Lecture 35 - Coordinating Metabolism: Diabetes (Type II) Flashcards
What is the main diagnostic criteria for type 2 diabetes?
HbA1C >50mmol/mol
What are common symptoms of type 2 diabetes?
Glycosuria, osmotic diuresis and dehydration
What is more common in type 1 diabetes?
Ketoacidosis
What is a possible complication associated with type 2 diabetes?
Vascular diseases
What causes glycated haemoglobin? (HbA1c)
When glucose builds up in your blood, it binds to the haemoglobin in RBCs.
Why is HbA1C used as a measure of diabetes?
It measures how much glucose is bound and as RBCs have a half-life of ~3 months it shows blood glucose concentration over a long period of time
How does diabetes increase risk of vascular disease?
Structural proteins in arteries can be made less compliant from glycosylation and the formation of advanced glycation end-products
What would you see in a glucose tolerance test for a diabetic?
Elevated fasting glucose >7mmol/L and impaired lowering after ingestion
What would you see in a glucose tolerance test for a pre-diabetic?
Slightly elevated fasting level of glucose 5.6-7mmol/L and impaired lowering after ingestion
What would you see in a glucose tolerance test for someone without diabetes?
Fasting level ~3.5, peaks after ingested and returns to fasting levels within 2 hours
What happens to lead to type 2 diabetes?
Over time hyperinsulinaemia diminishes the ability of beta-cells to respond to further increases in blood glucose and the individual becomes glucose-tolerant (prediabetic) and eventually diabetic
What does insulin resistance do in fat storage?
Reduces the hydrolysis of TAGs in chylomicrons and VLDL by LPL. This leads to their accumulation and increase in blood TAGs
What does insulin resistance do in the whole body?
Processes normally stimulated/inhibited by insulin aren’t. Decreases glucose uptake and gluconeogenesis, elevated FFAs and sometimes beta-cells responses diminish and insulin levels drop
What processes are normally stimulated by insulin?
Glucose uptake, glycolysis, glycogenesis, lipogenesis
What processes are normally inhibited by insulin?
Gluconeogenesis, lipolysis, fatty acid oxidation and ketogenesis
What can diabetics develop?
Fatty livers which can lead to cirrhosis
What happens in the cell with insulin resistance?
Reduced levels of phosphorylation and mis-phosphorylation occur in insulin signalling proteins which reduces GLUT4 translocation likely promoted by FFAs, inflammatory cytokines and oxidative stress
What are treatments for type 2 diabetes?
Lifestyle changes e.g. dietary and exercise and some drugs e.g. metformin sulfonylureas, GLP-1 agonist, SGLT2 inhibitors and insulin
How do metformin and exercise act to treat type 2 diabetes?
Both metformin and exercise increase AMP levels, which activates AMPK, which reduces gluconeogenesis. This reduces blood glucose levels.
How is insulin secretion increased in beta cells?
GLP-1 peptide hormone synthesised in the liver acts through its receptor to stimulate insulin secretion
How do sulfonylureas increase insulin secretion?
Block the K+ channel
What is empaglifozin?
A SGLT2 inhibitor
How do SGLT2 inhibitors work?
They block glucose reabsorption in the kidney by blocking the receptor. Therefore glucose is urinated to lower blood levels
