Type 2 Diabetes Flashcards
What is Type 2 Diabetes?
condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia
What is type 2 diabetes associated with?
obesity but not always
How can you manage the resultant croci hyperglycaemia?
changes to diet / weight loss and may even be reversible
and With time glucose lowering therapy including insulin, is needed
What are the different classifications of diabetes?
•Type 1 Diabetes •Type 2 Diabetes •Hybrid forms •Other •Unclassified -During pregnancy
What is latent autoimmune diabetes in adults (LADA)
Autoimmune diabetes leading to insulin deficiency can present later in life
Can T2D? develop in youth?
Yes, increasing prevalence
In which ethnic groups is the prevalence of T2D?
ethnic groups that move from rural to urban lifestyle
Where is insulin produced?
pancreatic beta-cells
What is relative insulin deficiency?
- not enough insulin produced to overcome insulin resistance
- explains why the hyperglycaemia encountered does not cause ketosis under ‘usual’ circumstances: prevent lipolysis and form ketones
What happens in long duration type 2 diabetes?
beta-cell failure may progress to complete insulin deficiency
Why is it important to be aware of long duration T2D as usually they are already on insulin?
Important not to stop as at risk of ketoacidosis
What causes T2D (pathophysiology)?
- Genes
- intrauterine environment
- adult environment
What is the other pathophysiology of T2 like?
- Insulin resistance and insulin secretion defects
2. Fatty acids important in pathogenesis and complications
When do people develop T2D?
- HETEROGENOUS
* People develop T2D at variable BMI, ages and progress differently
How is the factor that in response to a meal stored insulin is released and more is produced hindered in T2D?
People with T2DM or those who are about to develop diabetes do not have this stored insulin
What does the reduced insulin action cause in T2D?
less uptake of glucose into skeletal muscle
How is hepatic glucose production changed in T2D?
increased due to both a reduction in insulin action and increase in glucagon action
What is the relationship between insulin resistance and insulin secretion in T2D?
- People developing type 2 diabetes have ‘fallen off the curve’
- for a given degree of insulin sensitivity secrete less insulin
What does the excess of TNF-α IL-6
mean?
- Stimulates lipolysis and VLDL secretion
- increases IR Whole body and muscle
- decreases adiponectin expression
What does the excess of Endocannabinoids
mean?
- Insulin inhibits expression in fat
2. Fat IR > increased circulating EC
What does the excess of leptin mean?
- Elevated in obesity
- Increased IR Whole body muscle and liver
- Decreased appetite
- Increased metabolic rate
What does the excess of resistin mean?
- Elevated in obesity and T2DM
- Increased IR Whole body and liver
- Increased Liver TG secretion
What does the excess of glucocorticoids mean?
- Increased 11β HSD-1 in fat
- Increased fat cell size and IR
- Increased glucose BP Lipids
What does excess adoponectin mean?
- Increased insulin resistance
2. Predictive of diabetes
What does excess fatty acids mean?
- Elevated in obesity and T2DM
- Increased IR Whole body muscle and liver
- Decreased B cell function
- Increased Liver TG secretion
- Increased Organ fat, oxidative stress
What does excess apelin mean?
- Insulin stimulates expression in fat
- Elevated in hyperInsulin
- CV effects
What does excess visfatin mean?
- Visceral fat
2. Decreased IR Whole body
What is the monogenic?
- Single gene mutation ==> Diabetes (MODY)
- Born with always gonna develop
What is the polygenic?
- Polymorphisms increasing risk of diabetes
- ‘Not born with it but high risk and may develop later depending on other factors’
What are GWAS in T2 Diabetes?
Look at nucleotide changes present in Type 2 diabetes group but not in controls and asses effect size- 400 different SNP that affect risk - cumulative SNP have bigger effect
What is the role of obesity in T2D?
- Major risk factor for T2DM
- Fatty acids and adipocytokines important
- Central vs visceral obesity
- 80% T2DM are obese
- Weight reduction useful treatment
How are perturbations in gut microbiota in T2D?
- Obesity, insulin resistance T2DM
- Bacterial lipopolysaccharides fermentation to short chain FA, bacterial modulation bile acids
- Inflammation, signaling metabolic pathways
How is Intra-uterine growth retardation associated with T2D?
- Weight at age 1 year <8.16kg, 22% had type 2 diabetes of IGT
- Weight age 1 year >12.25 kg, 6% had type 2 diabetes or IGT
What is the presentation of T2D?
- Hyperglycaemia
- Overweight
- Dyslipidaemia
- Fewer osmotic symptoms
- With complications
- Insulin resistance
- Later insulin deficiency
What are the risk factors for T2DM?
- Age
- PCOS
- Increased BMI
- Family Hx
- Ethnicity
- Inactivity
What is needed for the diagnosis of type 2 diabetes? What are some presentations?
- Osmotic symptoms
- Infections
- Screening test: incidental finding
- at presentation of complication
- Acute; hyperosmolar hyperglycaemic state,
- Chronic; ischaemic heart disease, retinopathy