Type 2 Diabetes mellitus Flashcards
What is type 2 diabetes?
A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia
Associated with obesity but not always
What is another term for type 2 diabetes?
Relative insulin deficiency
How does development of type 2 diabetes associate with age?
Can present in any decade of life
Increasing in all ages but rapidly in early-adulthood
Outline the epidemiology of type 2 diabetes
Prevalence varies across countries enormously
Increasing prevalence
Occurring and being diagnosed younger
Greatest in ethnic groups that move from rural to urban lifestyle
What are the stages of development of type 2 diabetes?
How is type 2 diabetes diagnosed?
Random glucose >11.1 mmol/L + osmotic symptoms
Describe beta-cell function at diagnosis of T2DM
Usually dropped quite low before diagnosis ~ 50%
Why doesn’t hyperglycaemia normally cause ketosis in T2DM?
Insulin is still being produced by beta cells and this is enough to prevent ketosis
What may be observed in long-duration T2DM?
Beta-cell failure may progress to complete insulin deficiency
Usually on insulin at this point but important not to stop as at risk of ketoacidosis
What factors are involved in the pathophysiology of T2DM?
Genes, intrauterine environment and adult environment
Fatty acids are important in pathogenesis and complications
Insulin resistance and insulin secretion defects
Heterogenous - variable BMI, age and progression across individuals
What happens when an individual with T2DM is given an IV glucose challenge?
First phase insulin release is lost
How does T2DM affect skeletal muscle and hepatic glucose production?
Less uptake of glucose into skeletal muscle
Hepatic glucose production is increased due to both a reduction in insulin action and increase in glucagon action
Aside from diet, what also contributes to high plasma glucose in T2DM?
Impaired glucose disposal (clearance) and increased hepatic glucose production (HGP) contribute to increased fasting plasma glucose
How does insulin secretion differ in an individual with T2DM vs an individual without?
For a given degree of insulin sensitivity, people with T2DM secrete less insulin
Describe the genetics of T2DM
Monogenic -> Single gene mutation ==> Diabetes (MODY)
Polygenic -> Polymorphisms increasing risk of diabetes
Approximately how many hits were there in the GWAS for T2DM and how much did they affect risk?
Approximately 450 hits
Each individual SNP has only a mild effect on risk
However cumulative effect of all SNPs have a bigger effect
What is the role of obesity in T2DM?
Major risk factor for T2DM
Fatty acids and adipocytokines important
Central vs visceral obesity
80% T2DM are obese
Weight reduction useful treatment
What other factors, aside from obesity, are associated with T2DM?
Perturbations in gut microbiota:
- Bacterial lipopolysaccharides fermentation to short chain FA
- Bacterial modulation of bile acids
- Inflammation
Intra-uterine growth retardation
How does T2DM present?
Hyperglycaemia
Overweight
Dyslipidaemia
Fewer osmotic symptoms
With complications
Insulin resistance
Later insulin deficiency
What are the risk factors of T2DM?
Age
PCOS
Higher BMI
Family Hx
Ethnicity
Inactivity
How is type 2 diabetes diagnosed?
First line test: HbA1c
1x HbA1c >/= 48 mmol/L with symptoms
Or
2x HbA1c >/= 48 mmol/L if asymptomatic
What can lead to a type 2 diabetes diagnosis?
Osmotic symptoms
Infections
Screening test: incidental finding
At presentation of complication:
- Acute; hyperosmolar hyperglycaemic state
- Chronic; ischaemic heart disease, retinopathy
What is hyperosmolar hyperglycaemic state?
Insufficient insulin for prevention of hyperglycemia but sufficient insulin for suppression of lipolysis and ketogenesis
Absence of significant acidosis
Often identifiable precipitating event (infection, MI)
What does hyperosmolar hyperglycaemic state commonly present with?
Presents commonly with renal failure
