MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Diabetes and Other Carbohydrate Disorders

Hyperglycemia Increase in plasma glucose levels due to hormone imbalance Healthy patients Insulin is secreted by the β cells of the pancreatic islets of Langerhans Reference Range Increased plasma glucose: > 110 mg / dl Glucose reference range: 74 - 106 mg / dl

Effects of Hyperglycemia Immediate Effects Increased extracellular osmotic pressure The increased glucose in plasma pulls water out of cells Results in dehydration Acidosis - metabolic acidosis. May result If the patient’s cells are not able to take in glucose, they may begin to convert fats to fatty acids, which then become keto acids.

Effects of Hyperglycemia: Long term Physiological Heart attacks/strokes, Diabetic retinopathy(Blindness), kidney failure, neurologic defects, susceptibility to infections Chemical Glycosylated hemoglobin the formation of glycosylated hemoglobin is the result of prolonged elevation of plasma glucose.

Diabetes Characterized by hyperglycemia Disorders differ in etiology, symptoms and consequences Lab’s role Assist in diagnosis of the disease Identification of the disorder Assessment of progression of tissue damage

Physiologic abnormalities of diabetes Hyperglycemia increase blood glucose. Doesn’t matter how the glucose is derived - diet, fat metabolism, protein destruction/wasting Ketosis from fat metabolism, ketonemia, ketonuria Hyperlipidemia -increase blood lipids from faulty glucose metabolism. Decrease blood pH - metabolic acidosis Urine abnormalities Glycosuria – glucose present Polyuria - increase in urine volume Loss of electrolytes - washing out with the urine

Diabetes World Health Organization (WHO) and American Diabetes Association (ADA) recommends four categories of diabetes: Type 1 diabetes Most severe and potentially lethal Type 2 diabetes Other (secondary diabetes) Gestational diabetes mellitus (GDM)

Type 1 Diabetes Insulin dependent diabetes mellitus ( IDDM ) 5-10 % of diabetes cases Demographics Non-Hispanic Whites/ Non-Hispanic Blacks Children & adolescents Pathology Disease triggered by viral illness or environmental factors that destroys beta cells in pancreas. Absolute Insulin deficiency Defect in secretion, production or action or all Autoimmune destruction of islet beta – cells in pancreas Auto-antibodies are present

Type 1 Diabetes Clinical Symptoms CLASSIC TRIAD Polyphagia (increased food uptake) Polydipsia (thirst) Polyuria ( increased urine production) Other symptoms Mental confusion Rapid weight loss Hyperventilation Diabetic ketoacidosis

Laboratory Findings Hyperglycemia- plasma levels > 110 mg/dL Glucosuria- plasma glucose > 180 mg / dl Decreased insulin Increased glucagon Stimulation causes Gluconeogenesis Lipolysis (breakdown of fat produces ketones) Ketoacidosis Decreased blood pH ( acidosis )  Sodium …  Potassium …  CO2

Type II Diabetes Non – Insulin Dependent Diabetes Mellitus( NIDDM ) Most common form of diabetes Demographics Adult onset Patients usually > 20 years old American Indians and non-Hispanic blacks

Type II Diabetes: Pathology Develops gradually Disorder in insulin resistance and relative deficiency of insulin Plasma glucose is unable to enter cells Contributory factors Obesity Lack of exercise Diet Genetics Drugs, such as diuretics, psychoactive drugs Increases in hormones that inhibit/antagonize insulin (GH & cortisol)

Laboratory Findings Hyperglycemia Glucosuria Insulin is present Glucagon is not elevated No lipolysis and no ketoacidosis Excess glucose is converted to triglycerides (  plasma triglycerides ) Normal / Increased Na / K Increased BUN & Creatinine ( Decreased renal function ) Hyperosmolar plasma from hyperglycemia

Other (SecondaryDiabetes) Genetic defects of beta cell function Genetic defects in insulin action Genetic syndromes Pancreatic disease Endocrinopathies Drug or chemical induced

Gestational Diabetes Glucose intolerance associated with pregnancy’s hormonal and metabolic changes Mothers usually return to normal after pregnancy, but with increased risk for diabetes later on in life Infants are at increased risk for respiratory complications and hypoglycemia after birth

Criteria for Diagnosis of Diabetes Symptoms of diabetes plus random plasma glucose concentration > 200 mg/dL. Random is defined as any time of day without regard to time OR Fasting plasma glucose > 126 mg/dL. Fasting is defined as no caloric intake for at least 8 hours. 2-Hour postprandial glucose > 200 mg/dL during an oral glucose tolerance test 4. A HgbA1C > 6.5%, confirmed on repeat measurement Side notes Glucose tolerance testing ( GTT ) is considered to be of limited additional use in the diagnosis of diabetes and not recommended, do 2 hour pp test as stated above. Urine glucose testing is also not recommended in diabetes diagnosis

Hypoglycemia Plasma glucose level falls below 60 mg/dL Glucagon is released when plasma glucose is < 70 mg / dL to inhibit insulin Epinephrine, cortisol, and growth hormone released from adrenal gland to increase glucose metabolism and inhibit insulin Treatment Varies with cause. Generally, hypoglycemia is treated with small, frequent meals, (5-6 / day) low in carbohydrates, high in protein

Hypoglycemia Lab Findings Symptoms Increased hunger Sweating Nausea Vomiting Dizziness Shaking Blurring of speech and sight Mental confusion Decreased plasma glucose Whipple’s Triad Symptoms of hypoglycemia Low plasma glucose at time of symptoms Alleviation of symptoms with glucose ingestion

Hypoglycemia Causes of: Reactive Fasting Insulin overdose in diabetics Ethanol ingestion Fasting Insulin-producing tumors Hepatic dysfunction Sepsis

Galactosemia Effects: Resulting from : Galactose 1, phosphate uridyl transferase deficiency enzyme that converts galactose to glucose, patients cannot change either galactose or lactose into glucose. results in galactosemia (galactose in blood) Effects: Can lead to mental retardation, cataracts, death check children < 3 yrs for reducing substances

References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. Centers for Disease Control. (2012). Diabetes Public Health Resource. Retrieved from http://www.cdc.gov/diabetes/pubs/factsheet11.htm Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson . http://crossfitovercome.com/2011/12/29/diabetes-primer/