How to differentiate between type 1 and 2 DM?
Type 1: genetics - inability to produce insulin by beta cells in pancreas (+ve antibodies, immune mediated destruction)
Type 2: lifestyle - insulin resistance (impaired glucose utilisation, increased hepatic glucose output)
What are the agents in DM?
- Biguanides - metformin
- Thiazolidinedione - pioglitizone
- Sulfonylurea - Glipizide, gliclazide, glibenclamide
- DPP4i - sitagliptin, vildagliptin, linagliptin
- SGLT2i - canagliflozin(ASCVD), empagliflozin (HF), dapagliflozin(for CKD/HF)
- Alpha-glucosidase inhibitors (x mono)- Acarbose,
- Insulin if HbA1c<10%
- GLP1 receptor agonists - semaglutide SC/PO, liraglutide, dulaglutide
What is the max dose for insulin?
0.5u/kg
What is the starting dose for insulin?
10u/day or 0.1-0.2u/kg/day
SE of metformin
- GI upset - NV
- metallic taste
- Loss of appetite
- B12 deficiency
MOA of antidiabetics
- Metformin: dec hep glucose production, increase glucose cell intake, increase insulin sensitivity
- Sulfonylurea: block k channels for increased secretion of insulin from beta cells, decr hep glucose o/p and incr insulin sensitivity
- Thiazolidinedione: peroxisome proliferator-activated receptor gamma (PPARgamma) agonist to promote glucose uptake into adipose/skeletal muscle)
- DPP4i: inhibit DPP4 enz and increase [endogenous incretin]
- SGLT2i: inhibit SGLT2 for increased renal glucose excretion thus decr. blood glucose
- Alpha-glucosidase inhibitors: delay glucose absorption and decr. PPG by competitively inhibiting brush border Alpha-glucosidase enz for breakdown of complex carbs
- Insulin: regulate carb(glycogenolysis + gluconeogenesis), fat (lipogenesis + lipolysis and free FA oxidation) and aa (incr. synthesis and inhibit proteolysis in muscle) + increase endo insulin secretion
- GLP1 Receptor Agonists: acts like endo GLP1 and binds to beta cell receptors, decreasing gastric emptying, increase glucose dependent insulin biosynthesis and secretion, dec glucagon, improves b cell fx and dec food intake
Comments for insulin
- SE: Lipohypertrophy - rotate site of administration
Lipoatrophy - use of pork/beef insulin - Unopened in fridge - until expiry,
Unopened not fridge - 28d
Opened in fridge or not - 28d - 90 deg angle (45 for frail/children)
What to continue/discontinue when start insulin
- Metformin- continue
- Thialidinedione - stop
- Sulfonylurea- discontinue/reduce dose
- SGLT2i- continue
- DPP4i - discontinue if GLP1 agonist initiated
When to decrease dose?
- Intermediate (NPH) to long acting insulin (glargine/detemir) decr. by 20%
- U-300 glargine to otrs –> decr 20%
FG is a 65 year old female who has been on insulin Mixtard 30.
She injects 30 units twice daily. As FG is getting older in age, her
physician wants to switch her to Glargine and Aspart to reduce the
risk of hypoglycemia. FG is able to afford the new medications. Her
current HbA1c hovers around 8%. How do we dose her new insulin
regimen?
Glargine = 70% x 60units × 80%= 33.6(34)units
Aspart = 30% x 60units = 18units
Aspart per meal = 18 /3 = 6u
ADR of insulin
- Hypoglycemia: tremors, shivering, blurry vision, sweating, hunger, confusion, anxiety, rapid HR, dizziness, headache, weakness, fatigue, irritability
Nocturnal: nightmarse, restless sleep, profuse sweating, morning headache - Weight gain = more than SU
- Lipodystrophy
- Local allergic rxn, systematic allergic rxn, insulin resistance
How to titrate insulin?
If a1c uncontrolled, continue to act on FBG:
- increase 2u every 3d until goal FPG
- may inc 4u/3d if FPG consistently >10mmol/L
- decr. 10-20% if no clear reason for hypoglycemia
If A1c still above goal despite basal dose > 0.5 units/kg OR FPG at goal
1. Add prandial coverage (either rapid/regular insulin)
- 1 dose with largest meal
- 4 units or 10% of basal
- If A1c < 8%, to also decrease
basal dose by 4 units or 10%
2. If on bedtime NPH, split dose into two: 2/3 am, 1/3 night
Target range for FPG?
5-7.0mmol/L
Possible add ons for ASCVD, HF, CKD, weight loss, hypoglycemia
ASCVD: GLP1agonist/SGLT2i
HF: SGLT2i
CKD: SGLT2i > GLP1agonist
Weight loss: SGLT2i, GLP1agonist
Hypoglycemia(elderly): avoid SU, insulin
When to add insulin:
- Addition of GLP1agonist not rch goal
- Weight loss
- Hyperglycemia sx (polyuria, polydipsia, polyphagia)
- A1c >10%
- BG >16.7mmol/L
What is the dawn phenomenon/somogyi effect?
Dawn phenomenon - release of
cortisol in the waking hours
causes BG levels to rise sharply
pooia
Somogyi effect (2am glucos alw low) - BG levels drop
sharping at night (miss bedtime
snack/ too much insulin, etc),
body responds by releasing
glucagon, BG level increase –> reduce night dose
Diabetic emergencies for t1dm and t2dm
T1DM: Diabetic ketoacidosis(DKA): ketones formed - fruity breath, acidosis, still alert but BG<14
T2DM: hyperglycemic hyperosmolar state(HHS): no ketones due to residual insulin, leading to extreme dehydration and BG>33mmol/L –> STUPOR/COMA
