Lecture 20: diabetes mellitus

Question 1

What is DM1?

Answer 1

Autoimmune attack on pancreatic ꞵ cells with unknown triggers (infection, genetics?). Causes complete insulin deficiency as no insulin produced as all which affects younger people mostly.
Thus no, glucose uptake into cells so results in hyperglycaemia and that can lead to Ketonaemia, ketoacidosis if not treated immediately.

Question 2

What are the 3 main symptoms (classic triad) of DM1?

Answer 2

Polyuria
Polydipsia
Unexplained weight loss

Question 3

For DM2, one way to control it is to change their lifestyle in terms of mainly diet, exercise and meds. How would you know that these modifications are effective or not?

Answer 3

You can measure the amount of HbA1c in their blood. A high concentration of HbA1c means that there still needs to be some more changes. HbA1c is a glycated form of Hb, more glycation means that there is still some hyperglycaemia.

Question 4

A man (BMI=30.1kg/m²) has blood glucose 11.9mmol/L and urine dip stick shows glycosuria with absence of ketone bodies. A fasting plasma glucose gives 9.0mmol/L. What is your diagnosis?

Answer 4

DM2

Question 5

A man (BMI=30.1kg/m²) has blood glucose 11.9mmol/L and urine dip stick shows glycosuria with absence of ketone bodies. You confirm DM2 so begin giving management strategies around lifestyle modifications. 3 months pass, BMI=30.9kg/m² and HbA1c=9%.

What is the most appropriate next step in managing his condition?

Answer 5

You can prescribe metformin which is a drug that inhibits gluconeogenesis: oral hypoglycaemic therapy to reduce their blood [glucose].

Question 6

HbA1c is a form of glycated Hb. Describe how glycation occurs.

Answer 6

A non-enzymatic random process that disrupts the Hb protein structure: hence function. Hyperglycaemia means that there is a higher chance of glucose covalently bonding to Hb which is glycation.

Question 7

What do we mean when we say someone has metabolic syndrome?

Answer 7

It is a combination of hyperglycaemia (DM2), central obesity, hypertension, hyperlipidaemia.

Question 8

What would be different in a blood lipid profile in a person with metabolic syndrome compared to a healthy person?

Answer 8

There would be less HDL which are known as “good cholesterol” which is significant in diagnosing metabolic syndrome.

Question 9

A 17yrs girl with DM1 self administers a subcutaneous injection of insulin in order to control her blood glucose level.

Why must it be delivered by injection rather than orally?

Answer 9

The peptide hormone would be broken down in the GI tract so the insulin would be inactive and would not allow glucose uptake into cells.

Injection directly to MSK will bypass the GI tract and prevent the insulin from breaking down.

Question 10

A 13yrs girl is presented to the ED after passing out in school. She recently suffered from rapid weight loss, polydipsia and polyuria. Then is diagnosed with DM1.

What is the main risk associated with this disease?

Answer 10

Ketoacidosis

No insulin means no glucose uptake into tissues. Hence, body will rely on lipolysis which produces ketone bodies (3-ꞵ-hydroxybutyrate, acetoacetate, acetone). These decrease the blood pH which can cause dizziness, vomiting, hyperventilation, coma.

Question 11

What is the normal range for blood glucose?

Answer 11

3.3mmol/L - 6.0mmol/L

Question 12

A 10yrs boy taken into GP with her Mum. He has far less energy than normal; states clothes are baggier; urinating more frequently (even at night); drinking a lot more water but still feels thirsty. Urine dipstick tests +ve for glucosuria, ketonuria and his blood glucose = 20mmol/L.

What’s the most appropriate action for the GP to take?

Answer 12

It would be an emergency same day referral by telephone to a diabetes consultant.

This boy has undiagnosed DM1 so he is at risk of life-threatening diabetic ketoacidosis as he already has ketones in his urine.

Question 13

If a 50yrs man has unexplained weight loss; polydipsia; polyuria; feels thirsty all the time and they are diagnosed with DM2,

what microvascular complications can occur in association with this disease (or chronic hyperglycaemia in general)?

Answer 13

Retinopathy: damage retina blood vessels = blindness
Nephropathy: damage glomeruli
Neuropathy: peripheral nerve damage = sensation loss
Diabetic eye disease: osmotic effects = lens changes
Diabetic foot: poor blood supply, damage nerves, increase infection risk, foot ulcers.

Question 14

What are the 2 most significant factors underlying the aetiology of metabolic syndrome?

Answer 14

Insulin resistance

Central obesity

Question 15

What symptoms and signs would a patient with untreated DM1 and ketosis present with?

Answer 15

drowsiness, confusion, fever, cough, diffuse abdominal pain, vomiting, hyperventilation, ketonaemia, hyperglycaemia, acidosis.

Question 16

What is the normal range of HbA1c?

Answer 16

4-6.1%

Question 17

A 17yrs girl with DM1 self administers a subcutaneous injection of insulin to control her blood glucose level.
How would her plasma C-peptide level be affected?

Answer 17

C-peptide levels would remain the same.

C-peptide is usually cleaved from proinsulin during biosyn. of insulin so there would be similar amounts of insulin: c-peptide when insulin is secreted from ꞵ cells.
However, since the injection contains commercial insulin, there would be no change to the c-peptide levels.

Question 18

How is C-peptide clinically important?

Answer 18

C=peptide is released in similar amounts to insulin from pancreatic ꞵ cells whereas synthetic insulin doesn’t contain any c-peptide. Therefore, you can measure plasma c-peptide levels to see if the pancreatic ꞵ cells are producing any/how much insulin.

This is a really useful clinical marker for DM1.

Question 19

How can you confirm DM?

Answer 19

Laboratory blood tests
Fasting glucose test
Oral glucose tolerance test (OTT)
HbA1c levels

Need symptoms and 1 abnormal test
OR
Need 2 abnormal tests if asymptomatic

Question 20

What is DM2?

Answer 20

Mainly due to obesity where the pancreas has relative insulin deficiency and insulin resistance.

It affects people<40yrs and is not usually found until later because DM2 can be asymptomatic.

Question 21

How are DM1 and DM2 treated?

Answer 21

DM1=subcutaneous insulin injection

DM2= WEIGHT LOSS
lifestyle modifications
education
insulin therapy
metformin
bariatric surgery

Question 22

What are the macrovascular complications that someone can experience when they have chronic hyperglycaemia?

Answer 22

Increased risk of stroke
Increased risk of MI
Poor circulation to the periphery (feet)