Background of diabetes Flashcards
Type 1 Diabetes pathophysiology + presentation?
Autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system
This results in an absolute deficiency of insulin resulting in raised glucose levels
Tends to develop in childhood/early adult life and typically present unwell, possibly in diabetic ketoacidosis
Type 2 diabetes pathophysiology?
Most common cause of diabetes in the developed world
caused by a relative deficiency of insulin due to an excess of adipose tissue
In simple terms there isn’t enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up.
Prediabetes term used for?
patients who don’t yet meet the criteria for a formal diagnosis of T2DM to be made but are likely to develop the condition over the next few years. They, therefore, require closer monitoring and lifestyle interventions such as weight loss
Gestational diabetes?
Some pregnant develop raised glucose levels during pregnancy. This is important to detect as untreated it may lead to adverse outcomes for the mother and baby
Maturity onset diabetes of the young (MODY)?
A group of inherited genetic disorders affecting the production of insulin. Results in younger patients developing symptoms similar to those with T2DM, i.e. asymptomatic hyperglycaemia with progression to more severe complications such as diabetic ketoacidosis
Latent autoimmune diabetes of adults (LADA)
The majority of patients with autoimmune-related diabetes present younger in life. There are however a small group of patients who develop such problems later in life. These patients are often misdiagnosed as having T2DM
Other types of diabetes?
Any pathological process which damages the insulin-producing cells of the pancreas may cause diabetes to develop. Examples include chronic pancreatitis and haemochromatosis.
Drugs may also cause raised glucose levels. A common example is glucocorticoids which commonly result in raised blood glucose levels
Symptoms and signs of Type 1
Weight loss
Polydipsia
Polyuria
May present with diabetic ketoacidosis
- abdominal pain
- vomiting
- reduced consciousness level
Signs and symptoms Type 2
Often picked up incidentally on routine blood tests
Polydipsia
Polyuria
What are polydipsia and polyuria due to?
water being ‘dragged’ out of the body due to the osmotic effects of excess blood glucose being excreted in the urine (glycosuria).
What are the 4 main ways to check blood glucose?
a finger-prick bedside glucose monitor
a one-off blood glucose. This may either be fasting or non-fasting
a HbA1c. This measures the amount of glycosylated haemoglobin and represents the average blood glucose over the past 2-3 months
a glucose tolerance test. In this test, a fasting blood glucose is taken after which a 75g glucose load is taken. After 2 hours a second blood glucose reading is then taken
The diagnostic criteria: if a patient is symptomatic?
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
The diagnostic criteria: if the patient is asymptomatic?
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
MUST be demonstrated on TWO separate occasions
supplementary guidance on the use of HbA1c for the diagnosis of diabetes:
a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus
a HbAlc value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)
in patients without symptoms, the test must be repeated to confirm the diagnosis
it should be remembered that misleading HbA1c results can be caused by increased red cell turnover
Type 1 diabetes general management
patients always require insulin to control the blood sugar levels. This is because there is an absolute deficiency of insulin with no pancreatic tissue left to stimulate with drugs
different types of insulin are available according to their duration of action
Type 2 diabetes general management
the majority of patients with type 2 diabetes are controlled using oral medication
the first-line drug for the vast majority of patients is metformin
second-line drugs include sulfonylureas, gliptins and pioglitazone. Please see the table below for further information
if oral medication is not controlling the blood glucose to a sufficient degree then insulin is used
Insulin: MoA, Route, Main side-effects, Notes
- Direct replacement of endogenous insulin
- Subcutaneous
- Hypoglycaemia, weight gain, Lipodystrophy
- Used in all patients with Type 1, and some patients with poorly controlled Type 2.
Metformin: MoA, Route, Main side-effects, Notes
- Increases insulin sensitivity, Decreases hepatic gluconeogenesis
- Oral
- Gastrointestinal upset, Lactic acidosis
- First line medication in the management of Type 2
- Cannot be used in patients an eGFR of <30 ml/min
Sulfonylureas: MoA, Route, Main side-effects, Notes
- Stimulate pancreatic beta cells to secrete insulin
- Oral
- Hypoglycaemia, Weight gain, Hyponatraemia
- Examples include gliclazide and glimepiride
Thiazolidinediones: MoA, Route, Main side-effects, Notes
- Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
- Oral
-Weight gain, fluid retention
- only currently available thiazolidinedione is pioglitazone
DPP-4 Inhibitors (-gliptins): Moa, route, notes
- Increases incretin levels which inhibit glucagon secretion
- Oral
- generally well tolerated but increased risk of pancreatitis
SGLT-2 inhibitors (gliflozins): MoA, route, side-effects, notes
- inhibits reabsorption of the glucose in the kidney
- oral
- UTI
- typically results in weight loss
GLP-1 antagonists (-tides): MoA, route, side-effects, notes
- incretin mimetic which inhibits glucagon secretion
- subcutaneous
- Nausea, vomiting, pancreatitis
- typically result in weight loss
Type 2 diabetes: Drug course if metformin tolerated and not CI:
Start on metformin, if HbA1c > 58 mmol/mol (7.5%) then do:
Metformin + DPP-4 inhibitor (gliptin)
OR
Metformin + sulfonylurea
OR
Metformin + pioglitazone
OR
Metformin + SGLT-2 inhibitor
if HbA1c still >58 mmol/mol (7.5%) then:
Insulin +
Metformin + DPP-4 inhibitor (gliptin) + sulfonylurea
OR
Metformin + sulfonylurea + pioglitazone
OR
Metformin + pioglitazone + sulfonylurea
OR
Metformin + SGLT-2 inhibitor + pioglitazone
if triple therapy “not effectivem not tolerated or CI” AND >BMI 35 then:
Metformin + sulfonylurea + GLP-1 mimetic
