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KCP 1-Hyperglycemia
Treatment for Type I DM
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What is the main treatment for DM type I?
Exogenous insulin
What is insulin?
Insulin
is a
peptide hormone
produced in the
pancreas
within the
beta cells
of
islets
of
Langerhans
What is the composition of insulin?
Two peptide chains
(
A
&
B
) connected by
sulfide bonds
What does basal insulin secretion indicate?
Administered to
mimic
basal
insulin
production
Only
subcutaneous
administration
Once or twice
daily
What does bolus insulin level indicate?
Administered to
mimic
the
prandial
release
of
insulin
Subcutaneous
or
intravenous
administration
Rapidly
lowers
blood glucose
Administered
3
times per day
20-30
mins
prior
to a meal
What is the mechanism of insulin synthesis?
Insulin gene
transcription
and
translation
in the rER of
pancreatic
β-cells
→
preproinsulin
(precursor protein)
Signal proteases
remove the signal peptide of preproinsulin →
proinsulin
Protein
folding
and
formation
of
one
disulfide bridge
in the α-chain and
two disulfide bridges
between the α-chain and β-chain
Proinsulin is transported to the
Golgi apparatus
→
packaged
in
membrane-bound secretory granules
with
proprotein convertases
Proinsulin is
cleaved
by
proteases
→
mature insulin
and
C-peptide
Secretion of
insulin
and C-peptide via
exocytosis
What is the mechanism of action of insulin?
Enzyme-linked receptors
Secretion pathway
Stimulated by an
increase
in
blood glucose
Glucose
enters the
pancreatic B-cells
via
GLUT2 transporters
& is
metabolized
to generated
ATP
Intracellular ATP binds
& blocks ATP-sensitive K+channels, increasing the
intracellular K+ conc.
&
raising membrane potential
(
depolarization
occurs)
Voltage gated Ca2+ channels opens
&
Ca2+ enters
the pancreatic B-cells
Increased intracellular Ca2+
triggers the
fusion
of
insulin-containing secretory granules
to the
cell membrane
Exocytosis
of
insulin
into the
bloodstream
What are the target organs of insulin?
Liver
Adipose
tissue
Muscles
What are the effects of insulin from the lowering blood glucose POV?
Facilitates glucose uptake
by
peripheral
tissues
Stimulates
glycogenesis
Inhibits
glycogenolysis
What are the effects of insulin from the fat-sparing effect?
Promotes lipogenesis
Inhibits lipolysis
What are the effects of insulin from the anabolic effect POV?
Stimulates amino acids
by
tissue
Increases protein synthesis
Inhibits proteolysis
What are the type of insulin preparations?
Human insulins
Humulin
R-short acting
Isophane
(NPH,Protamine) &
Lente
(Zinc)
-Intermediate
acting
Insulin analogues
Lispro-Ultrashort
acting
Glargine-Long
acting
Mixed insulins
What are the characteristics of human insulins?
Have the
same amino acid sequence
Produced by human
recombinant DNA tehnology
with
genetically altered E.Coli strains
What are the benefits of human insulins comapred to animal insulins?
Less
allergic
reactions
Less
insulin
resistance
Less
local
adverse
drug
reactions at the
site
of
injections
What are the characteristics of insulin analogues?
Genetic engineered altered
insulin
Has
modified pharmacokinetics
but performs the
same pharmacodynamic
effect
What are the characteristics of insulin Lispro?
Rapid
acting
Due to the
amino acid sequence
at position
28
&
29
in the
B-chain
What are the characteristics of insulin Glargine?
Long
acting
Has
no
peak plasma conc. due to
precipitation
at the injection site
Precipitates
due to
solubility
in
differrent
pH levels
7
& depot formation at
subcutaneous
tissue
Has
slower
onset &
prolonged
effect
Insulin preparations
Graph form of insulin preparations
When is insulin included part of the treatment?
Type
I
DM
Type
II
DM when it is not controlled by any
oral anti-diabetic
drugs
Complications like
DKA
Pregnancy
What are the sites of insulin injections?
Upper outer arm
Belly
(Below the
belly button
)
Upper outer thighs
Buttocks
Why must be the injection sites for insulin be rotated?
To avoid
lipodystrophy
What are the types of insulin delivery systems?
Syringe
Pen
Pump
Intranasal
insulin
What are the advantages of using an insulin pen?
More
convenient
More
accurate
dosage
Less
painful
What are the advantages of insulin pump?
Used for continuous
subcutaneous
insulin infusion therapy
Mimics both
basal
&
bolus
insulin releases
Decreases
the risk of
hypoglycemia
What are the adverse effects of insulin?
Hypoglycemia
Lipodystrophy
at injection sites
Allergy
Insulin resistance
What is meant by liposdystrophy?
Repeated
insulin injections
at the same spot causing
atrophy
of
subcutaneous fatty tissue
at the site of injection due to
local immune reaction
How to prevent lipodystrophy?
Rotate
the site of
insulin injections
What are the two types of hyperglycemic emergencies?
Diabetic ketoacidosis
(DKA)
Hyperglycemic hyperosmolar state
(HHS)
What are the characteristics of DKA?
Absolute
insulin
defieciency resulting in severe
hyperglycemia,
ketone
body
production &
systemic
acidosis
Develops over
hours
to
1-2
days
Most common in type
I
DM
Plasma glucose >
250mg
/dL
ArterialpH <
7.3
Bicarbonate
<15 mEq/L
Moderate
ketonuria
Anion
gap
>12mEq/L
What are the characteristics of HHS?
Severe
relative
insulin
deficiency resulting in profound
hyperglycemia
&
hyperosmolality
and no significant
ketone
production/
acidosis
Develops over
days
to
weeks
Most common in
type II
DM
Higher
mortality
rate
Plasma glucose >
600
mg/dL
Arterial
pH
>7.3
Bicarbonate
>15mEq/L
Minimal ketonuria
Serum
osmolality
>320
mosm/L
What is the pathophysiology of potassium loss?
Due to
acidosis
Extracellular
accumulation of
H+
ions
Leads to shift of
K+
from
intracellular
to
extracellular
space
Most
K+
is lost in
urine
due to
osmotic
diuresis
Leading to loss of
fluids
&
electrolytes
Dehydration
activates
RAA
axis
All which leads to
hypokalemia
What is the key component of hyperglycemic ketoacidosis?
Hyperglycemia
Glycosuria
Ketonuria
Acidosis
Low intracellular K+
Fluid
&
electrolyte imbalance
What are the recommended treatment for hyprglycemic ketoacidosis?
Correct
fluid
imbalance with normal
saline
Correct serum
potassium
Subcutaneous
rapid
/
Short
acting IV insulin
Bicarbonate
- Extreme acidosis
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