Carbohydrates

General Description
• Compounds containing C,H, and O
• Carb classification is based on the number of
carbons in a molecule (Glyceraldehyde- smallest
with 3 carbon)
• 2 projections for carbs are fisher and haworth
• Monosaccharides (glucose, fructose, galactose)
• Disaccharides (maltose, sucrose, lactose)
• Oligosaccharides – 2-10 sugar units
• Polysaccharides - composed of 10 monosaccharides
( Starch, Glycogen)
 Chemical properties
• Reducing substances ( Ketone or Aldehyde group)
• It can form glycosidic bond with another carbs or
non carbs
• The formation of the bond replaces the hemiacetal
into acetal
• If the bonding occurred In the anomeric group the
carb will not b reducing but if not the carb retains
its property ( sucrose non reducing)
 Metabolism
• The only carb used by the brain is glucose
• Nervous tissues cannot store glucose
• Glucose must be in narrow range and in steady
supply in the ECF of the CNS
• Polysaccharides ingested are digested in the SI by
Amylase (salivary and pancreatic) to dextrins and
disaccharides and further metabolized into
monosaccharides to be absorbed by the intestines.
• Absorbed glucose is transported to the liver by the
hepatic portal venous supply
 Metabolism
• The only carb that can be used directly as energy is
glucose
• Other monosaccharides must be converted to
glucose before absorption
• Glucose is then shunted into 3 different pathways
• The goal of every cell is to release Co2 and water
after utilizing glucose for energy
• ATP is obtained from inorganic phosphate and ADP
 Embden Myerhof pathway
• First step is conversion of Glucose to G6P by ATP
and the process is catalyzed by hexokinase,
• Glucose is then broken down to 2, 3 carbon mol of
pyruvic acid
• Then converted to Acetyl CoA and enters TCA
• Oxygen is needed in this pathway (Aerobic)
Hexose Monophosphate Shunt
 Insulin
• The only Hypoglycemic Hormone
• Produced in the Islet of Langerhans in Beta cells in
the Pancreas
• Decreases glucose in the blood by increasing the
entry of glucose to cells, glycogenesis, lipogenesis,
 Glucagon
• Produced by the Alpha cells in the Pancreas
• Hyperglycemic the stimulates Glycogenolysis and
Gluconeogenesis
 Other Hormones
• Epinephrine, Cortisol are the two Adrenal
Hormones that stimulate Hyperglycemia
• ACTH and GH are Pituitary hormones that stimulate
hyperglycemia
• Thyroxine is produced in the Thyroid gland which
stimulates Hyperglycemia
• Somatostatin is produced in the Pancreas that
causes hyperglycemia by inhibiting insulin activity
 Hyperglycemia
• Increase in plasma glucose
• Stimulates Insulin secretion to increase the entry of
glucose to cells
• An abnormality in hormone secretion which are
involved in glucose metabolism causes
hyperglycemia
 DiabetesMellitus
• A group of metabolic disorders characterized as
defective Insulin function or production
• Hyperglycemia is the net effect
• 2 classififcations are Type 1 and type 2
 Type 1
• Destruction of B cells
• Ketoacidosis prone, Brittle diabetes
• Absolute Insulin defeciency
• Autoantibodies to B cells, Insulin ,GAD, Tyrosine
phosphatases IA-2, IA-2Bs
• Idiopathic cases are also reported with no
autoantibodies detected
• Strong genetic association with HLA DR3 and DR4
 Type 2
• Insuline resistance with an Insulin secretion defect
• Relative Insulin defeciency
• Most common type of DM
 Other forms of DM
• Secondary conditions ( genetic defects in insulin
action or b cell function, Pancreatic or endocrine
disorders, Drug induced, insulin receptor defect)
• Gestational Dm –metabolic or hormonal changes in
pregnant women, but normalize after pregnancy
 Pathophysiolgy
• Hyperglycemia, glucosuria (<180mg/dl), A plateua is
mainatianed at (300 – 500mg/dl) if normal
excretion of glucose compensates hyperglycemia
• Type 1 is at risk of ketoacidosis but type 2 is at risk
of diabetic hyperosmolarity
• deep respirations(Kussmaul-kien) due to acidosis.
 Ketoacidosis
• Common in type 1
• Ketoacidosis due to increase B oxidation of fats
• Imbalance in (low)sodium and (high) potasium due
to acidosis
• Total potassium is decreased due to polyuria
• Low CO2 and bicarbonate (hyperventilation) deep
respirations(Kussmaul-kien) due to acidosis
 Non Ketotic Hyperosmolar
• Common in type 2
• Low ketones
• High glucose >1000mg/dl
• High osmolarity
• High BUN and CREa
• Inability to balance excess glucose production and
increase excretion in Kidneys
 Criteria for Pre DM
• >45 years of age test self with FBS every 3 years
only if the patient is not diabetic
• Test at early age (History of DM in family, Obese,
Ethnic race at risk of DM, GDM w/ babies weighing
>9lbs, hypertension, elevated TAG and Cholesterol,
Impaired fasting glucose, PCOS, Cardiovascular
diseases.)
• Type 2 DM in asymptomatic patients (Testing at 10
years of age)
• Oneset of puberty but if early puberty follow up
testing every 2 years
 Criteria for DM
• RBS >200mg/dl with DM symptoms
• FBS : >126mg/dl ,IFG :100-125mg/dl, Normal
: <100mg/dl
• 2 hr OGTT >200 mg/dl (75g load)
 RBS
• Random blood sugar
• Usually in bedside or in POCT
• No fasting requirement
 FBS
• Fasting blood sugar
• Fasting of 8-10 hours not > 16 hours
• <100mg /dl normal
 Oral Glucose Tolerance test
• Used to test if how can a patient metabolie glucose
in a given period of time
• OGTT
• 75g load for adults 100g for pregnant women
1. BS >95mg/dl (fasting)
2. >180 mg/dl
3. >155 mg/dl
4. >140 mg/dl
2 out of 4 (DM)
 Pre DM
• 100-125 mg/dl FBS ( Impaired fasting)
• 140-199mg/dl 2hr OGTT (impaired glucose
tolerance)
• GDM (>25 years old) history of DM, Obese, PCOS,
Ethnic race, Glycosuria
 GDM Criteria
• Two step approach:
 1st method : Perform 3 hours OGTT immediately
 2nd method: Perform 1 hour postload (50 g) if
>140mg/dl >130mg/dl perform 3 hours OGTT
 Hypoglycemia
• 65-70mg/dl plasma glucose signals the release of
glucagon and other hyperglycemic hormones , 50-
55 mg/dl symptoms of hypoglycemia occurs
• Insulinoma- high insulin levels causes hypoglycemia
(>25mg/dl change in glucose conc, high C peptide
levels, high pro insulin)
 Laboratory methods
• Plasma, Serum, or whole blood is used
• Centrifuge within 1 hour to prevent glycolysis by
cells
• If cannot be processed immediately use gray top (
sodium fluoride to prevent glycolysis)
• In whole blood glucose is 11% lower than serum
glucose
• Diurnal variations in glucose measurement (high in
morning low in afternoon)
• Fasting of 8-1o hours not >16 hours
 Benedict’s/Fehlings
• Glucose is a reducing substance ( other sugars
except sucrose)
• Reduction of cupric to cuprous in an alkaline
medium stabilized by citrate or tartrate . The
reduction will show a change of color from deep
blue to red precipitate(Cu oxide).
• Used in other body fluids to measure reducing
sugars
 O Toluidine
• “Dubowski” reaction
• Schiff base formation and reacting with aromatic
amines
• O toluidine in a hot acidic solution will yield a color
with an absorbance maximum of 630 nm
• Other sugars can react and cause interferences
 Glucose Oxidase
• Enzymatic (most used)
• Coupled enzymatic reaction
• Very specific for B-D glucose
• Glucose oxidase converts BD glucose to gluconic
acid (Mutarotase may be used to convert AD
glucose to BD glucose)
• H2O2 is used to oxidize the chromogen and
Peroxidase is used to catalyze reaction.
Spectrophotometer is used to read the absorbance
proportional to amount of glucose
• Trinder reaction
 Glucose oxidase
• Polarographic method may be used to
directly measure oxygen using O2 electrode
to prevent interferences in the coupled
reaction.
• A decrease in O2 is inversely proportional to
the amount of glucose
 Glucose oxidase
• Glucose + O2 + H20 ---glucose oxidase-->
H2O2+Gluconic acid
H2O2+chromogen ---peroxidase--> oxidized
chromogen
 Hexokinase
• Reference method due to high specificity of G6PD
coupling enzyme
• Hexokinase with ATP converts glucose to
G6phosphate,G6phosphate with cofactor NADP is
converted to 6 Phophogluconate and NADPH by
G6PD.
• Measured spectrophotometrically
• NADPH has an absorbance maxima of 340 nm
 Hexokinase
• Glucose+ATP ---Hexokinase-->
Glucose6phosphate+ NADP -----G6PD--> 6
phosphogluconate+ NADPH
 Glycosylated hemoglobin
• Glycated hemoglobin
• HbA1C
• Hgb A irreversively glycosylated
• For monitoring long term glucose control
• Refelcts blood glucose level in the previous 2-3
months
• Performed twice a yeear fro every 3-6 months
• 5.7-6.4 % Pre diabetes
• >6.5%
 Fructosamine
• Glycated Albumin or glycosylated albumin
• Reflection of short term glucose control 3-6 weeks
• For patients with red cell disorder