Session 8 Flashcards
What are the differences between Type 1 and Type 2 diabetes?
- Type 1: - Type 2:
~ Commonest type in young ~ Large number of usually older
individuals
~ Characterised by ~ Characterised by slow
progressive loss of all or progressive loss of B-cells
most of pancreatic B-cells and with disorders of insulin
secretion/tissue resistance
~ Rapidly fatal if not treated ~ May be present a long time
before diagnosis
~ Must be treated with insulin. ~ May not need insulin
treatment initially, but all do
eventually
What is diabetes Mellitus?
- Group of metabolic disorders characterised by chronic hyperglycaemia due to insulin deficiency, insulin resistance or both
How are B-cells destroyed in Type 1 diabetes?
- Genetic predisposition to disease interacts with environmental trigger (maybe viral infection due to seasonal variation)
- Killer lymphocytes, macrophages and antibodies are produced
- Attack and progressively destroy B-cells
- Autoimmune process
What is the triad of symptoms?
- Polyuria: excess urine production (large quantities on glucose in the blood is filtered by kidneys and not all is reabsorbed, extra glucose in nephron places extra osmotic load on it, and less water is reabsorbed to maintain osmotic pressure)
- Polydipsia: thirst and drinking a lot (due to polyuria)
- Weight loss: fat and protein are metabolised as insulin is absent
How is type 1 diabetes diagnosed?
- Elevated blood glucose levels (due to lack of insulin)
- Glycosuria (glucose in urine)
- Diabetic ketoacidosis (if not treated rapidly)
How does lack of insulin caused elevated blood glucose levels?
- Decreased uptake of glucose into adipose tissue and skeletal muscle
- Decreased storage of
Why does blood glucose levels increase in Type 2 diabetes?
- Loss of 50% of B-cells
- Leads to disorders of insulin secretion and insulin resistance
What is the typical presentation of Type 1 diabetes?
- Can have relavant HLA markers and auto-antibodies but without glucose or insulin abnormalities
- May then develop impaired glucose tolerance, then diabetes (initially may be diet controlled)then becoming completely insulin dependant
What is the typical presentation of type 2 diabetes?
- Found with insulin resistance
- Can then develop impaired glucose tolerance as insulin production falls
- Finally will develop diabetes (initially controlled by diet, then tablets, then insulin)
- May eventually lose all insulin production
How is diabetes diagnosed in the presence of symptoms?
- I.e. Symptoms triad
- 1 test needed
- Random venous plasma glucose concentration: >11.1 mmol/
- Fasting plasma glucose concentration: >7 mmol/l
- Oral glucose tolerance test: >11.1 mmol/l (plasma glucose concentration 2 hours after 75g anhydrous glucose)
How is diabetes diagnosed without symptoms?
- 2 tests needed in different days including venous plasma glucose concentration and one other
How does ketoacidosis develop in an untreated diabetics?
- High B-oxidation of fats in liver and low insulin/anti-insulin ratio -> high ketone bodies production
- H+ from ketone bodies causes metabolic acidosis ie ketoacidosis
What are the symptoms of ketoacidosis?
- Prostration
- Hyperventilation
- Nausea
- Vomiting
- Dehydration
- Abdiminal pain
What is important to test for in diabetics?
- Ketones in urine
How can a diabetic become hypoglycaemic?
- Plasma glucose <3mmol/l
- Insulin or sulphonylurea treatment with increased activity, missed meal, accident/non-accidental overdose
What are the consequences of hypoglycaemia?
- Plasma glucose below 2 mmol/l can be fatal
- CNS and other glucose dependant tissues require a constant supply of glucose
- Symptoms/signs: sweating; anxiety; hunger; tremor; palpitations; confusion; drowsiness; seizures; coma
What is the cause of hyperglycaemia?
- Blood glucose above 10 mmol/l
- Symptoms: Polyuria; Polydipsia; weight loss; fatigue; blurred vision; dry or itchy skin; poor wound healing
- Also plasma proteins can be glycosylated, affecting their function
How is Type 1 diabetes managed?
- Lifelong subcutaneous injections of insulin
- Patients are educated to treat themselves at appropriate times and with appropriate doses
- Dose may need to be increased following infection/trauma in case of ketoacidosis
- Dietary management and regular exercise are also vital
- Need frequent blood glucose measurements (finger prick using BM stick and reader)
- Awareness of signs and symptoms of hypoglycaemia of patient and their associates
How can hypoglycaemia be treated?
- Oral or infusion of glucose
How is Type 2 diabetes managed?
- Diet
- Oral hypoglycaemic drugs eg sulphonylurea (increase insulin release of remaining B cells; reduce insulin resistance; metformin reduces gluconeogenesis)
Why are the peripheral nerves, the eye and the kidney affected by persistent hyperglycaemia?
- Uptake of glucose into the cells in these tissues is determined by extracellular glucose concentration
- During hyperglycaemia Intracellular concentration of glucose increases
- Glucose is metabolised by aldose reductase:
Glucose + NADPH + H+ -> Sorbitol + NADP+ - NADPH is depleted and causes increase disulphide bond formation in cellular proteins altering their structure and function
- Sorbitol accumulation also causes osmotic damage
What happens to plasma proteins eg lipoproteins in hyperglycaemia?
- Increased non-enzymatic glycosylation
- Causes disturbances in function
- Glucose reacts with free amino groups in proteins to form stable linkages
- Changes net charge on the protein and the 3D structure, affecting the function of the protein
