DIABETES MELLITUS

DKA & HHS

DR MOHAMMAD DAOUD CONSULTANT ENDOCRINOLOGIST KAMC -JEDDAH

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?

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 ?

OBJECTIVES

Introduction

Pathogenesis

Clinical Picture

Management ; Your Role

TYPE 1 VS TYPE 2

Type 1 DM

Immune system stops insulin from being

madeAlmost 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 groupCan affect children

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 !

ACUTE DIABETIC COMPLICATIONS

1-Hyperglycemia : High

-Diabetic Ketoacidosis (DKA)..Type 1 DM

-Hyperosmolar Hyperglycemia Syndrome (HHS) ..Old Type 2 DM

2-Hypoglycemia : Low

Amount of CHO loadPhysical activity

-Insulin …Lowers-Glucagon…Increases

-Other Pancreatic hormones : Amylin-Intestinal Hormones : GLP-1…

Stress factors Counter Regulatory Hormones

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

WHAT CONTROLS YOUR BLOOD SUGAR?

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)

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

GLUCOSE PHYSIOLOGY

Glycogen Breakdown -

LiverIncreased 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

GLUCOSE :FACTSIn 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

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

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 )

HYPERGLYCEMIA

Due to variable reasons…

Insulin deficiency (Absolute / Relative) Insulin Resistance

Excess counter regulatory hormones (Glucagon, Cortisol…)

Defected secretion of GLP-1…

Electrolyte LossesRenal Failure

Shock CV Collapse

INSULIN DEFICIENCY

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Hyperglycemia

Hyper-osmolality

Δ MS

CV Collapse

Glycosuria

Dehydration

Lipolysis

FFAs

Acidosis

Ketones

CV Collapse

INSULIN DEFICIENCY

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Electrolyte LossesRenal Failure

Shock CV Collapse

INSULIN DEFICIENCY

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Hyperglycemia

Hyper-osmolality

Δ MS

Lipolysis

FFAs

Acidosis

Ketones

CV Collapse

Glycosuria

Dehydration

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

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)

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

HYPERGLYCEMIAPRECIPITATING 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)

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

HHS -PRECIPITATING FACTORS

Acute illness : Infection : Pneumonia UTI, Sepsis

CVA, MI, Pancreatitis , PE, Severe burns…

Endocrine Acromegaly ,Thyrotoxicosis,

Cushing's syndrome

DrugsEx ;Steroids Thiazides,TPN

Previously undiagnosed DM

HYPERGLYCEMIAWHAT 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

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

HYPERGLYCEMIADKA

Inadequate insulin & excess glucagon,catecholamines…

Body cannot burn glucose properlyGlucose builds up in the bloodstream

HYPERGLYCEMIADKA

Symptoms of DKA include:

Nausea, vomiting Abdomen/Stomach pain

Frequent urination Excessive thirst

Weakness, fatigue Speech problems

Confusion /Unconsciousness

HYPERGLYCEMIADKA

Signs of DKA include:Kussmaul respirations : Heavy, deep breathing

Fruity breath – the smell of ketoacid

TachycardiaSupine hypotension,

Orthostatic drop of BP (feel dizzy when standing)

Dry mucous membranes Poor skin turgor

Confusion /Unconsciousness

HYPERGLYCEMIADKA

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

HYPERGLYCEMIAHHS

1- Severe hyperglycemia 2- S. Osmolality > 320 msom/kg

3- Severe dehydration 4- No ketonemia 5- No acidosis

HHS

There is just enough insulin

to keep fat in fat cells and prevent ketone /acids formation

ketone levels are usually normal in HHS.

Hyperglycemia

Hyperosmolarity

Ketoacidosis

HHSDK

A

Take Home Messages

HYPERGLYCEMIC CRISISDKA & 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

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 diabetesHigher mortality rate

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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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

TO PREVENT = EDUCATION • ADHERENCE /COMPLIANCE TO RX : BASAL INSULIN / CORRECTIVE DOSES …ETC

• SICK DAYS RULES

• RECOGNIZE CLINICAL PICTURE / SMBG

• SEEK MEDICAL CARE WHEN NEEDED40