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Glucose Metabolism and Abnormalities MLT554 Clinical Chemistry I Norhisham Haron Centre for Medical Laboratory Technology Studies Faculty of Health Sciences UiTM Selangor Puncak Alam Campus Learning Objectives 1. Describe the ge...

Glucose Metabolism and Abnormalities MLT554 Clinical Chemistry I Norhisham Haron Centre for Medical Laboratory Technology Studies Faculty of Health Sciences UiTM Selangor Puncak Alam Campus Learning Objectives 1. Describe the general biochemistry of carbohydrate: function and metabolism 2. Discuss the clinical application of glucose measurement: diabetes and other carbohydrate disorders 3. Describe the specimen collection and handling for glucose measurement. 4. Explain the methods of glucose measurement and diabetic management. CHO Function Major food source Primary energy source and calories Used as energy (ATP) Stored as liver and muscle glycogen, fat Classification:  Monosaccharides, eg: glucose  Disaccharides, eg: sucrose  Polysaccharides, eg: starch CHO Metabolism Glycolysis: metabolism of glucose to pyruvate or lactate Glycogenesis: synthesis of glycogen from glucose Glycogenolysis: breakdown of glycogen to glucose for energy Gluconeogenesis: formation of glucose-6- phosphate (G6P) from a non-carbohydrate source Lipogenesis: conversion of carbohydrates to fatty acids and adipose tissue Lipolysis: breakdown of fats Plasma Glucose Regulation Maintained within a narrow range by hormones that modulate the movement of glucose into and out of circulation Primary regulators: INSULIN and GLUCAGON Other hormones also ‘hyperglycemic’ agents: epinephrine, growth hormone (GH), cortisol, thyroxine (T4) and somatostatin Plasma Glucose Regulation Hormone Insulin Glucagon Source Beta cells of the islets Alpha cells of the islet of Langerhans of Langerhans Released High plasma glucose Low plasma glucose when? Function Decrease plasma Increase plasma glucose glucose Action Promotes Increases glycogenesis & glycogenolysis & glycolysis gluconeogenesis Inhibits glycogenolysis & gluconeogenesis  Clinical Application Hyperglycemia Plasma glucose > 110 mg/dL Generally referred to as Diabetes Mellitus Immediate effects:  Increased ECF osmotic pressure  Acidosis Hyperglycemia: Sign & Symptom Polyuria Polydipsia Polyphagia Rapid weight loss Hyperventilation Mental confusion Loss of consciousness Diabetes Mellitus Hyperglycemia Ketosis: ketonemia, ketonuria Hyperlipidemia Decreased blood pH Glycosuria Loss of electrolytes: Na+ WHO and ADA Classification Type 1 diabetes mellitus Type 2 diabetes mellitus Gestational diabetes mellitus Secondary diabetes Type 1 Diabetes Mellitus Less common: 10-20% of cases Cause: lack of insulin secretion due to destruction of pancreatic beta cells Juvenile onset diabetes Most severe form of DM Ketosis prone Insulin dependent Type 2 Diabetes Mellitus Most common: 90% of cases Causes: peripheral tissues are not able to respond to insulin, insulin secretion is delayed Adult onset diabetes Less severe form of DM Not ketosis prone Non-insulin dependent Gestational Diabetes Mellitus Diabetes mellitus that develops during pregnancy (and resolves after pregnancy) GDM associated with increased infant morbidity and mortality GDM mothers are at increased risk of developing diabetes mellitus Secondary Diabetes Pancreatic disease Endocrine disease: excess GH, cortisol, epinephrine Severe liver disease Drug or chemical induced Criteria for Diagnosis DM 1. Symptoms of diabetes plus random plasma glucose concentration > 200 mg/dL, OR 2. Fasting plasma glucose > 126 mg/dL, OR 3. 2-hour postprandial glucose > 200 mg/dL during an oral glucose tolerance test, OR 4. HbA1c > 6.5%, confirmed on repeat measurement Hypoglycemia Low plasma glucose levels Overnight FPG < 45 – 50 mg/dl Symptoms: non-specific  Increased hunger  Sweating, nausea, vomiting, dizziness, nervousness  Blurring of speech and sight, mental confusion Galactosemia Deficiency of galactose-1-phosphate uridyl transferase enzyme Galactose or lactose cannot metabolize to glucose Galactose in blood (galactosemia) and urine Can lead to mental retardation, cataracts, death  Specimen Collection & Handling Specimen Collection/Handling Fasting specimen for FBS/FPG (8-10 hour fast/overnight) Collect in sodium fluoride tube (grey top) Must separate viable cells within 1 hour of collection Preferred specimen: plasma, serum, whole blood, CSF and urine Expected values FPG: 70-99 mg/dl Random (non-fasting): 70-125 mg/dl 2-hour post prandial: 126 mg/dL usually indicate a problem FBS should be repeated on another day to confirm diagnosis Lab. Test: 2-hour Post Prandial Patient has FBS drawn Ingests 75 gram high carbo breakfast/ drinks glucola Has repeated glucose test at 2 hours Glucose level should have returned to fasting levels If glucose >200 mg/dL on the postprandial test, a fasting or random glucose level, should be performed on a subsequent day to diagnose with diabetes Lab. Test: Oral Glucose Tolerance Test Patient directions: important Eat an adequate carbohydrate diet at least three (3) days prior to test Obtain fasting specimen Test is begun in early a.m. Test dose (glucose load): 75 gm for adults and 1.75 gm/kg for children Patient is to remain resting, no smoking or eating during test period Blood is collected at timed intervals and measured Lab. Test: Oral Glucose Tolerance Test Lab. Test: Glycosylated Hb/HbA1c Glycosylated hemoglobin (A1c test): glucose is bound to amino group of hemoglobin molecule Increased plasma glucose, increased glycation; glycation occurs throughout lifespan of RBC Monitors long-term diabetic control (2- 3 months) Eliminates day-to-day fluctuations Unaffected by exercise, activity, recent food intake Lab. Test: Glycosylated Hb/HbA1c Specimen collection and method for HbA1c: EDTA whole blood, prepare hemolysate Stable for 1 week when stored at 4 0C Chromatography: Ion-exchange or affinity chromatography HbA1c reference range: 4-6% Lab. Test: Ketones Produced by the liver Metabolism by-products of fatty acids Increase in cases of carbohydrate deprivation or decreased carbohydrate use. Eg: diabetes mellitus, starvation/fasting, prolonged vomiting etc. Lab. Test: Microalbumin Assists in the diagnosis of early proteinuria Normal urine dipsticks are insensitive to low concentrations of urine albumin Normal urine albumin: