Diabetes (IC12-14) + 11(DM) Flashcards
what are the values we must test for pre-diabetes?
impaired fasting glucose
impaired glucose tolerance
what are the lifestyle recommendations for ppl at risk of pre-DM
1) healthy lifestyle
- ≥ 150 minutes of moderate-intensity exercise or ≥75 min of vigorous- intensity exercise.
- healthy diet
2) metformin
- if unable to receive lifestyle modifications
- if not able to achieve glycaemic control despite healthy lifestyle
who are the patients at risk of pre-DM and should receive lifestyle modifications
if
BMI > 23
gestational women
<60 years old
what are the types of DM
t1dm
t2dm
gestational (50% might develop in the long term)
infection
drugs (hiv, steroids, immunosuppressants, etc)
endocrinopathy or pancreas destruction (no insulin production)
monogenic diabetes syndrome
profile of t1dm
t1dm = pancreatic b cell destruction
autoimmune disease
presence of autoantibodies:
- GAD65, tyrosine phosphotases (IA-2, IA2B), islet cell autoantiboides, ZnT8
typically manifest early on <30 years old and is abrupt
gradual loss of b cell mass (measured with C-protein levels) before a brief period of remission that ultimately leads to no b cell left.
individuals are often slim due to low or no sugar intake.
ketosis is more frequent as the body breaks down fats .
what is the LADA subtype of T1DM
late onset diabetes in adults
usually no need for glycaemic control in the first 6 months
similar characteristics to t1 and 2dm
profile of t2dm
progressive b cell loss with background of insulin resistance
c protein should still be normal to abnormal and insulin production should remain.
onset is later and gradual
patients are typically obese and ketosis is rare.
DM screening parameters and when to screen? (what to screen for and when to screen)
high risk factors or more than 40 years old
HbA1C and FPG
2 tests over consecutive days to confirm diagnosis
what are the glucose monitoring tests?
HbA1C = avg glucose for 3 months
FPG = after 8h of caloric intake
PPG = post pandrial, taken 2hours after food, or done with OGTT (75g oral glucose tolerance test)
what is the glucose monitoring regimen?
test HBA1C first
less than 6%c = low probability of glucose = maintain lifestyle control and diet and retest after 3 years
6.1-6.9% = test for FPG or OGTT (ALSO requires 2 confirmed tests) =
- FPG <6, OGTT<7.8 mmol/L = low probability
- FPG 6.1-6.9, OGTT 7.8-11 = pre DM
- FPG >7, OGTT >11.1 = DM confirmed
> 7 = DM confirmed
what are the complications of diabetes? include the screenings required for each
microvascular
1) retinopathy
Diabetic retinal photography (DRP)
- taken within 5 years for T1 and on diagnosis if T2
- if no complications (after ≥1 tests/glycemia controlled) = test every 1-2 years
- if complications = test at least annually (6 MONTHS)
2) nephropathy
- taken within 5 years for T1 and on diagnosis if T2
- 2 test types:
(a) = eGFR or SCr
normal SCr = 0.7 to 1.3 mg/dL (61.9 to 114.9 µmol/L) for men and 0.6 to 1.1 mg/dL (53 to 97.2 µmol/L) for women; eGFR > 60mL/min)
(b) = uACR or UPCr (<0.2mg/mg)
- albuminurea (normal levels= <30ug/mg or <3.3mg/mM)
- microalbuminuria (30-299 or 3.4-33.9)
- macro (>300, >33.9)
- test every 6 months oR annually depending on presence.
3) neuropathy
- DFS (annual by podiatrist, daily by patient)
- encourage patients to maintain foot care, quit smoking, optimal glycaemic control
MACRO
4) CVS
- no correlation between CVS mortality and HBA1C control (appears to fall initially before increasing again)
what other labs to check for DM
lipid panel, BP
lipid = every 3-6 mth if not controlled, annually if controlled
BP = every visitw
what is the target FPG and HBA1C for DM?
FPG = 5-7mmol/L
HBA1C =
(1) 6-6.5 if
- long life expectancy, no sig CVD, short disease duration
(2) 7.5-8
- hx of severe hypo, short life exp, advanced complications, extensive comorbidities, not responsive to treatment (and lifestyle mods)
Biguanides
indication and moa
Indication: Monotherapy with diet and exercise OR in combination with other agents/insulin for T2DM
- Off label: polycystic ovarian syndrome (PCOS).
MOA:
Primary: decrease hepatic glucose production (inhibits gluconeogenesis in liver = increase AMP-activated protein kinase)
Secondary: increase peripheral/muscle glucose uptake and utilization (increase insulin sensitivity)
Biguanides
(Dosages and administration)
Metformin IR
250mg 500mg 850mg 1000mg
Start with 500-850mg OD
Increase by 500-850mg OD every 1-2 weeks in divided doses.
Max dose 2500 – 2550 mg OD.
Metformin XR
500mg 750mg 1000mg
Start with 500mg OD
Increase by 500mg weekly.
Max dose 2000mg OD. May divide dose to 1000mg BD if glycaemic control not achieved with OD dosing.
If dose >2000mg needed, switch to IR
Biguanides
PD PK
PD
Onset within days max 2 weeks
PK
A: Oral, F 40-60%, DOA: 8-12h
D: Rapidly distributed, minimal plasma protein binding. T1/2 3h
M: NA
E: Renal elimination, 90% in urine unchanged.
Biguanides
ADR
Common:
GI disturbances (diarrhoea, N/V, indigestion), anorexia, loss of appetite, metallic taste.
Usually transient and to take with food and increase dose regularly to minimise GI disturbance.
Long term:
May decrease serum B12.
Consider periodic measurement esp in those with anemia, peripheral neuropathy, or symptoms such as numbness, tingling.
Rare but fatal:
Lactic acidosis (3/100,000 patients/year)
Symptoms – N/V, abdominal pain, shallow/labored breathing, mental confusion.
Biguanides
Contra
DDI
Contraindications
Severe renal impairment (GFR <30ml/min)
Hypoxic states/hypoxia risk (increased risk of lactic acidosis)
E.g.,
HF (avoid use in acute decompensated heart failure), sepsis, respiratory failure, liver impairment, alcoholism, ≥80 yo
DDI
EtOH/alcohol:
Increase risk of lactic acidosis.
Iodinated contrast material (for radiologic procedures e.g., x-rays, CT scan):
Temporarily withhold metformin for ≥48 hours after administration. Restart when renal function is stable and acceptable post procedure.
(Metformin may accumulate)
Organic cationic transporters (OCT) inhibitors/inducers e.g., cimetidine, dolutegravir, ranolazine):
May increase metformin by decreasing its renal elimination.
Biguanides
Special population
May be considered for pregnancy patients with T2DM (low risk)
Require renal dose adjustment.
Metformin IR suitable for children ≥10 years; metformin XR not suitable for children.
Biguanides
Comments
Decreases A1c by 1.5%.
Negligible weight gain and hypoglycaemia.
- Good for obese patients (loss of appetite) and elderly patients (low risk of hypoglycaemia)
Possible reduction in CV with T2DM.
Prevent and delay T2DM.
OK for pregnancy.
thiazolidinediones
MOA
Peroxisome proliferator activated receptor gamma ( PPARgamma ) agonist to promote
glucose uptake into target cells (skeletal muscle/adipose tissue)
- ↓insulin resistance; ↑ increase insulin sensitivity
- No effects on insulin secretion
thiazolidinediones
(Drug Dosage Administration PD PK
Pioglitazone 15mg , 30mg (tablet)
Start with 15mg or 30mg OD
Increase dose by 15mg
Max 45mg OD
PD
Up to one month for max effect
PK
Liver elimination
thiazolidinediones
(ADR)
Hepatotoxicity
Monitor LFT prior to initiation and periodically thereafter.
Do not initiate therapy/discontinue if ALT > 3xUNL.
If ALT > 1.5xULN during therapy, repeat LFT weekly until normal.
Discontinue if s/sx of hepatic dysfunction regardless of ALT level.
Fluid retention
Caution use in NYHA Class I and II HF
Monitor s/sx of HF after initiation/dose adjustment.
Monitor weight gain from fluid retention.
Fracture (increased risk, esp women)
Risk of bladder cancer
Increased risk of hypoglycaemia with insulin therapy.
thiazolidinediones
(Contraindications DDI Special population )
Contraindications
Active liver disease
Symptomatic or history of HF (esp class III to IV)
Active/history of bladder cancer.
DDI
CYP3A4 AND CYP2C8 inhibitors and inducers
thiazolidinediones
(comments)
Decreases A1c by 0.4 - 1.4%.
Appears beneficial to patients with fatty liver disease (NAFLD and NASH)
CV effects
Potential reduction in risk of stroke
Increase risk of HF
Progression of diabetes kidney disease (neutral)
has some weight gain effects
sulfonylureas
MOA
Primary: stimulate insulin secretion by blocking K+ channel of b-cells in pancreas islets (NEED BETA CELLS TO WORK).
- Targets the b-cell ATP-sensitive potassium (K ATP) channel, which controls the b-cell membrane potential.
- Binds to the SU receptor protein subunits of the K ATP channel inhibits K ATP channel mediated K+ efflux depolarisation opens voltage gated Ca channel trigger calcium dependent exocytosis of insulin granules from b-cells.
Secondary: decrease hepatic glucose output and increase insulin sensitivity.
glipizide
(Drug Dosage Administration PD PK )
Glipizide
5mg 10mg (tablet)
5 mg BD (max dose 40mg/day)
Onset 12-24 hours
Inactive metabolite
A: F>95%
Onset: 1/2h
DOA: 12-24h
D: Binds extensively (99%) to plasma proteins (primarily albumin)
T1/2 4h
M: Hepatic 90%, hydroxylation
E: <10% excreted unchanged in urine + faeces. metabolites are excreted in urine + faeces.
sulfonylureas
ADR
Hypoglycaemia
Use with caution in patients with irregular meal schedules.
Use with caution in elderly patients as more likely to have kidney failure titrate dose.
Weight gain (appx 2-5kg)
Exercise to minimise weight gain.
sulfonylureas
Contraindications DDI
Contraindications
Hypersx due to SUs
DDI
Betablockers
May mask the signs and symptoms of hypoglycaemia.
EtOH/alcohol
Disulfiram-like reactions
(1st gen»> 2nd/3rd gen)
Flushing, tremors. Usually, 1-2 glasses a day is okay, however if patient drinks a lot, to avoid dosing.
CYP2C9 inhibitors e.g., amiodarone, 5FU, fluoxetine)
sulfonylurea comments
Decreases A1c by 1.5%.
No apparent benefits other than blood glucose lowering.
Take 15-30min before meal.
Glipizide has lowest risk of hypoglycaemia compared to other SUs.
Glipizide and tolbutamide recommended for renal impairment, however still need to watch for kidney function in glipizide as overdose can cause hypoglycaemia.
vitagliptin special population instructions
Hepatic dose adjustment:
CrCL ≥50ml/min: 50mg BD CrCL <50ml/min: 50mg daily
Use with caution if ≥75 years old.
linagliptin special population + DDI
DDI
CYP3A4 inducers
Decreases linagliptin concentration.
Special populations
No renal or hepatic dose adjustment
