Type 2 Diabetes Mellitus Flashcards
What is T2 diabetes mellitus?
A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia. Is associated with obesity but not always. Resultant chronic hyperglycaemia may initially be managed by changes to diet / weight loss and may even be reversible. With time glucose lowering therapy including insulin, is needed.
What are 5 points to remember about real life diabetes classification?
- Autoimmune diabetes leading to insulin deficiency can present later in life = latent autoimmune diabetes in adults (LADA)
- T2DM may present in youth / young adults
- Diabetic ketoacidosis can be a feature of T2DM
- Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)
- Diabetes may present following pancreatic damage or other endocrine disease
What are 4 points about the changing epidemiology of T2 DM?
- Prevalence of T2DM varies enormously
- Increasing prevalence
- Occurring and being diagnosed younger
- Greatest in ethnic groups that move from rural to urban lifestyle
What are the 3 Stages of development of type 2 diabetes in terms of glucose levels?
- Impaired fasting glycaemia
- Impaired glucose tolerance
- Pre-diabetes or non-diabetic hyperglycaemia
- T2 DM
Draw the 3 stage graph of insulin production vs resistance in the development of T2 DM
Slide 8
What counts as a diagnosis of T2 DM?
Random glucose with symptoms of diabetes (equal to or over 11.1mmol/L) or 2 fasting glucose.
Why is there a relative insulin deficiency in type 2 diabetes?
Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance. There is therefore a relative deficiency of insulin but the insulin produced prevents formation of ketone bodies.
What is a feature of long duration type 2 diabetes?
Due to relative insulin deficiency, beta cells overproduce insulin and eventually fail resulting in loss of beta cell function. In long-duration type 2 diabetes, beta-cell failure may progress to complete insulin deficiency. While person usually already on insulin at this point, important not to stop as at risk of ketoacidosis.
Draw the pathophysiology map of diabetes
Slide 15
What is observed in a hyperglycaemic map?
Hyperglycaemic state maintained steadily. Basal glucose level is already higher in person with diabetes. However, normal person would experience an insulin spike when hyperglycaemic state induced, no change to insulin levels of person with T2 DM.
What does an IV glucose challenge help identify?
First phase insulin release is lost in T2 DM. This is when stored insulin in beta cells is released in a brief spike lasting only several minutes. This promotes peripheral utilization of the prandial nutrient load, suppresses hepatic glucose production, and limits postprandial glucose elevation.
What are 2 consequences of T2 DM?
In type 2 diabetes, reduced insulin action causes less uptake of glucose into skeletal muscle. Hepatic glucose production is also increased due to both a reduction in insulin action and increase in glucagon action.
Why is free plasma glucose so high in T2 DM?
- The diminished ability to store or oxidize glucose in muscle due to impaired insulin activity reduces the metabolic clearance rate of glucose so glucose made into lactate. Lactate metabolised to glucose in liver (Cori cycling).
- Inadequate insulin action also causes an increased flux of substrates – glycerol and free fatty acids – to the liver, resulting in increased gluconeogenesis.
- Inappropriate glucagon secretion induces continued glucose production by stimulating glycogenolysis and gluconeogenesis
Describe the genetics of T2 DM
Monogenic –> MODY
Polygenic –> multiple polymorphisms that increase risk depending on environmental factors.
What is the role of obesity in T2 DM?
Major risk factor for T2DM Fatty acids and adipocytokines important Central vs visceral obesity 80% T2DM are obese Weight reduction useful treatment
