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

2. 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:
mg / dl

3. 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.

4. 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.

5. 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

6. 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

7. 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)

8. 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

9. 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

10. 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

11. 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

12. 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)

13. 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

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

15. 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

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 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

17. 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

18. 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

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

21. 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

22. 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
Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .