Acute complications of

Diabetes Mellitus
Dr Yemane G (MD, assis. prof. EMCC)
 OBJECTIVES
At the end of the session you will be able to:
 Define and classify DM
 Describe the pathophysiology of dm, DKA and

HHS
 Differentiate clinical presentation of DKA and

HHS
 Develop skill of diagnosing and managing

patient with DKA

Outline
-Introduction
-Definition
-epidemiology
-pathogenesis
-clinical features
-Diagnosis
-management options
Brainstorming?
 What do you know about DM (definition and
classification)?
Diabetes mellitus
 Diabetes mellitus is a heterogeneous group of
hyperglycemic disorders characterized by high
serum glucose and disturbances of
carbohydrate, lipid and protein metabolism.
 And can have both acute and chronic

complications
 Acute include hypoglycemia,(DKA), and

hyperglycemic hyperosmolar non ketotic coma

(HHNC). Long-term complications include
disorders of blood vessels, especially the
microvasculature.
Types
National Diabetes Data Group classifies
diabetes mellitus in to Four:
I. Type 1 DM
II. Type 2 DM
III. Gestational DM
IV. Other specific types
Causes
 The causes of diabetes mellitus is usually
deficiency of insulin in the case of type-1 DM
and is due to insulin resistance to its receptor
or post receptor site in the case of type-2
DM/GDM/others
Functions of insulin
Insulin’s main action occurs at the three
principal tissues of energy storage and
metabolism—the liver, adipose tissue, and
skeletal muscle.
 Insulin acts on the liver to facilitate the

uptake of glucose and its conversion to

glycogen while inhibiting glycogen
breakdown (glycogenolysis) and suppressing
gluconeogenesis.
Cont’d
 Insulin increases lipogenesis in the liver and
adipose cells by producing triglycerides from
free fatty acids and glycerol while inhibiting
the breakdown of triglycerides (lipolysis).
 Insulin stimulates the uptake of aminoacids

into muscle cells with subsequent

incorporation into muscle protein while
preventing the release of amino acids from
muscle and hepatic protein sources.
Definition
 DKA is a syndrome in which insulin deficiency
and glucagon excess combine to produce a
hyperglycemic, dehydrated, acidotic patient
with profound electrolyte imbalance
 Hyperglycemic hyperosmolar non ketotic coma
(HHNC) represents a syndrome of acute diabetic
decompensation characterized by marked
hyperglycemia, hyperosmolarity, dehydration,
and decreased mental functioning that may
progress to frank coma with minimal or absent
ketosis and acidosis
Epidemiology
 ED visits for DKA was 64 per 10,000
 Mortality to <5% of reported episodes in

experienced centers.
 Mortality is higher in the elderly due to

underlying renal disease or coexisting

infection and in the presence of coma or
hypotension.
Pathophysiology
- Two interrelated hormonal abnormalities are
largely responsible for the development of
hyperglycemia and ketoacidosis in patients with
uncontrolled diabetes:
1-Insulin deficiency and/or resistance.
2-Glucagon excess, which may result from
removal of the normal suppressive effects of
insulin
Cont’d
 As serum glucose concentration increases, an
osmotic gradient develops, attracting water
from the intracellular space into the
intravascular compartment, causing cellular
dehydration.
 The initial increase in intravascular volume is

accompanied by a temporary increase in the

glomerular filtration rate.
Cont’d
 As serum glucose concentration increases,
the capacity of the kidneys to reabsorb
glucose is exceeded, glucosuria and osmotic
diuresis occur.
 During osmotic diuresis, significant urinary

loss of sodium and potassium, as well as

more modest losses of calcium, phosphate,
and magnesium may occur.
Cont’d
 As volume depletion progresses, renal
perfusion decreases, and the glomerular
filtration rate is reduced.
 Renal tubular excretion of glucose is

impaired, which further worsens

hyperglycemia.
 A sustained osmotic diuresis may result in

total body water losses that often exceed 20%

to 25% of total body weight, or approximately
8 to 12 L in a 70-kg patient
Cont’d
 This osmotic diuresis combined with poor
intake and vomiting produces the profound
dehydration and electrolyte imbalance
associated with DKA
 The hyperosmolarity produced by

hyperglycemia and dehydration is the most

important determinant of the patient’s mental
status
DKA/HHS
Pathogenesis
Precipitating Factors
Absolute Relative
Insulin Glucagon Insulin
Deficiency Catecholamines Deficiency
Cortisol
Growth Hormone

Lipolysis Proteolysis Minimal Lipolysis

FFAs Gluconeogenic
Substrates

Ketogenesis Gluconeogenesis Glycogenolysis

Ketoacidosis Hyperglycemia Hyperosmolality

Glucosuria
Triglycerides (Osmotic Diuresis) Decreased GFR

Hyperlipidemia Loss of Water

& Electrolytes Dehydration
 DKA/HHS
Ketone Body Formation in Liver

Glucose Glucagon Fatty Acids Insulin

Fatty Acyl-CoA Triglycerides

Fatty Acyl-CoA

Acetyl-CoA

Acetoacetyl-CoA

b-Hydroxy-b-methylglutaryl CoA

Acetoacetate b -Hydroxybutyrate

AcetoneNADH NAD
Clinical features
Usually requires precipitants which includes
7 I’S:
 Infections—40%

 Insulin missed—25%

 Initial presentation-15%

 Ischemia or infarction

 Iatrogenic …glucocorticoids, Thiazide diuretics

 Intoxication

 Intra abdominal process-

pancreatits,cholecystitis

21
Cont`d
 The clinical manifestations of DKA are related
directly to hyperglycemia, volume depletion,
and acidosis which includes
-polyuria
-polydypsia
- weight loss
-nausea
-vomiting
-abdominal pain: common in DKA
-impaired mental status: common in HHS
Cont’d
 On P/E
-tachycardia
-tachypnea(kussmaul`s respiration)
-hypotension
-fever/hypothermia
-abdominal pain n tenderness
Diagnosis
DKA is diagnosed with
-A blood glucose level >250 milligrams/dL
(13.8 mmol/L)
-an anion gap >10 mEq/L (>10 mmol/L)
-a bicarbonate level <15 mEq/L (<15 mmol/L),
and
-pH <7.3 with moderate ketonuria or
ketonemia
Cont’d
 HHS is “defined” by severe hyperglycemia
with serum glucose usually >600
milligrams/dL (>33.3 mmol/L), an elevated
calculated plasma osmolality of >315
mOsm/kg (>315 mmol/kg), serum
bicarbonate >15 mEq/L (>15 mmol/L), an
arterial pH >7.3, and serum ketones that are
negative to mildly positive
 Cont’d
DKA HHS

Plasma glucose >250 milligrams/dL >600 milligrams/dL

Serum bicarbonate ≤18 mEq/L (<18 >15 mEq/L (>15

mmol/L mmol/l)

Urine acetoacetate + – or small

Serum ketones + – or small

Serum osmolality Variable >320 mOsm/kg

Anion gap >12 mEq/L <12 mEq/L (<

Arterial/venous pH <7.30 >7.30

Cont’d
 RBS might be normal (euglycemic DKA) in
-Patients presenting shortly after receiving
insulin
-Type 1 diabetics who are young and
vomiting
-Patients with impaired gluconeogenesis
-Low caloric intake/starvation
-Depression
-Pregnancy
Laboratory abnormalities
-CBC:Leukocytosis is often present because of
hemoconcentration and stress. However, a WBC
count >25,000 mm3 and/or an absolute band
count of 10,000 mm3 or more is suggestive of
infection.
-Elevation of C-reactive protein
-U/A :ketonuria
Cont’d
Serum electrolyte
-Na+: decreased due to Osmotic diuresis
-K+: serum potassium level is normal or
elevated, despite total body k depletion due
to extracellular shift of potassium secondary
to acidemia and increased intravascular
osmolarity caused by hyperglycemia
-phosphorous, calcium, and magnesium:
initially elevated due to hemoconcentration
but later become decreased due to renal loss.
Cont’d
-Cr: might be elevated due to pre renal
azothemia
-CXR : might be normal or features of
precipitant like pneumonia, PE
-HgA1C- elevated
 Severity of DKA
mild moderate severe
Mental status Alert Alert/drowsy Stupor/coma
Arterial pH 7.25-7.30 7.00-7.24 <7.00
Serum 15-18 10 to <15 <10
bicarbonate
(mEq/L)
Urine ketones* Positive Positive Positive
Serum ketones* Positive Positive Positive
Effective serum Variable Variable Variable
osmolality
(mOsm/kg)•
Anion gap >10 >12 >12
 Be Aware of Conditions that may
make DKA Diagnosis Difficult
 Mixed acid base disorder (e.g.. vomiting may raise the
bicarbonate)
 Pregnancy  normal to minimally elevated glucose
levels
 Normal AG due to loss of ketones from osmotic diuresis
 Negative serum ketones due to β-hydroxybutarate
  AG + negative serum ketones = order serum
β-hydroxybutarate
 Always order both urine and serum ketones
Cont`d
ESO = 2[measured Na (mEq/L)] + glucose
(mg/dL)/18.
 AG = (Na+) - (Cl- + HCO3-) (mEq/L).
DDx
 Alcoholic ketoacidosis
 Starvation ketoacidosis
 Renal failure
 Lactic acidosis
 Ingestions

-Salicylates
-Ethylene glycol
-Methanol
Treatment
The goals of therapy are:
1. Volume repletion
2. Reversal of the metabolic consequences of
insulin insufficiency
3. Correction of electrolyte
4. Recognition and treatment of precipitating
causes; and
5. Avoidance of complications
Volume repletion
 Restore intravascular volume and normal
tonicity
 Perfuse vital organs
 Improve GFR and lower serum glucose and
ketone level
 Improves the response to low dose
 Insulin therapy.
Typical Water and Electrolyte Deficits
DKA HHS
Total Water (l) 6 9
Water (ml/kg) 50-100 100-200
Na+ (mEq/kg) 7-10 5-13
Cl- (mEq/kg) 4-7 5-15
K+ (mEq/kg) 3-12 4-6
PO4 (mmol/kg) 1 3-7
Mg++ (mEq/kg) 1 1-2
Ca++ (mEq/kg) 1 1-2
Cont’d
-The average adult patient has a water deficit of
100 mL/kg (5 to 10 L) and a sodium deficit of 7
to 10 mEq/kg
-NS is the preferred fluid
-before initial electrolyte results, administer the
initial fluid bolus of isotonic saline at a rate of
15 to 20 mL/kg/h during the first hour
Cont’d
-After the initial bolus, administer normal saline
at 250 to 500 cc/h in hyponatremic patients, or
give 0.45% normal saline at 250 to 500 cc/h for
eunatremic and hypernatremic patients.
OR
-the first 2 L are administered rapidly over 0 to 2
hours, the next 2 L over 2 to 6 hours, and then
an additional 2 L over 6 to 12 hours. This will
replace 50% of the volume lost and the next 50 %
will be administered over the next 12 hrs.
Cont’d
-When the blood glucose level is 250
milligrams/dL (13.8 mmol/L), change fluid to
5% dextrose in 0.45% normal saline
- During this phase of treatment consider CVP
or PAWP monitoring in the elderly or in those
with heart or renal disease, and malnourished
patients for the development of ARDS and
cerebral edema.
POTASSIUM REPLACEMENT
-Total body potassium deficits in the range of 3 to 5
mEq/kg due to insulin deficiency, metabolic acidosis,
osmotic diuresis, and frequent vomiting
-The initial serum concentration is usually normal or
high because of the intracellular exchange of
potassium for hydrogen ions during acidosis, the
total body fluid deficit, and diminished renal function
- Initial hypokalemia indicates severe total-body
potassium deficits, and large amounts of
replacement potassium are usually necessary in the
first 24 to 36 hours.
Cont’d
 Replacement depends on initial serum k+
- If initial [K+] >5.2 initiate IV infusion of
regular insulin at 0.1-0.14 units/kg/hr*. Repeat
[K+] STAT in 2 hours
-If initial [K+] is >3.3 and <5.2 add 20-30
mEq of K+ to each liter of fluid and insulin drip
Cont’d
-If initial [K+] is <3.3 hold insulin drip and give
K+ at 20-30 mEq/h until [K+] is >3.3 then
initiate insulin drip
-the rate of Kcl infusion is at a rate no faster
than 10 mEq/h via peripheral IV or 20 mEq/h
via central line access
-During the first 24 hours, 100 to 200 mEq or
of Kcl is usually required
INSULIN
-once hypokalemia ([K+] <3.3 mEq/L [<3.3
mmol/L]) is excluded regular insulin can be
administered after the initial fluid bolus, or
simultaneously in a second IV line at a rate of
0.1 to 0.14 unit/kg/h
-rate of drop of RBS expected/hr is 50-75
mg/dl, if the drop is <expected give a 0.14
unit/kg bolus and resume insulin drip rate
Cont’d
-so once the serum glucose is 200 mg/dL add
dextrose to the IV fluids and reduce the insulin
drip rate to 0.02 to 0.05 unit/kg/h
-Maintain the serum glucose between 150 and
200 milligrams/dL (8.3 and 11 mmol/L) until
the resolution of DKA
Cont’d
-Continue the insulin infusion until the
resolution of DKA:
• glucose <200 milligrams/dL (<11 mmol/L)
and two of the following:
1. a serum bicarbonate level >15 mEq/L,
2. a venous pH >7.3, and/or a normal
calculated anion gap
Transition from IV Insulin
 The method of insulin transition varies, and
there is no set protocol
 In patients who can eat, the transition should

include a short-acting and long-acting

insulin given when DKA has resolved.
 One method consists of giving 10 units of SC

regular insulin 30 to 60 minutes before the

insulin infusion is stopped and 80% of the
usual long-acting insulin dose 1 to 2 hours
before discontinuing the IV insulin infusion
Cont’d
 Another method is to give 50% of the usual
long-acting insulin dose 2 hours before the
IV insulin infusion is stopped
 starting dose of longacting insulin at 0.1 to

0.2 unit/kg.
Can consider switch to SC insulin
when
• AG normalized
• BS < 250 mg/dl
• Insulin IV requirements < 2U/h
• Patient able to eat
• Hemodynamically stable
Cont’d
- IV potassium phosphate if phosphate level is
<1mg /dl at a dose of 2.5 mg/kg IV
- MgSO4 if magnesium concentration is
<2mEq/L
- HCO3 if PH is <7 at a dose of 100 mEq of
sodium bicarbonate in 400 mL of water with 20
mEq KCl at a rate of 200 mL/h for 2 hours until
the venous pH >7.0 and If the pH remains <7.0
despite the infusion, repeat NaHCO3
ADA recommendation
 If PH 6.9-7.0, give 50 mEq of NaHCo3 in
200ml of sterile water with 10mEq KCl over 1
hour
 If PH <6.9, give 100mEq of NaHCo3 in 400ml

sterile water with 10mEq KCl over 2 hours

-Repeat dose of bicarb every 2 hours till PH>7

Advantage of bicarbonate
More of theoretical advantage
In case of severe acidosis
-Improve myocardial contractility
- Improve catecholamine tissue response
- Decrease work of breathing
In case of Hyperkalemia
-Elevate ventricular fibrillation threshold
Disadvantages
 Severe & worsening hypokalaemia
 Paradoxical CNS acidosis
 Impair oxyhemoglobin dissociation
 Hypertonicity
 Sodium overload
Identify and Treat the Precipitating
Factor
 Insulin omission – MOST COMMON CAUSE of DKA
 New diagnosis of diabetes
 Infection / Sepsis
 Myocardial infarction
◦ Small rise in troponin may occur without overt ischemia
◦ ECG changes may reflect hyperkalemia
 Thyrotoxicosis
 Drugs
DKA/HHS
Complications of Therapy
 Hypoglycemia
 Hypokalemia or Hyperkalemia
 Fluid Overload
 Hyperchloremic Acidosis
 Cerebral Edema
 ARDS
 Thromboembolic Episodes
Special populations
 RECURRENT DKA PATIENTS
-insulin noncompliance and cocaine use are
the commonest causes
-pts. Benefit from drug rehabilitation and
social workers
Cont’d
 PATIENTS WITH INSULIN PUMPS
-their pumps disconnected and turned off
and should be treated just like any other
patient.
Cont’d
 DKA IN PREGNANCY
-pregnant women prone to DKA due to
relative insulin deficiency , vomiting and urinary
tract infections
DKA/HHS
Poor Prognostic Indicators
 Advanced Age
 Low pH
 Hypotension
 Marked Hyperosmolality
 High BUN
 Associated Diseases
Summary
 ???
References
 Tintinallis Text book of Emergency medicine
8th edition
 Rosen’s Text book of Emergency medicine
 Harrison’s text book of Internal Medicine
Cont`d

THE END