**_🧪Endocrinology🧪 - Type 2 Diabetes Mellitus Flashcards
Define type 2 diabetes
Condition in which the combination of insulin resistance and beta-cell failure results in hyperglycaemia
Explain type 2 diabetes
A person who has large amounts of visceral adipose tissue, and continuously high blood glucose (usually due to foods with high sugar content) will have their cells become insulin resistant. This means more insulin is required. Beta-cells can match this demand as it increases and so pump out more and more insulin, to a point. Then they begin to fail, and so the combination of insulin resistance increasing and less insulin being able to be produced leads to type 2 diabetes
What condition is T2DM usually associated with?
Obesity (usually, but not always)
How is T2DM managed?
Changes to diet/weight loss
May even be reversible in early stages
With time, glucose lowering therapy and insulin may be needed
When does T2DM present?
Typically in older people, but can present in youth/young adults
Is DKA a sign of T1/T2DM?
Usually T1, much more common in T1
Possible in T2 however
What are the current epidemiological trends for T2DM?
Varies enormously between countries/regions
Increasing prevalence
Occurring and being diagnosed younger
Greatest in ethnic groups moving from rural to urban lifestyles
What are the parameters for glucose blood tests in the normal range?
Fasting glucose levels <6mmol/L
2hr glucose (DGTT) <7.7mmol/L
HbA1c <42mmol/mol
What is the range of values for glucose blood tests showing intermediate state of diabetic development
6 < Fasting glucose levels < 7
7.7 < 2hr glucose (DGTT) < 11
42 < HbA1c < 48
What values in glucose blood tests would indicate a diagnosis of T2DM?
Fasting glucose >7mmol/L
2-hr glucose (DGTT) >11mmol/L
HbA1c >48mmol/mol
How does DKA usually not arise in T2DM?
Insulin is still produced, but there is increased resistance
It is a relative insulin deficieny
Insulin inhibits production of ketone bodies (lack of insulin in T1DM, so no inhibition of ketone body formation)
When can T2DM lead to DKA?
In T2DM, there is continuous decline in beta-cell function until total failure
Then there is a lack of insulin, leading to the chain of events that causes DKA
Briefly outline the pathophysiology of T2DM
Genes and intrauterine+adult environments
Insulin resistance and eventually insulin secretion defects
Fatty acids important in pathogenesis
How does hyperglycaemia occur in T2DM?
Reduced insulin action leads to less uptake of glucose into skeletal muscle
Lack of insulin action leads to increased hepatic glucose production (and increased glucagon action)
What is the consequence of insulin resistance in adipose tissue?
Less inhibition of lipolysis (i.e. more lipolysis)
Results in the release of NEFAs
What are the 2 genetic forms of diabetes?
Monogenic - single gene mutation
MODY, “born with it, development of diabetes is inevitable”
Polygenic - many mutations
Polymorphisms increase risk - “not born with, but increased risk later depending on environment”
What effect do SNPs (single nucleotide polymorphisms) have on the risk of diabetes?
Individual SNPs have mild effect on risk
Many SNPs can have a cumulative significant effect on risk
What is the role of obesity in T2DM?
Major risk factor for T2DM
80% T2DM sufferers are obese
Fatty acids and adipocytokines play significant role
Weight reduction is effective treatment
What is the role of adipocytokines in the pathogenesis of T2DM?
They contribute to insulin resistance and chronic inflammation
What is the mechanism of action of Sulphonylureas?
Block potassium channel in beta-cells (independent of ATP or glucose) allowing continuous insulin secretion
