5.3 Chemistry - Glucose, Hemoglobin, Iron, and Bilirubin (1-35)

Which of the following biochemical processes is promoted by insulin?

A. Glycogenolysis

B. Gluconeogenesis

C. Lipolysis

D. Uptake of glucose by cells

D. Uptake of glucose by cells

D Insulin reduces blood glucose levels by increasing glucose uptake by cells. It promotes lipid and glycogen production, induces synthesis of glycolytic enzymes, and inhibits formation of glucose from pyruvate and Krebs cycle intermediates.

Which of the following hormones promotes hyperglycemia?

A. Calcitonin

B. Growth hormone

C. Aldosterone

D. Renin

B. Growth hormone

B Growth hormone and cortisol promote gluconeogenesis and epinephrine stimulates glycogenolysis. Excess thyroid hormone causes hyperglycemia by increasing glucagon and inactivation of insulin, thereby promoting both gluconeogenesis and glycogenolysis. An increase in any of these hormones can cause hyperglycemia. Calcitonin opposes the action of parathyroid hormone. Aldosterone is the primary mineralocorticoid hormone and stimulates sodium reabsorption and potassium secretion by the kidneys. Renin is released from the kidney due to ineffective arterial pressure and promotes activation of angiotensinogen and aldosterone secretion.

Which of the following is characteristic of type 1 diabetes mellitus?

A. Requires an oral glucose tolerance test for diagnosis

B. Is the most common form of diabetes mellitus

C. Usually occurs after age 40

D. Requires insulin replacement to prevent ketosis

D. Requires insulin replacement to prevent ketosis

D Type 1, or juvenile, diabetes is also called insulindependent diabetes because patients must be given insulin to prevent ketosis. Type 1 accounts for only about 10%-20% of cases of diabetes mellitus, and is usually diagnosed by a fasting plasma glucose. Two consecutive results ≥126 mg/dL is diagnostic. Approximately 95% of patients

produce autoantibodies against the beta cells of the pancreatic islets. Other autoantibodies may be produced against insulin, glutamate decarboxylase, and tyrosine phosphorylase IA2. There is genetic association between type 1 diabetes and human leukocyte antigens (HLA) DR3 and DR4.

Which of the following is characteristic of type 2 diabetes mellitus?

A. Insulin levels are consistently low

B. Most cases require a 3-hour oral glucose tolerance test to diagnose

C. Hyperglycemia is often controlled without insulin replacement

D. The condition is associated with unexplained weight loss

C. Hyperglycemia is often controlled without insulin replacement

C. Hyperglycemia is often controlled without insulin replacement

C Type 2, or late-onset diabetes, is associated with a defect in the receptor site for insulin. Insulin levels may be low, normal, or high. Patients are usually

obese and over 40 years of age, although the incidence is increasing in both children and young adults. The American Diabetes Association (ADA) recommends screening all adults for diabetes who are overweight and have one additional risk factor and all adults over age 45, and to retest them every 3 years, if negative. Patients do not require insulin to prevent ketosis and hyperglycemia can be controlled in most patients by diet and drugs that promote insulin release. Type 2 accounts for 80%-90% of all diabetes mellitus.

Which of the following results falls within the diagnostic criteria for diabetes mellitus?

A. Fasting plasma glucose of 120 mg/dL

B. Two-hour postprandial plasma glucose of 160 mg/dL

C. Two-hour plasma glucose of 180 mg/dL following a 75 g oral glucose challenge

D. Random plasma glucose of 250 mg/dL and presence of symptoms

D. Random plasma glucose of 250 mg/dL and presence of symptoms

D The American Diabetes Association recommends the following criteria for diagnosing diabetes mellitus: fasting glucose ≥ 126 mg/dL, casual (random) glucose ≥ 200 mg/dL in the presence of symptoms (polyuria, increased thirst, weight loss), glucose ≥ 200 mg/dL at 2 hours after an oral dose of 75 g of glucose, and hemoglobin A1c ≥ 6.5%. A diagnosis of diabetes mellitus is indicated if any one or combination of these four criteria is met on more than a single testing event. The fasting plasma glucose test requires at least 8 hours with no food or drink except water. The 2-hour postloading test should be conducted according to the oral glucose tolerance guidelines currently recommended by the World Health Organization

Select the most appropriate adult reference range for fasting blood glucose.

A. 40-105 mg/dL (2.22-5.82 mmol/L)

B. 60-140 mg/dL (3.33-7.77 mmol/L)

C. 65-99 mg/dL (3.61-5.50 mmol/L)

D. 75-150 mg/dL (4.16-8.32 mmol/L)

C. 65-99 mg/dL (3.61-5.50 mmol/L)

C Reference ranges vary slightly depending upon method and specimen type. Enzymatic methods specific for glucose have an upper limit of normal no greater than 99 mg/dL. This is the cutoff value for impaired fasting plasma glucose (prediabetes) recommended by the American Diabetes Association. Although 65 mg/dL is considered the 2.5 percentile, a fasting level below 50 mg/dL is often seen without associated clinical hypoglycemia, and neonates have a lower limit of approximately 40 mg/dL owing to maternal insulin

When preparing a patient for an oral glucose tolerance test (OGTT), which of the following conditions will lead to erroneous results?

A. The patient remains ambulatory for 3 days prior to the test

B. Carbohydrate intake is restricted to below 150 g/day for 3 days prior to test

C. No food, coffee, tea, or smoking is allowed 8 hours before and during the test

D. Administration of 75 g of glucose is given to an adult patient following a 10-12-hour fast

B. Carbohydrate intake is restricted to below 150 g/day for 3 days prior to test

B Standardized OGTTs require that patients receive at least 150 grams of carbohydrate per day for 3 days prior to the test in order to stabilize the synthesis of inducible glycolytic enzymes. The 2-hour OGTT test is no longer recommended for screening and should be reserved for confirmation of diabetes in cases that are difficult to diagnose, such as persons who lack symptoms and signs of fasting hyperglycemia.

Which of the following 2-hour glucose challenge results would be classified as impaired glucose tolerance (IGT)?

Two-hour serum glucose:

A. 130 mg/dL

B. 135 mg/dL

C. 150 mg/dL

D. 204 mg/dL

C. 150 mg/dL

C With the exception of pregnant females, impaired glucose tolerance is defined by the ADA as a serum or plasma glucose at 2 hours following a 75-g oral glucose load of ≥140 mg/dL and < 200 mg/dL. Persons who have a fasting plasma glucose of ≥100 but < 126 mg/dL are classified as having impaired fasting glucose (IFG). Both IGT and IFG are risk factors for developing diabetes later in life. Such persons are classified as having prediabetes and should be tested annually.

Which statement regarding gestational diabetes mellitus (GDM) is correct?

A. Is diagnosed using the same oral glucose tolerance criteria as in nonpregnancy

B. Converts to diabetes mellitus after pregnancy in 60%-75% of cases

C. Presents no increased health risk to the fetus

D. Is defined as glucose intolerance originating during pregnancy

D. Is defined as glucose intolerance originating during pregnancy

D Control of GDM reduces perinatal complications such as respiratory distress syndrome, high birth weight, and neonatal jaundice. Women at risk are usually screened between 24 and 28 weeks' gestation. The screening test can be performed nonfasting and consists of an oral 50-g glucose challenge followed by serum or plasma glucose measurement at 1 hour. A result ≥ 140 mg/dL is followed by a 2-hour or 3-hour oral glucose tolerance test to confirm gestational diabetes. For the 3-hour test, a 100-g dose of glucose is used and at least two of the following cutoffs must be exceeded: fasting, ≥ 95 mg/dL or higher; 1 hour, ≥ 180 mg/dL or higher; 2 hour ≥ 155 mg/dL or higher; 3 hour, ≥ 140 mg/dL or higher. The same cutpoints are used for the 2-hour test except that a 75-g dose is used. GDM converts to diabetes mellitus within 10 years in 30%-40% of cases. ADA recommends testing persons with GDM for diabetes 6-12 weeks after delivery

Which of the following findings is characteristic of all forms of clinical hypoglycemia?

A. A fasting blood glucose value below 55 mg/dL

B. High fasting insulin levels

C. Neuroglycopenic symptoms at the time of low blood sugar

D. Decreased serum C peptide

C Clinical hypoglycemia can be caused by insulinoma, drugs, alcoholism, and reactive hypoglycemia. Neuroglycopenic symptoms at the time of low blood sugar

C. Reactive hypoglycemia is characterized by delayed or excessive insulin output after eating and is very rare. Fasting insulin is normal but postprandial levels are increased. High fasting insulin levels (usually > 6 μg/L) are seen in insulinoma, and patients with insulinoma almost always display fasting hypoglycemia, especially when the fast is extended to 48 72 hours. C peptide is a subunit of proinsulin that is hydrolyzed when insulin is released. In hypoglycemia, low levels indicate an exogenous insulin source, whereas high levels indicate overproduction of insulin.

Which statement regarding glycated (glycosylated) Hgb (G-Hgb) is true?

A. Has a sugar attached to the C-terminal end of the β chain

B. Is a highly reversible aminoglycan

C. Reflects the extent of glucose regulation in the 8- to 12-week interval prior to sampling

D. Will be abnormal within 4 days following an episode of hyperglycemia

C. Reflects the extent of glucose regulation in the 8- to 12-week interval prior to sampling

C G-Hgb results from the nonenzymatic attachment of a sugar such as glucose to the N-terminal valine of the β chain. The reaction is nonreversible and is related to the time-averaged blood glucose concentration over the life span of the RBCs. There are three G-Hgb fractions designated A1a, A1b, and Alc. Hemoglobin A1c makes up about 80% of glycated hemoglobin, and is used to determine the adequacy of insulin therapy. The time-averaged blood glucose is approximated by the formula (G-Hgb × 33.3) - 86 mg/dL, and insulin adjustments can be made to bring this level to within reference limits. Also, glycated protein assay (called fructosamine) provides similar data for the period between 2 and 4 weeks before sampling.

What is the American Diabetes Association recommended cutoff value for adequate control of blood glucose in diabetics as measured by glycated hemoglobin?

A. 5%

B. 6.5%

C. 9.5%

D. 11%

B. 6.5%

B The ADA recommends that 6.5% be used as the cutoff for determining the adequacy of treatment for diabetes. A glycated hemoglobin test should be performed at the time of diagnosis and every 6 months thereafter if the result is < 6.5%. If the result is 6.5% or more, the treatment plan should be adjusted to achieve a lower level, and the test performed every 3 months until control is improved.

Which statement regarding measurement of Hgb A1c is true?

A. Levels do not need to be done fasting

B. Both the labile and stable Hgb A1c fractions are measured

C. Samples should be measured within 2 hours of collection

D. The assay must be done by chromatography

A. Levels do not need to be done fasting

A Since Hgb A1C represents the average blood glucose 2-3 months prior to blood collection, the dietary status of the patient on the day of the test has no effect upon the results. Refrigerated whole-blood samples are stable for up to 1 week. Hgb A1C is assayed by cation exchange high-performance liquid chromatography or immunoassay (immunoturbidimetric inhibition) because both methods are specific for stable Hgb A1C, and do not demonstrate errors caused by abnormal hemoglobins, temperature of reagents, or fractions other than A1c.

Which stationary phase is used for the measurement of hemoglobin A1c by high performance liquid chromatography?

A. Octadecylsilane (C18)

B. Cation exchanger

C. Anion exchanger

D. Polystyrene divinylbenzene

B. Cation exchanger

B HPLC methods for measuring Hgb A1c are performed by diluting whole blood with an acid buffer that hemolyzes the sample. Normal hemoglobin A has a weak positive charge at an acidic pH and binds weakly to the resin. Glycated hemoglobin has an even weaker positive charge and is eluted before hemoglobin A. Abnormal hemoglobin molecules S, D, E, and C have a higher positive charge than hemoglobin A and are retained longer on the column. Elution is accomplished by increasing the ionic strength of the mobile phase. Cations in the buffer displace the hemoglobin pigments from the column.

Evaluate the following chromatogram of a whole-blood hemolysate, and identify the cause and best course of action.

A. Result is not reportable because hemoglobin F is present and interferes

B. The result is not reportable because hemoglobin C is present and interferes

C. The result is not reportable because labile hemoglobin A1c is present

D. The result is reportable; neither hemoglobin F or C interfere

D. The result is reportable; neither hemoglobin F or C interfere

D The chromatogram is from a person with hemoglobin AC; however, hemoglobin C is completely separated from Hgb A1c and does not interfere. Hgb F is also present, but does not interfere unless its concentration is > 30%. Labile hemoglobin is formed initially when the aldehyde of glucose reacts with the N-terminal valine of the β globin chain. This Shiff base is reversible but is converted to Hgb A1c by rearrangement to a ketoamine. It is called labile A1c and produces a peak (LA1c) after HgF and before Hgb A1c. Therefore, it does not interfere.

Which statement best describes the use of the Hgb A1C test?

Peak / Calibrated % Area / % Area / Retention Time / Peak Area

Alb / 0.60/ 0.25/ 12500

F/ 0.50/ 0.50/ 11300

LA1c/ 0.75/ 0.70/ 15545

A1c/ 6.2/ 0.90/ 45112

P3/ 2.6 /1.60 /57489

Ao /48.0/ 1.8/ 994813

C/ 43.0 /2.00/ 926745

A. Should be used for monitoring glucose control only

B. May be used for both diagnosis and monitoring

C. Should be used only to monitor persons with type 1 diabetes

D. May be used only to monitor persons with type 2 diabetes

B. May be used for both diagnosis and monitoring

B The ADA now recommends that the hemoglobin A1c test be used for both diagnosis and monitoring blood glucose levels. The cutpoint for diabetes is an A1c of 6.5. Persons with an A1c of 5.7%-6.4% are classified as being at high risk for diabetes within 5 years. An A1c between 4.0%-5.5% is defined as within normal limits

According to American Diabetes Association criteria, which result is consistent with a diagnosis of impaired fasting glucose?

A. 99 mg/dL

B. 117 mg/dL

C. 126 mg/dL

D. 135 mg/dL

B. 117 mg/dL

B Impaired fasting glucose is defined as a plasma glucose ≥100 but <126 mg/dL. A fasting glucose of 126 or higher on two consecutive occasions indicates diabetes. A fasting glucose of 99 mg/dL is considered normal.

What is the recommended cutoff for the early detection of chronic kidney disease in diabetics using the test for microalbuminuria?

A. >30 mg/g creatinine

B. >80 mg/g creatinine

C. >200 mg/g creatinine

D. >80 mg/L

A. >30 mg/g creatinine

A Microalbuminuria is the excretion of small quantities of albumin in the urine. In diabetics, excretion of albumin that is within allowable limits for healthy persons may signal the onset of chronic kidney disease. The term microalbuminuria is defined as albumin excretion ≥ 30 mg/g creatinine but ≤ 300 mg/g creatinine. The use of the albumin to creatinine ratio is preferred to measures of albumin excretory rate (μg/min) because the latter is subject to error associated with timed specimen collection. ADA recommends the test be done annually for all type 2 diabetics and type 1 diabetics who have had the disease for > 5 years

In addition to measuring blood glucose, Hgb A1c, and microalbumin, which test should be done on diabetic persons once per year?

A. Urine glucose

B. Urine ketones

C. Plasma fructosamines

D. Estimated glomerular filtration rate

D. Estimated glomerular filtration rate

D While urinary glucose can identify persons who may have diabetes, it is not sensitive enough to manage glucose control on a daily basis, and has been replaced by whole-blood glucose monitoring or continuous glucose monitoring. While the urinary ketone test is a useful screening test for diabetic and other forms of ketosis, the plasma β hydroxybutyrate test should be used to identify and monitor ketosis in diabetic persons. Fructosamine is a useful adjunct to Hgb A1c to identify poor control of blood glucose in the past 2-4 weeks, but has not been recommended for routine use in all diabetic patients.

Which testing situation is appropriate for the use of point-of-care whole-blood glucose methods?

A. Screening for type 2 diabetes mellitus

B. Diagnosis of diabetes mellitus

C. Monitoring of blood glucose control in type 1 and type 2 diabetics

D. Monitoring diabetics for hyperglycemic episodes only

C. Monitoring of blood glucose control in type 1 and type 2 diabetics

C The ADA does not recommend the use of whole-blood glucose monitors for establishing a diagnosis of diabetes or screening persons for diabetes. The analytical measurement range of these devices varies greatly, and whole blood glucose is approximately 10% lower than serum or plasma glucose. In addition, analytical variance is greater and accuracy less than for laboratory instruments. Whole blood glucose meters should be used by diabetics and caregivers to monitor glucose control and can detect both hyper- and hypoglycemic states that result from too little or too much insulin replacement. Therefore, postprandial monitoring with such a device is recommended for all persons who receive insulin therapy.

Which of the following is the reference method for measuring serum glucose?

A. Somogyi-Nelson

B. Hexokinase

C. Glucose oxidase

D. Glucose dehydrogenase

B. Hexokinase

B The hexokinase method is considered more accurate than glucose oxidase methods because the coupling reaction using glucose-6-phosphate dehydrogenase (G-6-PD) is highly specific. The hexokinase method may be done on serum or plasma collected using heparin, EDTA, fluoride, oxalate, or citrate. The method can also be used for urine, cerebrospinal

fluid, and serous fluids.

Polarographic methods for glucose analysis are based upon which principle of measurement?

A. Nonenzymatic oxidation of glucose

B. The rate of O2 depletion

C. Chemiluminescence caused by formation of adenosine triphosphate (ATP)

D. The change in electrical potential as glucose is oxidized

B. The rate of O2 depletion

B Polarographic glucose electrodes measure the consumption of O2 as glucose is oxidized. Glucose oxidase in the reagent catalyzes the oxidation of glucose by O2 under first order conditions, forming hydrogen peroxide (H2O2). As the dissolved O2 decreases, less is reduced at the cathode, resulting in a decrease in current proportional to glucose concentration. It is important that the H2O2 not breakdown to re-form O2. This is prevented by adding molybdate and iodide that react with H2O2, forming iodine and water, and by adding catalase and ethanol that react with H2O2, forming acetaldehyde and water

In addition to polarography, what other electrochemical method can be used to measure glucose in plasma?

A. Conductivity

B. Potentiometry

C. Anodic stripping voltammetry

D. Amperometry

D. Amperometry

D In some critical care analyzers, amperometric measurement of glucose is used. The glucose oxidaseis impregnated into the membrane covering the electrode. It reacts with glucose in the sample, forming H2O2. This diffuses across the membrane to the anode of the electrode, where it is oxidized to O2. The electrons produced are used to reduce oxygen at the cathode, completing the current path. At the anode (usually platinum), 2H2O2 → 4e- + 2O2 + 4H+. At the cathode (usually silver), O2 + 4H+ + 4e- → 2H2O. The net equation is 2H2O2 → O2 + 2H2O.

Select the enzyme that is most specific for β-D-glucose.

A. Hexokinase

B. G-6-PD

C. Phosphohexisomerase

D. Glucose oxidase

D. Glucose oxidase

D Glucose oxidase is the most specific enzyme reacting with only β-D-glucose. However, the peroxida coupling reaction used in the glucose oxidase method is subject to positive and negative interference. Therefore, hexokinase is used in the reference method.

Select the coupling enzyme used in the hexokinase method for glucose.

A. Glucose-6-phosphate dehydrogenase

B. Peroxidase

C. Glucose dehydrogenase

D. Glucose-6-phosphatase

A. Glucose-6-phosphate dehydrogenase

A The hexokinase reference method uses a protein-free filtrate prepared with barium hydroxide (BaOH) and zinc sulfate (ZnSO4). Hexokinase catalyzes the phosphorylation of glucose in the filtrate using ATP as the phosphate donor. Glucose-6-phosphate (glucose-6-PO4) is oxidized to 6-phosphogluconate and NAD+ is reduced to NADH using G-6-PD. The increase in absorbance at 340 nm is proportional to glucose concentration. Although hexokinase will phosphorylate some other hexoses including mannose, fructose, and glucosamine, the coupling reaction is entirely specific for glucose-6-PO4 eliminating interference from other sugars.

Which glucose method is subject to falsely low results caused by ascorbate?

A. Hexokinase

B. Glucose dehydrogenase

C. Trinder glucose oxidase

D. Polarography

C. Trinder glucose oxidase

C Although glucose oxidase is specific for β-D-glucose, the coupling (indicator) reaction is prone to negative interference from ascorbate, uric acid, acetoacetic acid, and other reducing agents. These compete with the chromogen (e.g., o-dianisidine) for peroxide, resulting in less dye being oxidized to chromophore. The choice of chromogen determines the specificity and linearity. 4-aminophenazone and phenol is more resistant to interference from azo compounds and proteins than is o-dianisidine.

Which of the following is a potential source of error in the hexokinase method?

A. Galactosemia

B. Hemolysis

C. Sample collected in fluoride

D. Ascorbic acid

B. Hemolysis

B The hexokinase method can be performed on serum or plasma using heparin, EDTA, citrate, or oxalate. RBCs contain glucose-6-PO4 and intracellular enzymes that generate NADH, causing positiveinterference. Therefore, hemolyzed samples require a serum blank correction (subtraction of the reaction rate with hexokinase omitted from the reagent).

Which statement about glucose in cerebrospinal fluid (CSF) is correct?

A. Levels below 40 mg/dL occur in septic meningitis, cancer, and multiple sclerosis

B. CSF glucose is normally the same as the plasma glucose level

C. Hyperglycorrhachia is caused by dehydration

D. In some clinical conditions, the CSF glucose can be greater than the plasma glucose

A. Levels below 40 mg/dL occur in septic meningitis, cancer, and multiple sclerosis

A High glucose in CSF is a reflection of hyperglycemia and not central nervous system disease. The CSF glucose is usually 50%-65% of the plasma glucose. Low levels are significant and are most often associated with bacterial or fungal meningitis, malignancy in the central nervous system, and some cases of subarachnoid hemorrhage, rheumatoid arthritis, and multiple sclerosis.

In peroxidase-coupled glucose methods, which reagent complexes with the chromogen?

A. Nitroprusside

B. Phenol

C. Tartrate

D. Hydroxide

B. Phenol

B The coupling step in the Trinder glucose oxidase method uses peroxidase to catalyze the oxidation of a dye by H2O2. Dyes such as 4 aminophenozone or

4-aminoantipyrine are coupled to phenol to form a quinoneimine dye that is red and is measured at about 500 nm.

Point-of-care-tests (POCTs) for whole-blood glucose monitoring are based mainly on the use of:

A. Glucose oxidase as the enzyme

B. Amperometric detection

C. Immunochromatography

D. Peroxidase coupling reactions

B. Amperometric detection

B All POCT devices for monitoring blood glucose use either glucose dehydrogenase (GDH) or glucose oxidase and are amperometric. For glucose oxidase methods, the electrons derive from the oxidation of hydrogen peroxide. For GDH, the electrons are transferred from one of several coenzymes that are reduced when glucose is oxidized, FAD+, NAD+, or PQQ (pyrroloquinoline quinone). Interferences depend upon which enzyme/coenzyme pair are used. For example, maltose and xylose interference can be pronounced with GDH/PQQ-based strips, but not with other GDH or glucose oxidase strips. Uric acid depresses glucose oxidase reactions but has no effect on GDH reactions.

What effect does hematocrit have on POCT tests for whole-blood glucose monitoring?

A. Low hematocrit decreases glucose readings on all devices

B. High hematocrit raises glucose readings on all devices

C. The effect is variable and dependent on the enzyme/coenzyme system

D. Low hematocrit raises readings and high hematocrit lowers readings unless corrected

D. Low hematocrit raises readings and high hematocrit lowers readings unless corrected

D Hematocrit affects POCT glucose measurements. High hematocrit lowers the glucose because RBC glucose concentration is lower than plasma concentration. Other factors include binding of oxygen to hemoglobin and the slower diffusion of glucose onto the solid phase—both of which occur when the hematocrit is high. Bias due to an abnormal hematocrit can be avoided by simultaneously measuring the conductivity of the sample. The

hematocrit is calculated and used to mathematically

correct the glucose measurement.

Which of the following is classified as a mucopolysaccharide storage disease?

A. Pompe's disease

B. von Gierke disease

C. Hers' disease

D. Hurler's syndrome

D. Hurler's syndrome

D Hurler's syndrome is an autosomal recessive disease resulting from a deficiency of iduronidase. Glycosaminoglycans (mucopolysaccharides) accumulate in the lysosomes. Multiple organ failure and mental retardation occur, resulting in early mortality. Excess dermatan and heparin sulfate are excreted in urine. Other mucopolysaccharidoses (MPS storage diseases) are Hunter's, Scheie's, Sanfilippo's, and Morquio's syndromes.

Identify the enzyme deficiency responsible for type 1 glycogen storage disease (von Gierke's disease).

A. Glucose-6-phosphatase

B. Glycogen phosphorylase

C. Glycogen synthetase

D. β-Glucosidase

A. Glucose-6-phosphatase

A Type 1 glycogen storage disease (von Gierke's disease) is an autosomal recessive deficiency of glucose-6 phosphatase. Glycogen accumulates in tissues, causing hypoglycemia, ketosis, and fatty liver. There are seven types of glycogen storage disease, designated type 1 through type 7, involving deficiency of an enzyme that acts on glycogen. Types 1, 4, and 6 cause deficient glycogen breakdown in the liver. Types 2, 5, and 7 involve skeletal muscle and are less severe. Type 3 usually involves both liver and muscle, although an uncommon subtype (3B) involves only the liver

Which of the following abnormal laboratory results is found in von Gierke's disease?

A. Hyperglycemia

B. Increased glucose response to epinephrine administration

C. Metabolic alkalosis

D. Hyperlipidemia

D. Hyperlipidemia

D Von Gierke's disease (type 1 glycogen storage disease) results from a deficiency of glucose-6-phosphatase. This blocks the hydrolysis of glucose-6-PO4 to glucose and Pi, preventing degradation of glycogen to glucose. The disease is associated with increased triglyceride levels because fats are mobilized for energy and lactate acidosis caused by increased glycolysis. A presumptive diagnosis is made when intravenous galactose administration fails to increase serum glucose, and can be confirmed by demonstrating glucose-6-phosphatase deficiency or decreased glucose production in response to epinephrine.

The D-xylose absorption test is used for the differential diagnosis of which two diseases?

A. Pancreatic insufficiency from malabsorption

B. Primary from secondary disorders of glycogen synthesis

C. Type 1 and type 2 diabetes mellitus

D. Generalized from specific carbohydrate intolerance

A. Pancreatic insufficiency from malabsorption

A Xylose is a pentose that is absorbed without the help of pancreatic enzymes and is not metabolized. In normal adults, more than 25% of the dose is excreted into the urine after 5 hours. Low blood or urine levels are seen in malabsorption syndrome, sprue, Crohn's disease, and other intestinal disorders, but not pancreatitis.