Type 2 diabetes Flashcards
What is the definition of diabetes?
A state of chronic hyperglycaemia sufficient to cause long term damage to specific tissues notably the retina, kidneys, nerves and arteries
What is the clinical definition of diabetes?
Fasting blood glucose > 7mmol/l
What is impaired fasting glucose?
Space in between the defining markers for diabetes and normal when measuring fasting blood glucose
What is impaired glucose tolerance?
Space in between the defining markers for diabetes and normal when measuring the 2 hour response in a glucose tolerance test
What factors affect pathophysiology of T2DM?
Genetic
Intrauterine environment
Adult environment
What is the aetiology of Maturity Onset Diabetes of the Young?
Several hereditary forms- autosomal dominant for ineffective pancreatic beta cell insulin production
As a baby, what makes you more likely to develop T2DM?
Being small- intrauterine growth restriction (IUGR)
What other problems apart from an increase in blood glucose does insulin resistance cause?
Dyslipidaemia which stimulates the mitogenic pathway causing smooth muscle hypertrophy and an increase in blood pressure which increases the risk of microvascular disease
What happens to insulin production and resistance as we get older?
Production decreases and resistance increases
Eventually, insulin production will intersect with insulin resistance and the insulin production won’t be enough to overcome the resistance, when does this happen in caucasians?
110 years
What percentage of patients with T2DM are obese?
80%
What are the 2 phases of insulin release in a normal person?
1st phase- stored insulin that is ready to be released in one go
2nd phase- over a period of time, more insulin is produced and released
What happens to the insulin phases in people developing diabetes?
They will still have some insulin production but will lose their 1st phase response
How can diabetes get round their lack of a 1st phase response?
Eating complex carbohydrates which release the glucose slowly and decrease the need for a 1st phase response
What are triglycerides broken down into?
Glycerol and non-esterified fatty acids (NEFA)
What is insulin’s effect on the breakdown of triglycerides?
It inhibits it because you don’t need to break down fat stores after a meal
Where does the glycerol and NEFA go after formation?
To the liver
What happens to the glycerol in the liver?
Converted to glucose (gluconeogenesis)
How is glucose released from the liver?
Glycogenolysis
What happens to the NEFA when they get to the liver?
They are chopped up into 2-carbon segments which can’t be used to make glucose but are used to make very low density lipoprotein triglycerides which are atherogenic
What is insulin resistance modulated by?
Adipocytokines
What system is thought to be associated with obesity, insulin resistance and T2DM?
Gut microbiota
What is a common side effect of diabetes treatment and what is the only treatment that doesn’t cause this side effect?
Weight gain and metformin
How does T2DM present?
Microvascular:
Retinopathy
Nephropathy
Neuropathy
Microvascular: Ischaemic heart disease Cerebrovascular Renal artery stenosis PVD
Metabolic:
Lactic acidosis
Hyperosmolar
In terms of metabolic issues, how often do they present in T2DM compared to T1DM?
Much more common in T1DM with ketoacidosis
What is the basis of management of T2DM?
Education
Diet
Pharmacological treatment
Complication screening
How should someone with T2DM control their diet?
Control total calories/increase exercise Reduce refined carbohydrates Increase complex carbohydrates Reduce fat as proportion of calories Increase unsaturated fat as proportion of fat Increase soluble fibre
How do you monitor T2DM?
Weight
Glycaemia
Blood pressure
Dyslipidaemia
What is orlistat and how does it work?
Pancreatic lipase inhibitor- it stops the breakdown of fat thus restricting fat absorption in the gut
What is metformin and how does it work?
Biguanide- Treats insulin resistance in the liver
How do sulphonylureas work?
Makes the existing pancreas secrete more insulin
How do alpha glucosidase inhibitors work?
Delay glucose inhibition
How do thiazolidinediones work?
They act on the adipocytes and addresses insulin resistance peripherally in fat and muscle
How common is metformin as a treatment?
Used in more or less everyone with T2DM in particular overweight patients
When would metformin not be used?
Severe liver failure
Severe cardiac failure
Mild renal failure
How can beta cells gage the blood glucose levels and what does it lead to?
Glucokinase and insulin secretion
How do sulphonylureas work?
They act on specific receptors and block the ATP sensitive potassium channel and cause the influx of calcium which leads to insulin secretion
What is glibenclamide?
Sulphonylurea and insulin secretagogue
What are the side effects of glibenclamide?
Hypoglycaemia
Weight gain
What is acarbose?
Alpha gluconidase inhibitor
How does acarbose work?
Prolongs the absorption of oligosaccharides which allows insulin secretion to cope following the loss of the first phase insulin response
What are the side effects of acarbose?
Sugars reach the large intestine where they are fermented so flatus (gas) is an issue
What are thiazolidinediones?
Peroxisome proliferator-activated receptor (PPAR-y) agonists
What is an example of a thiazolidinedione?
Pioglitazone
How do thiazolidinediones work?
They are an insulin sensitiser- mainly peripheral and cause weight gain- improvement in glycaemia and lipids
What are the side effects of thiazolidinediones?
Hepatitis and heart failure
What is the incretin effect?
Oral glucose load triggers a bigger release in insulin than IV glucose
Why does the incretin effect occur?
Due to GLP-1 which is a gut hormone that is released on response to food in the gut and stimulate insulin and suppresses glucagon
Where and how is GLP-1 produced?
It is produced by L-cells and is the transcription product of pro-glucagon gene
What is a problem with GLP-1?
Short half life as it is rapidly degenerated by dipeptidyl peptidase-4 (DPP-IV)
How do Gliptins work?
They make the GLP-1 that is present last longer because they are DPP-IV inhibitors
What is gestational diabetes?
Temporary diabetes that is present in some pregnant women- helps identify women that are high risk for diabetes later in life
In which type of diabetes is weight loss common in?
Type 1
Which type of diabetes is ketone prone?
Type 1
In which type of diabetes is serum insulin low or absent?
Type 1
Which type of diabetes has HLA association?
Type 1- DR3 and DR4
In which type of diabetes do islet B cells function?
Type 2
In which type of diabetes are islet cell antibodies present?
Type 1
