Diabetes Flashcards
Why need to have ideal blood glucose level?
For brain and cellular function (energy)
Hormones secreted by alpha and beta cells of islets of Langerhans (in the pancreas) respectively? Exocrine or endocrine function?
Glucagon; Insulin
Endocrine
effects of insulin (5)
- Lower blood glucose
- Lower blood fatty acids
- Lower blood amino acids
- Increase protein synthesis
- Increase fuel storage
which GLUTs are freely permeable to glucose at all times?
GLUT1 and GLUT3
How does adaption to metabolic demands increase glucose uptake into cells?
during exercise: insulin bind to insulin receptors on muscle cells and GLUTs like GLUT4 can increase presence on cell membrane to transport more glucose into the cell –> meet energy demand of muscle
Insulin is a (catabolic/anabolic) hormone that
1. (increase/decrease) glucose uptake into muscle cells
2. (increase/decrease) glycogenesis (storage of glucose as glycogen in liver cells)
3. (increase/decrease) gluconeogenesis
anabolic; increase; increase; decrease
hallmark signs and symptoms of hyperglycemia
3Ps
polyuria
polydipsia
polyphagia
Insulin sensitisers
metformin
thiazolidinediones (TZDs)
MOA of metformin
reduce gluconeogenesis in liver
increase glucose uptake into tissues
What can be started for pre-diabetic patients who does not respond to lifestyle intervention?
start metformin to prevent and delay onset of T2DM especially when BMI >= 23, younger than 60 and have history of gestational DM
Metformin HbA1c reduction
1.5 - 2.0%
Renal dose adjustment for metformin
eGFR 30 - 45 ml/min/1.73m2 –> half dose
eGFR < 30 –> discontinue
What constitutes hypoxic state or at risk for hypoxemia?
HF, sepsis, respiratory failure, liver impairment, alcoholism, >=80yo
ADHF due to increase risk for hypoxemia and hypoperfusion
For patient on metformin and require a radiologic procedure, what should be done?
withhold metformin for at least 48h (risk of AKI with procedure)
restart when renal function stable
Metformin is a substrate of organic cationic transporters (OCT) in proximal tubules. What drugs can possibly interact with metformin?
OCT Inhibitors: cimetidine, dolutegravir, ranolazine
HbA1c reduction in thiazolidinediones (TZD)
0.5 - 1.4%
Indication for TZD
alternative monotherapy for patients who cannot take metformin or in combination with other antidiabetic agents
contraindications to TZD
- active liver disease
- symptomatic or history of HF (NYHA class iii or iv)
- active or history of bladder cancer
First gen sulfonylurea
tolbutamide
Second gen sulfonylurea
glipizide, gliclazide, glibenclamide
(glibenclamide: risk of prolonged hypoglycemia and highly protein bound – more affected by hypoalbuminemia; used less)
Why is sulfonylureas only indicated for T2DM?
Sulfonylureas require residual beta cell function since it stimulates insulin secretion in beta cells
Sulfonylurea target
beta cell ATP-sensitive potassium channel
Why should SUs be given 15-30mins before meals? In what group of patients should be cautioned when using SUs?
MUST eat after taking SU (works by increasing insulin secretion. if dont eat, patient will be hypoglycemic)
cannot miss or delay any meal
caution in patients with irregular meal schedules (hypoglycemia risk)
Sulfonylurea HbA1c reduction
1.5%
How does hypoalbuminemia affect the PK of SU?
SUs have extensive plasma protein binding mainly to albumin (>99%)
Hypoalbuminemia will lead to increased [free drug] and have greater clearance of drug
Agents that cause weight gain?
Sulfonylurea, TZD, insulin
DPP-4i HbA1c reduction
0.5 - 0.8%
MOA of DPP-4i
binds and inhibits DPP4 enzyme > prevents degradation of incretin > stimulate pancreas to release MORE insulin
Renal adjustment for sitagliptin
eGFR 30 - 45 > half dose to 50mg OD
eGFR <30 > half dose further to 25mg OD
Common autoimmune skin reaction caused by gliptins (DPP-4i) in elderly
bullous pemphigoid
Adverse effects of gliptins (DPP-4i)
- GI disturbances
- Flu like symptoms (headache, running nose, sore throat)
- Acute pancreatitis
- Skin reactions (bullous pemphigoid)
- Use with caution in patients with history of pancreatitis (since action is on pancreatic cells)
- Severe joint pain that can be disabling (arthralgia, rare AE)
Adverse effects of sulfonylureas
- Hypoglycemia (more risk in elderly, bring sweets around)
- Weight gain (not very suitable for obese patients (2-5kg, dose-dependent))
Action of active GLP-1
- Lower gastric emptying (acting on stomach)
- Increase glucose-dependent insulin biosynthesis and secretion
- Lower glucagon
- Improved beta cell function
- Decrease food intake (acting on brain – higher satiety and eat less)
GLP-1 RA HbA1c reduction
1-2%
GLP-1 RA with CKD benefit
SC semaglutide
GLP-1 RA with ASCVD benefit
liraglutide, dulaglutide, SC semaglutide
Adverse effects of GLP-1 RA
- N/V (better when body adjusts to treatment)
- Diarrhea/constipation
- Headache/tiredness
Can GLP-1 RA be used in pregnant mothers?
No
PO semaglutide is co-formulated with absorption enhancer SNAC. What does it do?
Cause temporary and reversible local increase in pH which protects against proteolytic degradation
When should PO semaglutide be taken?
at least 30min-1h before other medications/food/drinks
MOA of SGLT2i
Inhibit sodium-glucose co-transporter-2 (SGLT2) > less reabsorption of filtered glucose > lower renal threshold for glucose > increase urinary glucose excretion
Which big 3 benefit does SGLT2i have?
ASCVD, HF, CKD (all 3)
SGLT2i HbA1c reduction
0.8 - 1.0%
Why is SGLT2i not indicated for T1DM?
Risk of DKA, further exacerbated in T1DM
eGFR cut offs for dapagliflozin and empagliflozin initiation for cardiorenal benefit
Dapa: eGFR < 25
Empa: eGFR < 20
Discontinue SGLT2i when for cardiorenal benefit?
Start of dialysis
Discontinue SGLT2i when for glycemic control?
eGFR persistently < 45
Adverse effects of SGLT2i
- UTI (glucosuria)
- Increase urination
- Hypotension, hypoglycemia, increase LDL
- Renal impairment – initially within 2 weeks, but long term is supposed renoprotective
- Female genital mycotic (fungal) infection (glucosuria)
- Fournier’s gangrene
- Euglycemia DKA
- N/D/V
When is alpha-glucosidase inhibitor most effective?
When taken with large carbohydrate meal
Top reason for discontinuation of alpha-glucosidase inhibitor?
Flatulence
alpha-glucosidase inhibitor HbA1c reduction
0.5 - 0.8%
Tirzepatide (dual GLP-1/GIP RA) HbA1c reduction
2 - 2.4%
Antidiabetic agents with weight loss benefits
Metformin, GLP-1 RA, SGLT2i
Diabetes screening recommended for:
Individuals >=40 and/or risk factors for diabetes
To diagnose pre-diabetes, what are the test ranges for
HbA1c
FPG
2hOGTT
HbA1c: 6.1 - 6.9%
FPG: 6.1 - 6.9 mmol/L
2hOGTT: 7.8 - 11.0 mmol/L
If a patient presents with HbA1c of 6.4%, what FPG & 2hOGTT level should he have to diagnose diabetes?
FPG => 7.0 mmol/L
2hOGTT => 11.1 mmol/L
Mr Tan sees the doctor for annual health screening. His HbA1c is 6.8%. He took a further test (2hOGTT) and his 2hOGTT results was 10.8 mmol/L.
What is his diagnosis?
Pre-diabetes
Frequency of diabetic foot screening, kidney panel, retinal funal photography
At least once a year. More frequent for higher risk
Jane has T2DM and she wants to get pregnant in the next few months. What should she do with regards to her screening for retinopathy?
Do eye exam before getting pregnant or during first trimester and closely following during and after pregnancy up to 1 year
Frequency of HbA1c screening
Every 3 months; every 6 months if stable
Frequency of lipid panel
every 3-6months if uncontrolled.
Annually if controlled
Frequency of BP screening
Every visit
Insulin HbA1c reduction
up to 2.5%
Route of elimination of insulin?
Exogenous insulin: mainly by kidneys
Endogenous insulin: mainly by liver
Common gauge sizes
31 and 32
Stability of unopened insulin and opened insulin
Unopened insulin: good until expiration if refrigerated, if not refrigerated: 4 weeks
Opened insulin: 4 weeks regardless of refrigeration
Rapid acting insulin
Aspart, lispro, glulisine
Short acting insulin
Regular insulin (Actrapid)
Intermediate acting insulin
NPH (BD dosing)
Long acting insulin
glargine, detemir
Ultra long acting insulin
Degludec, U-300 glargine
Stable mixes of insulin
NPH + regular
NPH + rapid acting (aspart, lispro, glulisine)
rapid acting + rapid acting insulin with protamine (becomes intermediate acting)
What oral therapeutics to stop/continue when injectable therapy is started?
Stop dose: TZD (or reduce; risk of hypogly), SU (or reduce when basal started; stop when premix or prandial insulin start), DPP-4i (when GLP-1 RA initiated)
Continue: Metformin, SGLT2i
How to convert when switching from BD NPH to OD glargine/detemir
Decrease by 20%
Conversion from U-300 glargine to other basal insulin
decrease by 20%
Basal initiation of insulin
Bedtime NPH 10u
OR
0.1-0.2units/kg/day basal insulin
How to titrate basal insulin to hit FPG goal?
o Increase insulin 2u every 3 days until FPG goal
o May increase 4u every 3 days if FPG constantly >10mmol/L
o Decrease by 10-20% if no clear reason for hypoglycemia
o Target range 5.0-7.0mmol/L
How to intensify therapy after hitting basal dose > 0.5units/kg OR FPG already at goal?
Add prandial coverage (1 dose with largest meal - 4u or 10% of basal whichever is lower)
if A1c < 8% then decrease basal dose by 4u or 10%
IF on bedtime NPH: consider splitting dose into 2 dose (2/3 AM and 1/3 PM)
How does DKA happen?
Result from absolute/relative insulin deficiency
Insulin inhibits lipolysis but insulin deficiency = stimulate lipolysis > increase circulating levels of free fatty acids > increase oxidation to ketone bodies in liver (strong acids) > DKA
How does HHS happen? (hyperglycemic hyperosmolar state)
Stress: Stimulates insulin counter-regulatory hormones (glucagon, catecholamines, glucocorticoids, growth hormone) when v sick > hyperglycemia
Also increases gluconeogenesis, lower peripheral insulin sensitivity and lead to hyperglycemia
How to check if patient’s high FPG is due to Somogyi effect?
Check BG levels at 2-3am to confirm.
Cut down on antidiabetic meds especially @ night
(BG levels drop sharply at night then feedback mechanism kicks in to bump up BG levels)
If patient has history of ASCVD, HF, CKD, what agents should he be put on to reduce cardiorenal risk?
ASCVD: SGLT2i or GLP-1 RA
HF: SGLT2i
CKD: SGLT2i > GLP-1 RA
When to consider insulin instead of GLP-1 RA?
- Ongoing catabolism (weight loss, muscle wasting, appearing cachexic)
- Symptoms of hyperglycemia (3Ps)
- A1c > 10%
- BG > 16.7mmol/L
(no area for weight loss and need for glucose lowering)
Recommended blood pressure? and the benefits (2)?
130/80mmHg
1. reduce CVD mortality
2. slow CKD progression
First line agents for diabetic patients with hypertension
ACEi/ARBs because it’s renoprotective!
Secondary prevention for lipids for diabetic patients with ASCVD
High intensity statin therapy
Atorvastatin 40mg (avoiding 80mg bc risk of rhabdomyolysis)
OR
Rosuvastatin 20-40mg
LDL cholesterol goals for secondary prevention of ASCVD (lipid management)
LDL reduction of 50% from baseline or LDL goal 1.4mmol/L, whichever is lower
Primary prevention for lipids for ______y/o and agents indicated
40-75y/o
Moderate intensity statin therapy:
atorvastatin 10-20mg
rosuvastatin 5-10mg
simvastatin 20-40mg
etc
High intensity if additional ASCVD factors
Target LDL for primary prevention of ASCVD (Lipid management)
LDL reduction of 50% from baseline or LDL goal 1.8mmol/L, whichever is lower
ASCVD risk factors
LDL >2.6, high BP, smoking, CKD, albuminuria, family hx of premature ASCVD
Secondary prevention of diabetic patients with ASCVD (Antiplatelet therapy)
Aspirin
Clopidogrel if allergic to aspirin
Primary prevention of ASCVD in what group of patients?
Patients >50 years and with at least 1 additional major risk factors (after discussion with patient)
ACEi/ARB recommended for what kidney condition?
Micro- and macroalbuminuria
Primary prevention for CKD:
Blood glucose control
Blood pressure control
Target glucose variability in ambulatory glucose profile
lower than or equal to 36%
Target proportion of time in range (3.9-10mmol/L)
70% to achieve A1c of 7.0%
What else can be added on to optimise lipids after statin therapy is insufficient to hit LDL goal?
Ezetimibe or PCSK9i (repatha, alirocumab, inclisiran)
Benefits of ACEi/ARBs, SGLT2i and finerenone in terms of cardiorenal risk?
Reduce kidney disease progression and reduce CV events
GM is a 59 year old female here for follow up evaluation of her diabetes. She also has a history of hypertension and dyslipidemia, currently controlled. She states her diet and exercise habits are healthy. Her labs and vitals are within normal limits except:
A1c 8.6% (goal <7.5%)
Weight 89 kg (BMI 34 kg/m2)
Current medications: metformin 1g BD, canagliflozin 300 mg OM, lisinopril 10 mg OM, atorvastatin 20 mg OM
Which treatment options would likely have the greatest therapeutic benefits for this patient?
Initiating GLP-1 RA
* weight loss benefits (GM is overweight with BMI > 30)
* uncontrolled A1c
* insulin cause weight gain > not preferred
A patient with type 2 diabetes has adopted several lifestyle changes. He has lost 7 kg in the past 3 months. All lab work, vital signs, and physical examination findings are normal except for mild nonproliferative retinopathy and chronic kidney disease (eGFR consistently between 35 and 50 mL/min/1.73 m2 for the past year) with albuminuria. The patient’s A1C today is 6.2%. The patient’s current treatment regimen includes metformin 500 mg BD with meals, lisinopril 40 mg daily, rosuvastatin 20 mg daily.
Which of the following medication changes should be recommended today?
Start dapagliflozin
Discontinue metformin
Discontinue lisinopril
Increase metformin
Start dapagliflozin > cardiorenal benefits
* keep metformin since eGFR > 30 and A1c is okay
* keep lisinopril because ACEi have cardiorenal benefits
