Lecture 27: Treatment of Diabetes 2 Flashcards
describe the two main classifications of diabetes
Type 1
- autoimmune response to pancreatic B cell component
Type 2
- hyperglycaemia due to impaired insulin secretion, insulin resistance, ^ hepatic gluc. prod.
describe LADA classification of diabetes
- latent autoimmune diabetes in adulthood
- 6-10% of T2D Px
- lack of metabolic syndrome features
- poor glucose control w/ oral agents
- patient losing weight
- evidence of autoimmune disease (thyroid disease and pernicious anaemia)
- anti-GAD (glutamic acid decarboxylase) antibodies
give the diagnostic criteria for T1D and T2D
Type 1
- hyperglycaemia
- w/ DKA, rapid weight loss, BMI <25, PHx/FHx of autoimmune disease
Type 2
- HbA1c>48mmol/mol on 2 occasions >3 months apart
- fasting plasma gluc. > 7
- random plasma gluc. > 11.1
when can you NOT use HbA1c in diagnosis of diabetes
- T1D
- ^ RBC turnover –> pregnancy, anaemia, haemoglobinopathies
- blood sugar levels rapidly risen (e.g from drugs or acute illness)
how might you set a target HbA1c for a Px
- set individual target (may be above 48mmol/mol)
- offer lifestyle advice and meds to help achieve and maintain target
- inform Px w/ higher HbA1c that any reduction towards target is good for their health
- avoid intensive management levels
give examples of non-pharmacological management of T2D
- education
- diet
- lifestyle –> weight loss and exercise
- foot care
- retinal photography
what to look out for in a Px suspected of diabetes
KEVIN’S got DM
K - kidneys E - eyes V - vascular I - infections N - neuropathy S - skin
list some of the choices of drug treatments in diabetes
- biguanides (metformin)
- sulfonylureas (e.g. gliclazide)
- glucagon like peptide-1 analogue (e.g. liraglutide, exanitide)
- dipeptidylpeptidase IV inhibitors (e.g. sitagliptin)
- sodium-glucose co-transport 2-inhibitors (SGLT2i) (e.g. dapagliflozin)
- thiazolidinediones (e.g. pioglitazone)
- meglitinides (e.g. repaglinide)
- a-glucosidase inhibitors (acarbose)
list choices of therapy for diabetes
- lifestyle measures
if HbA1c >48mmol/mol after lifestyle interventions
- monotherapy –> first line metformin
- alternative monotherapy if metformin not tolerated or contraindicated
- -> depends on severity of hyperglycaemia
- -> comorbidities
- -> need to avoid hypoglycaemia
- -> patient preference
what drugs would be the preferred choice for Px w/ established or high risk of CVD
- GLP-1 RA
- SGLT2 inhibitors
describe MoA of metformin in diabetes treatment
- activates liver AMP-kinase reducing liver glucose output
- ^ liver, muscle, and fat cell sensitivity to insulin
- ^ peripheral glucose uptake and utilisation
give a benefit of using metformin to treat diabetes
enhances natural insulin signal therefore unlikely to cause hypoglycaemia on its own
give some side effects of using metformin
- causes weight loss
- GI adverse effects v common e.g. flatulence, nausea, diarrhoea
describe MoA of sulfonylureas (SU) in diabetes treatment
- bind to sulfonylurea receptor (SUR)
- closing ATP-K+ channels
- dec. K+ efflux
- B cell depolarisation and insulin release
what diabetes Px can SU be prescribed to
T2D Px w/ functioning B cells
give some contraindications for SU
therapeutic effect may be antagonised by corticosteroids and thiazide-like diuretics
list some side effects of SU
- prolonged hypoglycaemia (esp w/ alcohol, B blockers)
- weight gain
- hyponatraemia
- oedema
- hepatotoxicity
- photosensitivity, allergy, rash
describe incretin effect after oral glucose in T2D
diminished incretin effect
give an example of an incretin hormone
glucagon like peptide -1 (GLP-1)
what is the function of incretin hormones
- found in L cells of small intestine
- stimulated by lipids and carbs (food)
- binds to G protein coupled receptors on B cell
- stimulate insulin secretion
what is the function of dipeptidylpeptidase IV (DPP-IV)
- degrades/metabolises GLP-1
- inhibits glucagon secretion, hepatic gluc. output, gastric emptying
- promotes satiety
how to promote incretin effect using drugs
- use GLP-1 analogue (incretine mimetic)
e. g. exenatide, liraglutide, lixisenatide - use DPP-IV inhibitors (incretin enhancers)
- -> prevents GLP-1 metabolism
e. g. sitagliptin, vildagliptin, saxagliptin, linagliptin
what is the GLP-1 analogue MoA
- GLP-1 analogue is more resistant to DPP-IV
- ^ gluc. uptake
- dec. glucagon secretion
- dec. hepatic gluc. output
- delay gastric emptying
- promote satiety
–> dec. blood glucose levels
how are GLP-1 analogues administered and what are the side effects
- given by subcutaneous injection (daily/weekly)
- 2x3 mL pens
side effects:
- GI disturbance
- weight loss
- rarely assc. w/ hypoglycaemia
- assc. w/ ^ risk of pancreatitis
what are some contraindications w/ GLP-1 RA use
- caution in renal disease
- avoid if eGFR <30
- avoid in Px w/ gastroparesis
MoA for DPP-IVi
- target DPP4 enzymes
- competitive inhibitor
- inhibits degradation of incretin hormones
- ^ levels of GLP-1
- ^ synthesis and release of insulin
how are DPP4i administered and what are the side effects
- tablet formulation
side effects
- hypoglycaemia (min ^ risk)
- nasopharyngitis
- upper resp tract infection
- headache, nausea, peripheral oedema
- weight neutral/small weight gain
contraindications of DPP4i
- risk of heart failure esp if heart/kidney disease
- caution if renal impairment
