Flashcards in Type 2 Diabetes Deck (81):
What age range do T2DM patients present?
Middle age +
What is the BMI range in T2DM patients?
What history of autoimmune disease do T2DM patients have?
No history usually
Is there family history link with T2DM?
Yes, often have FHx
What will ketones appear as on T2DM urinalysis?
0 to +
Is HbA1c helpful at presentation?
What are the glucose levels at presentation?
How does T2DM present acutely?
Hyperglycaemic Hyperosmolar Syndrome
What are the C-peptide levels at presentation?
Are C-peptides present at 5 years post diagnosis?
Do T2DM patients present with complications? If so, how many?
What is the definition of T2DM?
Insulin resistance with relative insulin deficiency
How can obesity cause insulin resistance?
Obesity + lack of activity
Adiposity (inc FFAs, inc Adipokines)
How can obesity lead to relative insulin deficiency?
Obesisty + lack of activity
Adiposity (inc FFAs, inc Adipokines)
Vulnerable beta cells (genetics) can't respond and produce more insulin
How do normal beta cells respond to obesity?
Compensatory increase in insulin production
Why is T2DM a progressive disease?
Beta cells deteriorate
No change in insulin sensitivity
What symptoms do T2DM patients present with?
What is the typical underlying cause of HHS?
T2DM treated with diet only
What can trigger HHS?
CVS event (MI/Stroke)
High refined sugar intake
What is the aetiology in HHS?
If young then non white
What can precipitate HHS and why?
Stress hormone release
(eg glucagon -> inc blood sugar)
What is the median glucose in HHS?
What will renal function be in HHS?
How is Na+ affected in HHS?
How is osmolality affected in HHS? To what value? Why?
Hyperglycaemia/Hypernatraemia (ie concentrated blood)
What are the biochemical differences in HHS and DKA?
HHS is less ketonaemic/acidotic
How do you treat HHS compared to DKA? Why?
Fluids: more slowly in HHS(risk cerebral oedema)
Insulin: more slowly in HHS (more sensitive)
Na+: avoid rapid fluctuations (0.45%saline maybe)
LMWH for all unless contraindicated
What conditions are associated with insulin resistance syndrome?
How is metabolic syndrome defined?
Insulin resistance syndrome OR T2DM
With 2+ :
Dislipidaemia (TG>1.7, HDL<1.0)
What are the aims of treatment in diabetes?
Manage hyperglycaemia symptoms
Improve glycaemic control
Minimise weight gain
Help with weight loss
Reduce Micro/Macro complications
What is the first line treatment of T2DM?
What of drug is metformin?
What is the action of metformin?
Reduces hepatic gluconeogenesis by stimulating AMPK
Increasing glucose uptake and utilization in skeletal muscle
Insulin signalling increased
Reduces CHO absorption
Increased fatty acid oxidation
What effect does metformin have on:
c) micro/macro complications
d) Lipid profile
a) lowers HbA1c by lowering insulin resistance
b) reduces weight
c) prevents Micro/Macro complications
d) reduces TG and LDL
Why is metformin used in pregnancy?
Safe in gestational diabetes
What effect does metformin have on hyper/hypoglycaemia?
What are the adverse effects of metformin?
GI symptoms: nausea, vomiting, abdo pain, diarrhoea, taste disturbance.
How do you try and prevent GI effects with metformin?
Start low, go slow
What are the risk factors for lactic acidosis when using metformin?
high pre-existing risk
MI, HF etc
Why do you have to measure eGFR with metformin?
Risk of renal toxicity
What changes in metformin dose have to be made with a) eGFR 30-45
b) eGFR < 30?
a) half dose
b) stop meds
What is the second line treatment in T2DM?
What kind of drugs are SUs?
Give an example of 1st generation SUs
Give examples of 2nd generation SUs
Glibemclamide (aka Glyburide)
Why are 2nd generation SUs used more frequently?
When are sulphonylureas used?
intolerant to metformin
add on to metformin
What is the action of SUs?
Bind to SUR1 sub unit
close kATP channel
beta cell depolarisation
Why is it important that SUs act independently of plasma glucose?
can cause insulin to be released even with normal-low glucose levels
What effect do sulphonylureas have on:
b) micro/macro complications
a) reduces HbA1c by inc insulin secretion
b) reduces MICRO complications only
c) weight gain
What are the adverse effects of SUs?
Can cause hypos
Does not prevent MACRO complications
Blood dyscrasias (rare)
Liver dysfunction (rare)
When would SUs be 1st line?
Underweight T2DM patients
What groups of patients should care be taken with SUs?
What is the aim of Thiazolodinediones in T2DM?
Increase action of insulin at target sites
What is the action of mechanism in TZDs?
Allows transcription of GLUT4, lipoprotein lipase and fatty acid transport protein
Increased fatty acid storage
Reduced hepatic gluconeogenesis
How does PPARy act?
binds with RXR
PPARy-RXR = transcription factor
How do TZDs effect:
a) reduces HbA1c by inc insulin sensitivity
b) Reduces hyper/ no hypos
What are the adverse effects of TZDs?
Does not prevent micro/macro complications
Increased bone fractures
Why do you get weight gain with TZDs?
Subcutaneous fat and fluid retention
Why do you get fluid retention with TZDs?
Na+ reabsorption in the kidney
What patients should you be aware of when perscribing TZDs?
Fluid retention could worsen HF
What contraindications are there for TZDs?
patients over 65
Give examples of TZDs
Why is pioglitazone the only licensed TZD?
Rosiglitazone causes MI
Troglitazone causes liver failure
What are incretins derived from?
intestinal secretion of insulin
What is GLP-1 and where is it secreted?
Glucagon like peptide
secreted from L cells in ileum and colon
What is GIP and where is it secreted from?
Glucose dependent Insulinotropic peptide
K cells in jejunum/duodenum
What action do GIP and GLP-1 carry out on pancreas and what is the effect?
increase insulin production
increase glucose uptake in skeletal muscle
Decrease blood glucose
What action do GLP-1 have on alpha cells?
Decreases glucagon release
reduces glucose release
decreased blood glucose
What enzyme terminates action of GLP-1 dnd GIP?
Dipeptidyl peptidase 4 (DPP4)
What are incretin analogues?
What are the effects of incretin analogues?
Promote insulin secretion
Increases weight loss
What are the adverse effects of incretin analogues?
nausea (resolves in 6-8weeks)
What are examples of incretin analogues? What are their modes of administration? what are their half lives?
Exendin LAR-once weekly
Liraglutide-OD-subcut injection-10-14hrs (DPP4 resistant)
Lixisenatide-OD- subcut injection
What is the action of DPP4 inhibitors?
inhibit action of DPP4
prolongs action of GLP1 and GIP
What are examples of DPP4 inhibitors?
What are the effects of DPP4 inhibitors?
Promotes insulin secretion (reduces HbA1c)
What are the adverse effects of DPP4 inhibitors?
Not very potent
No weight loss
What is the action of SGLT2 inhibitors?
prevent glucose re-absorption in proximal tubule
Reduce blood glucose
What are the effects of SGLT2 inhibitors?