Genes for DM and integration of patient care Flashcards
What markers are there of nourishment?
Albumin
Body weight
Weight loss
What is albumin and what affects its levels?
It is a plasma protein and levels fall in someone who is malnourished but also rapidly following sepsis
What are albumin levels linked to?
When malnourished/sepsis, liver slows the synthesis of albumin and seems to start making CRP instead. Albumin levels correlate inversely with CRP levels
When should body weight be recorded?
Whenever you see a patient. It is useful to know the dry weight of a patient who is in renal failure.
How does fluid overload affect weight?
Rapid increase
What can cause unintentional weight loss?
Low grade infection (gradual sepsis) e.g. bacterial endocarditis
Undiagnosed malignancy
Loss of appetite
Paraneoplastic syndrome
What causes true ketoacidosis?
Complete insulin deficiency
What happens with insulin during starvation?
Insulin levels fall in a normal person and trigger the release of energy
Triggers the conversion of fats to ketones in liver which are a useful fuel for the brain (brain cells can use fatty acids but these can’t cross the BBB
Since insulin rises after meals, fall during starving
What does insulin do?
Signals that you have been fed
Switches on all pathways that use up glucose and store glycogen and fat:
Glycogen synthase: switched on > glycogen synthesis
Glycolysis in liver and muscle: on> glucose breakdown
Gluconeogenesis switched off
What happens during starvation?
Insulin levels fall- glycogenolysis and gluconeogenesis and fatty oxidation
Substrates available:
Glucose, glycogen (<24 hrs), triglyceride and protein
What occurs with prolonged starvation?
Insulin levels continue to drop. Liver switches on exponential ketogenesis.
How does insulin communicate with muscle and fat cells?
Following food intake, pancreas releases insulin which binds to insulin receptor on muscle and fat cells. This causes glucose to enter the muscle and fat cells via the GLUT4 receptor
What does insulin do once bound to the insulin receptor?
Stimulates uptake of glucose from blood into tissues and conversion into storage molecules
Stimulates fat generation
Suppresses ketone production
What causes type 1 diabetes?
Immune system destroys the islets of Langerhans in the pancreas. Resultant total deficiency of insulin
What is the peak onset of type 1 diabetes?
Age 13
What does the total deficiency of insulin cause?
All cells of body fail to take up glucose so plasma glucose rises. Glucose leaks into urine. Large volumes of urine result.
What does complete insulin deficiency cause?
Acidosis (liver makes excess ketones)
Death as blood turns acidic with ketones in urine and brain can’t function in an acid pH
What causes diabetic ketoacidosis?
Blood glucose is high as it can’t get into cells. Blood is full of ketone (acids). Severe dehydration on presentation to A and E. Air hunger- overbreathing (deep sighing slow respiration) where the patient looks like they are trying to eat air -> respiratory alkalosis
What is the primary defect in type 2 diabetes?
Resistance to action of insulin- binds poorly to receptor so only some is stimulated to enter fat and muscle cells via GLUT4 so insulin levels increase and completely turn off ketogenesis
What is normal blood pH?
7.40
What does mild ketosis cause?
pH 7.35 with increased respiratory
Give a summary of the differences between type 1 and 2 diabtes?
Type 1: Ketoacidosis Acute onset Non obese Young HLA DR3 and DR4 Islet cell antibodies 30-50% concordance Need insulin
Type 2: No ketoacidosis Insidious onset Patients overweight Older No HLA associations No islet cell antibodies 100% concordance Can manage with diet or hypoglycaemic agents but insulin can be used
What does the 100% concordance suggest?
Genetic influences such as thrifty genes. People who are thrifty with energy are more likely to survive during starvation periods
How does obesity cause insulin resistance?
Type 2 diabetes has 100% concordance which suggests obesity is strongly heritable (hypothalamus set weight?)
Obesity has been linked to a high serum leptin which correlates with weight
