MTY1209 CLINICAL CHEMISTRY 1 (LECTURE)

W13
Carbohydrates
Mr. Aaron Jan S. Palmares, RMT, MSMT | FEU BS Medical Technology 2023
L6
OUTLINE
CARBOHYDRATES 1
General Description Of Carbohydrates 1
Classification Of Carbohydrates 1
Fisher Projection 1
Haworth Projection 1
Stereoisomers 2
FIGURE 14.1 Pathways in glucose metabolism.
Monosaccharides, Disaccharides, Polysaccharides 2
Monosaccharides 2
• The two forms of carbohydrates are aldose and ketose.
Disaccharides 2
Polysaccharides 2 o Aldose form has a terminal carbonyl group
Chemical Properties Of Carbohydrates 2 (O=CH–) called an aldehyde group
Glucose Metabolism 3 o Ketose form has a carbonyl group (O=C) in the
Fate Of Glucose 3 middle linked to two other carbon atoms (called a
Embden-Meyerhof Pathway 3 ketone group)
Anaerobic Glycolysis 3
Hexose Monophosphate Shunt 3
Glycogenesis 4
Glycogenolysis 4
Conclusion In Glucose Metabolism 4
Regulation Of Carbohydrate Metabolism 4
Insulin 4
Glucagon 4
HYPERGLYCEMIA 5
Diabetes Mellitus 5
Classification Of Diabetes Mellitus 5
Type 1 Diabetes Mellitus 5 FIGURE 14.2 Two forms of carbohydrates
Type 2 Diabetes Mellitus 6
Other Specific Types Of Diabetes 6
GDM 6 FISHER PROJECTION
Pathophysiology Of Diabetes Mellitus 6 • has the aldehyde or ketone at the top of the drawing.
Laboratory Findings 6 • The carbons are numbered starting at the aldehyde or
Untreated Patients With Type 2 Diabetes 7 ketone end.
Criteria For Testing For Prediabetes And Diabetes 7
Criteria For The Diagnosis Of Diabetes Mellitus 7 • The compound can be represented as a straight chain
Criteria For The Testing And Diagnosis Of Gdm 8 or might be linked to show a representation of the
HYPOGLYCEMIA 8 cyclic, hemiacetal form
Genetic Defects in Carbohydrate Metabolism 9

CARBOHYDRATES
● carbohydrates are the primary source for brain,
erythrocytes, and retinal cells in humans.
● the major food source and energy supply for the body
and are stored primarily as liver and muscle glycogen
● Disease states involving carbohydrates are split into two
groups
o hyperglycemia FIGURE 14.3 Fischer projection of glucose. Left: Open-chain Fisher
o hypoglycemia projections. Right: Cyclic Fisher projection.

GENERAL DESCRIPTION OF CARBOHYDRATES HAWORTH PROJECTION

• are compounds containing C, H, and O • represents the compound in the cyclic form that is
• The general formula for a carbohydrate is Cx(H2O)y. more representative of the actual structure.
• All carbohydrates contain C=O and –OH functional • formed when the functional (carbonyl) group (ketone
groups. or aldehyde) reacts with an alcohol group on the
• carbohydrate derivatives can be formed by the same sugar to form a ring called either a hemiketal or a
addition of other chemical groups, such as hemiacetal ring
phosphates, sulfates, and amines.
• The classification of carbohydrates is based on four
different properties
➢ the size of the base carbon chain
➢ the location of the CO function group
➢ the number of sugar units
➢ the stereochemistry of the compound

CLASSIFICATION OF CARBOHYDRATES
• Carbohydrates can be grouped into generic FIGURE 14.4 Haworth projection of glucose.
classifications based on the number of carbons in the
molecule
➢ trioses contain three carbons
➢ tetroses contain four
➢ pentoses contain five
➢ hexoses contain six
• Carbohydrates are hydrates of aldehyde or ketone
derivatives based on the location of the CO functional
group
FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 1 of 10
 MTY1209 | LEC Carbohydrates

STEREOISOMERS Disaccharides
• The central carbons of a carbohydrate are • formed when two monosaccharide units are joined
asymmetric (chiral)—four different groups are attached by a glycosidic linkage.
to the carbon atoms. • On hydrolysis, disaccharides will be split into two
• allows for various spatial arrangements around each monosaccharides by disaccharide enzymes (e.g.,
asymmetric carbon (also called stereogenic centers) lactase) located on the microvilli of the intestine;
forming molecules monosaccharides are then actively absorbed.
• have the same order and types of bonds but different • The most common disaccharides are maltose
spatial arrangements and different properties (comprising two D-glucose molecules in a 1 → 4 linkage),
• Each asymmetric carbon lactose, and sucrose.
o there are 2n possible isomers
o there are 21, or two, forms of glyceraldehyde. Polysaccharides
o Because an aldohexose contains four asymmetric
• Oligosaccharides are the chaining of 2 to 10 sugar units,
carbons, there are 24, or 16, possible isomers.
whereas polysaccharides are formed by the linkage of
• Monosaccharide many monosaccharide units.
o is assigned to the D or the L series according to the
• On hydrolysis, polysaccharides will yield more than 10
configuration at the highest numbered asymmetric
monosaccharides.
carbon.
• The most common polysaccharides are starch
o This asymmetrically substituted carbon atom is
(glucose molecules) and glycogen
called the “configurational atom” or chiral center.
o if the hydroxyl group (or the oxygen bridge of the ring
form) projects to the right in the Fisher projection, the
sugar belongs to the D series and receives the prefix
D-, and if it projects to the left, then it belongs to the
L series and receives the prefix L-.
o These are called enantiomers, are images that
cannot be overlapped and are nonsuperimposable. FIGURE 14.6 Linkage of monosaccharides.

CHEMICAL PROPERTIES OF CARBOHYDRATES

• Some carbohydrates are reducing substances
o To be a reducing substance, the carbohydrate must
contain a ketone or an aldehyde group.
• Carbohydrates can form glycosidic bonds with other
carbohydrates and with noncarbohydrates.
• Two sugar molecules can be joined in tandem forming a
glycosidic bond between the hemiacetal group of one
molecule and the hydroxyl group on the other molecule.
• Forming glycosidic bond
o acetal is generated on one sugar (at C1) in place of
the hemiacetal.
o If the bond forms with one of the other carbons on
the carbohydrate other than the anomeric (reducing)
FIGURE 14.5 Stereoisomers of glucose. carbon, the anomeric carbon is unaltered and the
• D-glucose is represented in the Fisher projection with the resulting compound remains a reducing substance.
hydroxyl group on carbon number 5 positioned on the • Examples of reducing substance
right. o glucose, maltose, fructose, lactose, and galactose.
• L-glucose has the hydroxyl group of carbon number 5 • If the bond is formed with the anomeric carbon on the
positioned on the left. Most sugars in humans are in the other carbohydrate, the resulting compound is no longer
D-form. a reducing substance.
• Nonreducing carbohydrates do not have an active
MONOSACCHARIDES, DISACCHARIDES, ketone or aldehyde group; not reduce other
POLYSACCHARIDES compounds. T
• This chaining of sugars relies on the formation of o The most common nonreducing sugar is
glycoside bonds that are bridges of oxygen atoms. sucrose—table sugar
• Hydrolysis
– When two carbohydrate molecules join, a water
molecule is produced.
– When they split, one molecule of water is used to
form the individual compounds

CLASSIFICATION EXAMPLES
FIGURE 14.7 Haworth projection of sucrose.
Monosaccharides glucose, galactose, fructose
Disaccharides maltose, lactose, sucrose • All monosaccharides and many disaccharides are
reducing agents
Polysaccharides starch, glycogen, cellulose
o because a free aldehyde or ketone (the open-chain
form) can be oxidized under the proper conditions.
Monosaccharides o As disaccharide remains a reducing agent when the
• Simple sugars that cannot be hydrolyzed to a simpler hemiacetal or ketal hydroxyl group is not linked to
form. another molecule, both maltose and lactose are
• These sugars can contain three, four, five, and six or reducing agents, whereas sucrose is not
more carbon atoms (known as trioses, tetroses,
pentoses, and hexoses).
• The most common include glucose, fructose, and
galactose.

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 2 of 10

 MTY1209 | LEC Carbohydrates

GLUCOSE METABOLISM • Ultimate Goal:

• Glucose is a primary source of energy for humans. ✓ to convert glucose to carbon dioxide and water.
• The nervous system, including the brain, totally depends ✓ During this process, the cell obtains the high-energy
on glucose from the surrounding extracellular fluid (ECF) molecule adenosine triphosphate (ATP) from
for energy. inorganic phosphate and adenosine diphosphate.
• Nervous tissue cannot concentrate or store ✓ cell requires oxygen for the final steps in the electron
carbohydrates; therefore transport chain (ETC).
• it is critical to maintain a steady supply of glucose to the ✓ Nicotinamide adenine dinucleotide (NAD) in its
tissue. reduced form (NADH) will act as an intermediate to
• the concentration of glucose in the ECF must be couple glucose oxidation to the ETC in the
maintained in a narrow range. mitochondria where much of the ATP is gained.
o When the concentration falls below a certain level, • The first step for all three pathways requires glucose
the nervous tissue loses the primary energy source to be converted to glucose-6-phosphate using the
and is incapable of maintaining normal function high-energy molecule, ATP.
o catalyzed by the enzyme hexokinase
FATE OF GLUCOSE • Glucose-6-phosphate can enter the Embden-
• Most of our ingested carbohydrates are polymers, such Meyerhof pathway or the hexose monophosphate
as starch and glycogen. pathway (HMP) or can be converted to glycogen
• Salivary amylase and pancreatic amylase o important for the generation of energy from glucose
o responsible for the digestion of these nonabsorbable o the conversion to glycogen pathway is important for
polymers to dextrins and disaccharides the storage of glucose
o further hydrolyzed to monosaccharides by maltase,
an enzyme released by the intestinal mucosa Embden-Meyerhof Pathway
• Sucrase and lactase • glucose is broken down into two- and three-carbon
o two other important gut-derived enzymes that molecules of pyruvic acid that can enter the tricarboxylic
hydrolyze sucrose to glucose and fructose and acid (TCA) cycle on conversion to acetyl-coenzyme A
lactose to glucose and galactose. (acetyl-CoA).
• requires oxygen and is called the aerobic pathway
• Glycerol released from the hydrolysis of triglycerides can
enter at 3-phosphoglycerate, and fatty acids and ketones;
some amino acids are converted or catabolized to acetyl-
CoA, which is part of the TCA cycle.
• Other AA enters the pathway as pyruvate or as
deaminated α-ketoacids and α-oxoacids
• Gluconeogenesis
o conversion of amino acids by the liver and other
specialized tissue to substrates that can be
converted to glucose
o encompasses the conversion of glycerol, lactate,
and pyruvate to glucose.

Anaerobic Glycolysis
• important for tissue such as muscle, which often have
important energy requirements without an adequate
oxygen supply.
• These tissues can derive ATP from glucose in an oxygen-
deficient environment by converting pyruvic acid into
lactic acid.
o lactic acid diffuses from the muscle cell, enters the
systemic circulation, and is then taken up and used
by the liver
• For anaerobic glycolysis to occur
o 2 mol of ATP must be consumed for each mole of
glucose
o 4 mol of ATP are directly produced, resulting in a net
gain of 2 mol of ATP.
o Further gains of ATP result from the introduction of
pyruvate into the TCA cycle and NADH into the ETC

FIGURE 14.8 The Embden-Meyerhof pathway for anaerobic glycosis. Hexose Monophosphate Shunt
• When disaccharides are converted to monosaccharides, • a detour of glucose-6-phosphate from the glycolytic
they are absorbed by the gut and transported to the liver pathway to become 6-phosphogluconic acid.
by the hepatic portal venous blood supply. • This oxidized product permits the formation of ribose-5-
• Glucose is the only carbohydrate to be directly used phosphate and NADP in its reduced form (NADPH).
for energy or stored as glycogen o NADPH is important to erythrocytes that lack
• Galactose and fructose must be converted to glucose mitochondria and are therefore incapable of the TCA
before they can be used. cycle.
• After glucose enters the cell, it is quickly shunted into one o The reducing power of NADPH is required for the
of three possible metabolic pathways, depending on the protection of the cell from oxidative and free radical
availability of substrates or the nutritional status of the damage.
cell. o Without NADPH, the lipid bilayer membrane of the
cell and critical enzymes would eventually be
destroyed, resulting in cell death

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 3 of 10

 MTY1209 | LEC Carbohydrates

Glycogenesis Insulin
• Glucose-6-phosphate is converted to glucose-1- • The primary hormone responsible for the entry of glucose
phosphate, which is then converted to uridine into the cell.
diphosphoglucose and then to glycogen by glycogen • It is synthesized by the β-cells of islets of Langerhans in
synthase. the pancreas.
• Hepatocytes are capable of releasing glucose from • When these cells detect an increase in body glucose,
glycogen or other sources to maintain the blood they release insulin.
glucose concentration. • The release of insulin causes an increased movement of
o the liver synthesizes the enzyme glucose-6- glucose into the cells and increased glucose metabolism.
phosphatase. Without this enzyme, glucose is • Insulin is the only hormone that decreases glucose levels
trapped in the glycolytic pathway and can be referred to as a hypoglycemic agent.
• Muscle cells do not synthesize glucose-6-
phosphatase and, therefore, they are incapable of Glucagon
dephosphorylating glucose. • The primary hormone responsible for increasing glucose
• Once glucose enters a muscle cell, it remains as levels.
glycogen unless it is catabolized. • It is synthesized by the α-cells of islets of Langerhans in
the pancreas and released during stress and fasting
Glycogenolysis states.
• is the process by which glycogen is converted back to • When these cells detect a decrease in body glucose, they
glucose-6-phosphate for entry into the glycolytic pathway release glucagon.
• Glucagon acts by increasing plasma glucose levels by
Table 14.1 glycogenolysis in the liver and an increase in
PATHWAYS IN GLUCOSE METABOLISM gluconeogenesis.
glucose → pyruvate/lactate (energy • It can be referred to as a hyperglycemic agent
Glycolysis
production) • Two hormones produced by the adrenal gland affect
carbohydrate metabolism.
noncarbohydrate sources → o Epinephrine is released during times of stress.
Gluconeogenesis
glucose-6-phosphate o Glucocorticoids, primarily cortisol, are released
Glycogenolysis glycogen →glucose (for energy use) from the adrenal cortex on stimulation by
Glycogenesis glucose → glycogen (storage) adrenocorticotropic hormone (ACTH).
o Cortisol increases plasma glucose by decreasing
Lipogenesis carbohydrates → fatty acids intestinal entry into the cell and increasing
Lipolysis secomposition of fat gluconeogenesis, liver glycogen, and lipolysis.
• Two anterior pituitary hormones, growth hormone and
CONCLUSION IN GLUCOSE METABOLISM ACTH, promote increased plasma glucose.
• dietary glucose and other carbohydrates either can be • Growth hormone increases plasma glucose by
used by the liver and other cells for energy or can be decreasing the entry of glucose into the cells and
stored as glycogen for later use. increasing glycolysis.
• When the supply of glucose is low, the liver will use o Its release from the pituitary is stimulated by
glycogen and other substrates to elevate the blood decreased glucose levels and inhibited by increased
glucose concentration. glucose.
o These include glycerol from triglycerides, lactic acid o Decreased levels of cortisol stimulate the anterior
from skin and muscles, and amino acids. pituitary to release ACTH.
o ACTH, in turn, stimulates the adrenal cortex to
• If the lipolysis of triglycerides is unregulated, it results in
release cortisol and increases plasma glucose levels
the formation of ketone bodies, which the brain can use
by converting liver glycogen to glucose and
as a source of energy through the TCA cycle.
promoting gluconeogenesis.
• The synthesis of glucose from amino acids is
• Two other hormones affect glucose levels: thyroxine
gluconeogenesis.
and somatostatin.
o used in conjunction with the formation of ketone
bodies when glycogen stores are depleted— • The thyroid gland is stimulated by the production of
conditions normally associated with starvation. thyroid-stimulating hormone to release thyroxine that
increases plasma glucose levels by increasing
• The principal pathway for glucose oxidation is
glycogenolysis, gluconeogenesis, and intestinal
through the Embden-Meyerhof pathway.
absorption of glucose.
• NADPH can be synthesized through the HMP shunt,
• Somatostatin, produced by the δ-cells of the islets of
which is a side pathway from the anaerobic glycolytic
Langerhans of the pancreas, increases plasma glucose
pathway
levels by the inhibition of insulin, glucagon, growth
hormone, and other endocrine hormones.
REGULATION OF CARBOHYDRATE METABOLISM
• The liver, pancreas, and other endocrine glands are
all involved in controlling the blood glucose Table 14.2 THE ACTION OF HORMONES
concentrations within a narrow range. Action of INSULIN
• During a brief fast, glucose is supplied to the ECF from
INCREASE DECREASE
the liver through glycogenolysis.
• Glycogenesis and glycolysis: • glycogenolysis
• When the fasting period is longer than 1 day, glucose is Glucose → glycogen → pyruvate → acetyl
synthesized from other sources through CoA
gluconeogenesis. • lipogenesis
• Control of blood glucose is under two major hormones: Action of GLUCAGON
insulin and glucagon, both produced by the pancreas.
• Other hormones and neuroendocrine substances also INCREASE
exert some control over blood glucose concentrations, • Glycogenolysis:
Glycogen → glucose
permitting the body to respond to increased demands for
glucose or to survive prolonged fasts. • gluconeogenesis
fatty acids → acetyl-CoA → ketone, proteins → amino acids

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 4 of 10

 MTY1209 | LEC Carbohydrates

Hormone Site of Synthesis Others CLASSIFICATION OF DIABETES MELLITUS

• Type 1 diabetes is characterized by inappropriate
Insulin primary hormone
beta cells of hyperglycemia primarily a result of pancreatic islet β-cell
(hypoglycemic responsible to
Islet of Langerhans destruction and a tendency to keto acidosis.
agent) ↓ plasma glucose
• Type 2 diabetes, in contrast, includes hyperglycemia
Glucagon primary hormone cases that result from insulin resistance with an insulin
alpha cells of
(hyperglycemic responsible to secretory defect.
Islet of Langerhans
agent) ↑ plasma glucose • An intermediate stage, in which the fasting glucose is
Released during increased above normal limits but not to the level of
times of physical diabetes, has been named impaired fasting glucose.
Epinephrine adrenal medulla & emotional • Use of the term impaired glucose tolerance to indicate
stress glucose tolerance values above normal but below
↑ plasma glucose diabetes levels was retained.
• Also, the term GDM was retained for women who
Adrenal cortex
Cortisol develop glucose intolerance during pregnancy.
(glucocorticoids)
(in response to
ACTH)
Type 1 Diabetes Mellitus
Growth Anterior pituitary
↑ plasma glucose • Type 1 diabetes mellitus is a result of cellular-mediated
hormone gland (w/ ACTH)
autoimmune destruction of the β-cells of the
Thyroxine Thyroid gland pancreas, causing an absolute deficiency of insulin
delta cells of secretion.
Somatostatin • Upper limit of 110 mg/dL on the fasting plasma glucose is
Islet of Langerhans
designated as the upper limit of normal blood glucose.
HYPERGLYCEMIA • Type 1 constitutes only 10% to 20% of all cases of
diabetes and commonly occurs in childhood and
• Hyperglycemia is an increase in plasma glucose levels.
adolescence.
• In healthy patients, during a hyperglycemia state, insulin
• This disease is usually initiated by an environmental
is secreted by the β-cells of the pancreatic islets of
factor or infection (usually a virus) in individuals with a
Langerhans.
genetic predisposition and causes the immune
• Insulin enhances membrane permeability to cells in the
destruction of the β-cells of the pancreas and, therefore,
liver, muscle, and adipose tissue.
a decreased production of insulin.
• It also alters the glucose metabolic pathways.
• Characteristics of type 1 diabetes include abrupt onset,
• Hyperglycemia, or increased plasma glucose levels, is insulin dependence, and ketosis tendency.
caused by an imbalance of hormones. o This diabetic type is genetically related.
• One or more of the following markers are found in 85% to
DIABETES MELLITUS
90% of individuals with fasting hyperglycemia: islet cell
• Diabetes mellitus is actually a group of metabolic autoantibodies, insulin autoantibodies, glutamic acid
diseases characterized by hyperglycemia resulting decarboxylase autoantibodies, and tyrosine phosphatase
from defects in insulin secretion, insulin action, or both. IA-2 and IA-2B autoantibodies.
• In 1979, the National Diabetes Data Group developed o Signs and symptoms include polydipsia (excessive
a classification and diagnosis scheme for diabetes thirst), polyphagia (increased food intake), polyuria
mellitus. (excessive urine production), rapid weight loss,
• This scheme included dividing diabetes into two broad hyperventilation, mental confusion, and possible
categories: loss of consciousness (due to increased glucose
1) Type 1, insulin-dependent diabetes mellitus (IDDM), to brain).
2) Type 2, non–insulin-dependent diabetes mellitus • Complications include microvascular problems such
(NIDDM). as nephropathy, neuropathy, and retinopathy.
• In 1995, the International Expert Committee on the o Increased heart disease is also found in patients
Diagnosis and Classification of Diabetes Mellitus, with diabetes.
working under the sponsorship of the ADA, was given the • Idiopathic type 1 diabetes is a form of type 1 diabetes
task of updating the 1979 classification system. that has no known etiology, is strongly inherited, and
• The proposed changes included eliminating the older does not have β-cell autoimmunity.
terms of IDDM and NIDDM. The categories of type 1 and o Individuals with this form of diabetes have episodic
type 2 were retained, with the adoption of Arabic requirements for insulin replacement.
numerals instead of Roman numerals
Table 14.4
***See Table 14.3 at the end
LABORATORY FINDINGS IN HYPERGLYCEMIA
Therefore, the ADA/World Health Organization (WHO) Increased glucose in plasma and urine
guidelines recommend the following categories of diabetes: Increased urine-specific gravity
• Type 1 diabetes Increased serum and urine osmolality
• Type 2 diabetes Ketones in serum and urine (ketonemia and ketonuria)
• Other specific types of diabetes Decreased blood and urine pH (acidosis)
• Gestational diabetes mellitus (GDM) (diagnosed in the Electrolyte imbalance
second or third
• trimester of pregnancy that is not clearly overt
diabetes)

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 5 of 10

 MTY1209 | LEC Carbohydrates

Type 2 Diabetes Mellitus ✓ HbA1c, hemoglobin A1c; NGSP, National

• Type 2 diabetes mellitus is characterized by Glycohemoglobin Standardization Program; OGTT, oral
hyperglycemia as a result of an individual’s resistance to glucose tolerance test.
insulin with an insulin secretory defect. ✓ aIn the absence of unequivocal hyperglycemia, these

• This resistance results in a relative, not an absolute, criteria should be confirmed by repeat testing on a
insulin deficiency. different day. The fourth measure (OGTT) is not
• Type 2 constitutes the majority of the diabetes cases. recommended for routine clinical use.
• Most patients in this type are obese or have an
PATHOPHYSIOLOGY OF DIABETES MELLITUS
increased percentage of body fat distribution in the
abdominal region. • In both type 1 and type 2 diabetes, the individual will be
hyperglycemic, which can be severe.
• This type of diabetes often goes undiagnosed for many
years and is associated with a strong genetic • Glucosuria can also occur after the renal tubular
predisposition, with patients at increased risk with an transporter system for glucose becomes saturated.
increase in age, obesity, and lack of physical o This happens when the glucose concentration of
exercise. plasma exceeds roughly 180 mg/dL in an individual
with normal renal function and urine output.
• Characteristics usually include adult onset of the disease
o As hepatic glucose overproduction continues, the
and milder symptoms than in type 1, with ketoacidosis
plasma glucose concentration reaches a plateau
seldom occurring.
around 300 to 500mg/dL (17 to 28 mmol/L).
• However, these patients are more likely to go into a
o Provided renal output is maintained, glucose
hyperosmolar coma and are at an increased risk of
excretion will match the overproduction, causing the
developing macrovascular and microvascular
plateau.
complications.
• The individual with type 1 diabetes has a higher tendency
to produce ketones.
Other Specific Types of Diabetes
• Patients with type 2 diabetes seldom generate ketones
• Other specific types of diabetes are associated with but instead have a greater tendency to develop
certain conditions(secondary), including genetic defects hyperosmolar nonketotic states.
of β-cell function or insulin action, pancreatic disease, o The difference in glucagon and insulin
diseases of endocrine origin, drug- or chemical-induced concentrations in these two groups appears to be
insulin receptor abnormalities, and certain genetic responsible for the generation of ketones through
syndromes. increased β-oxidation.
• The characteristics and prognosis of this form of diabetes • In type1, there is an absence of insulin with an excess of
depend on the primary disorder. glucagon.
• Maturity-onset diabetes of youth is a rare form of diabetes o This permits gluconeogenesis and lipolysis to occur.
that is inherited in an autosomal dominant fashion. • In type 2, insulin is not absent and may, in fact, present
as hyperinsulinemia at times; therefore, glucagon is
GDM attenuated.
• GDM has been defined as any degree of glucose o Fatty acid oxidation is inhibited in type 2.
intolerance with onset or first recognition during o This causes fatty acids to be incorporated into
pregnancy. triglycerides for release as very low-density
• However, the latest recommendations suggest that "high- lipoproteins.
risk women found to have diabetes at their initial prenatal
visit, using standard criteria (Table 14.5), receive a LABORATORY FINDINGS
diagnosis of overt, not gestational, diabetes”. • The laboratory findings of a patient with diabetes with
• Women identified through the oral glucose tolerance, ketoacidosis tend to reflect dehydration, electrolyte
listed in Table14.8, should receive a diagnosis of GDM. disturbances, and acidosis.
• Causes of GDM include metabolic and hormonal o Acetoacetate, β-hydroxybutyrate, and acetone are
changes. produced from the oxidation of fatty acids.
• Patients with GDM frequently return to normal o The two former ketone bodies contribute to the
postpartum. acidosis.
o However, this disease is associated with increased • Lactate, fatty acids, and other organic acids can also
perinatal complications and an increased risk for the contribute to a lesser degree.
development of diabetes in later years. • Bicarbonate and total carbon dioxide are usually
• Infants born to mothers with diabetes are at increased risk decreased due to Kussmaul-Kien respiration (deep
for respiratory distress syndrome, hypocalcemia, and respirations).
hyperbilirubinemia. • The anion gap in this acidosis can exceed16 mmol/L.
• Fetal insulin secretion is stimulated in the neonate of a Serum osmolality is high as a result of hyperglycemia;
mother with diabetes. sodium concentrations tend to be lower due in part to
o However, when the infant is born and the umbilical losses (polyuria) and in part to a shift of water from cells
cord is severed, the infant's oversupply of glucose is because of the hyperglycemia.
abruptly terminated, causing severe hypoglycemia. • The sodium value should not be falsely underestimated
because of hypertriglyceridemia.
Table 14.5 • Grossly elevated triglycerides will displace plasma
DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS volume and give the appearance of decreased
1) HbA1c≥6.5% using a method that is NGSP certified electrolytes when flame photometry or prediluted, ion-
and standardized to the DCCT assaya. specific electrodes are used for sodium determinations.
2) Fasting plasma glucose≥126 mg/dL (≥7.0 mmol/L). • Hyperkalemia is almost always present as a result of the
3) 2-h plasma glucose≥200 mg/dL (≥11.1 mmol/L) displacement of potassium from cells in acidosis.
during an OGTTa. o This is somewhat misleading because the patient's
4) Random plasma glucose≥200 mg/dL (≥11.1 mmol/L) total body potassium is usually decreased.
plus symptoms of diabetesa.
a
In the absence of unequivocal hyperglycemia, these criteria should be confirmed by
repeat testing on a different day. The fourth measure (OGTT) is not recommended for
routine clinical use.

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 6 of 10

 MTY1209 | LEC Carbohydrates

Untreated Patients with Type 2 Diabetes • In the absence of the above criteria, testing for
• More typical of the untreated patient with type 2 diabetes prediabetes and diabetes should begin at the age of 45
is the nonketotic hyperosmolar state. years.
• The individual presenting with this syndrome has an o If results are normal, testing should be repeated at
overproduction of glucose; however, there appears to be least at 3-year intervals, with consideration of more
an imbalance between production and elimination in frequent testing depending on initial results and risk
urine. status.
• Often, this state is precipitated by heart disease, stroke, • Testing for Type 2 Diabetes (asymptomatic children)
or pancreatitis. have been develop. Criteria:
➢ testing at 10 years old
• Glucose concentrations exceed 300 to 500 mg/dL (17 to ➢ onset of puberty (if earlier, follow-up test every 2 yrs)
28 mmol/L) and severe dehydration is present. • Test children who are overweight:
o The severe dehydration contributes to the inability to ✓ BMI >85th percentile for age and sex
excrete glucose in the urine. ✓ weight for height >85th percentile
o Mortality is high with this condition. ✓ weight >120% of ideal for height
• Ketones are not observed because the severe • Test also those who fit the ff criteria:
hyperosmolar state inhibits the ability of glucagon to a) Family history of type 2 diabetes in first- or second-
stimulate lipolysis. degree relative
• The laboratory findings of nonketotic hyperosmolar b) Race/ethnicity (e.g., Native American, African
coma include plasma glucose values exceeding American, Latino, Asian American, and Pacific
1,000mg/dL (55 mmol/L), normal or elevated plasma Islander)
sodium and potassium, slightly decreased bicarbonate, c) Signs of insulin resistance or conditions associated
elevated blood urea nitrogen (BUN) and creatinine, and with insulin resistance
an elevated osmolality (>320 mOsm/dL). – acanthosis nigricans
• The gross elevation in glucose and osmolality, the – hypertension
elevation in BUN, and the absence of ketones distinguish – dyslipidemia
this condition from diabetic ketoacidosis. – PCOS
d) Maternal history of diabetes or GDM
CRITERIA FOR TESTING FOR PREDIABETES AND
DIABETES CRITERIA FOR THE DIAGNOSIS OF DIABETES
MELLITUS
• The testing criteria for asymptomatic adults for type 2
diabetes mellitus were modified by the ADA Expert • FOUR SUGGESTED METHODS:
Committee to allow for earlier detection of the disease. 1) HbA1c greater than or equal to 6.5% using a
National Glycohemoglobin Standardization Program
• According to the ADA recommendations,
(NGSP)- certified method
o all adults beginning at the age of 45 years should be
2) a fasting plasma glucose ≥126 mg/dL (7.0 mmol/L)
tested for diabetes every 3 years using the
3) an OGTT with a 2-hour postload (75 g glucose load)
hemoglobin A1c(HbA1c), fasting plasma glucose, or
level ≥200 mg/dL (11.1 mmol/L)
a 2-hour 75 g oral glucose tolerance test (OGTT)
4) symptoms of diabetes plus a random plasma
unless the individual has otherwise been diagnosed
glucose level ≥200 mg/dL (11.1 mmol/L)
with diabetes.
• these 4 methods should be confirmed on a subsequent
• Testing should be carried out at an earlier age or more
day by any one of the first three methods
frequently in individuals who display overweight
tendencies, that is, BMI greater than or equal to
25kg/m2(at-risk BMI may be lower in some ethnic groups, TABLE 14.6
i.e., Asian Americans≥23 kg/m2), and have additional risk Categories of FASTING PLASMA GLUCOSE
factors, as follows: Normal fasting
▪ Habitually physically inactive FPG 70–99 mg/dL 3.9–5.5 mmol/L
glucose
▪ Family history of diabetes in a first-degree relative
Impaired FPG 100–125
▪ In a high-risk minority population (e.g., African 5.6–6.9 mmol/L
fasting glucose mg/dL
American, Latino, Native
▪ American, Asian American, and Pacific Islander) Provisional
▪ History of GDM or delivering a baby weighing more diabetes FPG ≥126 mg/dL ≥7.0 mmol/L
than 9 lb (4.1 kg) diagnosis
▪ Hypertension (blood pressure ≥ 140/90 mm Hg)
▪ Low high-density lipoprotein (HDL) cholesterol TABLE 14.7
concentrations (<35 mg/dL Categories of ORAL GLUCOSE TOLERANCE
▪ [0.90 mmol/L])
▪ Elevated triglyceride concentrations > 250 mg/dL Normal
2-h PG
(2.82 mmol/L) Glucose ≤7.8 mmol/L
≤140 mg/dL
▪ A1C ≥ 5.7% (33 mmol/mol), IGT, or IFG on Tolerance
previous testing Impaired
▪ History of impaired fasting glucose/impaired 2-h PG
Glucose 7.8–11.1 mmol/L
glucose tolerance 140–199 mg/dL
Tolerance
▪ Women with polycystic ovarian syndrome (PCOS)
Provisional
▪ Other clinical conditions associated with insulin 2-h PG
diabetes ≥11.1 mmol/L
resistance (e.g., severe ≥200 mg/dL
diagnosis
▪ obesity and acanthosis nigricans)
▪ History of cardiovascular disease
• those who did NOT MEET the criteria of DM but have
above normal glucose levels = place them in 3 categories
for the Risk of Developing Diabetes (“Prediabetes”)
1) Impaired Fasting Glucose (Table 14.6)
2) Impaired Glucose Tolerance (Table 14.7)
3) HbA1c of 5.7–6.4 %

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 7 of 10

 MTY1209 | LEC Carbohydrates

CRITERIA FOR THE TESTING AND DIAGNOSIS OF GDM • Cortisol and Growth Hormone
• revised by International Association of the Diabetes and o released and increase glucose metabolism
Pregnancy Study Groups • CLASSIFIED AS:
➢ recommend that all nondiabetic pregnant women 1) Postabsorptive (fasting) hypoglycemia
should be screened for GDM at 24 to 28 weeks of 2) Postprandial (reactive) hypoglycemia
gestation – timing of hypoglycemia (within 4 hours after
• One-Step Approach meals)
o performance of a 2-hour OGTT using a 75 g glucose – Current approaches suggest classifying
load postprandial hypoglycemia based on the
o Glucose measurements should be taken : severity of symptoms and measured plasma
a) fasting, glucose levels (impt for those with diabetes or at
b) 1 hour, risk of hypoglycemic episodes)
c) 2 hours • ADA and the Endocrine Society
o Diagnostic of GDM if any one of the 3 criteria are met o cuoff/alert value (to prevent hypoglycemic episode)
(performed in the morning after overnight 8-hr fast): – plasma concentration: ≤70 mg/dL (3.9 mmol/L)
➢ FPG ≥180 mg/dL (10 mmol/L) • Px with diabetes (with iatrogenic hypoglycemia) may
➢ 2-hr G ≥153 mg/dL (8.5 mmol/L) potentially be harmed by low glucose level
• Two-Step Approach • rare in individuals with normal glucose metabolism
o initial measurement of PG at 1-hr postload • Individuals w/o diabetes: diagnosis is made in those who
(50g glucose load) demonstrate Whipple triad:
o PG 140 mg/dL = perform 3-hr OGTT (100g glucose (1) hypoglycemic symptoms
load) (2) plasma glucose concentration is low (<50 mg/dL),
o Diagnose GDM if the ff are met or exceeded: symptoms present
➢ fasting: >95 mg/dL (5.3 mmol/L) (3) symptoms relieved by correction of hypoglycemia
➢ 1 hour: ≥180 mg/dL (10.0 mmol/L) (after administration of glucose or glucagon)
➢ 2 hours: ≥155 mg/dL (8.6 mmol/L) • SYMPTOMS of Hypoglycemia
➢ 3 hours: ≥140 mg/dL (7.8 mmol/L) ✓ increased hunger,
o PERFORM: ✓ sweating,
a) in the morning after overnight fast of 8-14 hrs, ✓ nausea and vomiting,
b) after 3 days unrestricted diet (≥150 carbs/day), ✓ dizziness,
c) unlimited physical activity ✓ nervousness and shaking,
✓ blurring of speech and sight,
TABLE 14.8 ✓ mental confusion
Diagnostic Criteria for GESTATIONAL DIABETES • When symptoms are present in a postabsorptive (fasting)
ONE-STEP APPROACH state, insulinoma might be suspected
Fasting PG ≥92 mg/dL (5.1 mmol/L)
TABLE 14.9
1-h PG ≥180 mg/dL (10 mmol/L) Classification of HYPOGLYCEMIA
2-h PG ≥153 mg/dL (8.5 mmol/L) • Requires assistance to actively
TWO-STEP APPROACH administer carbohydrates and
Severe
glucagon or take other corrective
Fasting ≥95 mg/dL (5.3 mmol/L)
actions
1-h PG ≥180 mg/dL (10.0 mmol/L)
• Symptoms of hypoglycemia
≥155 mg/dL (8.6 mmol/L) Documented
2-h PG • Measured PGC ≤70 mg/dL (≤3.9
Symptomatic
3-h PG ≥140 mg/dL (7.8 mmol/L) mmol/)
• No symptoms of hypoglycemia
HYPOGLYCEMIA Asymptomatic • measured PGC ≤70 mg/dL (≤3.9
• involves decreased plasma glucose levels mmol/)
• many cause (some are transient and relatively • Symptoms typical of
insignificant, others can be life threatening) Probable hypoglycemia
• causes brain fuel deprivation that can result to: Symptomatic • No plasma glucose determination
o impaired judgment and behavior, performed
o seizures,
o comas, • Symptoms of hypoglycemia
o functional brain failure, Pseudohypoglycemia • Measured PGC ≥70 mg/dL (≥3.9
o death mmol/)
• result of an imbalance in the rate of glucose appearance PGC Plasma Glucose Concentration
and disappearance from the circulation
• imbalance may be caused by treatment (diabetic drugs or LABORATORY FINDINGS
biological factors)
• Plasma Glucose Concentration INCREASED DECREASED
– Glucagon and other glycemic factors released is insulin levels
between 65–70 mg/dL (3.6–3.9 mmol/L) to 50–55 Px with pancreatic β-cell plasma glucose levels
mg/dL (2.8–3.1 mmol/L) (hypoglycemia symptoms tumors (insulinoma)
appear)
• Warning signs and symptoms are related to CNS
• To increase PG, in unison with glucagon:
➢ release of epinephrine into the systemic circulation
➢ norepinephrine at nerve endings of specific neurons
• Glucagon
o released from the islet (alpha) cells of the pancreas
o inhibits insulin

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 8 of 10

 MTY1209 | LEC Carbohydrates

• To investigate an insulinoma, the patient is required to • Other causes of hypoglycemia:

fast under controlle conditions. (1) inborn errors of amino acid metabolism
• Men and women have different metabolic patterns in (2) long-chain fatty acid oxidation
prolonged fasts. (3) alimentary hypoglycemias
Healthy Male PG 55–60 mg/dL (3.1–3.3 mmol/L) – caused by an increase in the release of insulin
in response to rapid absorption of nutrients after
produce ketones more readily a meal or the rapid secretion of insulin-releasing
Healthy
and permit PG to decrease to gastric factors
Female
≤40 mg/dL (2.2 mmol/L) (4) idiopathic hypoglycemias

Diagnostic Criteria for INSULINOMA

Glucose ≥25 mg/dL (1.4 mmol/L)
Insulin ≥6 μU/mL (41.7 pmol/L) References
C-peptide ≥0.2 nmol/L Bishop, M.L., Fody, E.P., & Schoeff, L.E. (2018). Carbohydrates. Clinical
chemistry : principles, techniques, and correlations (8th edition). Wolters
Proinsulin ≥5 pmol/L Kluwer.
β-hydroxybutyrate
≤2.7 mmol/L Canvas modules
levels Handout by Mr. Aaron Jan S. Palmares, RMT, MSMT
FEU MNL IAS Department of Medical Technology
Genetic Defects in Carbohydrate Metabolism
• Glycogen storage diseases are the result of the
deficiency of a specific enzyme that causes an alternation
of glycogen metabolism
• glucose-6-phosphatase deficiency type 1 (Gierke
disease)
o most common congenital form of glycogen storage
disease
o autosomal recessive
o characterized by severe hypoglycemia that coincides
with
▪ metabolic acidosis
▪ ketonemia
▪ elevated lactate and alanine
• Hypoglycemia occurs because glycogen cannot be
converted back to glucose by way of hepatic
glycogenolysis.
• Glycogen buildup in liver (hepatomegaly)
• Patients will have: hypoglycemia, hyperlipidemia,
uricemia, and growth retardation.
• Liver biopsy: (+) glycogen stain
• Although the glycogen accumulation is irreversible, the
disease can be kept under control by avoiding the
development of hypoglycemia
• Liver transplantation corrects the hypoglycemic
condition
• Other Enzyme Defects of Deficiencies that cause
hypoglycemia:
a) glycogen synthase
b) fructose-1,6-bisphosphatase
c) phosphoenolpyruvate carboxykinase
d) pyruvate carboxylase
• Glycogen debrancher enzyme deficiency
o (X) hypoglycemia
o (✓) hepatomegaly
• Galactosemia
o occurs because of the inhibition of glycogenolysis
o accompanied by diarrhea and vomiting
• Galactose must be removed from the diet to prevent the
development of irreversible complications.
• left untreated: Px will develop mental retardation and
cataracts
• Disorder is identified by measuring:
➢ erythrocyte galactose-1-phosphate uridyltransferase
activity
• LABORATORY FINDINGS:
✓ hypoglycemia
✓ hyperbilirubinemia
✓ galactose accumulation in blood, tissur, and milk
• fructose-1-phosphate aldolase deficiency
o causes nausea and hypoglycemia after fructose
ingestion

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 9 of 10

 MTY1209 | LEC Carbohydrates

TABLE 14.3
Classification of DIABETES MELLITUS
Classification Pathogenesis Epidemiology Characteristics
• β-Cell destruction • 10-20 of all cases • abrupt
• Absolute insulin deficiency • childhood & adolescence • insulin dependence, ketosis
tendency (acetoacetate, acetone,
B-hydroxybutyrate)
• Autoantibodies • Symptoms:
Type 1
- Islet cell autoantibodies ➢ Polydipsia, Polyphagia, Polyuria
- Insulin autoantibodies ➢ Microvascular problems
- Glutamic acid decarboxylase - nephropathy
autoantibodies - neuropathy
- Tyrosine phosphatase IA-2 - retinopathy
and IA-2B autoantibodies
• Relative insulin deficiency • 90% of all cases • non-insulin dependent
• Insulin resistance with an insulin • adult onset • ketosis tendency is seldom
secretory defect (↓ lipolysis)
• Insulin is present • Greater tendency to develop:
(hyperinsulinemia) nonketotic hyperosmolar states
Type 2
• attenuated glucagon secretion • Symptoms:
• ↑ with age, obesity, lack of ➢ Polydipsia, Polyphagia, Polyuria
➢ Microvascular problems
exercise
- nephropathy
- neuropathy
- retinopathy
• Due to metabolic and hormonal • during pregnancy • Glucose intolerance
changes • Risk of:
➢ respiratory distress
Gestational ➢ hypocalcemia
➢ hyperbilirubinemia
• Glucose intolerance during
pregnancy
• Associated with secondary
conditions
- Genetic defects of β-cell
function
Other - Pancreatic disease
- Endocrine disease
- Drug or chemical induced
- Insulin receptor abnormalities
- Other genetic syndromes

ADDITIONAL INFO for HYPERGLYCEMIA:

Diagnostic Criteria For DIABETES MELLITUS Criteria for GESTATIONAL DIABETES

(1) Random Plasma Glucose: >200 mg/dL + symptoms of DM (1) Fasting Plasma Glucose: >92 mg/dL
(2) Fasting Plasma Glucose: >126 mg/dL (2) 1-h plasma glucose: >180 mg/dL
(3) 2-h PG (OGTT): >200 mg/dL during an OGTT (3) 2-h plasma glucose (OGTT): >153 mg/dL
(4) HbA1c: >6.5%

HYPOGLYCEMIA

Causes of HYPOGLYCEMIA
(1) Insulinoma
(2) Islet Hyperplasia
(3) Factitial Hypoglycemia (insulin/sulfonylurea)
(4) Severe exercise
(5) Ketotic Hypoglycemia
(6) Von Gierke disease (↓ G-6-P, inhibit glycogenolysis)
(7) Galactosemia (↓ G-1-PUT, inhibit glycogenolysis)

FP DE JESUS, AE NATIVIDAD, KNJ SAYNES | 2021 Page 10 of 10