Lecture 6: Metabolic complications of diabetes Flashcards
Name the main acute metabolic complications of diabetes
- Diabetes ketoacidosis
- Byperosmolar hyperglycaemic (non-ketotoic) state- HHS
- Hypoglycaemia
Diabetic ketoacidosis (DKA) is the hallmark of type ___ diabetes
Type 1
Diabetic ketoacidosis (DKA) is usually seen in patients who present with which characteristics?
- Previously undiagnosed diabetes
- Non-compliance: dietary, exercise or/and interrupted insulin therapy
- Intercurrent illness
Why does many patients interrupt their insulin therapy?
Patient education is lacking
Often they feel ill so do not eat so they think they shouldn’t take their insulin because they haven’t eaten.
Insulin may need adjusting up or down but should never be stopped
Define diabetic ketoacidosis
- A state of uncontrolled catabolism associated with insulin deficiency.
- Insulin deficiency is a necessary precondition since only a modest elevation in insulin levels is sufficient to inhibit hepatic ketogenesis.
- Characteristed by:
- Hyperglycaemia
- Dehydration
- Ketoacidosis
Describe the pathogenesis of diabetic ketoacidosis?
- Patient is insulin deficient
- In the absence of insulin, gluconeogenesis occurs and peripheral glucose uptake by tissues such as muscle is reduced
- Rising glucose levels lead to an osmotic diuresis, loss of fluid and electrolytes, and dehydration. Resulting in a rise of the plasma osmolarity (hyperosmolarity).
- Lipolysis occurs (breakdown of triglycerides to fatty acids and glycerol) to be used as fueld for gluconeogenesis
- The free fatty acids are broken down to acetyl-coenzyme A (CoA) within the liver cells, and this, in turn, is converted to ketone bodies within the mitochondria. Accumulation of ketone bodies produces a metabolic acidosis.
- As the pH falls below 7, pH-dependent enzyme systems in many cells function less effectively.
- Untreated, severe ketoacidosis is invariably fatal
Explain how osmotic diuresis occurs in relation to hyperglycaemic
- In a state of hyperglycaemia, you have high levels of glucose in the blood (hypoosmolality).
- Glucose is freely filtered at the glomerulus. The kidneys are able to reabsorb the glucose.
- However, at a certain point in hyperglycaemia, the amount of glucose in the tubule exceeds the ability of the kidney to reabsorb it. Leading to glucosuria.
- This glucose in the tubule s ismotically active, therefore the glucose sucks the water out of the blood into the tubule.
- This causes the dehyration that is assocaited with diabetic ketoacidosis
Explain why diabetic ketoacidosis is known as “starvation in the midst of plenty”
As adequate amounts of glucose is in the blood but the body is unable to utilise it and the cells are essentially starving
The brain needs a supply of energy to survive. However, it is very picky. Which two types of energy does the brain use?
- Glucose
- Ketones
Describe what happens to potassium levels during diabetic ketoacidosis
- After a meal, the post-prandial release of insulin functions to not only regulate the serum glucose concentration but also shift dietary potassium into cells until the kidneys excretes the potassium load re-establishing potassium homeostasis.
- These effects are mediated through insulin binding to cell surface receptors, which stimulates glucose uptake in insulin-responsive tissues through the insertion of the glucose transporter protein, GLUT4. An increase in the activity of the sodium potassium ATPase mediates potassium uptake.
- In DKA, the lack of insulin prevents potassium from entering the cell. Therefore, plasma potassium levels may be elevated but total body potassium depleted.
Why do you get hyperaldosteronism in diabetes ketoacidosis
- Increase in water loss causes a decrease in blood volume.
- A reduction in afferent arteriole pressure causes the release of renin from the JG cells.
- When renin is released into the blood, it acts upon a circulating substrate, angiotensinogen, that undergoes proteolytic cleavage to form angiotensin 1. Vascular endothelium, particularly in the lungs, has an enzyme, angiotensin conveting enzyme (ACE), that cleaves angiotensin 1 to form angiotensin II.
- Angiotensin II acts on the adrenal cortex to release aldosterone, which in turn acts on the kidneys to increase sodium and water retention.
- Therefore, in osmotic diuresis you get hyperaldosterone
Describe how ketone bodies are formed in diabetic ketoacidosis
- As glucose cannot enter the skeletal muscle, adipose tissue and liver cells, due to insulin resistance, the body starts to break down lipid stores as fuel.
- Beta oxidaton is the process that breaks down fatty acids
- Initially, the fatty acids are attached to acetyl CoA to form fatty acyl-CoA.
- Fatty acyl CoA are degraded by oxidation at the beta-carbon in the inner mitochondria. Reduces the fatty acyl CoA molecule by 2 carbons each time. This process keeps occuring until only acetyl CoA is left.
- This acetyl CoA can be used as fuel for TCA cycle, however in diabetic ketoacidosis the levels of acetyl Coa produced exceed the level of oxaloactate (the molecule the acetyl CoA must bind to to enter the TCA cycle).
- Therefore, so energy is not lost, the liver converts these excess acetyl CoA molecules into ketones, which can be used as fuel in other tissues e.g. brain
What is the effect of high level of ketones that is associated with DKA
Ketone bodies are important fuel for the brain during periods of starvation- like DKA.
Ketone bodies are acids so they lower the pH of the blood.
The body is able to buffer this effect to an extent, however because in DKA the ketone bodies are produced in such large quantities, the result is metabolic acidosis (acidosis due to a metabolic process)
In a state of metaboli acidosis what do you expect the following values to be (High or low).
A) H+
B) pH
C) HCO3
D) CO2
A) H+ = High
B) pH = Low
C) HCO3 = Low
D) CO2 = Low
The counter regulatory hormones- adrenaline, growth hormone and cortisol- act to stimulate key endogenous glucose production pathways during diabetic ketoacidosis.
Which endogenous pathway does adrenaline stimulate?
Glucogenolysis - breakdown of glucogen into glucose
Gluconeogenesis- formation of glucose from non-carbohydrate sources
Lipolysis- breakdown of triglycerides into fatty acids and glycerol
The counter regulatory hormones- adrenaline, growth hormone and cortisol- act to stimulate key endogenous glucose production pathways during diabetic ketoacidosis.
Which endogenous pathway does cortisol stimulate?
Gluconeogenesis- formation of glucose from non-carbohydrate sources.
Lipolysis- breakdown of triglycerides into fatty acids and glycerol
Inhibits peripheral glucose uptake - by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane in adipose tissue and skeletal muscle. The cells require the glucose so they do not want to store them for future use- want to use them now.
The counter regulatory hormones- adrenaline, growth hormone and cortisol- act to stimulate key endogenous glucose production pathways during diabetic ketoacidosis.
Which endogenous pathway does growth hormone stimulate?
Gluconeogenesis - formation of glucose from non- cabrohydrate sources.
Lipolysis - breakdown of triglycerides into fatty acids and glycerol
Inhibits peripheral glucose uptake - by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane in adipose tissue and skeletal muscle. The cells require the glucose so they do not want to store them for future use- want to use them now.
What is the clinical presentation of diabetic ketoacidosis?
- Abdominal pain, nauesea and vomiting
- Dehydration
- Altered mental status
- Polyuria
What is the treatment for diabetic ketoacidosis
IV fluids containing insulin and potassium
Intravenous fluids are important in treating the ____ associated with diabetic acidosis
Intravenous fluids are important in treating the hypovolaemia (low blood volume) associated with diabetic acidosis
Intravenous insulin are important in treating the ____ associated with diabetic acidosis
Intravenous insulin are important in treating the absence of insulin in order to utilise the hyperglycaemia associated with diabetic acidosis
Intravenous potassium are important in treating the ____ associated with diabetic acidosis
Low intracellular potassium level
On admission, the serum potassium may be high, normal or low. But this does not reflect the level of potassium in the cells (which would be low)
Hyperosmolar Hyperglycaemic state (HHS) is the hallmark of type ___ diabetes
Type 2 diabetes
Which condition has a higher associated mortality rate:
A) Diabetes Ketoacidosis (DKA)
B) Hyperosmolar hyperglycaemic state (HHS)
B) Hyperosmolar hyperglycaemic state (HHS)
NOTE: HHS is associated with T2DM. Therefore, these patients are usually older and have co-morbidities
