1 MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Diabetes and Other Carbohydrate Disorders
2 HyperglycemiaIncrease in plasma glucose levels due to hormone imbalanceHealthy patientsInsulin is secreted by the β cells of the pancreatic islets of LangerhansReference RangeIncreased plasma glucose:> 110 mg / dlGlucose reference range:mg / dl
3 Effects of Hyperglycemia Immediate EffectsIncreased extracellular osmotic pressureThe increased glucose in plasma pulls water out of cellsResults in dehydrationAcidosis - metabolic acidosis.May resultIf 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.
4 Effects of Hyperglycemia: Long term PhysiologicalHeart attacks/strokes, Diabetic retinopathy(Blindness), kidney failure, neurologic defects, susceptibility to infectionsChemicalGlycosylated hemoglobinthe formation of glycosylated hemoglobin is the result of prolonged elevation of plasma glucose.
5 Diabetes Characterized by hyperglycemia Disorders differ in etiology, symptoms and consequencesLab’s roleAssist in diagnosis of the diseaseIdentification of the disorderAssessment of progression of tissue damage
6 Physiologic abnormalities of diabetes Hyperglycemiaincrease blood glucose.Doesn’t matter how the glucose is derived - diet, fat metabolism, protein destruction/wastingKetosisfrom fat metabolism, ketonemia, ketonuriaHyperlipidemia -increase blood lipids from faulty glucose metabolism.Decrease blood pH - metabolic acidosisUrine abnormalitiesGlycosuria – glucose presentPolyuria - increase in urine volumeLoss of electrolytes - washing out with the urine
7 DiabetesWorld Health Organization (WHO) and American Diabetes Association (ADA) recommends four categories of diabetes:Type 1 diabetesMost severe and potentially lethalType 2 diabetesOther (secondary diabetes)Gestational diabetes mellitus (GDM)
8 Type 1 Diabetes Insulin dependent diabetes mellitus ( IDDM ) 5-10 % of diabetes casesDemographicsNon-Hispanic Whites/ Non-Hispanic BlacksChildren & adolescentsPathologyDisease triggered by viral illness or environmental factors that destroys beta cells in pancreas.Absolute Insulin deficiencyDefect in secretion, production or action or allAutoimmune destruction of islet beta – cells in pancreasAuto-antibodies are present
11 Type II Diabetes Non – Insulin Dependent Diabetes Mellitus( NIDDM ) Most common form of diabetesDemographicsAdult onsetPatients usually > 20 years oldAmerican Indians and non-Hispanic blacks
12 Type II Diabetes: Pathology Develops graduallyDisorder in insulin resistance and relative deficiency of insulinPlasma glucose is unable to enter cellsContributory factorsObesityLack of exerciseDietGeneticsDrugs, such as diuretics, psychoactive drugsIncreases in hormones that inhibit/antagonize insulin (GH & cortisol)
13 Laboratory Findings Hyperglycemia Glucosuria Insulin is present Glucagon is not elevatedNo lipolysis and no ketoacidosisExcess glucose is converted to triglycerides ( plasma triglycerides )Normal / Increased Na / KIncreased BUN & Creatinine ( Decreased renal function )Hyperosmolar plasma from hyperglycemia
14 Other (SecondaryDiabetes) Genetic defects of beta cell functionGenetic defects in insulin actionGenetic syndromesPancreatic diseaseEndocrinopathiesDrug or chemical induced
15 Gestational DiabetesGlucose intolerance associated with pregnancy’s hormonal and metabolic changesMothers usually return to normal after pregnancy, but with increased risk for diabetes later on in lifeInfants are at increased risk for respiratory complications and hypoglycemia after birth
16 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 timeORFasting 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 test4. A HgbA1C > 6.5%, confirmed on repeat measurementSide notesGlucose 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
17 Hypoglycemia Plasma glucose level falls below 60 mg/dL Glucagon is released when plasma glucose is < 70 mg / dL to inhibit insulinEpinephrine, cortisol, and growth hormone released from adrenal gland to increase glucose metabolism and inhibit insulinTreatmentVaries with cause. Generally, hypoglycemia is treated with small, frequent meals, (5-6 / day) low in carbohydrates, high in protein
18 Hypoglycemia Lab Findings Symptoms Increased hunger Sweating Nausea VomitingDizzinessShakingBlurring of speech and sightMental confusionDecreased plasma glucoseWhipple’s TriadSymptoms of hypoglycemiaLow plasma glucose at time of symptomsAlleviation of symptoms with glucose ingestion
21 Galactosemia Effects: Resulting from :Galactose 1, phosphate uridyl transferase deficiencyenzyme 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, deathcheck children < 3 yrs for reducing substances
22 ReferencesBishop, 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 fromSunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .