Diabetes Flashcards
What is type I diabetes mellitus?
Autoimmune destruction of the beta cells in the pancreas which produce insulin
What is the only current therapy for type I diabetes mellitus?
Insulin injection or insulin pumps to maintain blood glucose
The prevalence of type I diabetes is increasing. T/F?
True
Type 2 diabetes is associated with obesity. T/F?
True
What is type II diabetes mellitus?
Insulin resistance where tissues are no longer sensitive to endogenous insulin
How do sulphonylureas act as hypoglycaemic drugs?
These inhibit ATP-sensitive potassium channels to increase the release of insulin
Give examples of sulphonylureas which are used clinically as hypoglycaemic drugs?
Glibenclamide Gliclazide Glimepiride Tolbutamide Glipizide
Metformin is an example of a biguanide which is used as a hypoglycaemic drug. How does it work?
It mimics insulin by inhibiting hepatic gluconeogenesis
How do thiazolidinediones work as a hypoglaemic drug?
They stop the inappropriate deposition of lipid in non-adipose tissue by acting as a ligand to stimulate the expression of genes involved in TAG storage. This improves insulin sensitivity
Give an example of a thiazolidineione used as a hypoglycaemic drug?
Pioglitazone
What are incretins?
GI hormones which potentiate insulin secretion
Give examples of incretins
Glucagon like peptide 1
gastric inhibitory peptide
Which enzyme rapidly inactive incretins?
dipeptidyl peptidase 4 (DDP-4)
Incretins are endogenous molecules which potentiate the effects of insulin but are rapidly broken down by DDP-4. Give examples of incretin mimics which are used as hypoglycaemic drugs as they are not cleaved by DDP-4?
Exenatide
Liraglutide
Give examples of drugs which inhibit DDP4 to increase endogenous incretin mediated increase in insulin secretion?
Sidagliptin
Vildagliptin
Canagliflozin, dapagliflozin and empagilflozin are SGLT2 inhibitors. How do these work to reduce hyperglycaemia?
These inhibit renal reabsorption glucose through SGLT2
What type of. hypersensitivity reaction is type 1 diabetes mellitus?
Type 4 cell mediated hypersensitivity
What antibodies may exist in a patient with type I diabetes?
GAD65 - against glutamic acid decarboxylase
IAA - against insulin
I-A2 against tyrosine phosphatase like molecule
ICA - against islet cells
ZnT8 - against beta cell specific zinc transporter
Beta cell destruction proceeds for months or years without detection as inflammation of the beta cells. Often, what percentage of beta cells needs to be destroyed before hyperglycaemia develops?
80-90%
How does the lack of insulin in type 1 diabetes lead to hyperglycaemia?
GLUT4 not translocated onto muscle, liver or adipose cells so there is limited glucose uptake by these cells. This results in decrease glycogenesis and protein synthesis and an increase in glycogen-lysis, gluconeogenesis and lipolysis
Which HLA genes provide a genetic susceptibility to type 1 diabetes?
HLA-DR3
HLA-DR4
As well as genetic factors, environmental factors have been implicated in the development of type 1 diabetes mellitus. What are these environmental factors?
Congenital rubella syndrome Human enteroviruses Vitamin D deficiency Wheat proteins (gluten) Cow's milk Psychological stress
What are some of the microvascular complications of diabetes?
retinopathy
neuropathy
nephropathy
What are some of the microvascular complications of diabetes?
Cardiovascular, cerebrovascular and peripheral vascular disease
In what age group does type I diabetes usually present?
Young people
What is the acute complication of type I diabetes mellitus?
Diabetic ketoacidosis
A random plasma glucose test above what level may indicate diabetes?
> 11mmol/l
A fasting plasma glucose above what level may indicate diabetes?
> 6.9mmol/l
A plasma glucose above what level, two hours after the administration of 75g of oral glucose, may indicate diabetes?
> 11mmol/l
What is the AC1 test for diabetes?
Tests glycosylated haemoglobin to measure the 3 month average plasma glucose concentration this will be >48mmol/l in patients with diabetes
How can the diagnosis of diabetes be determined by investigation?
random plasma glucose, fasting plasma glucose, glucose tolerance test, AC1 test
Two positive tests or one positive test plus symptoms indicates diabetes
How can the diagnosis of specifically type 1 diabetes be identified?
low c-peptide levels
presence of type 1 diabetes autoantibodies
How is good glycemic control obtained in type I diabetes mellitus?
Diet
Exercise
Insulin therapy
Explain the difference between a twice daily insulin regime and a basal-bolus regime?
Twice daily regime - take insulin before breakfast and dinner
Basal-bolus routine - intermediate or long-acting insulin given at bedtime to provide a basal level of insulin then a bolus amount of insulin is added using short/rapid acting insulin to cover mealtimes
Explain the difference between insulin pumps and insulin pens?
Insulin pens require injection and deliver a metered dose of insulin
Insulin pumps deliver insulin subcutaneously, continuously over 24 hrs
How is hypoglycaemia defined?
Normal fasting glucose <3.3 mol/l
What may be the cause of diabetic hypoglycaemia?
Taking too much insulin Not eating enough Postponing or skipping meals or snacks Increasing exercise without eating more or adjusting medications Drinking alcohol
What are the symptoms of hypoglycaemia?
Diaphoresis Anxiety Tremor Hunger Generalised tingling Nausea Palpations Confusion Irritability Blurred vision Drowsiness
How are mild episodes of hypolglycaemia treated?
Usually be the patient themselves by taking a glucose tablet or by eating/drinking refined sugar
How are more severe/acute presentations of hypoglycaemia treated?
Glucose administered by IV
injection of 1mg of glucagon
What are the symptoms of type I diabetes mellitus?
Polyuria Polyphagia Polydipsia Glycosuria Weight loss Generalised weakness Blurred vision
What is the prevalence of type I diabetes in the UK population?
0.5%