DM Flashcards
(115 cards)
1
Q
how does the body increase blood glucose levels
A
1) absorption of glucose from GIT
2) glycogenolysis in muscle & liver
3) gluconeogenesis in liver
2
Q
how does body decrease blood glucose levels
A
1) uptake & utilisation of glucose by tissues
2) glycogen synthesis in muscle & liver
3
Q
pre-DM - general
A
- can be asymptomatic
- predispose individuals to T2DM & cardiovascular disease
4
Q
pre-DM components
A
1) impaired fasting glucose (IFT)
2) impaired glucose tolerance (IGT)
5
Q
nonpharmaco for pre DM
A
1) lifestyle intervention to prevent/delay progression
- healthy diet
- increase physical activity (150 min moderate or 75 mins vigorous)
6
Q
pharamco for pre DM
A
metformin
- only used when:
1) glycaemic status X improve despite lifestyle intervention
2) X to do lifestyle intervention esp if BMI ≥ 23 kg/m^2, younger than 60, women w history of gestational DM
7
Q
what is type 1 DM associated with
A
insufficient secretion of insulin
8
Q
pathogenesis for type 1 DM
A
absolute deficiency of pancreatic beta cell function due to immune mediated destruction or positive antibodies
9
Q
staging for type 1 DM
A
1) type 1, type 2
- +ve antibodies, asymptomatic
2) type 3
- +Ve antibodies, symptomatic
10
Q
what is type 2 DM associated with
A
body resistant to insulin
11
Q
pathogenesis for type 2 DM
A
- progressive loss of adequate beta-cell insulin secretion on the background of insulin resistance
- insulin resistance:
1) glucose utilisation impaired
2) hepatic glucose output increased
12
Q
how is the levels of insulin and glucose like at the early stage of type 2 DM
A
high levels
13
Q
Type 1 vs Type 2 DM
A
1) primary cause
- type 1: autoimmune-mediated pancreatic beta cell destruction, +ve antibodies
- type 2: insulin resistance, impaired insulin secretion, negative antibodies
2) insulin production
- type 1: absent, type 2: normal/abnormal
3) age of onset
- type 1: < 30 yo, type 2: often > 40 yo but increasing prevalent in obese children/younger adult
4) onset of clinical presentation
- type 1 abrupt, type 2 gradual
5) physical appearance
- type 1 thin, type 2 overweight
6) proneness to ketosis
- type 1 frequent, type 2 uncommon
14
Q
signs and symptoms of hyperglycaemia
A
1) polydipsia, polyuria, polyphagia
2) decreased healing, dry skin
3) drowsiness, blur vision
15
Q
signs and symptoms of hypoglycaemia
A
1) fast heartbeat, shaking
2) Sweating, dizziness
3) hungry, impaired vision
16
Q
DM measuring parameters
A
1) fasting plasma glucose (FPG)
- X calorie intake for ≥ 8 hrs
2) random/casual plasma glucose
3) postprandial plasma glucose (PPG)
- glucose level after meal, usually after 2 hrs (time taken for glucose to be stable)
- 75g oral glucose tolerance test (OGTT)
4) HbA1c
- average amt of glucose over 3 months (glucose stay attached to haemoglobin over lifespan of RBC
- 3 month average of FPG + PPG
17
Q
diagnosis of DM (MOH guidelines)
A
- 2 abnormal test results required to diagnose DM
- HbA1c values
1) ≥ 7%: X further test, confirm DM
2) 6.1% - 6.9%: take second test
** FPG values: > 7 confirm DM | 6.1 - 6.9 pre DM | < 6 no DM
** OGTT: > 11.1 confirm DM | 7.8 - 11.0 pre DM | < 7.8 no DM
3) < 6% no further test, no possibility of DM
18
Q
complications of DM
A
1) microvascular
- retinopathy, blindness
- nephropathy, kidney failure
- neuropathy, amputation
2) macrovascular
- increase cardiovascular disease
3) others
- decrease life expectancy for 5-10 yrs
19
Q
screening tests before confirming DM
A
- recommended for asymptomatic individuals ≥ 40 yo +/- risk factors
- FPG, HbA1c
20
Q
what are the 4 screening tests to do after confirming DM
A
1) Retinal fundal photography
2) urine microalbumin/creatinine ratio
3) diabetic foot screening
4) diabetic nephropathy test
21
Q
screening test after confirmed DM - retinal fundal photography
A
- test for diabetic retinopathy
- within 5 yrs of onset for adults w T1DM
- at time of diagnosis for T2DM
- every 1-2 yrs if X evidence of retinopathy & well controlled hyperglycaemia
- annual if any level of diabetic retinopathy present
- pregnant ladies w DM: before pregnant/1st trimester, followed up to 1 year after giving birth
22
Q
screening test after confirming DM - urine microalbumin/creatinine ratio
A
test for diabetic nephropathy/albuminuria
23
Q
screening test after confirming DM - diabetic foot screening
A
- reduce risk of diabetic foot ulcer
- at least once a year
- process: inspection of skin, assess foot deformities, neurological assessment, vascular assessment
- non pharmacotherapy for this (glycaemic control, quit smoking, good foot care)
24
Q
screening test after confirming DM - diabetic nephropathy test
A
- T1DM within 5 yrs of onset
- T2DM upon diagnosis
- components
1) serum Cr +/- eGFR
2) urine albumin/creatinine ratio or protein-creatinine ratio if albuminuria heavy (≥ 300mg/g)
25
monitoring cardiovascular risk factors for DM
- macrovascular
1) HbA1c: X well controlled every 3 months, controlled every 6 month
2) lipid panel: X well controlled every 3-6 month, controlled annually
3) BP: Every visit
26
treatment goals for DM - HbA1c
1) less stringent: 7.5 - 8.0%
- history of severe hypoglycaemia
- limited life expectancy
- advanced complications
- extensive comorbid conditions
- target hard to attain despite intensive SMBG, repeated counselling, effective pharmacotherapy
2) normal: < 7.0%
3) more stringent: 6.0 - 6.5%
- short disease duration
- long life expectancy
- X significant cardiovascular disease
27
target for FBG & PPG
- mmol/L X 18 = mg/dL
- FBG: 4.4 - 7.2 mmol/L
- PPG: < 10 mmol/L
28
metformin - change in lab values
- 1.5 - 2.0% reduction in HbA1c
- marked reduction FBG
- mild reduce PPG
29
metformin - non DM uses
- polycystic ovarian syndrome (POS)
- weight loss
- improve lipid levels
30
metformin formulations
- immediate release: 250, 500, 850, 1000mg
- extended release: 500, 750,1000mg (BD)
31
metformin dosing
1) immediate release
- start 500 - 850 mg OD
- titrate 500 - 850mg every 1 - 2 wks in divided doses (OD - TDS)
- max 2550mg per day
2) extended release
- 500mg OD
- increase 500mg weekly
- max 2000mg OD, can divide into 1000mg BD
32
MOA of metformin
1) primary
- lower hepatic glucose production (gluconeogenesis)
2) Secondary
- enhance tissue sensitivity to insulin
- enhance peripheral glucose uptake & utilisation
- increase AMP activated protein kinase
33
PD for metformin
- onset within days
- duration of action 8-12 hrs
- max effect 2 wks
34
metformin PK
- absorption: oral
- elimination: renal, excreted unchanged in urine
35
metformin AE
1) common: GI disturbances (V/D/indigestion), metallic taste
- transient
- take w food/increase dose gradually
- diarrhoea -> weight loss
2) long term
- increase risk of Vit B12 malabsorption -> deficiency
3) rare but fatal
- lactic acidosis (block gluconeogenesis -> prevent lactic broken down to glucose -> increase lactate concentration -> lactic acidosis)
36
metformin special population
can use for pregnant & > 10 yo
37
metformin CI
- severe renal impairment (GFR < 30ml/min, worse than stage 4)
- hypoxic state/risk of hypovolemia (HF, sepsis, respi failure, liver impairment)
38
metformin drug interactions
1) alcohol: increase risk for lactic acidosis
2) iodinated contrast material
- radiologic procedure
- temporarily withhold metformin for 48 hrs after iodinated contrast administration
- restart when renal function stable & acceptable post procedure
3) inhibitor/inducer of organic cationic transporter (OCT)
- OCT 2 inhibitor: cimetidine, dolutegravir, ranolazine
- increase metformin by reducing renal elimination
39
Thiazolidinediones (TZD) indication
1) combination to reduce HbA1c when X tolerate metformin
2) change in lab values
- 0.5-.14% reduction HbA1c
- moderate reduction FBG & PPG
3) good for fatty liver disease
4) CV effect: reduce stroke risk, increase HF risk
40
thiazolidinediones (TZD) - formulation
15, 30mg tablets
41
thiazolidinediones (TZD) - MOA
PPARgamma agonist -> promote glucose uptake into target cells (skeletal/adipose), decrease insulin resistance & increase insulin sensitivity
42
thiazolidinediones (TZD) - PDPK
- 1 month max effect
- liver elimination
43
thiazolidinediones (TZD) - adverse effect
1) hepatotox
- monitor LFT prior initiation & after
- X use if ALT > 3x ULN
- if > 1.5x ULN then repeat tests
- discontinue if sign of hepatic dysfunction
2) fluid retention (monitor HF)
3) increase fracture risk (esp women)
4) weight gain (dose-related)
5) risk of bladder cancer
6) increased risk of hypoglycaemia w insulin therapy
44
thiazolidinediones (TZD) - CI
1) acute liver disease
2) symptomatic/history of HF
3) active/history of bladder cancer
45
thiazolidinediones (TZD) - drug interaction
- coadministered w CYP inhibitor/inducer
46
sulfonylureas (SU) - change in lab values
- 1.5% reduction HbA1c
- mild reduction FBG
- marked reduction PPG
47
types of sulfonylureas (SU)
1) 1st gen: tolbutamide
2) 2nd gen: glipizide, gliclazide, glibenclamide
3) 3rd gen: glimepiride
48
sulfonylureas dosage
- OD dosage improve adherence but $$
- take immediately after meal, X miss/delay meal
- caution if irregular meal schedule
49
sulfonylureas MOA
1) primary
- bind to SU receptor proteins of ATP sensitive potassium channels -> inhibit channel mediated K+ efflux -> trigger calcium dependent exocytosis of insulin granules from pancreatic beta cells
2) Secondary
- decrease hepatic glucose output & increase insulin sensitivity
50
sulfonylureas PD
onset 30 mins, duration of action 12-24 hrs
51
sulfonylureas PK
- oral absorption
- highly plasma protein bound, t1/2 4h
- hydroxylation in liver
- < 10% excreted unchanged in urine & faeces
52
AE sulfonylureas
hypoglycaemia (Esp elderly), weight gain
53
drug interaction sulfonylureas
- BB mask signs of hyperglycaemia
- disulfiram-like reaction w alcohol (more common w 1st gen)
- CYP2C9 inhibitor increase glimepiride & glipizide
54
DPP-4i - incretin
- released after eating
- augment secretion of insulin from pancreatic beta cells in glucose-dependent manner (presence of hyperglycaemia)
55
DPP-4i change in lab values
- 0.5 - 0.8% decrease HbA1c
- mild reduction FBG
- moderate reduction PPG
56
DPP-4i types
1) sitagliptin
- eGFR < 30 -> 25 mg OD
- eGFR 30 - 45 -> 50 mg OD
2) vildagliptin
- CrCl < 50 -> 50mg daily
- CrCl >50 -> 50mg BD
3) linagliptin
- X dose adjustment
57
DPP-4i MOA
- GLP-1 make you full by
1) decrease gastric emptying
2) improve beta cell function -> increase more insulin, reduce glucagon
3) decrease food intake
- DPP-4 inactivate GLP-1 so DPP-4i extends GLP-1 action
58
DDP-4i PK
- oral absorption
- t1/2 10-12h
- low liver metabolism
- 80% unchanged urine, rest shit
59
DDP-4i AE
- severe joint pain
- skin reaction (Rash, itch)
- hypersensitivity
- flu like symptoms
- GI
- rare: acute pancreatitis, bullous pemphigod (blister on skin)
60
DDP-4i drug interaction
CYP3A4 inhibitor
61
SGLT2-i cariorenal beneift
- cana & empa
- HF & CKD
- discontinue when start dialysis
62
SGLT2-i change in lab values
- reduce HbA1c by 0.8-1%
- moderate reduction FBG
- mild reduction PPG
63
types of SGLT2-i
1) Canagliflozin
- 100, 300mg
- X initiate if eGFR < 30ml/min
2) empagliflozin
- 10, 25mg
- X initiate if eGFR < 45ml/min
3) dapagliflozin
- 5, 10 mg
- X initiate if eGFR < 45 ml/min
64
SGLT2-i MOA
- inhibit SGLT2
- reduce absorption of filtered glucose
- reduce renal threshold for glucose & increase urinary glucose excretion
65
SGLT2-i PK
1) absorption
- oral, Cmax 1-2 hr
2) distribution
- highly plasma protein bound
- t1/2 12 hr, OD
3) minimal liver metabolism (glucuronidation)
4) excreted unchanged pee/shit
66
SGLT2-i AE
1) hypotension (titrate anti HTN)
2) hypoglycaemia
3) increase urination
4) genital mycotic infection/UTI
- more for female
- check UTI/history of fungal infection in vagina
- good toilet hygiene, drink more water
5) euglycemia diabetic ketoacidosis (DKA)
- more common if undergoing severe stress (dehydrated, alcohol abuse, X eating well, poor oral intake)
- hold of SGLT2-i until recover from stress
6) fournier's gangrene
- more for males
- necrotising fascitis of perineum
- good toilet hygiene, drink more water
7) canagliflozin: lower limb amputation, hyperkalaemia, fracture
67
SGLT2-i CI
X dialysis
68
MOA of insulin - liver
1) decrease gluconeogenesis (make glucose
2) increase glycogenesis (convert to glycogen for storage)
3) decrease glycogenolysis (reduce breakdown of glycogen to glucose)
69
MOA of insulin - pancreas
increase insulin secretion
70
MOA of insulin - muscle
1) increase glucose transport
2) increase glycogenesis
3) inhibit proteolysis
71
MOA of insulin - adipocyte
1) increase glucose transport
2) increase protein synthesis
3) increase lipogenesis (make more fat cell)
4) decrease lipolysis & FFA oxidation (reduce breakdown of fat tissue)
72
metabolism of insulin
- exogenous: kidney
- endogenous: liver
73
insulin needle length
- pen needle: 4mm - 12.7mm
- syringe needle: 6mm - 12.7mm
74
insulin gauge size (needle thickness)
- 28, 29, 30, 31
- higher gauge = finer needle - lesser pain but increase needle weakness & decrease speed of injection
75
insulin syringe size
- 100 IU/ml
- 1cc: max dose 100, increment 2
- 1/2 cc: max dose 50, increment 1
- 3/10 cc: max dose 30, increment 1
76
insulin vial size
- U-100 (100 units/1mL of solution)
77
stability of insulin
1) unopened: good till expiration if store in fridge
2) opened: good for 28 days regardless of fridge
3) insulin containing device: product insert
4) detemir: opened good for 42 days
78
insulin administration sites
- outer upper arms: fatty tissue area
- abdomen: 2 inch circle around navel
- top & outer thigh: avoid bony area above knees
- rotate sites to prevent lipohypertrophy
- speed of absorption: abdomen > outer upper arm > top & outer thigh > buttock
79
factors that increase insulin absorption
1) heat
2) massage
3) exercise
4) lipoatrophy (concavity/pitting of adipose tissue)
5) IM administration
80
factors that decrease insulin absorption
1) cold
2) lipohypertrophy (bulging of adipose tissue)
81
indication for basal-prandial (basal/bolus)
- T1DM w severe insulin deficiency
- insulin deficiency - longer duration of T2DM
- tighter glucose control (coronary artery bypass grafting, gestational DM)
82
ultra short acting insulin
- added excipients to increase rate of absorption & stabilise
83
rapid acting insulin
- e.g. aspart (novorapid), lispro (humalog)
- target PPG (shjort action)
- 5 mins before meals
84
short acting/regular insulin
- e.g. actrapid
- target PPG, 30 mins before meals
85
intermediate acting insulin
- e.g. NPH (insulatard)
- target FPG, 16 hrs (inject 2x for 24 hrs coverage)
86
long acting insulin
- glargine (lantus), detemir (levemir)
- target FBG
87
what insulins cannot be mixed with others (pre/self mix)
1) glargine (incompatible pH)
2) glulisine (only can w NPH)
3) detemir
88
stable mixes for insulin
regular/rapid insulin + NPH
89
examples of compatible insulin mixtures
1) Novomix 30
- 30% short, 70% long, within 15 mins meal
2) humalog 75/25
- 25% short, 75% long, within 15 mins meal
3) humalog 50/50
- 50% short, 50% long, within 15 mins meal
4) mixtard 70/30
- 30% regular, 70% intermediate, within 30 mins meal
90
insulin + concurrent oral therapy
1) continue metformin
2) discontinue TZD or reduce dose when initiating
3) sulfonylureas
- discontinue/reduce dose by 50% when initiate basal
- discontinue if initiate prandial/premix
- effectiveness decrease over time
4) continue SGLT2-i
5) discontinue DPP-4i if initiate GLP-1
91
insulin dose conversion
- most 1:1 (basically same AM & PM doses)
- reduce by 10-20% if high risk of hypoglycaemia
- if switch from BD NPH (intermediate) -> OD glargine/detemir (long acting) -> decrease by 20%
- if switch from ultra long acting to other -> decrease by 20%
92
insulin AE
1) hypoglycaemia (BG < 4 mmol/L)
- S&S: blur vision, sweat, tremor, hunger, confuse, anxiety, shake, rapid heart beat, dizzy, headache, weakness & fatigue, irritability
- management: 15-15-15 (15g fast acting carbs, 15 mins waiting time, another 15g if still BG < 4.0 mmol/L)
2) weight gain
- dose dependent
- management: diet, exercise, lose weight
3) lipodystrophy
4) local allergic reaction
5) rare: systemic allergy, insulin resistance
93
types of GLP-1 agonist - liraglutide
- SC OD regardless of meals
- initiate 0.6 mg -> titrate 1.2 mg after 1 wk
- max 1.8 mg
94
types of GLP-1 agonist - Dulaglutide
- SC injection once weekly regardless of meals
- initiate 0.75mg -> titrate 1.5mg after 4 wks
- max 3/4.5mg
95
types of GLP-1 agonist - semaglutide (Ozempic)
- SC injection once wkly regardless of meals
- initiate 0.25 mg -> titrate to 0.5mg after 4 wks
- max 1mg
96
types of GLP-1 agonist - semaglutide (Rybelsus)
- PO OD 30 mins before first meal of day
** empty stomach (30 mins before meal, med, drink)
** X more than 120ml water
- initiate 3mg -> titrate to 7mg after 30 days
- max 14mg
97
MOA of GLP-1 agonist
- activate GLP-1 receptor (GPCR) on pancreatic beta cell -> activate adenylate cyclase -> increase cAMP -> activate PKA -> phosphorylate all downstream proteins -> increase insulin secretion & decrease glucagon release
98
what extra thing does liraglutide & semaglutide have
- C-16 fatty acid on Lys -> Delay degradation & bind to plasma protein -> longer acting
99
GLP-1 agonist PK
- endogenously metabolised in similar manner to polypeptides wo specific major route of elimination
- little/non excreted unchanged
100
AE of GLP-1 agonist
headache, N/V, acute pancreatitis, acute cholecystitis, injection site reaction
101
special precaution for GLP-1 agonist
- X pregnant
- black box warning: thyroid C-cell tumour in animals -> counsel on risk of medullary thyroid carcinoma & symptoms of thyroid cancer
102
insulin dosing
1) initiation: basal control (FPG)
- bedtime NPH 10 units or 0.2/kg/day
- bedtime/morning glargine/detemir/degludex but $$
2) still controlled
- increase insulin 2 units every 3 days until FPG at goal
- increase insulin 4 units every 3 days if FPG consistently > 10 mmol/L
- decrease insulin by 10-0% if X clear reason for hypoglycaemia
3) uncontrolled after basal dose > 0.5 units/kg (ceiling effective dose or FPG at goal)
- prandial dose (rapid/regular)
** 1 dose (4 units/10% basal) w largest meal
** reduce basal by 4 units/10% if A1c < 8%
- if bedtime NPH: split dose into 2 (2/3 morn, 1/3 evening)
103
treatment algorithm for DM from start to end
1) metformin 1st line if no CI
2) if A1c still elevated
- history of ASCVD/HD/CKD regardless of A1c
** ASCVD: GLP-1 agonist or SGLT-2i
** HF: SGLT2i
** CKD: SGLT2i then GLP-1 agonist
- other combinations
** glucose lowering: insulin, GLP-1
** minimise hypoglycaemia: avoid SU, insulin
** promote weight loss: GLP-1, SGLT-2
104
when to initiate insulin?
1) ongoing catabolism (weight loss)
2) symptoms of hyperglycaemia
3) A1c > 10%
4) BG > 16.7 mmol/L
105
diabetic emergency - how is ketones formed
- break down fats -> produce fatty acids -> travel back to liver + glucagon -> change fatty acid into ketone (beta hydroxybutyrate measured in hospital)
106
diabetic emergency - diabetic ketoacidosis (DKA)
- more for type 1
- ketones formed
- testing: blood & urine, fruity breath, acidosis
- usually still alert
- BG > 14 mmol/L
107
diabetic emergency - hyperglycaemic hyperosmolar state (HHS)
- more for type 2
- residual insulin so X ketones & acidosis
- extremely dehydrated so BG can > 33
- stupor
108
why early morning blood sugar high but bedtime low?
1) Dawn phenomenon
- release of cortisol in waking hours -> BG rise sharply
2) Somogyi effect
- BG levels drop sharply at night (X eat + meds) -> body respond by releasing glucagon -> rebound increase BG
109
differentiate Somogyi effect & Dawn phenomenon
- consistently low sugar -> somogyi effect
110
BP management for DM
- target: BP < 130/80
- 1st line: ACEi/ARB w/wo kidney disease
111
lipid management in DM - primary prevention
- X cardiovascular disease but T2DM + risk factors
- 45-70 yo: moderate intensity statin
- additional ASCVD: high intensity
- goal: reduce LDL 50% baseline, < 70 mg/dL
112
lipid management in DM - secondary prevention
- already have cardiovascular disease
- target: LDL reduction 50% from baseline, < 55 mg/dL
- ASCVD: high intensity
- if X achieved then + ezetimibe/PCSK9i
113
CKD management in DM - primary prevention
- blood glucose, BP control
114
CKD management in DM - secondary prevention
1) ACEi/ARB for micro/macroalbuminuria
2) finerenone
- non steroidal MRA
- eGFR > 25
- SE: hyperkalaemia, hypotension, lesser risk of gynaecomastia
3) SGLT-2i
- T2DM + DKD + eGFR > 20
- + ACEi/ARB
115
use of aspirin w insulin
- primary preventive measure for DM + increased CV risk + counsel on benefit vs risk of bleeding
- secondary preventive measure for DM + history of ASCVD
** use clopidogrel if allergic to aspirin
- X for > 60 yo & low ASCVD risk
