- autoimmune disease affecting beta cells - onset adulthood - don't have to have elevated BMI which see in most type 2 - will lose weight and be non-responsive to medications

- Rare genetic diabetes - may not need insulin

- glycosylated Haemoglobin - Testing for the sugar present on the surface of the haemoglobin molecules - if in sugary blood will have higher levels - Higher the HbA1c the greater the risk of complications

Pharmacology of diabetes 2 Flashcards by mia Barry

Name two other types of diabetes outside type 1 & 2

Latent Autoimmune diabetes (adults)
Maturity Onset diabetes (young)
Gestational Diabetes (during pregnancy)
Steroid Induced diabetes (glucocorticoids elevate glucose)

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What is LADA?

autoimmune disease affecting beta cells
onset adulthood
don’t have to have elevated BMI which see in most type 2
will lose weight and be non-responsive to medications

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What is MODY?

Rare genetic diabetes

- may not need insulin

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What are the diagnostic criteria for Type 1?

rapid weight loss
BMI <25
possibly DKA
no autoimmune disease present

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What are the diagnostic criteria for Type 2?

HbA1c > 48 mmol/mol must be taken at least twice (3 month apart)
Fasting glucose > 7 mmol/L
Random plasma glucose >11.1 mmol/L

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What is HbA1c?

glycosylated Haemoglobin
Testing for the sugar present on the surface of the haemoglobin molecules
if in sugary blood will have higher levels
Higher the HbA1c the greater the risk of complications

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When can HbA1c not be used?

Not used in type 1
Can also be less sensitive then fasting blood glucose levels even in Type 2
If anaemic or pregnant where high RBC turnover can’t be used

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What should the target HbA1c be?

changes between individuals usually between (48-53 mmol/mol and 6.5%)
may end up being above the 48 mmol/mol used in diagnosis
advice that the lower they get there HbA1c the lower there risk for complications (any reduction will help)
Avoid suggesting highly intensive management levels try and bring it down gradually (otherwise may cause hypoglycaemia)

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What are the different treatments used in control of type 2 diabetes?

Education
Lifestyle (stop smoking + drinking)
Control BP
Metformin (control glucose)
Statin (lower lipids)
Aspirin (anti-platelet to reduce macro/microvascular disease)

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What are the non-pharmacological managements of diabetes?

Education (educational groups online)
Diet (dietician, diet sheets)
Lifestyle (increase exercise and weight loss)
Foot care (diabetic neuropathy)
Retinal photography (prevent diabetic retinopathy)

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What diabetes complications should be looked out for?

Kidneys
Neuropathy
Infections
Vascular
Eyes
Skin

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What are the different drug treatments in diabetes?

Biguanide
Sulfonylureas
Glucagon like peptide
Dipeptidylpeptidase IV inhibitors
Na/Glucose Co-transport 2-inhibitors
Thiazolidinesdiones
Meglitinides
aGlucosidase inhibitors

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Example of Biguanides?

Metformin (only one in the class)

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Example of Sulfonylureas?

Gliclazide

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Example of Glucagon like peptides?

Liraglutide

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Example of Dipeptidylpeptidase IV inhibitors?

sitagliptin

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Example of sodium glucose co-transport 2-inhibitors?

dapagliflozin

Example of Thiazolidinedione?

pioglitazone

Example of Meglitinides?

repaglinide

Example of alpha glucose inhibitors?

Acarbose

What is the first treatment tried to get HbA1c down?

1) Lifestyle mesures

What is the first line drug treatment for type 2 diabetes?

Monotherapy Metformin

What is currently second line treatment for diabetes?

SGLT2 inhibitors (sodium glucose transport proteins)
OR
GLP-1RA (glucagon-like peptide-1 receptor agonist)

When should SGLT2 inhibitors or GLP-1RA be preferentially used?

SGLT2 inhibitors = CKD
GLP-1RA = high risk CVD
SGLT2 inhibitors cautioned in those with neuropathic feet problems as increased risk of amputation so use GLP-1RA

What is the MoA of Metformin?

- activates liver AMP-kinase reducing glucose output from the liver - increases liver, muscle and fat cell sensitivity to insulin - enhances glucose peripheral uptake and utilisation

What are side effects of metformin/biguanide?

- Causes weight loss (may be useful) - GI adverse effects e.g. nausea, diarrhoea and flatulence - Unlikely to cause hypoglycaemia as enhances natural insulin signal - Lactic acidosis (very rare) only seen in whose with CKD already

How can side effects be prevented?

- Start on low dose then increase over period of weeks - Take with meals - If struggling to take pill give modified release preparation - Can damage kidneys so use with caution in those with renal damage check U&Es

Why should Metformin be stopped?

If serum creatinine above 150 micro mol/L or eGFR < 30mL/min/1.73m(squared)

What is the MoA of sulfonylureas?

- sulfonylurea binds to sulfonylurea receptor of pancreatic Beta cell - this closes ATP-K channels - less potassium leaves the cell - increase in calcium influx - beta cell depolarises and insulin is released

When is sulfonylurea used/not used?

- used less now used to be second line treatment - patients need to have functioning beta cells - antagonised by corticosteroids and thiazide-like diuretics

Side effects of Sulfonylurea?

- prolonged hypoglycaemia (bypass natural negative feedback loop so insulin constantly secreted) - weight gain - hyponatraemia - oedema - Hepatotoxicity - photosensitivity - allergy/rash

How do incretin effects differ in healthy and diabetic patients?

Diabetes: incretin signal reduced so less insulin secreted healthy: after meal get activity of incretin group which promotes insulin signal

What are the incretin hormones?

1) GLP-1 (Glucagon like peptide)

Where is GLP-1 released from and what stimulates release?

- L-cells in small intestines | - Stimulated by lipids and carbohydrates

What is MoA of GLP-1?

- Binds to G-protein coupled receptors on beta cells which stimulates insulin secretion - also stimulates B cell growth - insulin synthesis - inhibits glucagon secretion - decreases hepatic glucose output and gastric emptying - promotes satiety

What enzyme degrades GLP-1?

Dipeptidyl peptidase IV

What are the two drug types acting on the GLP-1 mechanism?

1) incretin mimetics Glucagon like peptides (analogues of GLP-1 which take longer to breakdown) 2) Incretin Enhancers (inhibitors of dipeptidyl Peptidase IV, keep natural GLP-1 levels larger for longer)

Why can GLP-1 analogues be disliked?

- Injection whereas tablets would be more convenient - causes GI disturbance (nausea and vomiting) - slight increase in pancreatitis risk and pancreatic cancer

Side effects of GLP-1 analogues?

- causes GI disturbance (nausea and vomiting) - causes weight loss - can cause Hypoglycaemia - slight increase in pancreatitis risk and pancreatic cancer - caution in renal disease - Delays gastric emptying so contraindicated in people with gastroparesis

What are the advantages and disadvantages of using DPPIV inhibitors over GLP-1 analogues?

- Tablet form - slight increased risk of hypoglycaemia - don't help in weight loss

Adverse effects of DPPIV inhibitors?

- nasopharyngitis - headache, nausea - possible risk of heart failure

What should be checked after 6 months of use of either incretin hormones?

HbA1c checked In GLP-1 if not decreased by 1% than stopped or If weight not decreased by more than 3% than stopped In DPPIV if not degreased by more than 0.5% stopped