Diabetes

Question 1

Characterise both type 1 and type 2 diabetes

Answer 1

Type 1 - have progressive loos of all or most of the pancreatic B-cells

Type 2 - have slow progressive loss of B-cells along with disorders of insulin secretion and tissue resistance to insulin

Question 2

What causes the destruction of the B-cells in type 1

Answer 2

Immune activation produces killer lymphocytes, macrophages and antibodies that attck and progressively destroy B-cells

Question 3

Why does a type 1 diabetic get polyuria

Answer 3

Large quantities of glucose are filtered but not reabsorbed by the kidney

This glucose remains in the nephron tubule, placing an extra osmotic load on the nephron so less water is reabsorbed to maintain the isosmotic character of the section of the tubule

This extra water remains with the glucose and is excreted as copious urine

Question 4

What are the triad of symptoms of type 1 diabetes

Answer 4

Polyuria

Thirst

Weight loss

Question 5

What do you test for in type 1 diabetics

Answer 5

High blood glucose

Glycosuria - glucose in urine

Ketones in the urine

Question 6

What life threatening crisis can develop in type 1 diabetics if they are not treat

Answer 6

Diabetic ketoacidosis

Question 7

What are the symptoms of ketoacidosis

Answer 7

Prostration

Hyperventilation

Nausea

Vomiting

Dehydration

Abdominal pain

Question 8

How does type 2 diabetes present

Answer 8

May present with classical triad of symptoms

Lack of energy

Persistant infections

Infections of the feet

Slow healing

Minor skin damage

Visual problems

Typically no weight loss

Question 9

Describe the mechanisms of type 2 diabetes - what causes the patient to become insulin resistant

Answer 9

Defective insulin receptor mechanism - change in receptor number and/or affinity

Defective post-receptor events

Excessive or inappropriate glucagon secretion

Question 10

What is the HbA1c test and how is it used

Answer 10

Test to measure the amount of glycated Hb which reflects the average glycaemia over a period of week

Glucose reacts with terminal valine of Hb to produce glycated Hb

If it is above 6.5% then it indicates a poor plasma glucose control and possible diabetes

Question 11

How is diabetes diagnosed

Answer 11

Diagnosed in the presence of symptoms plus one of the following:

Random venous plasma glucose ≥ 11.1 mmol/L

Fasting plasma glucose ≥7.0mmol/L (whole blood ≥6.1)

Plasma glucose ≥11.1mmol/L 2 hours after 75g anhydrous glucose in oral glucose tolerance test (OGTT)

Or diagnosed using two of the tests with no symptoms

Question 12

What is the treatment for type 1 diabetics

Answer 12

Insulin injection either subcutaneously or by insulin pump

Insulin injection given at dose and time to mimic behaviour of islets

Regular meal times

Regular exercise

Test blood glucose regularly - carry around sweets/sugar to avoid hypoglycaemia

Question 13

What is the treament for type 2 diabetes

Answer 13

Treat with insulin if disease progresses that far

Treat with sulphonylureas - increase insulin release and reduce insulin resistance

Metformin - reduces gluconeogenesis

Dietary management

Exercise

Question 14

What are the metabolic consequences of persistant hyperglycaemia

Answer 14

Excess intracellular glucose is metabolised using aldose reductase:

Glucose + NADPH + H⁺ -> Sorbitol + NADP⁺

This reduces NADPH and leads to increased disulphide bond formation. Accumulation of sorbitol causes osmotic damage

Increased glycation of plasma proteins causing abnormal function

HbA1c increases

Question 15

What are the macrovascular complications of diabetes

Answer 15

Increased stroke risk

Increased MI risk

Poor circulation to periphery

Question 16

What are the microvascular complications of diabetes

Answer 16

Diabetic eye disease - diabetic retinopathy where there is damage to blood vessels in retina which can lead to blindness: vessels leak and form protein exudates on retina or vessels rupture and cause bleeding into eye

Diabetic kidney disease (nephropathy) - damage to glomeruli, poor blood supply or damaged by infections of urinary tract. Early sign is increased protein in urine

Diabetic neuropathy - diabetes damages peripheral nerves: loss of sensation, altered function of ANS producing changes

Diabetic feet - poor blood supply, nerve damage and increased infection risk make feet of diabetics vulnerable

Question 17

What is metabolic syndrome

Answer 17

Group of symptoms including:

Insulin resistance

Dyslipidaemia

Glucose intolerance

Hypertension associated with central adiposity

Question 18

What is metabolic syndrome caused by

Answer 18

Insulin resistance

Central obesity

Genetics

Physical inactivity

Aging

Question 19

How does insulin resistance develop into type 2 diabetes in the young

Answer 19

Initially B cells compensate by upregulating insulin production to maintain normal plasma glucose

Eventually B cell become unable to maintain increased insulin production so become incapacitated and no longer function leading to glucose intolerance

Finally B cell dysfunction leads to relative insulin deficiency and type 2 diabetes

Question 20

What are the symptoms and final stage of ketoacidosis

Answer 20

Symptoms:

Hyperventilation

Nausea

Vomiting

Abdominal pain

Finally: coma