Lecture 35 - Diabetes Type 2 Flashcards
What distinguished Type 1 from Type 2 diabetes
Type 1: Autoimmune destruction of pancreatic B cells - little to no insulin produced
Type 2: Insulin resistance and impaired insulin secretion, typically linked to lifestyle
Symptoms of type 2 diabetes
Thirst, frequent unrination, fatigue, blurred vission. Can lead to vascular diseases and elevated blood TAG levels
What is diagnostic fasting glucose level for diabetes
Fasting glucose >7mmol/L or random 11.1> mmil/L is diagnostic for diabetes
What is the diagnostic HbA1c level for diabetes
HbA1c >50mmol/mol indicates diabetes
What is glycated haemoglobin HbA1c and why is it used for diagnosis
HbA1c reflects the average blood glucose level over the past 3 months by measuring glucose bound to haemoglobin in RBCs. It provides a long-term view of glucose control.
What does a glucose tolerance test (GTT) measure
GTT measures how the body handles glucose after an oral glucose load. Blood glucose is monitored for 2 hrs after ingestion
How do glucose tolerance test results differ for normal, pre diabetic, and diabetic individuals?
Normal: Glucose returns baseline after 2 hrs
Prediabetic: Elevated fasting glucose and slower return to baseline
Diabetic: Elevated fasting glucose and impaired return to baseline
What is Insulin resistance
IR is when cells fail to respond adequately to insulin, leading to elevated blood glucose levels and compensatory insulin production.
Name two biological features of insulin resistance
- Decreased glucose uptake
- Increased gluconeogenesis
What dysregulations in glucose and lipid metabolism occur in insulin resistance
Reduced glucose uptake, increased gluconeogenesis, elevated blood FFAs and impaired lipolysis, leading to hyperglycaemia and elevated blood TAGs.
How does IR contribute to fatty liver in diabetes
IR leads to excess fat accumulation in the liver due to impaired fatty acid oxidation and excess lipogenesis, causing fatty liver
How does exercise enhances insulin sensitivity
Exercise activated AMPK, which promotes glucose uptake in muscle cells and increases GLUT4 translocation, reducing blood glucose levels
What drug enhance insulin sensitivity and how does it work
Metformin - enhances insulin sensitivity by activating AMPK, which reduces gluconeogenesis in the liver and lowers blood glucose
What are treatments aiming for
Treatments are mainly aimed at promoting insulin secretion and improving insulin sensitivity
Name two drugs that promote insulin secretion and describe how they work
- Sulfonyureas: Block K+ channels in B cells, triggering Insulin release
- GLP-1 Agonist: stimulates insulin secretion in response to nutrients
What are SGLT2 inhibitors and how do they work
SGLT2 inhibitors block glucose reabsorption in the kidneys, allowing excess glucose to be excreted in urine and lowering blood glucose levels
What is the role of GLP-1 in treating type 2 diabetes
GLP-1 potentiates insulin secretion by stimulation B cells in response to nutrient intake. GLP1 agonists are used to treat type 2 diabetes
How does insulin resistance impair glucose uptake in tissues
Insulin resistance reduces phosphorylation of insulin signalling proteins, impairing GLUT4 translocation and glucose uptake in muscle and adipose tissue
What are advanced glycation end products AGE, why are they problematic
AGE products form when glucose binds to proteins. They promote inflammation and contribute to vascular complications like atherosclerosis in diabetics
How does insulin affect fat storage in adipose tissue
Insulin stimulates LPL to hydrolyse TAGs from chylomicrons and VLDL allowing FAs to enter adipocytes and be re synthesised into TAGs for storage
What is AMPK and how is it involved in glucose metabolism
AMPK is an enzyme activated by exercise and metformin that stimulates glucose uptake in muscles cells, increase fatty acid oxidation, reduced gluconeogenesis, thereby lowering blood glucose levels
How does exercise affect insulin response curves
Exercise improves insulin sensitivity, shifting the insulin response curve so that less insulin is required to lower blood glucose effectively
What happens in B cells during insulin resistance over time
Prolonged insulin resistance leads to B cell hyperplasia and increased insulin production initially, but eventually, B cell function deteriorates, reducing insulin secretions
