This document discusses diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), two life-threatening emergencies that can occur in patients with diabetes. It presents two case studies and provides information on the pathogenesis, clinical presentation, precipitating factors, management, and importance of patient education for prevention of DKA and HHS. The key differences between DKA and HHS are also summarized.

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

2. CASE 1
A young patient Mom is calling you for advice
Her 13-yr old boy with Type 1 DM is having abdominal
pain with N,V and diarrhea and refusing to eat
He is on Glargine 14 units bedtime and Aspart 6 units
with each meal
Should I give him his insulin ? What else?

3. CASE 2
A 68 year old woman with DM Type 2 on
Metformin 1g bd, Gliclazide 90 mg and Detemir 30 u am
He has fever and shortness of breath for 4 days and
since yesterday he is lethargic and sleepy
Also has polyuria and polydipsia
Your advice ?

4. OBJECTIVES
Introduction
Pathogenesis

Clinical Picture
Management ; Your Role

5. TYPE 1 VS TYPE 2
Type 1 DM
Immune system stops
insulin from being made
Almost absent !!
All ages :
More in younger
age groups
Type 2 DM
-Inadequate insulin/GLP1
-Insulin resistance
-Alpha cell :Glucagon
more than needed
-SGLT2 :excess glucose
reabsorbed
Affects older age group
Can affect children

6. TYPE 1 VS TYPE 2
How is it treated?
Type 1 DM
The insulin must be replaced
By injection or continuous infusion
Type 2 DM
-Lifestyle changes (TLC)
-Medications :
Tablets and/or
Injections ;Insulin / GLP! RA
-Surgery !

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

8. Amount of CHO load
Physical activity
-Insulin …Lowers
-Glucagon…Increases
-Other Pancreatic hormones : Amylin
-Intestinal Hormones : GLP-1…
Stress factors
Counter Regulatory Hormones
WHAT CONTROLS YOUR BLOOD SUGAR?

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

10. 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)

11. 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

12. 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

13. 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

14. 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

15. 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 )

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

17. Electrolyte
LossesRenal Failure
Shock CV
Collapse
INSULIN DEFICIENCY
17
Hyperglycemia
Hyper-
osmolality
Δ MS
CV
Collapse
Glycosuria
Dehydration

18. Lipolysis
FFAs
Acidosis
Ketones
CV
Collapse
INSULIN DEFICIENCY
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19. Electrolyte
LossesRenal Failure
Shock CV
Collapse
INSULIN DEFICIENCY
19
Hyperglycemia
Hyper-
osmolality
Δ MS
Lipolysis
FFAs
Acidosis
Ketones
CV
Collapse
Glycosuria
Dehydration

20. 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

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

22. 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

23. 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)

24. 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

25. 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

26. 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

27. 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

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

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

30. 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

31. HYPERGLYCEMIA
DKA
Inadequate insulin …
Fat comes out of fat cells (Free Fatty Acids)….
In the liver (Mitochondria/ Glucagon)…
to be used
as an alternative energy source
Makes ketoacids ( ketones) out of the fat

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

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

34. Hyperglycemi
a
Hyperosmolarit
y
Ketoacidosis
HHS
DK
A

35. Take Home
Messages

36. 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

37. 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

38. 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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39. PREDISCHARGE CHECKLIST
• EDUCATION = PREVENTION
• DIET INFORMATION
• TREATMENT GOALS
• “SURVIVAL SKILLS” TRAINING
• “MEDIC-ALERT” BRACELET
• PROVIDE :
GLUCOSE MONITOR AND STRIPS
MEDICATIONS, INSULIN, NEEDLES
• CONTACT PHONE NUMBERS

40. TO PREVENT = EDUCATION
• ADHERENCE /COMPLIANCE TO RX :
BASAL INSULIN / CORRECTIVE DOSES …ETC
• SICK DAYS RULES
• RECOGNIZE CLINICAL PICTURE / SMBG
• SEEK MEDICAL CARE WHEN NEEDED
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