Genes for DM and integration of patient care

Question 1

What markers are there of nourishment?

Answer 1

Albumin
Body weight
Weight loss

Question 2

What is albumin and what affects its levels?

Answer 2

It is a plasma protein and levels fall in someone who is malnourished but also rapidly following sepsis

Question 3

What are albumin levels linked to?

Answer 3

When malnourished/sepsis, liver slows the synthesis of albumin and seems to start making CRP instead. Albumin levels correlate inversely with CRP levels

Question 4

When should body weight be recorded?

Answer 4

Whenever you see a patient. It is useful to know the dry weight of a patient who is in renal failure.

Question 5

How does fluid overload affect weight?

Answer 5

Rapid increase

Question 6

What can cause unintentional weight loss?

Answer 6

Low grade infection (gradual sepsis) e.g. bacterial endocarditis
Undiagnosed malignancy
Loss of appetite
Paraneoplastic syndrome

Question 7

What causes true ketoacidosis?

Answer 7

Complete insulin deficiency

Question 8

What happens with insulin during starvation?

Answer 8

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

Question 9

What does insulin do?

Answer 9

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

Question 10

What happens during starvation?

Answer 10

Insulin levels fall- glycogenolysis and gluconeogenesis and fatty oxidation
Substrates available:
Glucose, glycogen (<24 hrs), triglyceride and protein

Question 11

What occurs with prolonged starvation?

Answer 11

Insulin levels continue to drop. Liver switches on exponential ketogenesis.

Question 12

How does insulin communicate with muscle and fat cells?

Answer 12

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

Question 13

What does insulin do once bound to the insulin receptor?

Answer 13

Stimulates uptake of glucose from blood into tissues and conversion into storage molecules
Stimulates fat generation
Suppresses ketone production

Question 14

What causes type 1 diabetes?

Answer 14

Immune system destroys the islets of Langerhans in the pancreas. Resultant total deficiency of insulin

Question 15

What is the peak onset of type 1 diabetes?

Answer 15

Age 13

Question 16

What does the total deficiency of insulin cause?

Answer 16

All cells of body fail to take up glucose so plasma glucose rises. Glucose leaks into urine. Large volumes of urine result.

Question 17

What does complete insulin deficiency cause?

Answer 17

Acidosis (liver makes excess ketones)

Death as blood turns acidic with ketones in urine and brain can’t function in an acid pH

Question 18

What causes diabetic ketoacidosis?

Answer 18

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

Question 19

What is the primary defect in type 2 diabetes?

Answer 19

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

Question 20

What is normal blood pH?

Answer 20

7.40

Question 21

What does mild ketosis cause?

Answer 21

pH 7.35 with increased respiratory

Question 22

Give a summary of the differences between type 1 and 2 diabtes?

Answer 22

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

Question 23

What does the 100% concordance suggest?

Answer 23

Genetic influences such as thrifty genes. People who are thrifty with energy are more likely to survive during starvation periods

Question 24

How does obesity cause insulin resistance?

Answer 24

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