Diabetes Flashcards
What are the signs and symptoms of Hyperglycemia?
- Polydipsia (extreme thirst)
- Polyphagia (extreme hunger)
- Polyuria (frequent urination)
- Dry skin
- Blurry vision
- Decrease wound healing
- Drowsiness
What are the signs and symptoms of Hypoglycemia?
- Sweating
- Shaking
- Anxious
- Irritability
- Fast heartbeat
- Dizziness
- Hunger
- Fatigue and weakness
- Headache
- Impaired vision
What is the difference between T1DM and T2DM
Type 1 DM:
- Absolute deficiency of pancreatic B-cell function
- Positive antibodies
- Autoimmune
- C peptides absent
- Usually <30 years
- Highly prone to diabetic ketosis
Type 2 DM:
- Insulin resistance with progressive loss of adequate B-cell insulin secretion
- No antibodies
- Often overweight
- C peptides present or abnormal
- usually >40 years
Parameters used to measure glucose and their treatment goals for DM
FPG (after 8hrs of no calorie intake): 5 – 7 mmol/L
PPG (after 2hours of meal): ≤10 mmol/L
HbA1c (avg amount of glucose in the blood over past 3 months): ≤7% (7.5 – 8% in more vulnerable patient population)
Criteria for the diagnosis of T2DM
- HbA1c ≥7%
- HbA1c 6.1 – 6.9% + FPG ≥7.0mmol/L or PPG ≥11.1mmol/L
Criteria for the diagnosis of pre-diabetes
HbA1c 6.1 – 6.9% + FPG 6.1 – 6.9mmol/L or PPG 7.8-11.0mmol/L
When to rule out diabetes
- HbA1c ≤6%
- HbA1c 6.1 – 6.9% + FPG ≤6mmol/L or PPG <7.8mmol/L
What are the 3 microvascular complications of DM?
- Retinopathy
- Nephropathy
- Neuropathy
When is a less stringent hbA1c target used (7.5 – 8%)?
- Hx of hypoglycemia
- Limited life expectancy
- Advanced complications
- Extensive comorbid conditions
- Target is difficult to attain despite effective pharmacotherapy
Monitoring parameters in T2DM and frequency
- HbA1c: Every 3 months; 6 months if stable
- Lipid panel: Every 3-6 months; annually if stable
- BP: Every visit
- Eye exam: Every 6 months; annually if stable
- Albuminuria/ Renal panel: 6 month - yearly if stable depending on presence of albuminuria
- Foot exam: Daily by individual; yearly by podiatrist
Non-pharmacologic therapy for diabetes
- Smoking cessation
- Weight loss (>7% loss of initial body weight)
- Exercise (150mins per week spread over 3 days or more; strength training for 2 days to be included; and in older (>55yo) patients, balancing and functional training to be incorporated too
- Diet modification (green leafy vegetables, lean meat, low-fat dairy product
- Restrict alcohol consumption and simple carbohydrates (reduce TG)
List all the affordable therapeutics for diabetes
- Biguanide – metformin
- Sulfonylureas (SUs)
- Thiazolidinediones (TZDs) – Pioglitazone, Rosiglitazone
- Alpha-glucosidase inhibitors – Acarbose
MOA of metformin
- Decrease hepatic glucose output and production (Inhibit gluconeogenesis in liver)
- Increase insulin sensitivity –> increase intracellular glucose uptake into periphery or muscles
Side effects associated with metformin use
- Lactic acidosis (Black Box Warning; Rare)
- Anorexia
- Metallic taste
- GI disturbances
- Vitamin B12 deficiency –> lead to megaloblastic anemia
C/I to metformin
- Renal insufficiency
- Hypoxic state (eg. Heart failure, hypoperfusion, sepsis, liver impairment)
DDI with metformin
- Ethanol (increased risk of lactic acidosis)
- Iodinated contrast media (renal toxicity –> restart metformin after renal function normalize)
- Cationic drugs (eg. digoxin, cimetidine) –> may compete with metformin for renal excretion
Renal dose adjustment of metformin
eGFR ≥60: OK. Monitor renal function yearly.
eGFR 45-60: OK but monitor renal panel every 3-6 months
eGFR 30-45: Half-dose; do not start metformin in new patients. Monitor every 3 months.
eGFR <30: Stop metformin (c/i)
What other benefits does metformin have?
- Positive effect on lipid profile (TG, cholesterol, LDL)
- Weight loss (negligible weight gain)
Prevention/ delay of T2DM in pre-diabetic patients
- Lifestyle modifications (diet, exercise, weight loss, smoking cessation)
- metformin therapy (for obese [BMI ≥35], those age <60yo, women with prior gestational DM)
MOA of Glipizide
- Stimulate insulin secretion by inhibiting K+ channel in functional B-cell of the pancreas
- Increase insulin sensitivity
- Decrease hepatic output of glucose
Administration of glipizide
Take 15-30mins before food
Which SUs can be used in renal impairment
Glipizide, Tolbutamide
Which SUs are renally excreted?
Gliclazide, Glibenclamide, Glimepiride (hepatic > renal)
DDI of SUs
- Beta-blockers (mask hypoglycemic symptoms)
- Ethanol (disulfiram-like reaction; more common in 1st gen)
- CYP2C9 inhibitors (eg. amiodarone, 5FU, fluoxetine) –> may increase Glimepiride and glipizide concentrations)
What is the special requirement for SUs to work?
Functioning Beta-cells in pancreas
MOA of Pioglitazone
- Increase intracellular glucose uptake into target cells (peroxisome proliferation activated receptors agonist)
- Decrease insulin resistance
- Increase insulin sensitivity
ADR associated with TZDs
- Increase risk of congestive HF (NYHA group I and II)
- Hepatotoxicity (stop if ALT >3x ULN or signs of hepatic dysfunction)
- Bone fracture
- Edema
- Weight gain
- Bladder cancer (pioglitazone)
- Elevated LDL (Rosiglitazone)
Contraindication of TZDs
- NYHA class III and IV heart failure
- Acute liver disease
MOA of Acarbose
- Delay glucose absorption and decrease PPG by competitively inhibiting brush borders alpha-glucosidase enzymes required for the breakdown of complex carbohydrates
- Acts locally
Most prominent ADR of acarbose
Flatulence
other GI ADRs include diarrhea, abdominal pain
Contraindications of acarbose
- Breastfeeding
- GI impairment
What class of drug is liraglutide?
GLP-1 agonist
What is liraglutide MOA?
- Delay gastric emptying
- Increase insulin secretion (activates GLP-1 receptors –> increase adenylate cyclase –> increase cAMP -> increase PKA –> increase insulin secretion)
- Decrease glucagon release
- Reduce appetite
- Improve beta-cells function
ADR of liraglutide
- Acute pancreatitis
- GI disturbances (N/V/D)
What is the Black Box Warning for liraglutide?
Thyroid C cell tumour
Additional benefits of GLP-1 agonist?
- Weight loss
- Improve ASCVD
- Improve CKD (minimal benefits)
Examples of DPP-4 inhibitors?
- Sitagliptin
- Linagliptin
MOA of DPP-4 inhibitors
Decrease enzymatic degradation of endogenous GLP-1
Renal dose adjustment of Sitagliptin
Half-dose when CrCl ≥30 but <50 mL/min
ADR associated with Sitagliptin
- Acute pancreatitis (caution with use in patients with Hx of pancreatitis)
- Heart attack
- GI disturbances
- Abdominal pain
- Skin reaction
- Angioedema
- Flu-like symptoms
Warnings and precautions with DPP-4 inhibitors use
- Severe joint pain that can be disabling
- Acute pancreatitis with use of Sitagliptin
MOA of SGLT2i
- Decrease renal reabsorption of filtered glucose
- Decrease renal threshold for glucose –> increase urinary glucose excretion
Renal dose adjustments for SGLT2i agents
Canagliflozin: Stop if eGFR <30ml/min; but continue if albuminuria >300mg/dL
Empagliflozin and dapagliflozin: Stop if GFR <45ml/mion
ADR of SGLT2i
- Hypotension
- Hypoglycemia
- Renal impairment
- Increase LDL
- Urinary urgency
- UTI
- Genital mycotic infection
- Increased risk for euglycemic diabetic ketoacidosis
Contraindications of SGLT2i
- End stage renal failure
- Dialysis
Guidelines for SGLT2i use
As long as eGFR ≥30ml/min, it is safe to initiate SGLT2i and keep using once initiated
Additional benefits of SGLT2i
- Slgith weight loss
- HF
- ASCVD
- CKD
MOA of insulin
- Increase intracellular uptake of glucose
- inhibit hepatic glucose output (inhibit gluconeogenesis and glycogenolysis)
- Enhance lipogenesis
- Inhibit lypolysis
- Increase protein synthesis
- inhibit proteolysis
When do you need to inject the insulin needle at 45 degrees?
- Frail elderly
- Cachexic patients
- Childrens
Factors that increases absorption of insulin
- Heat
- Massage
- Exercise
- jet injection
- Lipoatrophy (when bovine or porcine insulin is used too much)
- IM administration
How does lipohypertrophy happen and what are the consequences?
When you never rotate the site of injection when injecting the lower abdomen
Lipohypertrophy leads to decreased absorption
Benefits of using ultra-short acting insulin
Can be administered with meal or 20mins after starting a meal
What are the modifications done to ultra-short acting insulin?
Insulin aspart (Fiasp): 2 excipients added (Vitamin B3 to increase speed of absorption and L-arginine to stabilize formulation
Insulin lispro aabc (Lyumjev): 2 excipients added (Treprostinil to enhance absorption via vasodilation and Citrate to increase vascular permeability)
List the 3 rapid acting insulin
- Aspart
- Lispro
- Glulisine
How would you counsel a patient taking rapid-acting insulin?
Take 15mins before each meal
List the 2 ultra-long acting insulin
- Glargine U-300
- Degludec
How would you counsel a patient taking long-acting insulin
Take once a day at the same time everyday
Which insulins are compatible when mixed together?
- Regular + NPH
- Rapid acting + NPH
- Aspart + Degludec
Which insulins are incompatible with each other?
- Glulisine + any other insulin (except NPH)
- Long-acting insulin (Glargine/ Detemir) + any other insulin
What is Novomix a mix of?
Aspart + NPH
What is Humalog a mix of?
Lispro + NPH
What is mixtard a mix of?
Regular + NPH
Insulin dose conversion from NPH to long-acting?
Reduce total NPH daily dose by 20% –> that will be the new dose of the long-acting
Management of hypoglycemia associated with insulin use?
15-15-15 rule
- 15g of fast acting carbohydrate
- Wait 15 mins
- Check blood glucose if it is still <4 mmol/L, give another. 15g fast-acting carbohydrate
When will insulin be considered?
Despite being on pharmacotherapy:
1. Ongoing catabolism (weight loss)
2. Symptoms of hyperglycemia
3. HbA1c >10%
4. FPG >16.7mmol./L
Insulin dosing?
- Start FPG insulin first (NPH or long-acting) at a dose of <10IU at bedtime (usually 0.1 IU/kg)
- If HbA1c and FPG is still uncontrolled (FPG goal: 5-7mmol/L) after 3 consecutive days of monitoring via SMBG, increase basal insulin dose by 2IU every 3 days (or 4IU if FPG >10mmol/L)
- If HbA1c is still above goal despite FPG insulin dose already at >0.5IU/kg or FPG at goal: Add PPG coverage one dose with largest meal of the day (or if on bedtime NPH, consider splitting dose into 2 doses –> 2/3 in the morning and 1/3 in the night)
- Dose of PPG insulin is 4IU or 10% of the FPG insulin dose (whichever is lower); if HbA1c is ≤8%, decrease FPG insulin dose by 4IU or 10% as well
Diabetic ketoacidosis (DKA) vs Hyperglycemic hyperosmolar state (HHS)
DKA:
1. Affects type 1 DM patients
2. Ketones can be found in blood and urine
3. Fruity breath and odour
4. patient is still alert
5. FPG >14mmol/L
HHS:
1. Affects type 2 DM patients (residual insulin left)
2. No ketones
3. Usually extremely dehydrated (FPG >33mmol/L
4. usually stupor
