DM Flashcards
symptoms of preDM
what does it predispose pt to
asymptomatic
- impaired fasting blood glucose and impaired glucose tolerance -> entities of pre-DM
predispose to T2DM and CVD
which asymptomatic people should screen for DM?
what test should be done?
asymptomatic individuals age >=40yo +/- RF for DM
screen:
1. fasting blood glucose (FPG)
2. HbA1c
asymptomatic individuals with results suggestive of DM, what next?
repeat test on a subsequent day
when 2 repeated tests are available and above threshold = DM confirmed
how to prevent T2DM for pre-DM (non pharm)
healthy diet
physical activity (150mins of moderate/ 75mins vigorous)
how to prevent T2DM for pre-DM (pharm)
- when should it be started?
metformin for pre-DM
- started when glycemic control not improved despite lifestyle intervention OR unable to adopt lifestyle interventions
what is DM? symptoms?
what are the different types of DM?
DM is a metabolic disorder characterised by resistance to insulin to insufficient insulin secretion or both
- main sx: hyperglycaemia
- types: type 1, 2, gestational DM
define type I DM
absolute deficiency of pancreatic beta cells function (no insulin)
- is an autoimmune disease
- with positive antibodies
stages in T1DM, glycemia level, symptoms
- autoimmunity (positive antobodies)
stage 1: normoglycemia, presymptomatic
stage 2: dysglycemia, presymptomatic
stage 3: new onset hyperglycemia, symptomatic
when is T1DM diagnosed
-> long pre-clinical period (from children - adults)
children (very early)
adults (LADA)
- Latent autoimmune diabetes of adults
what is C-peptide? when is it absent?
is a short chain aa that is released into blood as a byproduct of formation of insulin by pancreas
- absent when there is no insulin release (permanent DM)
define T2DM
progressive loss of adequate beta-cell insulin secretion + insulin resistance
early stage: high glucose, high insulin
- insulin resistance: in presence of insulin, glucose utilisation is impaired and hepatic glucose output increased
differentiate T1 and T2 DM
T1:
- autoimmune, positive antibodies
- insulin/ c-peptide absent
- onset usually <30yo
- abrupt onset
- very thin
- prone to diabetic ketosis, diabetic ketoacidosis (emergency)
T2:
- insulin resistance, impaired secretion (later stage), negative antibodies
- insulin/ c-peptide normal/abnormal
- gradual onset
- often overweight
- uncommon for diabetic ketosis, diabetic ketoacidosis (emergency)
metabolic syndrome management
abdominal obesity (measure waist circumference)
- need to recognise early and use aggressive CV reduction
S/S of hyperglycemia
- 3Ps: polyuria, polydipsia, polyphagia
- frequent urination
- dry skin
- blurred vision
- drowsiness
- decreased healing
S/S of hypoglycemia
- shaking
- fast HR
- sweating
- dizziness
- anxoius
- hunger
- impaired vision
- headache
- irritable
parameters used to measure DM
- fasting plasma glucose (FPG)
- no intake for past 8hrs - random/casual plasma glucose
- take at any time of the day - postprandial plasma glucose (PPG)
- glucose after meals/ OGTT 75mg glucose - HbA1c: measure bld glucose over past 3 mths (FPG + PPG)
higher HbA1c range is due to …
FPG (basal hyperglycemia) -> use insulin that targets FPG
less high HbA1c is due to PPG
criteria for T2DM
- HbA1c, FPG, 2HOGTT ranges
see notes eL 2 pg 8
complications of DM
macovascular: CV
microvascular: retinoapthy, nephropathy, neuropathy
during diabetic foot screening what to advice pt
- obtain glycemic control
- encourage smokers to quit
- good footcare and appropriate wound care
diabetic nephropathy test: what is tested?
SCr and/or eGFR
AND
uACR or uPCR
-uPCR used when albumin >= 300mg/g
how often to screen for macrovascular complications (HbA1c, lipid panel, BP)
HbA1c: every 3mth, 6mth if stable
lipid panel: every 3-6mths, 1yr if stable
BP: every visit
how often to screen for macrovascular complications (eye, kidney, foot)
eye, kidney: every 6mth, yearly if stable
foot: daily by pt, annually by podiatrist
treatment goals for HbA1c
<7%
tx goals for FPG
4.0 - 7.0 mg/dL
tx goals for PPG
<10 mg/dL
for t1dm <7% glycemic control, does it improve macro and micro complications?
improve micro
macro unknown
for t2dm <7% glycemic control, does it improve macro and micro complications?
micro improve
macro U shape (decrease until a certain point then increase macrovascular death)
when to use stringent HbA1c target
Short disease duration
long life expectancy
no significant CVD
when to use less stringent HbA1c target
hx of hypoglycemia
limited life span
advanced complications
extensive comorbidities
difficult to attain despite SMBG, counselling, effective tx
MOA of metformin
- ↓ hepatic glucose production
- ↑ peripheral/muscle glucose uptake and utilization (i. e.↑ insulin sensitivity)
onset of metformin
within days; max effects take up to 2 weeks
how is metformin eliminated
renal, mostly unchaged
max dose for metformin immediate release and extended release
immediate release: 2550mg/d (850mg TDS)
- can be used in children >= 10yo
extended release: 2000mg/d
- not to be used in children
AE of metformin
- GI disturbances (D/N?V), loss of appetite,
metallic taste - decr vit B12 concentrations
- lactic acidosis
CI of metformin
- eGFR <30mL/min (stage 4 CKD, severe renal impairment)
- hypoxic states or at risk of hypoxia (increase risk of lactic acidosis (eg HF, sepsis, repi failure, liver failure, alcholism)
Sign and symptoms of lactic acidosis
nausea, vomiting, abdominal pain shallow/labored breathing, mental confusion
- see dr
metformin DDI
- alcohol
- iodinated contrast material (eg CT scan)
-> hold metformin for >= 48hrs - inhibitors of organic cationic transporters (cimetidine, dolutegravir, ranolazine) -> increase metformin by decreasing renal elimination
metformin place in therapy
- ↓ A1C by 1.5% (up to 2.0%)
- Negligible weight gain and hypoglycemia
- Possible reduction in CV events
- Prevent and delay T2DM
- Can be used for pregnant patients with T2DM
TZD MOA:
PPARgamma agonist to promote glucose uptake into the target cells (increase insulin sensitivity, decrease insulin resistance)
- no effects on insulin secretion
TZD how long to take effect?
Takes up to a month for maximal effect
elimination of tzd
liver
eg of tzd
pioglitazone
ddi of pioglitazone
CYP3A4 and CYP2C8 inhibitors or inducers
AE of TZD
- Hepatotoxicity (monitor LFT_
- Do not initiate therapy/discontinue if ALT >3x UNL - Fluid retention (caution in HF)
- Fracture
- Weight gain (dose related)
- Risk of bladder cancer (black box warning)
- Increased risk of hypoglycemia with insulin therapy
CI of TZD
- Active liver disease
- Symptomatic or history heart failure
- Active or history of bladder cancer
TZD (pioglitazone) place in therapy
- ↓ HbA1c by 0.5 to 1.4%
- beneficial in patients with Fatty Liver Disease
- CV effects: reduce stroke, increase HF
SU MOA
- block K+ channels of beta cells, stimulate insulin secretion
- ↓ hepatic glucose output and ↑ insulin sensitivity (like metformin)
- Need functional Beta cells to work!
Eg of SU and how they are cleared
tobulamide (H)
glipizide (H), glibeclamide (R), glicazide (R)
glimepiride (R)
advantage of 3rd gen SU/ glicazide MR
once daily dosing improved adherece but higher cost
AE of SU
- hypoglycemia
- weight gain
CI of SU
hypersensitivity to any SU
DDI of SU
- betablockers (mask sx of hypoglycemia)
- alcohol (disulfiram like reaction) (1 gen» 2/3 gen)
- CYP2C9 inhibitors (amiodarone, fluoxetine) may increase glimpiride, glipizide
SU place in therapy
- ↓ HbA1c by 1.5% (Require the presence of functioning β cells to work)
- watch for hypoglycemia
- exercise to reduce weight gain
- cost effective therapy
DPP4i MOA
Inhibit DPP4 enzyme and increase concentrations of endogenous incretins (decrease gastric emptying, increase insulin, decrease glucagon, makes you full)
examples of DPP4i
sitagliptin
vildagliptin
linagliptin
doing for DDP4i
sitagliptin
- 100mg OD
- eGFR 30-45 -> 50mg OD
- eGFR <30 -> 25mg OD
vildagliptin
- 50mg BD (with metformin or TZD)
- 50mg OD witth SU
- CrCl<50 -> 50mg OD
linagliptin
- 5mg OD
AE of DPP4i
- sever joint pain that can be disabling
- headache
- acute pancreatitis
- hypersensitivity reaction
- bullous pemphigoid, skin rash (use prednisolone)
DDI for DPP4i
sitagliptin: digoxin (increase DPP4i)
vildagliptin: none
linagliptin: cyp3A4 inducers (decrease DPP4i)
DPP4i place in therapy
- ↓ HbA1c by 0.5-0.8%
- Usually used as dual or triple combination therapy
- Not recommended to be used in patients with hx of acute pancreatitis
Advantages over GLP 1 agonists:
-PO, lower incidence of GI adverse events, cheaper
Disadvantages compared to GLP 1 agonists:
weight neutral, smaller HbA1c reduction, no “big 3” benefits (ASCVD, HF, CKD)
