Treatment of DM

Treatment of acute emaergencies

Treatment of uncomplicated DM
 The acute emergencies are:
• DKA

• Hyperglycemic Hyperosmolar State

• Hypoglycemia
DKA
 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.
 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
 Pathogenesis
hyperglycemia 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.
 Signs & symptoms
 usually develop over 24 h
 May be the initial presentation in type 1 DM
 Classic presentation is :
 a history of Polyuria, Polydipsia, Polyphagia
 often prominent Nausea & vomiting
 Severe Abdominal pain which can minic acute
pancreatitis or other acute abdominal emergencies
 A fruity odor (acetone smell) on the patient’s breath
called Kussmaul’s breathing
 Hyperglycemia induces an osmotic diuresis that
leads to intravascular volume depletion causing
Tachycardia/hypotension
 Lethargy & CNS depression may evolve into coma
 Precipitating events
• On a detailed Hx and Examination we can find:
 Inadequate/missed insulin administration
 Evidence of infection e.g:
Pneumonia
UTI
Gastroenteritis
Spesis
 Infartion (cerabral,MI,mesenteric,peripheral..etc)
 Drugs (e.g. cocaine)
 Pregnancy
 Recent surgery/trauma
 Laboratory Findings
• The Cardinal Biochemical features of diabetic
ketoacidosis are:

 HYPERGLYCEMIA

 HYPERKETONAEMIA

 METABOLIC ACIDOSIS

Mmol/l Multiply by 18 = mg/dl

 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
 Interpretation of Lab Results 1
 Occasionally, the serum glucose is only minimally elevated.
 Serum bicarbonate is frequently <10 mmol/L
 Arterial pH ranges between 6.8 and 7.3, depending on the
severity of the acidosis.
 Despite a total-body potassium deficit, the serum potassium
at presentation may be mildly elevated, secondary to the
acidosis.
 Total body stores of sodium, chloride, phosphorous, and
magnesium are also reduced but are not accurately
reflected by their levels in the serum because of dehydration
and hyperglycemia.
 Elevated blood urea nitrogen (BUN) and serum creatinine
levels may reflect intravascular volume depletion rather
 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]
 Treatment plan
• Initial Evaluation
• Close Monitoring
• Fluid management
• Electrolyte Replacement
• Insulin Therapy
• Resolution & Conversion to home therapies
ASAP
1. Admit to ICU Management 1
2. ABC of resusitation may be needed
3. Cardiac monitor & Pulse oximeter
4. O2 mask/intranasal
5. NG tube if altered mental status
6. Blood sampling & ABG
7. 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<3.3mmol/l and
administer KCl by fluid infusion accordingly.
 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*********
 Insulin Later phase
• When plasma glucose level reaches 13.9mmol/l reduce
infusion of insulin to 0.05Units/kg/hour and
• add 5% dextrose with 0.45% NS.
• At this stage fast acting insulin S/C before each meal
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 much higher doses
 Management 3
• KCl 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
 Phosphate & Magnesium
• Hypophosphatemia does not usually require
Rx
 in pts with phos <1.0 mg/dl there can be
cardiac dysfunction, hemolytic anemia, or
respiratory depression. Therefore 20-30
meq/L of Potassium Phosphate is added to IVF

• Hypomagnesemia may develop during Rx,and

requires supplementation.
 complications
• Aspiration
 may occur due to decreased mental status at
presentation.

• Hypoglycemia

• Hypokalemia
• I would like to make a special note that insulin pushes K inside the
cells,so during the treatment,likelyhood of hypokalemia
[Link] frequent monitoring of K is VERY important.
 Complications of DKA
• Cerebral edema
An extremely serious complication of DKA, is seen
most 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 is
suspected.
Hyperglycemic Hyperosmolar
State
 Introduction to HHS
• Hyperosmolar hyperglycemic state (HHS) is a
serious metabolic derangement
• Also called hyperosmolar hyperglycemic nonketotic
coma (HHNC)
• occurs in mostly elderly patients with type 2
diabetes mellitus and
• can be a life-threatening emergency.
• it has a substantially higher mortality than DKA (up
to 15% more sometime)
 Pathophysiology
 HHS is a nonketotic state
• The absence of ketosis is not completely
understood.
• 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 body
synthesis
• or insulin/glucagon ratio does not favor
ketogenesis.
 Clinical picture Mostly similar to DKA
Notably absent are symptoms of nausea, vomiting, and
abdominal pain and the Kussmaul’s 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
 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 be
present secondary to increased lactic acid
• Moderate ketonuria, if present, is secondary to
starvation
 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.
• 1–3 L of 0.9% normal saline over the first 2–3 h
initially.
• The calculated free water deficit (which averages 9–
10 L) should be reversed over the next 1–2 days
(infusion rates of 200–300 mL/h of hypotonic
solution) then 5% dextrose)
 NOTE : too rapid a reversal of fluid deficit may worsen
neurologic function.
Hypoglycemia in DM
 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
<3mmol/L, however Individual threshold for
symptoms varies .
 Hypoglycemia

• the commonest cause is insulin or sulfonylurea

treatment with
• ↑ activity,
• missed meal,
• accidental or non-accidental overdose.
 Pathophysiology
The acute response to hypoglycemia is
counterregulatory effects of glucagon and
catecholamines
Initial symptoms occur secondary to catecholamine
release

Later on neuroglycopenic symptoms occur from the

direct effects of hypoglycemia on CNS function
 Signs & symptoms
symptoms secondary to catecholamine release are :

 Sweating
 Anxiety
 Hunger
 Tremor
 Palpitations
 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
 nocturnal hypoglycemia
• The same characteristic set of symptoms
 night sweats
 Nightmares
 morning headaches
Accompanies hypoglycemic episodes that
occur during sleep
 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 of counterregulatory hormones
(Somogyi phenomenon), an effect that can be
aggravated by excessive glucose administration.
Treatment of uncomplicated DM
 LONG-TERM TREATMENT
• 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
TREATMENT GOALS FOR ADULTS WITH DIABETES
• Symptoms of diabetes usually resolve when the
plasma glucose is <11.1 mmol/L
• The care of an individual with either type 1 or type
2 DM requires a multidisciplinary team.
 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:
• 1,500–2,000 calories with
• 50% from carbohydrate,
• 20% from protein
• 30% from fat
 Exercise
• increases insulin sensitivity
weight loss should be promoted.
ADA recommends 150 min/week (distributed over at least 3
days) of aerobic physical activity
 When to start drugs?
• If the patient’s glycemic target is not achieved
after 3 to 4 weeks of MNT & exercise regimen,
pharmacologic therapy is indicated.
 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)
Recap of Drugs
 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

 Diabetes treatment
• Anti-Diabetic medications
– Oral hypoglycemic agents
• Sulfonylureas
• Biguanides
• Thiazolidinediones
• Alpha-glucosidase inhibitors
• D-phenylalinine derivatives
• Combinations

– Insulins
Insulin Secretagogues (hypoglycemic agents)

Sulfonylureas Meglitinides
1st. Generation: Rapaglinide (0.25 - 4 mg tid/ qid)
Chlorpromamide(100-500 mg od) Nateglinide
Gliclazide ( 40- 80mg bd, up to
320mg/day)
2nd. Generation:
Gliblenclamide (5-15 mg bid ac)
Glimepiride (1-6 mg od)
 Sulfonylureas
• These drugs stimulate insulin secretion by
interacting with the ATP sensitive K+ channel on the
beta cells of pancreas

• 1st generation sulfonylureas have a longer

plasma half-life which causesa greater
incidence of hypoglycemia
• 2nd generation sulfonylureas are generally
preferred, because they cause much less
hypoglycemia due to their shorter half-life
 Sulfonylureas
Adverse 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
 Insulin Secretagogues (meglitinides)
Mechanism of Action:also interact with the ATP-sensitive K+ channel
and increase insulin secretion from β-cell of pancreas.
•They have
–Fast onset of action (<1h.)
–short half-lives (1h.)
–short duration of action(4h.)

•So these agents are taken immediately before each meal

•Clinical advantage: Effective in reducing post prandial hyperglycemia and
hypoglycemia is rare
•Dose: 0.25 – 4.0 mg (repaglinide) & 60-120 mg (nateglinide) tid / qid
•ADR: They should be cautiously used in hepatic & renal dysfunctions
 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 [Link] major
ADR of metformin is lactic acidosis
• Clinical Advantage: No hypoglycemia & No weight gain,hence
Useful 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)
 α-GLOCUSIDASE INHIBITORS
• Examples: acarbose and miglitol
• M.O.A.: Reduction in glucose absorption by
inhibiting the enzyme that breaks complex sugars
into simple sugars in the intestinal lumen.
• Dose: start with a low dose (25 mg of acarbose or
miglitol) and may be increased over weeks to
months
• ADRs: diarrhea, flatulence, abdominal distention
• Clinical advantage: Pre-diabetic, obese persons
 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
 Thiazolidinediones
• Increase cellular sensitivity to insulin
– Pioglitazone (Actos)
– Rosiglitazone (Avandia)

Client should have liver enzymes

checked periodically
 D-Phenylalanine derivatives

• Nateglinide (Starlix)

• Rapid onset, short half-life

– Good for those with rapid post prandial rise in
blood glucose
 Combinations
• Glucovance
– Glyburide and Metformin

• Avandamet
– Avandia and Metformin

[come tell me when you run into this question…]

 Insulin

• Made in beta cells of the pancreas

• Moves glucose into cells (thus acts like growth
hormone in a way)
• Moves potassium into cells (can buy time in
emergencies)
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]
 Your learning

• Onset of action

• Peak (blood glucose will be lowest then)

• Duration
 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
 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
 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
 Long acting insulins
• Ultralente
– Onset of action
• 4 – 8 hours

– Peak of action
• 18 hours

– Duration of action
• 24 – 36 hours
 Once a day insulin
• Glargine/Lantus
– Cannot be diluted or mixed in syringe with any
other insulin
– Slow, steady release
– Daily dosing [usually at bedtime]
– Refrigerated or tosses every 14 days
 Combination insulins
• 70/30 (70% NPH and 30% regular)
• Humolog 70/30 (Humolog and regular)

• Fewer injections
• Rotate sites to decrease lipodystrophy
To avoid exercise-related hyper- or hypoglycemia, individuals
with type 1 DM should:
(1) monitor blood glucose before, during, and afterexercise; (2) delay
exercise if blood glucose is >14 mmol/L (250 mg/dL) and ketones are
present;
(3) if the blood glucose is <5.6 mmol/L (100 mg/dL), ingest carbohydrate
before exercising;
(4) monitor glucose during exercise and ingest carbohydrate to prevent
hypoglycemia;
(5) decrease insulin doses (based on previous experience) before
exerciseand inject insulin into a nonexercising area; and
(6) learn individual glucose responses to different types of exercise and
increase food intake for up to 24 h after exercise, depending on
intensity and duration of exercise. In individuals with type 2 DM,
exercise-related hypoglycemia is less common but can occur in
individuals taking either insulin or insulin secretagogues.