Type 2 diabetes Flashcards by Sheryl O'Hare

Definition

Insufficient insulin to maintain glucose homeostasis

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Are beta cells present?

Yes

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Can the patient make their own insulin?

Yes

because beta cells are present
but the insulin doesn’t work well

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Who gets it?

Middle aged / elderly population

Obese

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Link between T2DM and obesity

Obese people are resistant to the actions of insulin
Pancreas tries to produce more beta cells to overcome the resistance but the pancreas can’t keep up
Patient becomes hyperglycaemic

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Pathogenesis

Insulin levels are sufficiently high over a prolonged period of time
Fibrosis of islets
Beta cells present but they loose ability to sense changes in glucose level
Increased lipolysis
Increased glucose reabsorption

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What happens if a person with T2DM looses weight?

Restores physiological glucose to normal levels
Beta cells start functioning properly again
Increased insulin secretion

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Risk factors

Obesity
Age
FH
Hx heart conditions

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Clinical features

Gradual onset 
Overweight 
Thirst (polydypsia)
Frequent urination (Polyuria)
Tiredness
Thrush
Blurred vision
Infections
Balantitis (inflammation of the glands of the penis)

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Discriminatory tests

GAD / anti-islet antibodies
Ketones
C-peptide

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Investigations

Fasting blood glucose 
Glucose tolerance test
Random fingerprick glucose test 
HbA1c 
Urinalysis 
Auto-antibodies -ve

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Management - initial

Try monitor by lifestyle factors (weight loss) for at least one month before starting any medication

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Management - first line drug therapy

Metformin

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Management - second line drug therapy

Sulphonylurea
OR
Meglitinides

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Management - third line drug therapy

Thiazolidenedione or DPPIV inhibitor
OR ADD
Injectible insulin or GLP-1 agonist

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Metformin - what class of drug is it?

Biguanide

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Metformin - administration route

Oral

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Metformin - dosage

Start on low dose and gradually increase

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Metformin - mechanism of action

Increases glucose uptake into skeletal muscle 
Reduces hepatic gluconeogenesis 
Increases fatty acid oxidation 
Reduces carb absorption 
Works by being toxic to cells

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Metformin - benefits

Reduces HbA1c levels
Weight loss (as it does not promote insulin release)
Decreases risk of CV events
Safe in pregnancy

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Metformin - side effects

GI disturbances 
Lactic acidosis (don't give in pts with renal impairment)

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Metformin - who doesn’t get it

Patients with renal impairment

Skinny patients

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Sulphonylureas - examples

Tolbutamide (short acting)

Glibenclamide and Glicazide (long acting)

Sulphonylureas - administration route

Oral

Sulphonylureas - mechanism of action

Stimulates insulin secretion Binds to and blocks K+ATP channel This depolarises functioning beta cells and stimulates insulin release

Sulphonylureas - caution

If blood glucose levels drop to normal levels and there is not as much need for insulin, sulphonylureas will continue to produce insulin. This could lead to a hypo which is very dangerous

Sulphonylureas - benefits

Reduces HbA1c levels | Improves microvascular complications of diabetes

Sulphonylureas - side effects

Weight gain (as it promotes insulin secretion) Hypoglycaemia (due to continuous insulin release) Not safe in pregnancy Hepatic failure Renal failure

Meglitinides - examples

Repaglinide, Nateglinide

Meglitinides - mechanism of action

Similar to sulphonylureas... Bind to K+ATP channels and block them This ultimately triggers insulin release

Thiazolidinediones (glitazones) - examples

pioglitazone

Thiazolidinediones (guitarrones) - administration route

Oral

Thiazolidinediones (glitazones) - mechanism of action

Activates PPAR-gamma | This promotes pre-adipocyte differentiation into mature adipocyte

Thiazolidinediones (glitazones) - benefits

Reduces HbA1c levels | Promotes fatty acid uptake and storage in adipocytes

Thiazolidinediones (glitazones) - side effects

Weight gain Fluid retention (contra-indicated in HF) Fractures Avoid in pregnancy

GLP-1 receptor agonists - examples

Exenatide

GLP-1 receptor agonists - administration route

IV (before first and last meal of the day)

GLP-1 receptor agonists - mechanism of action

mimics the action of GLP-1 (a peptide hormone released in response to a meal which provides early stimulus to insulin secretion). Acts on the incretin pathway Lowers blood glucose levels after a meal by - slowing gastric emptying - increasing insulin release

GLP-1 receptor agonists - benefits

Weight loss Decreased gastric emptying Reduces hepatic fat accumulation Prevents hypoglycaemia - when blood glucose levels are low, the drug responds accordingly by decreasing the secretion of insulin

GLP-1 receptor agonists - side effects

Nausea

DPP-IV inhibitors - examples

Gliptins

DPP-IV inhibitors - administration route

Oral

DPP-IV inhibitors - mechanism of action

Normally DPP-IV breaks down GIP and GLP-1, leading to increased glucose levels. By inhibiting DPP-IV, blood glucose levels are lowered as GIP and GLP-1 levels are prolonged and free to continue the release of insulin

DPP-IV inhibitors - benefits

Prevents hypoglycaemia

DPP IV inhibitors - side effects

Nausea | Avoid in pregnancy

SGLT2 inhibitors - examples

Canaglifozin

SGLT2 inhibitors - administration route

Oral

SGLT2 inhibitors - mechanism of action

Decreases glucose uptake | Causes you to pee out the glucose instead

SGLT2 inhibitors - benefits

Weight loss | Decreased cardiovascular risk

SGLT2 inhibitors - side effects

Thrush | Increased UTI's

Alpha-glucodiase inhibitor - examples

Acarbose

Alpha-glucodiase inhibitor - mechanism of action

alpha glucosidase b/d complex carbs to smaller, absorbable units. Inhibitors delay the absorption of glucose

Insulin - use

Last treatment option in T2DM | For patients who fail on non-insulin therapies

Insulin - side effects (driving)

Can only regain HGV drivers license if stable diabetes control for at least 3 months on insulin

Annual review

Check feet Check eyes - retinopathy Check urine Measure BP, weight, bloods