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Treatment of DM Treatment of acute emaergencies
Treatment of uncomplicated DM
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The acute emergencies are:
DKA
Hyperglycemic Hyperosmolar State
Hypoglycemia
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DKA
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Introduction to Diabetic ketoasidosis
(DKA) Is a major medical emergency.
Serious cause of morbidity, principally in type I
diabetes. Occur in Type 2 DM but at a much lower frequency.
Annual incidence: 4.6 to 8 episodes per 1000
patients with DM.
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DKA cont
It is a state of relative insulin deficiency
associated with high blood levels of sugar and
ketones. Dehydration is a very important feature
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Pathogenesishyperglycemia is a result of:
Increased hepatic glycolysis and gluconeogenesis Impaired glucose utilisation by peripheral tissues
There is an in counterregulatory hormones:
Cortisol
Growth hormone
Catecholemines
Glucagon These hormones promote lipolysis & release of
free fatty acids
In the liver, free fatty acids converted to ketones.
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Signs & symptomsusually develop over 24 h
May be the initial presentation in type 1 DM
Classic presentation is :
a history ofPolyuria, Polydipsia, Polyphagia
often prominent Nausea & vomiting
Severe Abdominal pain which can minic acutepancreatitis or other acute abdominal emergencies
A fruity odor (acetone smell) on the patients breathcalled Kussmauls breathing
Hyperglycemia induces an osmotic diuresis thatleads to intravascular volume depletion causingTachycardia/hypotension
Lethargy & CNS depression may evolve into coma
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Precipitating events On a detailed Hx and Examination we can find:
Inadequate/missed insulin administration
Evidence of infection e.g:
Pneumonia
UTIGastroenteritis
Spesis
Infartion (cerabral,MI,mesenteric,peripheral..etc)
Drugs (e.g. cocaine)
Pregnancy
Recent surgery/trauma
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Laboratory Findings
TheC
ardinal Biochemical features of diabeticketoacidosis are:
HY
PERGLY
CEM
IA
HYPERKETONAEMIA
METABOLIC ACIDOSIS
Mmol/l Multiply by 18 = mg/dl
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Investigation plan We will perform the following test:
Blood glucose level on admission by glucometer
FBC
Ketone bodies (B-hydroxybutyrate ) usually measured in urine,but to
avoid false positive,serum or plasma assays for B-hydroxybutyrate
should be preformed.
Serum electrolyte- sodium,potassium,chloride
ABG for; Arterial pH, pCO2,osmolality,Bicarbonate,Anion gap
LFT
CXR
ECG
Ultrasound abdomen
Culture & sensitivity of body fluids as guided by clinical presentation
CT scan of brain can be planned in case of poor response to
treatment to rule out any other cause of coma
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Interpretation of Lab Results 1
Occasionally, the serum glucose is only minimally elevated.
Serum bicarbonate is frequently
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Interpretation of Lab Results 2
Interference by acetoacetate may falsely elevate the serum
creatinine measurement.
Leukocytosis, hypertriglyceridemia,&
hyperlipoproteinemia are commonly found.
The measured serum sodium is reduced as a consequence
of the hyperglycemia NOTE: A normal serum sodium in the setting of DKA
indicates a more profound water deficit.
serum osmolality is mildly to moderately elevated
Osmolality can be calculated by the formula :
[2 (serum sodium + serum potassium) + plasma
glucose (mg/dL)/18 + BUN/2.8]
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Treatment plan
Initial Evaluation
Close Monitoring
Fluid management
Electrolyte Replacement
Insulin Therapy
Resolution & Conversion to home therapiesASAP
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Management 11. Admit to ICU2. ABC of resusitation may be needed
3. Cardiac monitor & Pulse oximeter4. O2 mask/intranasal
5. NG tube if altered mental status
6. Blood sampling & ABG7. Initial bolus of 0.9% N/S replacement of a deficit of ~ 3
5L is carried out over 24hours
8. hourly urine output monitoring with/without
catheterisation
9. For starting insulin infusion, serum potassium should be
maintained > 3.5 mmol/l.
10. NOTE
:Do not administer insulin if K
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Insulin Initial Phase
fast acting insulin iv bolus of 0.1Units/kg or
IM 0.3Units/kg
then
0.1Units/kg/hr via insulin pump.
NOTE: Hyperglycemia improves at a rate of ~ 4.6-5.6
mmol/l/hour, more rapidly in the 1st
-2nd
hours.
Sodium infusion*********
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Insulin Later phase When plasma glucose level reaches 13.9mmol/l
reduce infusion of insulin to 0.05Units/kg/hourand
add 5% dextrose with 0.45% NS.
At this stage fast acting insulin S/C before eachmeal and long actin insulin at night can be added.
NOTE:
Aim is to keep the plasma glucose at 11.1 13.9mmol/l
Normal insulin requirement of the body:
1Unit/kg/day but in DKA a person may require
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Management 3KCl 1g in 0.5L of iv fluid 4/6 hourly according to
fequently monitored serum K level *****
Sodium Bicarbonate is usually not needed in the 1st
48hours
ADA advise to give NaHCO3 with very low pH levels:
pH 6.9 7.0 : 50mmol/l NaHCO3 in 200ml DW
with 10meq/L KCl
pH < 6.9 : 100mmol/l NaHCO3 in 400ml of DW with
20meq/L KCl
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complications Aspiration
may occur due to decreased mental status at
presentation.
Hypoglycemia
Hypokalemia
Iwould like to make a special note that insulin pushes K inside the
cells,so during the treatment,likelyhood ofhypokalemia
increases.Therefore frequent monitoring of K is VERY important.
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Complications of DKA Cerebral edema
An extremely serious complication of DKA, is seenmost frequently in children. Coma ultimately ensue.
Pancreatitis
caused by severe Hypertriglyceridemia
NOTE: Hyperamylasemia of salivary origin is usually
seen.
Serum lipase should be obtained if pancreatitis issuspected.
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Hyperglycemic Hyperosmolar
State
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PathophysiologyHHS is a nonketotic state
The absence of ketosis is not completelyunderstood.
the insulin deficiency is only relative and less severe
than the absolute insulin deficiency of DKA. There are Lower levels of counterregulatory
hormones and free fatty acids than in DKA
Possibly the liver is less capable of ketone bodysynthesis
or insulin/glucagon ratio does not favor
ketogenesis.
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n ca p c ure os y s m ar o
Notably absent are symptoms of nausea, vomiting, and
abdominal pain and the Kussmauls Breathing
Usually several weeks history of : polyuria
weight loss
diminished oral intake
mental confusion
Lethargy
Coma
On Physical examination profound dehydration
tachycardia
and altered mental status.
Often a precipitation event is present as in DKA
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Lab Results Marked hyperglycemia [plasma glucose may be
>55.5 mmol/L (1000 mg/dL)] hyperosmolality (>350 mosmol/L) and
prerenal azotemia
serum sodium may be normal or slightly low
In contrast to DKA, acidosis and ketonemia are
absent or mild
A small anion gap metabolic acidosis may bepresent secondary to increased lactic acid
Moderate ketonuria, if present, is secondary to
starvation
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Treatment of HHS Rx is Mostly same as in DKA except for the fact that
In HHS, fluid losses and dehydration are usually
more pronounced than in DKA due to the longer
duration of the illness.
13 L of 0.9% normal saline over the first 23 h
initially.
The calculated free water deficit (which averages 9
10 L) should be reversed over the next 12 days
(infusion rates of 200300 mL/h of hypotonicsolution) then 5% dextrose)
NOTE : too rapid a reversal of fluid deficit may
worsen neurologic function.
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Hypoglycemia in DM
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Introduction to Hypoglycemia &
Diagnosis
This is the commonest endocrine emergency even
more dangerous than hyperglycemia
brain damage & death can occur in severe
prolonged cases
Diagnosis is based on finding a Plasma glucose
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Hypoglycemia
the commonest cause is insulin or sulfonylurea
treatment with activity,
missed meal,
accidental or non-accidental overdose.
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PathophysiologyThe acute response to hypoglycemia is
counterregulatory effects ofglucagon and
catecholamines
Initial symptoms occur secondary to catecholamine
release
Later on neuroglycopenic symptoms occur from the
direct effects of hypoglycemia on CNS function
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Signs & symptomssymptoms secondary to catecholamine release are :
Sweating
AnxietyHunger
Tremor
Palpitations
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Signs & symptoms
Neuroglycopenic symptoms are : Confusion, drowsiness, seizures, coma.
Rarely focal symptoms can occur,eg:
transient hemiplegia Mutism
personality change
Restlessness and incoherence
may lead to misdiagnosis of alcohol intoxication,
even psychosis or CVA
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nocturnal hypoglycemia
The same characteristic set of symptoms
night sweats
Nightmaresmorning headaches
Accompanies hypoglycemic episodes that
occur during sleep
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Treatment Treat with oral sugar, and a long-acting starch
If cannot swallow:
25-50ml 50% glucose IV (via large vein with 0.9%
saline flush to prevent phlebitis) or
glucagon 1mg IM if no IV access and
monitor plasma glucose level hourly
WARNING :
Rebound hyperglycemia can occur after
hypoglycemia because of the actions ofcounterregulatory hormones (Somogyi
phenomenon), an effect that can be aggravated by
excessive glucose administration.
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Treatment of uncomplicated DM
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LONG-TERMTREATMENT
The goals of therapy for type 1 or type 2 DM are to:
eliminate symptoms related to hyperglycemia
reduce or eliminate the long-term microvascular
and macrovascular complications of DM
Allow the patient to achieve as normal a lifestyle as
possible
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TREATMENT GOALS FOR ADULTS WITH DIABETES
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Symptoms of diabetes usually resolve when theplasma glucose is
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DIET management should begin with Medical
Nutrition Therapy (MNT) We advise a diet that includes fruits,
vegetables, fiber rich foods, and low-fat milk .
It should provide: 1,5002,000 calories with
50% from carbohydrate,
20% from protein
30% from fat
E i
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Exercise increases insulin sensitivity
weight loss should be promoted.
ADA recommends 150 min/week (distributed over at least 3
days) of aerobic physical activity
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When to start drugs?
If the patients glycemic target is not achieved
after 3 to 4 weeks of MNT & exercise regimen,
pharmacologic therapy is indicated.
h l i
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Pharmacologic management
Pharmacologic management of Type 1DM is
only insulin
Pharmacologic management of Type 2 DM
includes both oral glucose lowering agents or/
plus insulin (As Type 2 DM is a progressive
disorder, it ultimately requires multiple
therapeutic agents and often insulin)
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Recap of Drugs
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Oral Hypoglycemic Agents
Based on their mechanisms of action, oral glucose lowering
agents are subdivided into agents those:
Increase insulin secretion ( Insulin Secretagogues)
Reduce glucose production
Decrease glucose absorption from GIT
Increase insulin sensitivity
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Diabetes treatment
Anti-Diabetic medications
Oral hypoglycemic agents
Sulfonylureas
Biguanides Thiazolidinediones
Alpha-glucosidase inhibitors
D-phenylalinine derivatives
Combinations
Insulins
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Insulin Secretagogues (hypoglycemic agents)
1st. Generation:
Chlorpromamide(100-500 mg od)
Gliclazide ( 40- 80mg bd, up to
320mg/day)
2nd. Generation:
Gliblenclamide (5-15 mg bid ac)
Glimepiride (1-6 mg od)
Sulfonylureas Meglitinides
Rapaglinide (0.25 - 4 mg tid/ qid)
Nateglinide
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Sulfonylureas These drugs stimulate insulin secretion by
interacting with the ATP sensitive K+ channel on thebeta cells of pancreas
1st generation sulfonylureas have a longerplasma half-life which causesa greater
incidence of hypoglycemia
2nd generation sulfonylureas are generallypreferred, because they cause much less
hypoglycemia due to their shorter half-life
S lf l
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SulfonylureasAdverse effects : hypoglycemia, weight gain
Contraindications : Type 1 DM, liver or kidney disease,
sulfa allergy
Clinical advantage : Lean patients, with high
blood glucose
Drug interactions
Drugs which can increase hypoglycemic effects of
sulfonylureas: NSAIDs ,Sulfonamides, Warfarin, Beta -
blockers
Drugs which can decrease hypoglycemic effects of
sulfonylureas : Thiazides, Hydantoins, Oral
contraceptives
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Insulin Secretagogues (meglitinides)Mechanism of Action:also interact with the ATP-sensitive K+ channel
and increase insulin secretion from -cell of pancreas.They have
Fast onset of action (
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BIGUANIDES Metformin is the only drug used
Mechanisms of action:
Reduced hepatic gluconeogenesis
Increased glycolysis in peripheral tissues
Reduced absorption of glucose from GIT
Decreased plasma glucagon level. initial starting dose is 500 mg OD/ BID, upto 1000 mg TDS
ADR: diarrhea, anorexia, nausea, and loss of appetite.The major
ADR of metformin is lactic acidosis
Clinical Advantage: No hypoglycemia & No weight gain,henceUseful in OBESE diabetics with not very high Blood Glucose level
Metformin is contraindicated in patients with renal / liver
diseases any form of acidosis, congestive heart failure Use of
contrast radiography (MF stopped 48 hrs before)
GLOCUSI AS INHI I O S
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-GLOCUSIDASE INHIBITORS
Examples: acarbose and miglitol
M.O.A.: Reduction in glucose absorption byinhibiting the enzyme that breaks complex sugars
into simple sugars in the intestinal lumen.
Dose: start with a low dose (25 mg of acarbose ormiglitol) and may be increased over weeks to
months
ADRs: diarrhea, flatulence, abdominal distention
Clinical advantage: Pre-diabetic, obese persons
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Sulfonylureas
Stimulate pancreas to secrete insulin
Glyburide (Diabeta) [Prototype Pro p 393]
Glucotrol (Glipizide)
Diabenese (chlorpropamide)
Adverse reactions
Hypoglycemia
Water retention/edema
Photosensitivity
May need to add insulin in times of stress
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Thiazolidinediones
Increase cellular sensitivity to insulin
Pioglitazone (Actos)
Rosiglitazone (Avandia)
Client should have liver enzymes
checked periodically
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D-Phenylalanine derivatives
Nateglinide (Starlix)
Rapid onset, short half-life
Good for those with rapid post prandial rise in
blood glucose
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Combinations
Glucovance
Glyburide and Metformin
Avandamet
Avandia and Metformin
[come tell me when you run into this question]
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Insulin
Made in beta cells of the pancreas
Moves glucose into cells (thus acts like growthhormone in a way)
Moves potassium into cells (can buy time in
emergencies)
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Insulin preparations (Easy p 390)given ONLY with syringes marked in units
Rapid acting (lispro,
asparte)
Short acting (regular)
Intermediate acting
(NPH)
Long acting Ultralente
[Glargine/Lantus]
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Your learning
Onset of action
Peak (blood glucose will be lowest then)
Duration
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Rapid acting insulin
Lispro (Humolog, Novolog Aspart)
Onset of action
15-30 minutes [may come on in 5 minutes]
Peak of action
1 - 2 hours
Duration
3 4 hours
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Short acting insulins
Regular (clear so can be given IV)
Onset of action
0.5 to 1 hour
Peak of action
2 4 hours
Duration of action
6 8 hours
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Intermediate acting insulins
NPH, Lente (chemicals added. Cloudy)
Onset of action
1 4 hours
Peak of action
4 12 hours
Duration of action
18 24 hours
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Long acting insulins
Ultralente
Onset of action
4 8 hours
Peak of action
18 hours
Duration of action
24 36 hours
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Combination insulins
70/30 (70% NPH and 30% regular)
Humolog 70/30 (Humolog and regular)
Fewer injections
Rotate sites to decrease lipodystrophy
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