Type 2 Diabetes Flashcards
How does T2DM occur?
Repeated exposure to glucose and insulin makes the cells in the body become resistant to the effects of insulin. It therefore requires more and more insulin to produce a response from the cells and get them to take up and use glucose. Over time, the pancreas (specifically the beta cells) becomes fatigued and damaged by producing so much insulin and they start to produce less. A continued onslaught of glucose on the body in light of insulin resistance and pancreatic fatigue leads to chronic hyperglycaemia.
What are risk factors for T2DM?
Non-Modifiable
Older age
Ethnicity (Black, Chinese, South Asian)
Family history
Modifiable
Obesity
Sedentary lifestyles
High carbohydrate (particularly refined carbohydrate) diet
How does T2DM present?
Fatigue Polydipsia and polyuria (thirsty and urinating a lot) Unintentional weight loss Opportunistic infections Slow healing Glucose in urine (on dipstick)
What is an oral glucose tolerance test?
An oral glucose tolerance test (OGTT) is performed in the morning prior to having breakfast. It involves taking a baseline fasting plasma glucose result, giving a 75g glucose drink and then measuring plasma glucose 2 hours later. It tests the ability of the body to cope with a carbohydrate meal.
What is pre-diabetes and how is it diagnosed?
Pre-diabetes can be diagnosed with a HbA1c or by “impaired fasting glucose” or “impaired glucose tolerance”. Impaired fasting glucose means that their body struggles to get their blood glucose levels in to normal range, even after a prolonged period without eating carbohydrates. Impaired glucose tolerance means their body struggles to cope with processing a carbohydrate meal.
HbA1c – 42-47 mmol/mol
Impaired fasting glucose – fasting glucose 6.1 – 6.9 mmol/l
Impaired glucose tolerance – plasma glucose at 2 hours 7.8 – 11.1 mmol/l on an OGTT
What is the diagnostic criteria?
HbA1c > 48 mmol/mol
Random Glucose > 11 mmol/l
Fasting Glucose > 7 mmol/l
OGTT 2 hour result > 11 mmol/l
How can t2dm be managed (non-medically)?
Dietary Modification
Vegetables and oily fish
Typical advice is low glycaemic, high fibre diet
A low carbohydrate may in fact be more effective in treating and preventing diabetes but is not yet mainstream advice
Optimise Other Risk Factors
Exercise and weight loss
Stop smoking
Optimise treatment for other illnesses, for example hypertension, hyperlipidaemia and cardiovascular disease
Monitoring for Complications
Diabetic retinopathy
Kidney disease
Diabetic foot
What are the treatment targets for T2DM?
HbA1C of
48 mmol/mol for new type 2 diabetics
53 mmol/mol for diabetics that have moved beyond metformin alone
What are the guidelines for t2dm?
First line: metformin titrated from initially 500mg once daily as tolerated.
Second line add: sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor. The decision should be based on individual factors and drug tolerance.
Third line:
Triple therapy with metformin and two of the second line drugs combined, or;
Metformin plus insulin
SIGN Guidelines 2017 suggest the use of SGLT-2 inhibitors and GLP-1 inhibitors preferentially in patients with cardiovascular disease.
What is metformin and some se?
Metformin is a “biguanide”. It increases insulin sensitivity and decreases liver production of glucose. It is considered to be “weight neutral” and does not increase or decrease body weight.
Notable Side Effects:
Diarrhoea and abdominal pain. This is dose dependent and reducing the dose often resolves the symptoms
Lactic acidosis
What is pioglitazone?
Pioglitazone is a “thiazolidinedione”. It increases insulin sensitivity and decreases liver production of insulin.
Notable Side Effects:
Weight gain Fluid retention Anaemia Heart failure Extended use may increase the risk of bladder cancer
what is sulfonylurea?
The most common sulfonyluria is “gliclazide”. Sulfonylureas stimulate insulin release from the pancreas.
Notable Side Effects:
Weight gain
Hypoglycaemia
Increased risk of cardiovascular disease and myocardial infarction when used as monotherapy
What are incretins?
Incretins are hormones produced by the GI tract. They are secreted in response to large meals and act to reduce blood sugar. They:
Increase insulin secretions
Inhibit glucagon production
Slow absorption by the GI tract
The main incretin is “glucagon-like peptide-1” (GLP-1). Incretins are inhibited by an enzyme called “dipeptidyl peptidase-4” (DPP-4).
What are GLP-1 mimics?
These medications mimic the action of GLP-1. A common GLP-1 mimetic is “exenatide”. Exenatide is given as a subcutaneous injection either twice daily by the patient or once weekly in a modifiable-release form. Another GLP-1 mimetic is liraglutide, which is given daily as a subcutaneous injection. They are sometimes used in combination with metformin and a sulfonylurea in overweight patients.
Notable Side Effects:
GI tract upset
Weight loss
Dizziness
Low risk of hypoglycaemia
What are SGLT-2 inhibitors?
SGLT-2 inhibitors end with the suffix “-gliflozin”, such as empagliflozin, canagliflozin and dapagliflozin. The SGLT-2 protein is responsible for reabsorbing glucose from the urine in to the blood in the proximal tubules of the kidneys. SGLT-2 inhibitors block the action of this protein and cause glucose to be excreted in the urine.
Notable Side Effect:
Glucoseuria (glucose in the urine)
Increased rate of urinary tract infections
Weight loss
Diabetic ketoacidosis, notably with only moderately raised glucose. This is a rare complication
Lower limb amputation appears to be more common in patients on canagliflozin. It is not clear if this applies to other SGLT-2 inhibitors
