Carbohydrates - Chaining of 2 to 10 sugar units

- Major source of food and energy Polysaccharides

for the body. It is commonly stored
- Formed by a linkage of many
in the Liver and as Muscle
monosaccharide units.
Glycogen.
- The most common
- Generally, contains C, H, and O.
polysaccharides are starch, and
- All carbohydrates contain C=O and
glycogen.
–OH.
Glucose Metabolism
Classification of Carbohydrates
- For any pathway to start, glucose
Based on 4 different properties:
should first be converted into
1. The size of the base carbon chain glucose-6-phosphate by the use of
2. The location of the CO function high energy molecule, ATP.
group - The conversion is catalyzed by the
3. The number of sugar units enzyme hexokinase.
4. The stereochemistry of the - It then enters the Embden-
compound Meyerhof Pathway or also known
as the Hexoses Monophosphate
Two Forms of Carbohydrates
Pathway (HMP).
1. Aldose (O=CH-), which is an
Gluconeogenesis – the conversion of
aldehyde group
amino acids by the liver and other
2. Ketose (O=C), which is the ketone
specialized tissue, such as the kidney, to
group
substrates that can be converted to
Monosaccharides, Disaccharides, and glucose. Encompasses all of the
Polysaccharides conversion of glycerol, lactate, and
pyruvate to glucose.
- Carbohydrate classification based
on the number of sugar units in the Glycogenesis – conversion of glucose-6-
chain. phosphate to glucose-1-phosphate which
is then converted into uridine
Monosaccharides diphosphoglucose and then to glycogen
- Are simple sugars that cannot be by glycogen synthase.
hydrolyzed to a much simpler form. Glycogenolysis – is the process by which
- Contains trioses, tetroses, glycogen is converted by to glucose-6-
pentoses, and hexoses. phosphate for entry into the glycolytic
- The most common pathway.
monosaccharides are glucose,
fructose, and galactose. Regulation of Carbohydrate
Metabolism
Disaccharides
- Involves the liver, pancreas, and
- Formed by two monosaccharide other endocrine glands.
units joined by a glycosidic linkage. - Control of blood glucose is done
- Can be split into two by two major hormones from the
monosaccharide by a disaccharide pancreas: insulin and glucagon.
enzyme.
- Major disaccharides are maltose, Insulin
lactose, and sucrose.
- Primary hormone responsible for
Oligosaccharides the entry of glucose into the cell.
 - Synthesized by the beta-islets of
Langerhans in the pancreas.
- It is also responsible for the
regulation of an increase in the
glycogenesis, lipogenesis, and
glycolysis, and in the inhibition of
glycogenolysis.
- It is the only hormone that
decreases the level of glucose and
it is often referred to as the
hypoglycemic agent.
Glucagon
- It is the primary hormone
responsible for increasing the level
of glucose.
- It is synthesized in the alpha-cells
of islets of Langerhans in the
pancreas.
- It is often released during stress
and fasting states.
- It acts by increasing the plasma
glucose levels by glucogenolysis in
the liver and an increase in
gluconeogenesis.
- It is often referred to as the
hyperglycemic agent.
Two Hormone from the Adrenal Gland
that affects carbohydrate metabolism:
1. Epinephrine – produced by the
adrenal medulla.
- Increases plasma glucose by
inhibiting secretion of insulin,
increasing glycogenolysis, and
promoting lipolysis.
- Release during times of stress
2. Glucocorticoids – primarily
cortisol, released from the adrenal
cortex by the action of
adrenocorticotropic hormone
(ACTH).
- Increases plasma glucose by
decreasing intestinal entry into the
cell, and by increasing
gluconeogenesis, liver glycogen,
and lipolysis.
Two Pituitary Hormones that promotes
an increase in the plasma glucose:
1. Growth Hormone
- Increases plasma glucose by
decreasing the entry of glucose
into the cells and by increasing
glycolysis.
- Released when there is a
decreased levels of glucose and is
inhibited once the glucose is
increased.
2. ACTH
- Released when there is a
decrease in the levels of cortisol.
- Increases the levels of plasma
glucose by converting liver
glycogen to glucose and promoting
gluconeogenesis.
Two Other Hormones that affects the
Glucose Levels:
1. Thyroxine
- Produced by the thyroid gland
through the production of thyroid-
stimulating hormone.
- Increases the levels of plasma
glucose by increasing
glycogenolysis, gluconeogenesis,
and intestinal absorption of
glucose.
2. Somatostatin
- Produced by the delta-cells of the
islets of Langerhans of the
pancreas.
- Increases glucose levels in the
plasma by the inhibition of insulin,
glucagon, growth hormone, and
other endocrine hormones.
Hyperglycemia
- An increase in the levels of plasma
glucose.
- Usually caused by an imbalance of
hormones.
Diabetes Mellitus
- Group of metabolic diseases
characterized by hyperglycemia
resulting from defects in insulin
secretion, insulin action, or in both.
Two Categories of DM:
 1. DM Type 1, Insulin-Dependent
Diabetes Mellitus (IDDM)
2. DM Type 2, Non-Insulin
Dependent Diabetes Mellitus
(NIDDM)
Other Categories
3. Other specific types of Diabetes
4. Gestational Diabetes Mellitus
(GDM) – diagnosed during the
Second or Third Trimester of
pregnancy.
Type 1
- Characterized by inappropriate
hyperglycemia primarily result of
pancreatic islet beta-cell
destruction and a tendency of
ketoacidosis.
- A result of cellular-mediated
autoimmune destruction of the
beta-cells of pancreas, casing an
absolute deficiency of insulin
secretion.
- Characterized by abrupt onset,
insulin dependence, and ketosis
tendency.
- Markers of Type 1 DM: islet cell
autoantibodies, insulin
autoantibodies, glutamic acid
decarboxylase autoantibodies, and
tyrosine phosphatase IA-2 and IA-
2B autoantibodies.
Type 2 Diabetes Mellitus
- Characterized by hyperglycemia
as a result of an individual’s
resistance to insulin with an insulin
secretory defect, which may lead
to insulin deficiency.
- Most patient with this type are
obese or have an increase
percentage of body fat distribution
in the abdominal region.
- Associated with a strong genetic
predisposition.
- Characterized by adult onset, and
milder symptoms than type 1, with
ketoacidosis seldom occurring.
Gestational Diabetes Mellitus
- Defined as any degree of glucose
intolerance with onset or first
recognition during pregnancy.
- Caused by metabolic and
hormonal changes.
- Infants born to mothers with GDM
are at increased risk of respiratory
distress syndrome, hypocalcemia,
and hyperbilirubinemia, and in
most cases, severe hypoglycemia
because of the over production of
fetal insulin.
Pathophysiology of Diabetes Mellitus
- Hyperglycemic individual.
- Saturation of glucose in the renal
tubular transporter may lead to
Glucosuria, which usually happens
when the glucose in the plasma
exceeds 180 mg/dL.
- In type 1 DM, there is an absence
of insulin and excess of glucagon,
which leads to gluconeogenesis
and lipolysis to occur.
- In type 2 DM, there is sometimes
presence of hyperinsulinemia, and
attenuation of glucagon. In
addition, inhibition of fatty acid
oxidation is also present in type 2
DM.
- Patients diagnosed with DM with
ketoacidosis presents dehydration,
electrolyte disturbances, and
acidosis.
- People with Type 2 DM have
higher, especially those untreated
have higher risk of acquiring
nonketotic hyperosmolar state –
the production of glucose is in
excess but the elimination in urine
is lessen. Concentration of
Glucose exceed 300 to 500 mg/dL
(17 to 28 mmol/L), and severe
dehydration is present.
- Patients with impaired fasting
glucose, and impaired glucose
tolerance are not diagnosed to
have diabetes mellitus.
Criteria for the Diagnosis of Diabetes
Mellitus
Four Methods of Diagnosis: equal to 155 mg/Dl; or 3 hours:
greater than or equal to 140 mg/Dl.
1. HbA1C greater than or equal to
- The test should be performed after
6.5%
an overnight fast of 8 to 14 hours
2. A fasting plasma glucose greater
with 3 days of unrestricted diet and
than or equal to 126 mg/dL (7.0
unlimited physical activity.
mmol/L)
3. An OGTT with a 2-hour postload Hypoglycemia
(75 g glucose load) level greater
- Decreased plasma glucose levels.
than or equal to 200 mg/dL (11.1
- The result of an imbalance in the
mmol/L)
rate of glucose appearance and
4. Symptoms of diabetes plus a
disappearance from the circulation.
random plasma glucose level
- Plasma glucose levels of 50 – 55
greater than or equal to 200 mg/dL
mg/dL upon the release of
(11.1 mmol/L)
glucagon and other glycemic
Criteria for the Testing and Diagnosis factors may lead to hypoglycemia.
of GDM - When there is hypoglycemia,
epinephrine is released into the
- Done at 24 to 28 weeks of
systemic circulation and
gestation.
norepinephrine is released at the
- One-step approach or Two-step
nerve endings of specific neurons.
approach
Both acts in unison with glucagon
One-Step Approach to release plasma glucose.

- Performance of a 2-hour OGTT Classifications of Hypoglycemia

using a 75g glucose load.
1. Postabsorptive (Fasting)
- Measurement of glucose should be
2. Postprandial (Reactive)
taken at fasting, 1 hour, and 2
- The postprandial hypoglycemia
hours.
occurs in a timing, usually within 4
- A fasting plasma glucose value
hours after meals.
greater than or equal to 92 mg/dL,
a 1-hour value greater than or Whipple Triad
equal to 180 mg/dL, or a 2-hour
- Used to diagnosed hypoglycemia
glucose value greater or equal to
- Characterized by: Hypoglycemic
153 mg/dL is diagnostic of
symptoms; plasma glucose
gestational diabetes mellitus.
concentration is low (<50 mg/dL)
- The test for GDM is performed
when the symptoms are present,
during the morning after at least an
and relief of symptoms after
8 hours fast.
correction of hypoglycemia by
Two-Step Approach administration of glucose or
glucagon.
- An initial measurement of plasma
glucose at 1-hour postload of 50 g Genetic Defects in Carbohydrate
glucose load is performed. Metabolism
- If the plasma glucose value is 140
- Mostly are glycogen storage
mg/dL, a 3-hour OGTT test using
disease that are brought about by
100 glucose load should be done.
a deficiency in specific enzyme
- GDM is diagnosed when the
which causes an alternation the
results are: fasting: >95 mg/Dl; 1-
metabolism of glycogen.
hour: greater than or equal to 180
mg/Dl; 2-hours: greater than or
 - Glucose-6-phosphate deficiency - The concentration of glucose in
type 1 – is the most common type whole blood is 11% lower than that
of glycogen storage disease. It is of the plasma.
also called as the Von Gierke - The serum or plasma should be
Disease, an autosomal recessive refrigerated and separated from
disease. cells within 1 hour to prevent loss
- This disease is characterized by of glucose.
severe hypoglycemia with - Gray-Top Tubes that contains
metabolic acidosis, ketonemia, and sodium fluoride ion are used as
elevated lactate and alanine. anticoagulant and preservative.
- The glycogen build-up of this - Benedict’s and Fehling’s reagents
disease usually causes contain alkaline solution of cupric
Hepatomegaly. ions that are stabilized by citrate or
- Other enzyme defects or tartrate, which turns the solution in
deficiency that causes deep-blue color and a red
hypoglycemia include glycogen precipitate of cuprous oxide forms
synthase, fructose-1,6- if glucose is present.
biphosphatase, - The most common methods of
phosphoenolpyruvate glucose analysis use the enzyme
carboxykinase, and pyruvate glucose oxidase or hexokinase.
carboxylase.
Glucose Tolerance and 2-Hour
- Glycogen Debrancher Enzyme
Postprandial Tests
Deficiency does not cause
hypoglycemia but causes - A solution containing 75 g of
hepatomegaly. glucose is administered, and a
specimen for plasma glucose
Galactosemia
measurement is drawn 2 hours
- Causes failure to thrive syndrome later.
in infants. - Factors that affect the tolerance
- It is a congenital deficiency of one results include medications such
of three enzymes involved in as large doses of Salicylates,
galactose metabolism, resulting in diuretics, anticonvulsants, oral
increased levels of galactose in contraceptives, and
plasma. corticosteroids.
- The most common enzyme that is - Gastrointestinal problems such as
defective in this disease is the malabsorption, surgery, vomiting,
galactose-1-phosphate and endocrine dysfunctions may
uridylltransferase. affect the OGTT results.
- Occurs when glycogenolysis is - The adult dose solution (Glucola)
inhibited in combination with is 75 g; children are 1.75/kg of
diarrhea and vomiting. glucose to a maximum dose of 75
g.
Role of Laboratory in Differential
Diagnosis and Management of Patients Glycosylated Hemoglobin/ HbA1C
with Glucose Metabolic Alterations
- Term used to describe the
Methods of Glucose Measurement formation of hemoglobin
compound produced when glucose
- Serum, plasma, or whole blood
(a reducing sugar) reacts with the
could be used when measuring
amino group of hemoglobin (a
glucose.
protein).
 - Reflects the average blood three urine collection ratio of over
glucose level over the previous 2 3- to 6- months.
to 3 months. - Measured through random spot
- The most common glucose collection, 24-hour urine collection,
molecule in a protein is attached to or through timed 4-hour overnight
one or both the N-terminal valines collection.
of the Beta-Polypeptide chains.
- Normal Range is 4.0% to 6.0%.
Estimated Average Glucose
eAG = 28.7 x HbA1C – 46.7
- HbA1C is measured using EDTA
whole blood sample.
- Affinity chromatography is the
preferred method for HbA1C
testing.
Ketones
- Produced by the liver through fatty
acid metabolism and is responsible
for the source of energy coming
from the lipids in times where the
carbohydrate is low.
Three Ketone Bodies:
1. Acetone (2%)
2. Acetoacetic Acid (20%)
3. 3-beta-hydroxybutyric Acid
(78%)
Ketonemia – refers to the accumulation of
ketones in the blood.
Ketonuria – refers to the accumulation of
ketones in the urine.
- The method used to test ketones is
Gerhardt’s Test that uses ferric
chloride reacted with acetoacetic
acid to produce a red color.
- Another most common method is
the Sodium Nitroprusside Test
which uses acetoacetic acid in an
alkaline pH to form a purple color.
Albuminuria
- Caused by diabetic kidney
disease.
- Albumin-creatinine ratio of 30 to
299 mg/g creatinine in two out of