Diabetes Lecture 2: Type 2 Diabetes Flashcards
How is type 2 diabetes normally caused
Reduced insulin secretion and insulin resistance
What does insulin resistance mean
Normally biological effects are not observed at physiological insulin levels
What is beta cell dysfunction and describe the phases it goes through
when type 2 diabetics secrete less insulin daily
Phase 1: less insulin initially
Phase 2: exaggerated insulin response- may cause hypoglycaemia 3-4 hours after meal
What are the symptoms of type 2 diabetes
Increased thirst and hunger
Increased urination
Fatigue
Blurred vision
Infection
What is HYPEROSMOLAR HYPERGLYCAEMIA STATE (HHS)
Medical emergency to do with
Hyperglycaemia
Dehydration and Uraemia
How do you screen for type 2 diabetes
Random blood glucose levels
Fasted blood glucose levels
HbA1C levels
What are the risk factors for type 2 diabetes
Family history: Parents or sibling has it
Health problems: stroke, hypertension, coronary heart disease, peripheral artery disease
Ethnicity: afro carribean or african, south asian
Age: 40+ years
Waist measurement
BMI: greater than 25
Past: gestational diabetes
has known glucose intolerance or impaired fasting hyperglycaemia
What are the macrovascular complications that can occur in diabetic patients
Stroke
Heart attack
Angina
What are the microvascular complications that can occur in diabetic patients
Diabetic retinopathy
Erectile dysfunction
Autonomic neuropathy
What are the treatment goals of type 2 diabetes
Preserve life
Alleviate symptoms
Achieve good glycemic control- avoid long term complications
Avoid iatrogenic side effects- hypoglycaemia
how do you manage type 2 diabetes: DEED
Dietary modification
Exercise
Education
Drug treatment
What does the diabetic diet consist of in managing type 2 diabetes
Low fat- low saturated fat
Increase fibre and complex carbs
Weight loss- moderate caloric deficit diet
What does exercise consist of in managing type 2 diabetes
Exercise 30 minutes per day
Increases glycemic control, reduces CVD risk
Reduces blood pressure and improves lipid profile
Improves insulin sensitivity
What does education consist of in managing type 2 diabetes
Patient aware that good glycemic control will avoid diabetic complications
Diabetic patients have increased mortality and morbidity
Risk of CVD or diabetic retinopathy
Erectile dysfunction
What does drug treatment consist of in managing type 2 diabetes
Insulin secretagogues
Stimulates insulin release from pancreas, restores early phase insulin release
Example: Meglitinides and SULPHONYLUREAS
Insulin sensitisers
Metformin
Give examples of sulphonylureas
Short acting: Gliclazide or tolbutamide
Long acting: glibenclamide
What is the mechanism of action of sulphonylureas and Meglitinides
Increase insulin release from pancreas by binding to sulphonylurea receptor
Closes the K+ ATP channel which causes a rise in intracellular calcium and insulin release
Reduces HbA1c levels by 1.5 to 2%
What are the commonside effects of sulphonylureas
Weight gain
Hypoglycaemia
Give an example of Meglitinides
Nateglinide- can only be used with metformin
Repaglinide- derivative of glibenclamide
What is the mechanism of action of GLICLAZIDE
Promotes insulin secretion from pancreatic beta cells
Binds to the sulfonyl urea receptor (SUR1) which binds and blocks the ATP sensitive potassium channel
Decrease in potassium efflux leads to depolarisation of Beta cells, opens up voltage dependent calcium channels
Activation of CALMODULIN- releases insulin secretory granules
What is an insulin sensitiser
Enhances the effect of endogenous circulating insulin, reduces insulin resistance and decrease hepatic glucose production
What are the two examples of insulin sensitiser
BIGUANIDES
THIAZOLIDINEDIONES (glitazones)
Explain the role of the Biguanide METFORMIN
Increases glucose uptake in skeletal muscle and adipocytes, suppress hepatic glucose generation (gluconeogenesis)
Reduces glucose absorption from the small intestine (high drug concentration)
Suppress appetite, achieves weight loss and has cardio protective effect
Reduces HbA1c levels by 1 to 2%
What are the side effects of metformin
GI side effects, anorexia, nausea, pain in abdomen, diarrhoea
minimised with gradual increase to dose or modified release
What is the mechanism of action of metformin
Inhibit pyruvate mechanism which increases lactic acid production
Reduces glucose production in liver and decrease glucose absorption
Involves activating AMP activated protein kinase in liver and skeletal muscle
Give an example of Thiazolidinediones and risks associated with it
Pioglitazone
Risk in heart failure and bladder cancer patients
What is the mechanism of action of thiazolidinediones
Bind to PPAR-gamrha (peroxisome proliferator activated receptor gamma)
Regulates: gene transcription, enhances glucose and fatty acid uptake, utilises adipocytes, reduce secretion of cytokines that inhibit insulin action
Reduce glucose output of liver
What is an inhibitor of gastrointestinal glucose absorption
Acarbose
What is an mechanism of action of acarbose
Alpha-glucosidase inhibitor that reduces glucose uptake in small intestine
Slows digestion and absorption of glucose after a meal
Explain how therapies based on glucagon like peptide 1 (GLP-1) work
Glucagon release from alpha cell is regulated by pancreas secreting insulin
When stimulated, it has roles of slowing gastric emptying, slowing digestion and nutrient absorption, moderating blood glucose levels
Give examples of Dipeptidylpeptidase 4 inhibitors
Saxagliptin
Sitagliptin
Explain the mechanism of action of Dipeptidylpeptidase 4 inhibitors
Inhibits DPP-4 which decreases GLP-1 degradation which leads to increased insulin secretion and decrease glucagon secretion
Give examples of GLP-1 mimetic analogues
EXENATIDE and liraglutide (delivered by subcutaneous injection)
What is the mechanism of action for GLP-1 mimetic analogues
DPP4 resistant analogues that bind to and active GLP-1 receptor
Leads to increased insulin secretion, decrease of glucagon secretion, slow gastric emptying and promotes weight loss
How do selective sodium glucose co-transporter 2 (SGLT-2) inhibitors work and give examples of them
Dapaglifozin
Independent insulin mediated glucose control pathways, SGLT-2 block the reabsorption of glucose in the kidneys and promote urinary excretion
When is insulin used in type 2 diabetes
When impossible to control good glycemic control with oral hypoglycaemic drugs
Often given alongside metformin etc
What is gestational diabetes
Diabetes that occurs during the first time in pregnancy
How do you monitor for gestational diabetes
Routine tests for glycosuria
How do you treat gestational diabetes
Lifestyle modification
Exercise
First line: insulin therapy or some oral hypoglycaemic drugs
