This document provides an overview of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), two life-threatening complications of diabetes that result in severe hyperglycemia. It defines DKA and HHS, describes their pathophysiology including the role of insulin deficiency and counterregulatory hormones, and compares their typical presentations and precipitating factors. The key differences between DKA and HHS are noted, with DKA more common in type 1 diabetes and characterized by ketosis and acidosis, while HHS occurs more often in type 2 diabetes and lacks significant ketosis or acidosis. Early aggressive management of both conditions is emphasized through hydration, insulin administration, and electrolyte

1. DKA & HHS
PATHOGENESIS
DR MOHAMMAD DAOUD
CONSULTANT ENDOCRINOLOGIST
KAMC -JEDDAH

2. OBJECTIVES
Introduction
Definitions
Pathogenesis
S & S
Management

3. ACUTE DIABETIC COMPLICATIONS
1-Hyperglycemia : High
-Diabetic Ketoacidosis (DKA)..Type 1 DM
-Hyperosmolar Hyperglycemia Syndrome
(HHS) ..Old Type 2 DM
2-Hypoglycemia : Low

4. WHAT CONTROLS YOUR BLOOD SUGAR?
When we eat …blood sugar (Glucose)
increases
This stimulates insulin secretion
Insulin moves the glucose out of the
Blood Cells

5. GLUCOSE :FACTS
 Carbohydrates (Glucose) are the main
calorie source for our body
 Extra CHO are stored as:
Glycogen (liver and muscles)
OR
Fat (Adipose tissue)

6. GLUCOSE :FACTS
The brain relies almost exclusively on
glucose as a fuel, but cannot synthesize or
store it
Adequate uptake of glucose from the
plasma is essential for normal brain function
and survival

7. GLUCOSE PHYSIOLOGY
Glycogen
Breakdown -Liver
Increased
Glucagon
Energy
Fat Synthesis
Glycogen
Synthesis
Glucose release
to blood
(+) Pancreas secretion
of Glucagon
Blood
Glucose
Pool(+) Pancreas
secretion of
Insulin
(+) Circulating
Insulin
Uptake of glucose
by cells
Decrease blood
glucose

8. GLUCOSE :FACTS
In case of CHO shortage ( ex: Starvation)
OR
Unable to use CHO ( ex: No insulin as in
DKA)
Body shifts gear to other sources of energy

9. GLUCOSE :FACTS
Other sources of energy …
Protein breakdown to amino acids
and glucose synthesis
Fat breakdown into FFA and
ketones formation (with acidosis)..
Minimal amount of Insulin can prevent Ketogenesis

10. WHAT CONTROLS YOUR BLOOD SUGAR?
-Insulin …Lowers
-Glucagon…Increases
-Other hormones
Amount of CHO load
Physical activity
Stress factors
Counter Regulatory Hormones

11. HYPERGLYCEMIA
Hyperglycemia basic processes are :
1-Impaired/decreased glucose use
2-Increased gluconeogenesis
(Make up of glucose from other sources)
3-Increased glycogenolysis
(breakdown of Glycogen to Glucose )

12. HYPERGLYCEMIA
Due to variable reasons…
Insulin deficiency (Absolute / Relative)
Insulin Resistance
Excess counter regulatory hormones
(Glucagon, Cortisol…)
Defected secretion of GLP-1…

13. Electrolyte
LossesRenal Failure
Shock CV
Collapse
INSULIN DEFICIENCY
13
Hyperglycemia
Hyper-
osmolality
Δ MS
Lipolysis
FFAs
Acidosis
Ketones
CV
Collapse
Glycosuria
Dehydration

14. VS
Type 1DM
Immune system stops
insulin from being made
All ages :
More in younger
age groups
Type 2 DM
-Not enough insulin
-Insulin resistance)
Combination of the two
Alpha cell defect
Others: GLP-1 , SGLT2
Affects older age group
Can affect children

15. VS
Treatment ?
Type 1 DM
The insulin must be replaced
By injection or continuous infusion
Type 2 DM
Lifestyle changes (TLC)
Medications : tablets and/or Insulin

16. DIABETIC HYPERGLYCEMIC CRISES
Diabetic Ketoacidosis
(DKA)
Hyperglycemic
Hyperosmolar State (HHS)
Younger, type 1 diabetes Older, type 2 diabetes
No hyperosmolality Hyperosmolality
Volume depletion Volume depletion
Electrolyte disturbances Electrolyte disturbances
Acidosis No acidosis

17. DIABETIC KETOACIDOSIS (DKA)
PATHOPHYSIOLOGY
Unchecked gluconeogenesis  Hyperglycemia
Osmotic diuresis  Dehydration
Unchecked ketogenesis  Ketosis
Dissociation of ketone bodies
into hydrogen ion and anions

Acidosis
Anion-gap metabolic
17
Often a precipitating event is identified
(infection, lack of insulin administration)

18. HYPEROSMOLAR HYPERGLYCEMIC STATE
(HHS) PATHOPHYSIOLOGY
Unchecked gluconeogenesis  Hyperglycemia
Osmotic diuresis  Dehydration
• Presents commonly with renal failure
• Insufficient insulin for prevention of hyperglycemia but
sufficient insulin for suppression of lipolysis and ketogenesis
• Absence of significant acidosis
• Often identifiable precipitating event (infection, MI)
Major body water loss
DKA 5-7 L
HHS 8- 10 L

20. HYPERGLYCEMIA
PRECIPITATING FACTORS
Stress: through excess counter regulatory hormones:
-Glucagon
-Catecholamines (Adrenaline and Nor-Adrenaline)
-Cortisol
Medications: Steroids, Thiazides ,Beta blockers,…
Stopping DM medications
Acute illness: Infections (ex;UTI, Pneumonia) ,MI (ACS),
Stroke , Acute Pancreatitis, Burn
Others: Trauma ,Alcohol, Drug abuse (cocaine )
Feeding (NGT/ PEG/ TPN)

21. DKA -PRECIPITATING FACTORS
Inadequate insulin treatment
Noncompliance
Insulin error or insulin pump malfunction
Poor “sick-day” management
New onset diabetes (20 -25%)
 Acute illness
Infection ,CVA, MI ,Acute pancreatitis
 Drugs:
Steroids ,Clozapine or olanzapine
Cocaine Lithium ,Terbutaline

22. HHS -PRECIPITATING FACTORS
Acute illness :
Infection : Pneumonia UTI, Sepsis
CVA, MI, Pancreatitis , PE, Severe burns…
Endocrine
Acromegaly ,Thyrotoxicosis,
Cushing's syndrome
Drugs
Ex ;Steroids Thiazides,TPN
Previously undiagnosed DM

23. HYPERGLYCEMIA
WHAT IS DKA?
Severe hyperglycemia ; 250-300 mg/dl
Ketonemia : ketone bodies in the blood
(β-OH-butyric acid, Acetoacetic acid and Acetone)
Acidosis: PH <7.3
= Lack of insulin

24. Hyperglycemia
Ketosis
Acidosis
Adapted from Kitabchi AE, Fisher JN. Diabetes Mellitus. In: Glew RA, Peters SP, ed. Clinical
Studies in Medical Biochemistry. New York, NY: Oxford University Press; 1987:105.
DKA : DEFINITION

25. HYPERGLYCEMIA
DKA
Inadequate insulin &
excess glucagon,catecholamines…
Body cannot burn glucose properly
Glucose builds up in the bloodstream

26. HYPERGLYCEMIA
DKA
Symptoms of DKA include:
Nausea, vomiting Abdomen/Stomach pain
Frequent urination Excessive thirst
Weakness, fatigue Speech problems
Confusion /Unconsciousness

27. HYPERGLYCEMIA
DKA
Signs of DKA include:
Kussmaul respirations : Heavy, deep breathing
Fruity breath – the smell of ketoacid
Tachycardia
Supine hypotension,
Orthostatic drop of BP (feel dizzy when standing)
Dry mucous membranes Poor skin turgor
Confusion /Unconsciousness

28. HYPERGLYCEMIA
DKA
Inadequate insulin …
Fat comes out of fat cells (Free Fatty Acids)….
Free Fatty Acids >> Liver (Mitochondria/ Glucagon)
Used as an alternative energy source
Makes ketoacids ( ketones) out of the fat

29. HYPERGLYCEMIA
HHS
1- Severe hyperglycemia
2- S. Osmolality > 320 msom/kg
3- Severe dehydration
4- No ketonemia
5- No acidosis

30. HHS
There is just enough insulin
to keep fat in fat cells and
prevent ketone /acids formation
ketone levels are usually normal in HHS.

31. Hyperglycemi
a
Hyperosmolarit
y
Ketoacidosis
HHS
DKA

32. Take Home
Messages

33. HYPERGLYCEMIC CRISIS
DKA & HHS
• LIFE THREATENING EMERGENCIES
• DKA …MOSTLY TYPE 1 –YOUNG
INSULIN DEFICIENCY -ACIDOSIS
• HHS….TYPE 2 DM –OLDER
WORSE DEGREE OF DEHYDRATION
• BOTH: SIMILAR PRECIPITATING FACTORS
ELECTROLYTES DISTURBANCES

34. DKA VS HHS
Diabetic Ketoacidosis
(DKA)
Hyperglycemic
Hyperosmolar State (HHS)
Absolute (or near-absolute)
insulin deficiency, resulting in
• Severe hyperglycemia
• Ketone body production
• Systemic acidosis
Severe relative insulin deficiency,
resulting in
• Profound hyperglycemia and
hyperosmolality (from urinary
free water losses)
• No significant ketone
production or acidosis
Develops over hours to 1-2 days Develops over days to weeks
Most common in type 1 diabetes,
but increasingly seen in type 2
diabetes
Typically presents in type 2 or
previously unrecognized
diabetes
Higher mortality rate

35. DKA & HHS
• EARLY AGGRESSIVE MANAGEMENT
• HYDRATION
• INSULIN
• ELECTROLYTES DISTURBANCES RX
• LOOK FOR PRECIPITATING FACTORS :
TREAT AND TEACH TO AVOID ..IF POSSIBLE
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36. PREDISCHARGE CHECKLIST
• EDUCATION
• DIET INFORMATION
• TREATMENT GOALS
• “SURVIVAL SKILLS” TRAINING
• “MEDIC-ALERT” BRACELET
• PROVIDE :
GLUCOSE MONITOR AND STRIPS
MEDICATIONS, INSULIN, NEEDLES
• CONTACT PHONE NUMBERS

37. Thank You
Any Questions ?