic episode) ❖ Hypoglycemia - Causes Reactive hypoglycemia Fasting hypoglycemia Inappropriate or excessive insulin Insulinoma Drug-induced (e.g., Malignancy sulfonylureas) Hepatic and renal disease Alcohol decreased gluconeogenesis Addison’s disease Sepsis ❖In diabetic patients: Low carbohydrate intake Excess of insulin or sulfonylurea Strenuous exercise Excessive alcohol intake