Diabetes Flashcards
Characterise both type 1 and type 2 diabetes
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
What causes the destruction of the B-cells in type 1
Immune activation produces killer lymphocytes, macrophages and antibodies that attck and progressively destroy B-cells
Why does a type 1 diabetic get polyuria
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
What are the triad of symptoms of type 1 diabetes
Polyuria
Thirst
Weight loss
What do you test for in type 1 diabetics
High blood glucose
Glycosuria - glucose in urine
Ketones in the urine
What life threatening crisis can develop in type 1 diabetics if they are not treat
Diabetic ketoacidosis
What are the symptoms of ketoacidosis
Prostration
Hyperventilation
Nausea
Vomiting
Dehydration
Abdominal pain
How does type 2 diabetes present
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
Describe the mechanisms of type 2 diabetes - what causes the patient to become insulin resistant
Defective insulin receptor mechanism - change in receptor number and/or affinity
Defective post-receptor events
Excessive or inappropriate glucagon secretion
What is the HbA1c test and how is it used
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
How is diabetes diagnosed
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
What is the treatment for type 1 diabetics
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
What is the treament for type 2 diabetes
Treat with insulin if disease progresses that far
Treat with sulphonylureas - increase insulin release and reduce insulin resistance
Metformin - reduces gluconeogenesis
Dietary management
Exercise
What are the metabolic consequences of persistant hyperglycaemia
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
What are the macrovascular complications of diabetes
Increased stroke risk
Increased MI risk
Poor circulation to periphery
What are the microvascular complications of diabetes
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
What is metabolic syndrome
Group of symptoms including:
Insulin resistance
Dyslipidaemia
Glucose intolerance
Hypertension associated with central adiposity
What is metabolic syndrome caused by
Insulin resistance
Central obesity
Genetics
Physical inactivity
Aging
How does insulin resistance develop into type 2 diabetes in the young
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
What are the symptoms and final stage of ketoacidosis
Symptoms:
Hyperventilation
Nausea
Vomiting
Abdominal pain
Finally: coma
