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MLAB 2401: Clinical Chemistry

Keri Brophy-Martinez

Diabetes and Other Carbohydrate Disorders

HyperglycemiaIncrease 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

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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.

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Effects of Hyperglycemia: Long termPhysiological– 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 hyperglycemiaDisorders 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

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Physiologic abnormalities of diabetes

Hyperglycemia – increase blood glucose. – Doesn’t matter how the glucose is derived - diet, fat

metabolism, protein destruction/wastingKetosis – from fat metabolism, ketonemia, ketonuria

Hyperlipidemia -increase blood lipids from faulty glucose metabolism.Decrease blood pH - metabolic acidosisUrine abnormalities– Glycosuria – glucose present – Polyuria - increase in urine volume– Loss of electrolytes - washing out with the urine

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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 DiabetesInsulin 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

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Type 1 DiabetesClinical Symptoms– CLASSIC TRIAD

• Polyphagia (increased food uptake)

• Polydipsia (thirst)• Polyuria

( increased urine production)

– Other symptoms• Mental confusion • Rapid weight loss• Hyperventilation• Diabetic

ketoacidosis 9

Laboratory Findings

Hyperglycemia- plasma levels > 110 mg/dLGlucosuria- plasma glucose > 180 mg / dl

Decreased insulinIncreased glucagon– Stimulation causes

• Gluconeogenesis• Lipolysis (breakdown of fat produces ketones)

KetoacidosisDecreased blood pH ( acidosis ) Sodium … Potassium … CO2

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Type II Diabetes

Non – Insulin Dependent Diabetes Mellitus( NIDDM )

Most common form of diabetesDemographics– Adult onset – Patients usually > 20 years old– American Indians and non-Hispanic blacks

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Type II Diabetes: PathologyDevelops graduallyDisorder in insulin resistance and relative deficiency of insulinPlasma 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) 12

Laboratory FindingsHyperglycemiaGlucosuriaInsulin is present Glucagon is not elevated

No lipolysis and no ketoacidosisExcess glucose is converted to triglycerides ( plasma triglycerides )

Normal / Increased Na / K Increased BUN & Creatinine ( Decreased renal function )Hyperosmolar plasma from hyperglycemia

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Other (SecondaryDiabetes)

Genetic defects of beta cell functionGenetic defects in insulin actionGenetic syndromesPancreatic diseaseEndocrinopathies Drug or chemical induced

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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

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Criteria for Diagnosis of Diabetes1. Symptoms of diabetes plus random plasma glucose concentration

> 200 mg/dL. Random is defined as any time of day without regard to time

OR2. Fasting plasma glucose > 126 mg/dL. Fasting is defined as no

caloric intake for at least 8 hours.OR3. 2-Hour postprandial glucose > 200 mg/dL during an oral glucose

tolerance test OR4. 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

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HypoglycemiaPlasma 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 insulin

Treatment– Varies with cause. Generally, hypoglycemia

is treated with small, frequent meals, (5-6 / day) low in carbohydrates, high in protein

HypoglycemiaSymptoms

Increased hungerSweating NauseaVomitingDizzinessShakingBlurring of speech and sightMental confusion

Lab FindingsDecreased plasma glucose

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Whipple’s Triad• Symptoms of hypoglycemia• Low plasma glucose at time

of symptoms• Alleviation of symptoms with

glucose ingestion

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HypoglycemiaCauses of:– Reactive

• Insulin overdose in diabetics• Ethanol ingestion

– Fasting• Insulin-producing tumors• Hepatic dysfunction• Sepsis

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GalactosemiaResulting 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

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 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/

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