Diabetes Flashcards
What stimulates insulin release?
Increase glucose levels
Amino acids
Fatty acids
Peptide gut hormones - incretins
How is insulin stored?
In B cell granules as pro insulin.
Proteolytically cleaved to form mature insulin and c peptide.
What is the mechanism of action for insulin?
- Insulin binds to insulin receptor
- Insulin receptor dimerises - activation - auto phosphorylation
- Attracts and phosphorylated nearby substrates - IRS1-4 and associated proteins
- Downstream signalling pathways lead to:
- GLUT4 translocation
- enzyme activity: increase formation of glycogen, protein and fat, increase uptake of glucose, increase utilisation of glucose
- proliferation, growth and gene expression
What is diabetes mellitus?
Chronic metabolic disorder with insulin deficiency.
Increasing prevalence and huge undiagnosed numbers.
What is hyperglycemia?
Excess of glucose in the bloodstream.
It can be asymptomatic.
Characteristics: polyuria, thirst, weight loss, tiredness, confusion, infection
What is type 1 diabetes?
Insulin dependent diabetes mellitus.
Absolute insulin deficiency secondary to autoimmune destruction of B islet cells.
Usually juvenile onset.
What is type 2 diabetes?
Insulin resistance and relative insulin deficiency.
90-95% of adult cases
Strongly associated with obesity.
What are some acute complications of diabetes?
Diabetic ketoacidosis
Mostly seen in type 1 diabetes.
In the absence of insulin, fats are broken down for energy by acetyl coA, ketosis, acidosis, pH decreases, dehydration
Accumulation of dangerous chemical substances in the blood called ketones
Very high blood glucose levels.
Symptoms - flushed cheeks, vomiting, rapid breathing, abdominal pain
What are some chronic complications of diabetes?
Mostly due to blood vessel diseases.
Macrovascular: increase fatty deposits, hypertension, heart attacks, strokes, persistent infections, ulcers, amputations.
Microvascular: microangiopathy, blindness, renal failure, diabetic foot, ulcers, amputations.
What are the treatments for type 1 diabetes?
Insulin therapy Basal-bolus regimen - long acting insulin at bed time (basal) - rapid acting insulin - periprandial - more than 4 injections/day - superior control
What are the treatment types for type 2 diabetes?
- Lifestyle change to promote weightless, diet and exercise. Works <10%
- Insulin therapy when needed. Fixed proportion mixtures - 2 injections per day. But not flexible with diet and lifestyle.
- Bariatric surgery. Primary prevention. Best treatment.
- Biguanides - metformin.
- Sulphonylureas
- Thiazolidinediones
- A-glucosidase inhibitors - acarbose and miglitol
- Incretin based therapy
What are biguanides - metformin?
They are antihyperglycaemic agents.
Mechanism of action - decrease gluconeogenesis (glucose formation) and increase muscle uptake of glucose. No plasma binding so high volume of distribution.
Benefits - appetite does not increase, no hypoglycaemia, improved serum lipid levels.
Side effects - GI tract, anorexia, diarrhoea, mild nausea, lactic acidosis (very rare but may be fatal. Decrease clearance of lactic acid causing liver/kidney failure. Increased production of lactic acid can cause cardiac failure and chronic pulmonary obstructive disease)
What are sulphonylureas?
Drug of first choice for those who cannot tolerate metformin.
Mechanism of action - increase insulin release via B cells. Metabolised in liver and excrete renally.
Examples - glibenclamide, glipizide, glimepiride
Benefits - usually well tolerated
Side effects - hypoglycaemia (avoid long half lives in elderly alcoholics, irregular meals), weight gain, uncommon ones include skin rash, haemolytic anaemia and GI
There may be drug interactions
What are thiazolidinediones?
PRARy agonists - activates gene transcription
Increase insulin sensitivity
Side effects - weight gain, fluid retention
What are A-glucosidase inhibitors?
Competitive inhibitors of a-glucosidase in intestines
Inhibits breakdown of maltose to glucose
Side effects - flatulence and diarrhoea
