Treatment Insulin

&
Hyperglicemia
Crisis
PB.PERKENI

DISCUSSION

HYPOGLYCEMIA
HYPERGLYCEMIC HYPEROSMOLAR STATE
DIABETIC KETOACIDOSIS

In 1552 BC
1strecord
Described
In Writing
Diabetes
Earliest known
of diabetes
mentioned on 3rd Dynasty Eqyptian
papyrus by physician Hesy-Ra:
mentions polyuria as a symptom.
250 BC, Apollonius of Memphis coined

the name "diabetes meaning "to go

through" or siphon. He understood that
the disease drained more fluid than a
person could consume.
.

Early Diabetes
Discoveries
In the 1869, Paul Langerhans, a

German medical student announced

in a dissertation, that the pancreas
contains two systems of cells.
1889 Oskar Minkowski and Joseph

von Mering in France, removed the

pancreas from a dog to determine the
effect of an absent pancreas on
digestion

The Discovery of Insulin

(Toronto 1921)

Fred Banting (1891-1941)

James B. Collip
(1892-1965)

Charles H. Best (1899-1978)

John J.R. McLeod (1876-1935)

Marjorie (?-?)

Leonard Thompson
The first patient to receive injections of
pancreatic extract on January 11, 1922. He
was 14. The young Toronto resident had
been diabetic since 1919. He weighed only
65 pounds and was about to slip into a
coma and die. At first he received Dr, F.
Bantings and Dr. Charles Bests extract.
Two weeks later he used the purified
extract of Dr. J.B. Collip and Thompson's
symptoms began to disappear; his blood
sugar returned to normal and he was
brighter and stronger. Thompson lived
another 13 years with the insulin. He died
at the age of 27 due to pneumonia, a
complication of his diabetes
6

HYPOGLYCEMIA

Hypoglycemia is a blood glucose value of

less than 50 mg/dl
Clinically, it is defined by Whipple triad: low
plasma glucose level, symptoms consistent
with hypoglycemia, and resolution of
symptoms with correction of plasma
glucose

Epidemiology

30% of type 1 or type 2 diabetic patients on

insulin therapy
10% of type 2 diabetic patients
Mortality rate 3-4% especially elderly taking
long acting oral hypoglycemic agents

Symptoms
Adrenergic symptoms (catecholamine mediated):
diaphoresis, palpitations, pallor, tachycardia
apprehension, anxiety, sensation of hunger
headache, weakness, restlessness
Neuroglycopenic symptoms:
reduced intellectual capacity, irritability,
confusion, abnormal behavior,
convulsion, coma

Glucoregulatory factors

Blood-glucose-lowering
factor

Insulin

Blood-glucose-raising
factors
Glucose-counterregulatory
factors

Glucagon
Epinephrine
Growth hormone
Cortisol

in minutes
In hours

Physiologic response in hypoglycemia

Blood glucose 56-48 mg/dl

* adrenalin secretion
* diaphoresis, tremor
* reduced function of central nervous system
Blood glucose <48-36 mg/dl
* reduced consciousness
Blood glucose <36-18 mg/dl
* coma, convulsion
Blood glucose <18 mg/dl
* permanent brain damage

Syndromes of compromised glucose

counterregulation in type 1 diabetes mellitus

Defective glucose counterregulation

Impaired awareness of hypoglycemia
Elevated glycemic threshold during intensive therapy
Elevated glycemic threshold following recent
hypoglycemia
Elevated glycemic threshold during -adrenergic
blockade

Autonomic failure
The syndromes may occur in advanced type 2 diabetes mellitus
(insulin-deficient)

Schematic diagram of the concept of hypoglycemiaassociated autonomic failure in T1DM

Insulin deficiency

IDDM

No glucagon responses to decreased glucose levels

Epinephrine
responses

Imperfect insulin
responses

Episodes of hypoglycemia

Hypoglycemia-associated autonomic failure

@ symptomatic responses (awareness)
@ autonomic (including epinephrine) responses

Risk factors

Tight glycemic control

Age
Duration of diabetes
History of hypoglycemia
Sleeping
Alcoholism
Fasting
Increased insulin sensitivity: fitness, body weight
Clearance/metabolism of drugs: renal or hepatic
insufficiency

Mechanisms by which drugs increase the

hypoglycemic effect of sulfonilureas

Increase in half-life due to inhibition of metabolism

or excretion rate: ethanol, phenylbutazone,
coumarin anticoagulants, chloramphenicol,
doxycycline, sulfonamides, allopurinol
Competition for albumin-binding sites:
phenylbutazone, salicylates, sulfonamides
Inhibition of gluconeogenesis, increase in glucose
oxidation, or stimulation of insulin secretion:
ethanol, -adrenergic drugs, monoamine oxidase
inhibitors, tranylcypromine, t

Management of hypoglycemia

Mild hypoglycemia when self treatment

with oral carbohydrate suffices
Sever hypoglycemia when external help is
required to effect recovery

Management of hypoglycemia: Prevention

1.

2.
3.

4.
5.

Early familiarization with the symptoms of

hypoglycemia
Do reviewing at intervals
Explain the relationship between insulin
administration, timing of meals, and exercise
Explain methods of self-treating hypoglycemia
Choose appropriate insulin regimens, dose
schedules with appropriate therapeutic goals

Management of hypoglycemia: Treatment

Mild hypoglycemia: oral glucose 15-20 g, wait 10-15

min then check blood glucose. If glucose level does
not increase 18 mg/dl, give oral glucose again
Sever hypoglycemia: solution 50 ml of dextrose 50%
given intravenously, check blood glucose in 20 min.
If it is still hypoglycemia administrate once again
Glucagon 1.0 mg s.c/i.m/i.v. adverse effects include
nausea, vomiting, and headache. Contraindicated to
sulfonylureas-induced hypoglycemia. Ineffective in
patient who is anorectic, or with protracted
hypoglycemia

DIABETIC KETOACIDOSIS
AND
HYPERGLYCEMIC HYPEROSMOLAR STATE

Pathogenesis of DKA
and HHS

DIABETES CARE, VOLUME 29, NUMBER 12, DECEMBER 200

DKA
(DIABETIC KETOACIDOSIS)

Occurs when muscle cells become so starved for

energy that body takes emergency measures &
breaks down fat toxic acids as ketones
Most common type 1 DM insufficient insulin to
adjust raise of blood sugar
Cause by extreme stress or illness
Infection body produce adrenalin works
against insulin
Forget to take insulin

DKA diagnostic criteria:

serum glucose 250 mg/dl,
arterial pH 7.3,
serum bicarbonate 18 mEq/l,
moderate ketonuria or ketonemia.
HHS diagnostic criteria:
serum glucose 600 mg/dl,
arterial pH 7.3, serum
bicarbonate 15 mEq/l,
minimal ketonuria and ketonemia
DIABETES CARE, VOLUME 29, NUMBER 12, DECEMBER 2006

Signs & symptoms of DKA

Deep, rapid breathing

Sweet, fruity smell on breath
Loss of appetite
Nausea
Fatigue
Vomiting
Weakness
Fever
Confusion
Stomach pain
Drowsiness
Weight loss

Clinical presentation

Lost more than 5% body weight

More than 35 breaths a minute
Cant control blood sugar
Become confused
Nausea and vomiting

What should you do?

Check ketones if feeling especially

stressed or blood sugar persistently above
240mg/dL
High ketones in blood ketones excreted
in urine.
High ketones in urine should be treated &
n hospitalized
DKA can lead into coma and possibly
death.

Treatment

Correcting lost fluids through i.v. line

Glucose infusion with insulin may
stop ketones production
Decrease blood sugar level gradually,
decreasing glucose rapidly may
produce brain swelling

HHS (HYPERGLYCEMIC HYPEROSMOLAR STATE)

A high level of blood glucose may interfere blood

circulation (level >600 mg/dl)
Glucose uptake by the cells decreases, the glucose
passed from blood to urine draws tremendous
amounts of fluid from body and produces dehydration
Common in type 2 DM, especially who does not
monitor blood sugar, and who does not know have
DM
Trigger factors: high-dose steroid, diuretics, infection,
illness, stress or drinking excessive alcohol

HHS: signs & symptoms

Excessive thirst
Increased urination
Weakness
Leg cramps
Confusion
Rapid pulse
Convulsions
Coma

What should you do?

Check blood glucose level (> 600mg/dL)

Emergency treatment can correct the
problem within hours
Give intravenous fluids to restore water to
the tissue
Short acting insulin to help cells can uptake
glucose
Without prompt treatment can be fatal

Conclusion :
Very low dose insulin application and slow motion
re-equilibration plus monitored substitution of
electrolytes are the basic strategies in the treatment
of severe DKA

RESEARCH DESIGN & METHODS

GROUP I (Subcutant-1hour)

Initial dose SC : 0,3 units/kg

body wt, followed by

SC aspart insulin at 0,1

units/kg every hour

When blood glucose < 250

mg/dl, change IV fluids to
D5% 0,45% saline and reduce
SC aspart insulin to 0.05
units/kg/hour to keep
glucose at 200 mg/dl until
resolution of DKA

GROUP II (Subcutant-2hour)

Initial dose SC : 0,3 units/kg

body wt, followed by

SC aspart insulin at 0,2 units 1

hour later and every 2 hour

When blood glucose < 250

mg/dl, change IV fluids to
D5% 0,45% saline and reduce
SC aspart insulin to 0.1
units/kg every 2 hour to keep
glucose at 200 mg/dl until
resolution of DKA

GROUP III (Intravena RI)

Initial IV bolus : 0.1 units/kg

body wt, followed by

Continuous insulin infusion

at 0.1 units/kg/hour

When blood glucose < 250

mg/dl, change IV fluids to
D5% 0,45% saline and reduce
insulin infusion rate to 0.05
units/kg/ hour to keep
glucose at 200 mg/dl until
resolution of DKA

Laboratory check :
a.
b.
c.

Admission : Cell blood count with differential complete metabolic profile, venous pH, and serum hydroxybutyrate
During treatment : Basic metabolic profile (glucose, bicarbonate, sodium, potassium, chloride, urea, and
creatine), venous pH, phosporus, and -hydroxybutyrate at 2 h, 4 h and every 4 h until resolution of DKA
Glucose by finger stick : Check glucose every 1 h in patients receiving SC-1 h and every 2 h in patient IV
insulin or receiving SC-2 h

Umpierrez GE, Diabetes Care 2004 ; 27 : 1873-1878

Similar Response of Medical treatment

with SC Aspart in comparison with IV RI

Note : SC-1h : Subcutaneous aspart every 1 hour; SC- 2h : Subcutaneous aspart every 2 hour
Umpierrez GE, Diabetes Care 2004 ; 27 : 1873-1878

Similar glucose profile subcutaneous

Insulin Aspart in comparison with
intravenous Regular Insulin

Glucose (mg/dl)

1000

SC NovoRapid every 1 hr
SC NovoRapid every 2 hr
IV Regular Insulin

800

600

400

200

12

16

20

24

Duration of treatment (hours)

Umpierrez GE, Diabetes Care 2004 ; 27 : 1873-1878

Similar Bicarbonate profile with

subcutaneous Insulin Aspart in comparison
with intravenous Regular Insulin
2,4

Bicarbonate (mmol/L)

2,2
2,0
18
1,6
1,4

SC NovoRapid every 1 hr
SC NovoRapid every 2 hr
IV Regular Insulin

1,2
1,0
8
6
0

12

16

20

22

Duration of treatment (hours)

Umpierrez GE, Diabetes Care 2004 ; 27 : 1873-1878

Similar metabolic profile with

subcutaneous Insulin Aspart
in comparison with
Intravenous Regular Insulin
Umpierrez GE, Diabetes Care 2004 ; 27 : 1873-1878

Diabetes Care Publish Ahead of Print, published online April 14, 2009

Result :

Analog Insulin

Regular Insulin

Diabetes Care Publish Ahead of Print, published online April 14, 2009

Learning from Umpierrez Protocol

Subcutaneous insulin Aspart every 2 hour

Subcutaneous insulin Aspart every 2 hour

Initial dose SC : 0,3 units/kg body wt, followed by

SC aspart insulin at 0,2 units 1 hour later and every 2 hour

When blood glucose < 250 mg/dl, change IV fluids to D5% 0,45% saline and
reduce SC aspart insulin to 0.1 units/kg every 2 hour to keep glucose at 200
mg/dl until resolution of DKA
Laboratory check :
a.
Admission : Cell blood count with differential complete metabolic profile, venous pH, and serum hydroxybutyrate
b.
During treatment : Basic metabolic profile (glucose, bicarbonate, sodium, potassium, chloride, urea, and
creatine), venous pH, phosporus, and -hydroxybutyrate at 2 h, 4 h and every 4 h until resolution of DKA
c.
Glucose by finger stick : Check glucose every 2 h in patinet receiving SC-2 h
Umpierrez GE, Diabetes Care 2004 ; 27 : 1873-1878