Pathophysiology of Type 2 Diabetes Flashcards
What factors contribute to the development of insulin resistance?
Genetic predisposition and obesity lifestyle factors
What does insulin resistance cause?
Compensatory beta cell hyperplasia, leading to beta cell failure
What does early beta cell failure cause?
Impaired glucose tolerance = progresses to diabetes as beta cell failure progresses
What are the factors linked to hyperglycaemia?
Increased incretin effect, decreased insulin secretion
increased lipolysis, increased glucose reabsorption, neurotransmitter dysfunction, decreased glucose uptake, increased hepatic glucose production, increased glucagon secretion
What contributes to the susceptibility of an individual to type 2 diabetes?
Genetic component, foetal development, postnatal nutrition
What adaptions occur in the cells during type 2 diabetes?
Beta cell mass expansion, insulin secretion
Failure of what processes are linked to type 2 diabetes?
Glucolipotoxicity, oxidative stress, ER stress, de-differentiation
How do weight and insulin resistance change as the disease progresses?
They both increase
What affect does obesity have on disease progression?
It accelerates the disease presentation
What is type 2 diabetes a disease of in most people?
Disease of beta cells
How does beta cell dysfunction cause microvascular disease?
Beta cell dysfunction causes hyperglycaemia = chronic hyperglycaemia leads to microvascular disease
How can progression of microvascular disease be reduced?
By intensive glucose control
How is CVD risk best treated?
Through use of statins and anti-hypertensives
What is the first step of treating someone with type 2 diabetes?
Lifestyle advice = information, reduce weight by 5-10%, give exercise target
Medications = metformin, may need statin/ACE inhibitor
What does metformin do?
Decreases hepatic gluconeogenesis = increases peripheral glucose uptake
What are the adverse effects of metformin?
GI effects, lactic acidosis
What are the diabetic outcome of metformin?
Reduce HbA1c by 0.8-2.0%
Get weight to neutral
No hypoglycaemia
What are factors that lead to failure to meet glycaemic targets?
Younger patient, female, obese, not at BP/lipid targets, more complex glucose lowering therapy, poor adherence to drugs and lifestyle changes
What is the first step of drug prescription for type 2 diabetes?
Metformin
Sulphonylurea if intolerant to metformin
What is the second step of drug prescription for type 2 diabetes?
Add sulphonylurea
Use TZD if hypoglycaemia a concern
Use DPPIV if weight gain a concern
What is the third step of drug prescribing for type 2 diabetes?
Add TZD
Use DPPIV if weight gain a concern
Use insulin if osmotic symptoms or rising HbA1c
Use GLP-1 if BMI > 30mg/kg
How should glycaemic targets be created?
Must be individualised, as should glucose lowering therapies
What is the optimal first line drug for treating type 2 diabetes?
Metformin (unless contra-indicated)
What is the foundation of any type 2 diabetes treatment programme?
Diet, exercise and education
What should be the major focus of therapy for type 2 diabetics?
Comprehensive CV risk reduction
How does sulphonylurea act?
Blocks beta cell KATP channels = increases first and second phase insulin secretion
Efficacy reduced at higher doses
What are the diabetic outcomes for sulphonylurea?
Reduce HbA1c by 1.0-2.0%
Increase weight gain by 2kg
Increase hypoglycaemia
What are the adverse effects of sulphonylurea?
Abnormal LFTs, increased CHD
What are some features of GLP-1 and DPPIV?
GLP-1 = injected, affects hypoglycaemia when used in combination DPPIV = oral, weight stays the same or decreases
How does glitazone work?
PPAR gamma inhibitor = increases peripheral glucose uptake
What are the diabetic outcome for glitazone?
Decrease HbA1c by 0.6-1.5%
Increase weight gain by 3.5 kg
What are the adverse effects of glitazone?
Fracture risk increase, hepatotoxicity, fluid retention
What is the general treatment plan for type 2 diabetics?
Therapeutic lifestyle change = results in remission in 10-15%
Monotherapy
Combination therapy (not insulin)
Combination therapy with insulin
