19 Endocrine Pancreatic Function: Carbohydrates

Glucose

Enzymes Needed in Carbohydrate Metabolism

Primary energy source for the human body
Sources

Diet thru digestion of dietary carbohydrates

Food stores (glycogen)

Endogenous synthesis of glucose from

noncarbohydrate sources (amino acids,
glycerol, lactate)
Carbohydrate metabolism disorders

Hyperglycemia

Hypoglycemia
The most frequently occuring hyperglycemic disorder
diabetes mellitus

Salivary amylase

Hydrolyzes starch to form the disaccharide maltose

and intermediate products (dextrins)
Pancreatic amylase

Complete digestion of the intermediate products

(dextrins) to produce maltose
Intestinal enzymes

Maltose and other ingested disaccharides (lactose,

sucrose) are hydrolyzed to form monosaccharides
(glucose, galactose, fructose)
Liver enzymes

Convert the non-glucose monosaccharides to glucose

wherein glucose is reacted with adenosine
triphosphate (ATP) forming glucose-6-phosphate
dehydrogenase (G6PD)

GLUCOSE METABOLISM PROCESSES

Glycolysis (Anaerobic)
Anaerobic conversion of glucose to
pyruvate or lactate
Glycogenesis
Process of glycogen formation from
glucose
Glycogenolysis
Breakdown of glycogen to form glucose

SUBSTRATE
Glucose

PRODUCE
Pyruvate/
Lactate + ATP

GLUCOSE METABOLISM USE

Energy production (2 ATP)

Glucose

Glycogen

Storage of glucose as glycogen in liver and

muscle

Glycogen

Glucose

Gluconeogenesis
Formation of glucose from
noncarbohydrate sources (protein,
lipids)
TCA (Tricarboxylic Acid) Cycle and
Electron Transport System
Aerobic phase of glucose metabolism
within the mitochondria of the cell
Hexose Monophosphate Pathway (HMP)
Alternate pathway for glucose oxidation

Amino acids
Lactate
Glycerol

Glucose

Release of glucose from glycogen for energy

(muscle) or increase of blood glucose (liver) to
maintain homeostasis
Increase of blood glucose (liver) when
glycogen stores are depleted

Pyruvate
Acetyl CoA

ATP

Glucose

NADPH

Energy production (24 ATP, 12 per acetyl CoA

molecule)

Energy source for may anabolic reactions and

glucolysis in RBCs, since they lack mitochodria
NADPH, reduced form of nicotinamide adenine dinucleotide phosphate; RBCs, red blood cells
Regulation of Glucose Metabolism
Hormones

Insulin decreases blood glucose

Counter regulatory hormones (glucagon, cortisol, epinephrine and growth hormones) which increase blood glucose level
Action of Major Hormones Regulating Blood Glucose Concentration
HORMONE
EFFECT ON BLOOD GLUCOSE
SITE OF ORIGIN
CONCENTRATION
Insulin

cells of pancreas
Glucagon

cells of pancreas

Epinephrine

Adrenal medulla

Growth
Hormone ACTH
Cortisol

Anterior pituitary

Adrenal cortex

ACTION
Increases cell membrane permeability to glucose,
stimulates glycogenesis
Principal hormone to blood glucose stimulates liver
glycogenolysis, gluconeogenesis
Stimulates glycogenolysis, immediate glucose
production, and a back-up for glycogen
Insulin antagonist, inhibits glucose uptake by the
cells,also stimulates liver glycogenolysis
Stimulates gluconeogenesis and insulin antagonist

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Patient Preparation, Specimen Collection and Storage, Reference Range, Glucose Tests
TEST
PATIENT PREPARATION
Serum/Plasma
FBG
6-8 hr fast
(Fasting blood
glucose, formerly
FBS)

2-hr PP
(postprandial)

1-hr PP
Gestational
Diabetes Screen

Patient eats breakfast or

lunch containing
carbohydrates, or a
glucose solution (75 g) is
administered by mouth
Perform screening at 2428 wk of gestation.
Administer 50 g glucose
load by mouth; fasting
not required

Other Body Fluids

Whole Blood
Fasting specimen
(capillary)
requires 6-8 hr fast.

Urine
(24 hr,
quantitative)
Urine
(random,
qualitative,
semiquantitative)
CSF
-

SPECIMEN COLLECTION

SPECIMEN STORAGE

REFERENCE RANGE (mg/dL)

SERUM
Separate from cells within
30 min
PLASMA
Commonly collected using
Na fluoride preservative/
anticoagulant

SERUM
25C for 8 hr
4C for 72 hr
PLASMA
When preserved with Na
fluoride or iodoscetate,
25C for 24 hr
Same as FBG

Adult: 70-105
Adult > 60: 80-115
Neonate: 30-60
Glucose is physiologically
higher in arterial than in
venous blood

Collect plasma/serum
2 hr postprandially

120

Collect specimen I hr
postprandially

Same as FBG

> 140 mg/dL required full

OGTT work up using 100 g
glucose load and collecting
specimens at fasting and at 1
hr intervals for 3 hr

Collect from finger stick or

earlobe without excessive
squeezing

Avoid fluoride
preservative

Collect in dark container,

keep on ice

Preserve with 5 ml
glacial acetic acid

< 100
Whole blood glucose results
are -10%-15% lower than
simultaneously collected
plasma/serum values
<0.5 g/day
1-15 mg/dL

Analyze immediately or
store at 2-4C if testing
is delayed

Negative
Diabetics may have a
decreased renal threshold

Blood glucose may be

obtained 30-60 min prior
to lumbar puncture CSF
for correlation

Analyze CSF immediately 40 -70

Store at 20C
Changes in blood glucose are
reflected in CSF after 1-3 hr.

Hyperglycemia
Diabetes Mellitus

Hyperglycemic disorder caused by: 1) insulin deficiency; 2) insulin resistance to the tissue

Glucose utilization is impaired because the deficiency of insulin action hinders glucose entry into the cells resulting to elevated
glucose level and if level exceed the renal threshold, glucose is excreted in the urine (glycosuria)
TYPE

ONSET

PATHOGENESIS

SYMPTOMS

THERAPY/COMMENT

Type I, IDDM
(insulin-dependent
diabetes mellitus)
5- 10% prevalence

Juvenile
( 20 yr old)

Adult
( 20 yr old,
usually after
40)
Pregnancy,
Insulin resistance
usually
resolves after
delivery

Symptoms appear
abruptly and include
polyuria, polydipsia,
rapid weight loss, ketosis
Minimal symptoms;
obesity is commonly
associated with NIDDM;
generally no ketosis.
May be asymptomatic.
Family and/or
reproductive history is
sometimes helpful

Patient is dependent on exogenous insulin

administration to sustain life and prevent DKA

Type II, NIDDM

(non-insulin
dependent
diabetes mellitus)

Insulin deficiency
due to autoimmune
destruction of
pancreatic cells
Insulin resistance
and/or decreased
insulin amounts

GDM
-3% of pregnancies
prevalence

Patient may be controlled by diet, exercise, or

oral hypoglycemic agents or may require insulin
administration
Patient may be controlled by diet or oral
hypoglycemic agents or may require insulin
administration
Universal screening is recommended at 24-28
wk of gestation. Patients with positive history
or symptoms may be screened earlier.

Other causes of Hyperglycemia

Secondary Diabetes

Increased glucocosteroids

Acute stress including acute myocardial infarction

cerebrovascular accident

Anti-Insulin antibodies
Drug-induced pancreatic islet cell destruction

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Hypoglycemia

Plasma glucose level are usually less than 50 mg/dL but there is no universal agreement concerning exact diagnostic value

A transient hypoglycemia may normally occur about 2 hours after an oral glucose load
Hypoglycemia Types and Characteristics
SYMPTOMS CLASSIFICATION
GLUCOSE LEVEL AND RATE OF DECREASE
Adrenergic
Rapid
Activation of sympathetic nervous
Glucose level may or may not remain
system, which releases epinephrine
within reference range
Neuroglycopenia
Gradual
Depriving the brain of glucose
Glucose level of <20-30 mg/dL
causes CNS dysfunction

SYMPTOMS
Sweating, weakness, shakiness, lightheadedness,
rapid pulse, hunger, nausea
Headache, confusion, seizures, coma. May be
asymptomatic until the CNS is impaired.
Repeated or extended episodes may result in
irreversible CNS damage

Evaluating test results

Hyperglycemia

Diabetes mellitus classification

Glucose Tolerance Testing

most widely accepted for the diagnosis of diabetes mellitus
Adult, Nonpregnant (NDDG Diagnostic Criteria for Glucose Tolerance Testing)
CLASSIFICATION
FASTING GLUCOSE
POSTPRANDIAL GLUCOSE
(75 g GLUCOSE LOAD)
(1/2 hr, 1 HR, 1 hr)
Normal
IGT
Diabetes Mellitus

<115
<140
140 or meets
postprandial
glucose and 2 hr
glucose criteria

<200
200
200

Adult Pregnant (OSullivan Criteria for Gestational Diabetes)

CLASSIFICATION
FASTING GLUCOSE
Normal
105

Gestational Diabetes Test

(50 g glucose load)

Not recommended since just missing

one meal may lead to ketosis

Gestational Diabetes Test

(100 glucose load)

> 105

2 HR
GLUCOSE

COMMENT

<140
140-199
200

Must meet all three criteria

Must meet all three criteria
Can stop at fasting specimen if 140 on
two separate occasions or if one
increased glucose level is accompanies
by classic symptoms of diabetes mellitus

POSTPRANDIAL GLUCOSE
1 hr 190
2 hr 165
3 hr 145
1 hr > 140

1 hr > 190
2 hr > 165
3 hr > 145

COMMENT
3 hr OGTT is recommended for
gestational diabetes diagnosis
Positive screening, refer for
routine OGTT using 100 g
glucose load (criteria below)
At least two values must meet
the criteria

Diabetic Ketoacidosis (DKA)

There would be carbohydrate metabolism derangements such as inhibition of glycolysis while glycogenolysis or
gluconeogenesis are stimulated
Typical Laboratory Findings in Diabetic Ketoacidosis
ANALYTE
TYPICAL FINDINGS
MECHANISM/COMMENT
Glucose
300-500 mg/dL
Glucose usually remains within this range provided that renal function is maintained
Ketones
Positive
Excessive ketoacids: acetone, -hydroxybutyric acid, acetoacetic acid are produced during
gluconeogenesis, mainly by increased fatty acid oxidation to acetyl CoA.
Blood Gases

Electrolytes

Osmolality

Metabolic acidosis:
pH
Bicarbonate
After compensation:
Bicarbonate
PCO2
+
Na
+
K
Total CO2
Anion gap
Moderately

Bicarbonate and PCO2 are usually decreased owing to metabolic acidosis compensation
mechanism of Kussmaul breathing (deep respirations) to blow-off CO2 and remove
excess hydrogen ions

Hyperkalemia is due to movement of cellular K into the extracellular fluids, including the
+
blood. K must be monitored closely, since there is hyperkalemia even though total body
+
K is frequently .
Moderate

osmolality reflects plasma glucose levels, since plasma Na+ is commonly

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Initial step in diagnosis adult hypoglycemia

To determine whether hypoglycemia is reactive or fasting type

Rule out fasting hypoglycemia before a diagnosis of post prandial hypoglycemia

Diagnosis should be based on whipples triad criteria: low blood glucose

Hypoglycemia Classification
CLASSIFICATION
CAUSES
Postprandial
May occur in patients with
gastrointestinal surgery or mild
Reactive
diabetes
Usually benign and may be
considered a variant of normal
physiology

Postabsorptive
(fasting)
Loss of glycemic
control during a fast

Neonatal

Early Infancy

Drugs, e.g. insulin or oral

hypoglycemia agents,
administered in excess and
ethaniol abuse are most
common.
Other causes are rare but
usually serious underlying
organic disease, e.g.
insulinomas, liver dysfunction,
sepsis, depleted glycogen
stores, glucocorticoids
Prematurity
Maternal diabetes or toxemia,
which are usually transient

LABORATORY DIAGNOSIS
GLUCOSE:
Obtain blood specimen when patient is
symptomatic; if not possible, perform 5 hr
meal tolerance test.
Plasma glucose within the reference range
with the presence of symptoms is strongly
suggestive that hypoglycemia is not the
diagnosis.
INSULIN AND C PEPTIDE:
Insulin with normal or C-peptide
excessive exogenous insulin administration
Insulin with C peptide insulinoma

COMMENT
5 hr meal tolerance test is
preferred to 5 hr OGTT.

5 hr OGTT is not
appropriate testing for
suspected fasting
hypoglycemia.

GLUCOSE
Obtain blood specimen after prolonged
fast (up to 48 hr). Hypoglycemia is usually
detected within 12 hr.
GLUCOSE:
Full term < 30 mg/dL
Premature < 20 mg/dL

Neonates are less sensitive

to hypoglycemia and may
be asymptomatic even at
very low glucose levels

Inborn errors of carbohydrate metabolism, e.g. von Gierkes disease (type I)

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