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diabetes Flashcards

1
Q

What is pre-DM? Why is it impt to screen for pre-DM?

A

Asymptomatic, but can lead to T2DM and CVD

Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)

Very impt to screen for pre-DM as many with impaired glucose tolerance and without lifestyle changes progress to T2DM

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2
Q

Who is recommended to go for screening for DM?

A

Recommended for aged >40 years old with or without risk factors for diabetes

18-39 years old can consider Diabetes Risk Assessment Tool (DRAT)

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3
Q

Screen what? What can the results tell you?

A

Screen for fasting plasma glucose (FPG) and HbA1c

If results are suggestive of DM —> Repeat test on subsequent day —> If results still above diagnosis thresholds, DM is diagnosed

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4
Q

How to prevent or delay progression to T2DM? (Lifestyle interventions)

A
  1. Healthy diet
  2. Increase physical activity
    —– At least 150mins of moderate intensity exercise (brisk walking, leisure cycling) or 75mins of vigorous intensity exercise (jogging, fast-paced cycling, swimming) every week
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5
Q

How to prevent or delay progression to T2DM? (Pharmacology)

A

Metformin
—– When glycaemic status not improved despite lifestyle changes OR unable to adopt lifestyle interventions
—– Esp for those with BMI >23kg/m2, <60 years old , women with past gestational diabetes (aka diabetes during pregnancy which is normally temporary)

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6
Q

What is DM?

A

A metabolic disorder (not an illness) characterised by resistance to action of insulin or/and insufficient insulin secretion

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7
Q

What are the Clinical manifestations of DM?

A

Hyperglycemia which is when Blood sugar >10mmol

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8
Q

What are the Classifications of DM?

A

Type 1 and 2 can overlap, where the other type of DM can happen over time

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9
Q

What is Type 1 DM?

A

Insufficient secretion of insulin

Autoimmune disease where immune system mistakenly attacks and destroys beta cells, leading to an absolute deficiency of insulin

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10
Q

How to diagnose Type 1 DM?

A

Conduct blood test for positive antibodies to confirm diagnosis

  1. Islet cell autoantibodies (ICA)
  2. Autoantibodies to GAD (GAD65)
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11
Q

What are the stages of Type 1 DM?

A

All stages autoimmunity have Positive antibodies

Stage 1: Normoglycemia (Normal range) —- More commonly diagnosed in children
Stage 2: Dysglycemia (Abnormal range)
Stage 3: Hyperglycemia —- only stage that is symptomatic

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12
Q

What is Type 2 DM?

A
  1. Progressive loss of adequate insulin secretion by beta cells due to insulin resistance
    ——- Impaired glucose utilisation so muscle uptakes lesser glucose
    ——- Increased hepatic glucose output: Liver releases more than needed glucose from storage
  2. Simultaneous elevations in both:
    ——- Glucose (no mechanism to remove glucose —> Hyperglycemia) and hence
    ——- Blood insulin levels (stimulated by high glucose levels —> Hyperinsulinemia) at early stage
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13
Q

What are the differences between Type 1 and 2 DM? (primary cause)

A

Type 1 (5-10%): Secretion problem
Autoimmune-mediated pancreatic beta cell destruction

Positive antibodies

Type 2 (90%): Resistance problem
Insulin resistance —> Impaired insulin secretion over time (similar to Type 1)

Negative antibodies

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14
Q

What are the differences between Type 1 and 2 DM? (insulin production as measured by C-peptide level)

A

Type 1 (5-10%): Secretion problem
Absent

Type 2 (90%): Resistance problem
Normal initially and abnormal at later stage

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15
Q

What are the differences between Type 1 and 2 DM? (age of onset)

A

Type 1 (5-10%): Secretion problem
<30 years old: Due to genetic disposition

Type 2 (90%): Resistance problem
>40 years old, but increasingly prevalent in obese children and younger adults

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16
Q

What are the differences between Type 1 and 2 DM? (onset of clinical presentation)

A

Type 1 (5-10%): Secretion problem
Abrupt (cause no insulin at all)

Type 2 (90%): Resistance problem
Gradual (still have some insulin)

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17
Q

What are the differences between Type 1 and 2 DM? (physical appearance)

A

Type 1 (5-10%): Secretion problem
Thin (cause pass a lot of sugar out in urine)
- without insulin, body cannot effectively use glucose for energy, leading to a state of chronic hyperglycemia. In an attempt to compensate for the lack of energy from glucose, the body breaks down fat and muscle for energy, resulting in weight loss

Type 2 (90%): Resistance problem
Overweight
- insulin resistance and the associated elevated insulin levels can contribute to weight gain.

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18
Q

What are the differences between Type 1 and 2 DM? (Proneness to ketosis (diabetic ketoacidosis; compensate lack of glucose in cells so break down fats which produce ketones))

A

Type 1 (5-10%): Secretion problem
Frequent!!! SAD

Type 2 (90%): Resistance problem
Rare

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19
Q

What are the Signs and symptoms of Hyperglycemia DM?

A
  • High blood glucose
  • Causes: Too much food, too little insulin or diabetes medicine, illness, stress
  • Onset: Gradual, may progress to diabetic coma
  • S/s
    • Polydipsia (Extreme thirst)
    • Polyuria (Increase urination)
    • Polyphagia (Increase appetite)
    • Decrease healing (too much sugar in blood impairs immune system)
    • Dry skin (cause dehydrated) <—> Itchy skin
    • Blurred vision
    • Drowsiness
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20
Q

What are the Signs and symptoms of Hypoglycemia DM?

A

(more life-threatening)

  • Low blood glucose
  • Causes: Too little food, too much insulin or diabetes medicine, extra activity
  • Onset: Sudden, may progress to insulin shock
  • S/s
    • Shaking, tremor
    • Fast heartbeat
    • Sweating
    • Dizziness
    • Hungry
    • Blurry vision
    • Fatigue
    • Moody
    • Headache
    • Confusion
    • Nocturnal: Nightmares, restless sleep
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21
Q

What is defined as hypoglycemia? How to manage hypoglycemia?

A

Defined as Blood glucose <4mmol/L (70mg/dL)

15-15-15 rule
- Only applies to diabetic patients, for healthy patients is ok to have 3.7mmol/L BG
- 15g of fast acting carbs —> wait 15mins —> if still <4mmol/L then eat another 15g of fast acting carbs
- Fast-acting carbs or glucose tablets/gel

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22
Q

What are the 4 Measuring parameters to diagnose T2DM?

A
  1. Fasting plasma glucose (FPG)
  2. Random or casual plasma glucose
  3. Postprandial plasma glucose (PPG)
  4. Hemoglobin A1c (HbA1c or A1c)
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23
Q

What to take note of when using Fasting plasma glucose (FPG) to diagnose T2DM?

A

prior to measuring, ensure NO calorie intake for at least 8h

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24
Q

What to take note of when using Random or casual plasma glucose to diagnose T2DM?

A

can measure Any time of the day, regardless of meals

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25
Q

What to take note of when using Postprandial plasma glucose (PPG) to diagnose T2DM?

A

measure After meal (usually 2h): 2h postprandial glucose
- Because after 2h, level tends to be more stable

But since every meal consist of diff amounts of glucose —> can use a standardised 75g oral glucose tolerance test (OGTT) aka drink same amount of glucose to test each time

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26
Q

What to take note of when using Hemoglobin A1c (HbA1c or A1c) to diagnose T2DM?

A

Most common

HbA1c = 3 months average of (FPG + PPG)

  1. Basal (fasting; FPG) and postprandial (after meal; PPG) contribute to overall hyperglycemia
  2. Basal hyperglycemia is more important contributor at high HbA1c since constant high blood sugar are more concerning than spikes post eating

Measures average amount of glucose in blood over past 3 months
- Because glucose stays attached to hemoglobin for lifespan of RBC ~120days

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27
Q

What are the limitations of using Hemoglobin A1c (HbA1c or A1c) to diagnose T2DM?

A

Dependent on RBC
- Low RBC due to bleeding or menses —> Obv lower HbA1c
- High RBC where RBC dont turnover and last >120days —> Obv higher HbA1c

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28
Q

What is the Criteria to diagnose T2DM? Memorise cut off values!!!!

A

Asians tend to have higher HbA1c compared to caucasian, so dont follow American guidelines

Do screening for high risk of DM or age >40 years old

By MOH
1. HbA1c >7% —> No further test needed —> DM diagnosis

  1. HbA1c <6% —> No further tests if no symptoms —> No DM
    - If have symptoms, do FPG or 2hOGTT
  2. HbA1c between 6.1% - 6.9% —> FPG or OGTT
    - FPG >7mmol/L or 2hOGTT >11.1mmol/L —> DM diagnosis
    - FPG 6.1-6.9mmol/L or 2hOGTT 7.8-11mmol/L —> pre-DM diagnosis
    - If not, no DM
  3. If want to do via FPG or OGTT, need to have at least 2 abnormal results to confirm diagnosis of DM
    - Normal FPG is 5-7mmol/L
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29
Q

What are the complications for T2DM? (Macrovascular)

A

Reduce life expectancy by 5-10 years

  1. Increase CVD by 2-4 times (heart attack, stroke, artery clot at peripheral arteries in extremities)
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30
Q

What are the complications for T2DM? (Microvascular)

A

Reduce life expectancy by 5-10 years

  1. Neuropathy (Nerve damage to cause pain, numbness, tingling in extremities)
    • Severe cases: Amputation (majority toes, then foot, then lower and upper limb)
  2. Nephropathy —> Kidney failure
    • Due to albumin in urine (albuminuria)
    • Glucose are bigger molecules compared to urine, so cause kidney filter to create bigger holes which allow proteins like albumin to leak into urine
  3. Retinopathy (sugar enter eyeball and feed vessels and cause eye to swell —> burst blood vessels) —> Blindness
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31
Q

What to take note for this Screening tests for diabetic patients? (Microvascular- Retinopathy)

A

Retinopathy: Retinal fundal photography

  1. Test for diabetic retinopathy
  2. Initial dilated and comprehensive eye examination
    - Adults with type 1 DM: Within 5 years after DM onset
    - Indivs with type 2 DM: Upon DM diagnosis
  3. Every 6 months, but annually if no evidence of any retinopathy
  4. Women with DM have eye exam before pregnancy or during first trimester of pregnancy AND closely monitored during pregnancy and up to one year after giving birth
    - Because pregnancy can cause diabetic retinopathy to develop or worsen
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32
Q

What to take note for this Screening tests for diabetic patients? (Microvascular- Nephropathy)

A

Nephropathy: Urine microalbumin/ creatinine ratio

  1. Test for diabetic albuminuria/ nephropathy
  2. Every 6 months but annually if controlled
  3. Start screening after initial 5 years after T1DM diagnosis, and upon T2DM diagnosis

Methods of testing: 1 + 2 OR 3
1. Serum Cr and/or eGFR
——–If kidney not good, lower eGFR (filter blood slowly) and hence higher Serum Cr (lesser filtered out of blood)

  1. Urine Albumin/Creatinine ratio (uACR)
    ——–Check for presence of albumin
    —If kidney not good, more albumin may pass through into urine
    ——–If albuminuria is heavy, do uPCR instead
    —Abnormal albumin levels >30ug/mg
  2. Protein-Creatinine Ratio (uPCR)
    ——–When proteinuria levels are significant
    ——–Measures ALL types of urinary protein, not just albumin
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33
Q

What to take note for this Screening tests for diabetic patients? (Microvascular- Neuropathy)

A

Diabetic foot screening

  1. Reduce risk of foot ulcers
  2. Monitor everyday by patient
  3. Annual foot assessment by podiatrist if controlled, more frequent if have higher risk of foot ulcers
    - Inspect skin, assess foot deformities, neurological assessment, vascular assessment (include pulses in legs and feet)
  4. Advise
    - Maintain optimal glycaemic control
    - Stop smoking as smoking elevates lower extremity amputations risk
    - Good foot care and appropriate footwear
    - Daily monitoring of feet
    - Apply simple first aid for small wounds
    - Seek medical help if wound not healing or worsens
    - Moisturise regularly
    - Maintain good foot care and hygiene
    - Wear well-fitting and covered footwear
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34
Q

What to take note for this Screening tests for diabetic patients? (Macrovascular- HbA1c)

A

Every 3 months, but every 6 months if controlled

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35
Q

What to take note for this Screening tests for diabetic patients? (Macrovascular- Metabolic syndrome/ CVS: Lipid panel)

A
  • Every 3-6 months, but annually if controlled
  • If not controlled then start on statins
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36
Q

What to take note for this Screening tests for diabetic patients? (Macrovascular- Metabolic syndrome/ CVS: BP)

A
  • Every visit
  • If not controlled then start on anti-hypertensive drugs
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37
Q

What are the treatment goals for DM? (HbA1c (%))

A

Comparison with Non-DM: <5.7%

<7%
- Shows good stats on delaying microvascular outcomes (not sm on macrovascular)

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38
Q

What are the treatment goals for DM? (FPG (mmol/L or mg/dL))

A

Comparison with Non-DM: <5.6 or 100

4-7 or 72-126
- If less than 4, is hypoglycemia

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39
Q

What are the treatment goals for DM? (PPG (mmol/L or mg/dL))

A

Comparison with Non-DM: <7.8 or 140

<10 or 180

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40
Q

What is the general goal for diabetic patients?

A

General goal: <7%

More stringent of 6-6.5% if patient has:
- Short disease duration
- Younger; Long life expectancy
- No significant CVD

Less stringent of 7.5-8% if patient has:
- History of severe hypoglycemia
- Limited life expectancy
- Advanced complications
- Extensive comorbid conditions
- Target difficult to attain despite intensive self-monitoring blood glucose (SMBG), repeated counsellings, effective pharmacotherapy

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41
Q

what is the first line agent for dm type 2?

A

Metformin

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42
Q

when to do combi therapy for dm type 2?

A

if A1c still above goal (after first line agent)

  1. Glucose lowering efficacy: Insulin, certain GLP-1, Combi therapy
  2. Minimise hypoglycemia (eg. elderly): Avoid SU, Insulin
  3. Promote weight loss: GLP-1, SGLT-2
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43
Q

what meds to consider if have Hx of ASCVD, HF, CKD?

A

consider independently of A1c to add (but note costly)
- ASCVD: GLP-1 agonist, or SGLT-2
- HF: SGLT-2
- CKD: SGLT-2 > GLP-1 agonist

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44
Q

since GLP-1 agonist is preferred over insulin when possible (altho super costly), when to consider insulin then?

A

Consider insulin if have glucose toxicity
- Significant weight loss (since insulin can cause weight gain)
- Symptoms of hyperglycemia (3 Ps)
- A1c > 10% (means poorly controlled diabetes in which insulin can quickly and effectively bring down)
- BG > 16.7 mmol/L (likewise explanation as A1c)

GLP-1 agonist associated with weight loss or weight neutrality
GLP-1 agonist also have lower risk in causing hypoglycemia than insulin meaning insulin in a way is “more effective” in bringing down BG faster

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45
Q

how to counsel if dm type 2 patients rly dw injectables?

A

If die die dw injectables, counsel patients that even with multiple oral agents, may not be effective as pancreas working capabilities is very poor, might even aggravate pancreas and destroy pancreas further and faster —> Can eventually convert back to oral after using injectables if results improve

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46
Q

what happen if A1c still bad after adding basal insulin?

A

consider adding prandial insulin (eg. aspart 4units or 10% of basal insulin) for biggest meal —> Rmb to dose reduce basal insulin (eg. glargine) when adding on prandial insulin to make up the maximum of 0.5u/kg/day

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47
Q

what happen if A1c still bad after adding on oral agents, basal and prandial insulin?

A

consider full basal-bolus regimen (basal and prandial insulin with each meal) or BD pre-mixed insulin regimen

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48
Q

what are the meds that act on the gastro intestinal tract?

A
  1. Incretins
  2. Alpha-glucosidase inhibitors
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49
Q

what are the meds that act on the pancreas that INCREASE insulin secretion?

A
  1. Incretins
  2. Sulfonyureas
  3. Meglitinides
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50
Q

what are the meds that act on the pancreas that DECREASE insulin secretion?

A
  1. Incretins
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51
Q

what are the meds that act on the brain?

A

Appetite control: Feel full

  1. Incretins
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52
Q

how do drugs affect the kidney?

A

Drugs decrease Glucose reabsorption —> Increase urination of sugar

note: Different from how excess glucose (diabetes) overwhelms kidneys’ ability to reabsorb —> Glucose spill into urine

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53
Q

how do drugs affect the muscles and fats?

A

Drugs Increase insulin sensitivity

(i) Increase utilization of glucose by muscle cells
(ii) Storage of excess glucose by adipocytes via lipogenesis (carbs and proteins —> triglycerides)

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54
Q

what are the oral glucose lowering agents?

A
  1. biguanides: metformin
  2. thiazolidinediones (TZDs)
  3. Sulfonylureas (SUs)
  4. Meglitinides (fyi yay)
  5. DPP-4 Inhibitors
  6. SGLT-2 Inhibitors
  7. Alpha-Glucosidase Inhibitors
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55
Q

what is metformin used for?

A

First line, unless have contraindications (Not to be used if have kidney failure, use sulfonylureas instead)

Mono or in combi therapy

Indications
- Off-label use for polycystic ovarian syndrome (PCOS)
- High potency: Decreases HbA1C by 1.5% (up to 2%)
- Does not cause weight gain and hypoglycemia
- Possible reduction in CVD
- Prevent and delay T2DM

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56
Q

metformin CANNOT be used for…

A
  1. Not to be used if have kidney failure, use sulfonylureas instead
    • Severe renal impairement (Stage 4 CKD: GFR <30ml/min)
  2. Hypoxic (low O2) states or at risk for hypoxemia —> Increase risk of lactic acidosis when cells search for alternative energy production through anaerobic metabolism
    • Due to heart failure, sepsis, respiratory failure, liver impairement, alcoholism, >80 years old
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57
Q

metformin is safe for…

A
  1. Reco for preggos (insulin also)
    • Prescribed for gestational diabetes
  2. Safe for children >10 years old (only for immediate release… prof fkn unclear in her teaching)
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58
Q

how does metformin work?

A

Primary: Decrease hepatic glucose production

Secondary: Increase insulin sensitivity by increasing peripheral/ muscle glucose uptake and utilisation

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59
Q

is metformin renally eliminated?

A

YES! so may need to dose adj for pts with renal impairment

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60
Q

is metformin taken orally? is the onset fast?

A

Oral tablet

Onset: V fast as within days, max effects take up to 2 weeks

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61
Q

what are the two dosage forms of metformin?

A
  1. Immediate release
  2. Extended release (over 24h): cannot crush tablet
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62
Q

what are the dosage amts available for 1. Immediate release and 2. Extended release?

A
  1. Immediate release: 250mg, 500mg, 850mg (more common), 1000mg
  2. Extended release: 500mg (more common), 750mg, 1000mg
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63
Q

how are 1. Immediate release and 2. Extended release administered?

A
  1. Immediate release: Max daily dose is 2550mg (wont be effective beyond this dose)
    Max dose:
    TDS: 850mg
    BD: 850mg x2 during bigger meal, 850mg x1 during the other meal
  2. Extended release: Max daily dose: 2000mg
    >1000mg: Divide into two doses, 500mg x2 tablets in the morning, 500mg x2 tablets in the evening
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64
Q

whats the adr of metformin?

A
  1. GI disturbances (diarrhoea, n/v), loss of appetite, metallic taste
    • So start at lowest possible dose —> 250mg BD, but in hospital normally 500mg BD (cos dh 250mg) —> Every week titrate up to the desired outcome
    • Take after food to reduce GI side effects
    • Usually transient (temporary)
  2. Long term use may decrease serum B12 conc
    • So monitor B12 levels when there are numbness/ tingling in sensations in hands and legs —> B12 supplements
  3. Rare but fatal: Lactic acidosis
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65
Q

what are the ddi for metformin?

A
  1. Alcohol: Increase risk for lactic acidosis
    • If really need, give lower dose to curb the blood sugar levels
  2. Iodinated contrast material (Iodine dye used in CT scans
    • Iodine dye may cause worsening of renal function, and metformin is eliminated by kidney —> later metformin accumulate and cause toxicity
    • Temporarily withhold metformin for >48h after iodine admin, restart when renal function is stable and acceptable post-procedure
  3. Inhibitors of organic cationic transporters (OCT)
    • HIV meds (cimetidine, dolutegravir, ranolazine) —> Inhibit clearance of metformin
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66
Q

what is Thiazolidinediones used for?

A
  • Alternative monotherapy if intolerant to metformin
  • Combi therapy (more common)
  • High potency: Decrease HbA1c by 0.5-1.4%
  • Reduce fats in liver, so good for fatty liver disease (NAFLD, NASH)
  • Reduce stroke (but increase risk of heart failure)
  • No benefits to kidney

Not enough info if can give preggos

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67
Q

how does Thiazolidinediones work?

A
  • Increases insulin sensitivity
  • Acts on peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist to promote glucose uptake into muscles and fats
  • No effects on insulin secretion
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68
Q

does Thiazolidinediones work SLOW?

A

yes… :( Takes up to a month for maximal effect

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69
Q

how is Thiazolidinediones eliminated? isit the same as metformin?

A

nope, Eliminated via liver (so not used in liver failure patients)

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70
Q

what is the one type of dosing for Thiazolidinediones?

A

Pioglitazone: 15, 30mg (tablet), max dose is 45mg

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71
Q

whats the ddi for Thiazolidinediones?

A

DDI with CYP enzymes inhibitors/ inducers

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72
Q

what are the adr for Thiazolidinediones?

A
  1. Hepatotoxicity
    • So check liver function test prior to initiation and periodically thereafter if start
    • Dont start if ALT>3x UNL
    • Weekly monitor if ALT>x1.5UNL until normal
  2. Fluid retention
    • Legs and hands become puffy
    • Also a symptom of heart failure, so monitor for s/sx of heart failure
  3. Fracture
    • Higher risk in women
    • Non-spinal!!
  4. Weight gain
    • Likely due to fluid retention
    • Dose related
  5. Blackbox warning: Increased risk of bladder cancer
  6. Increased risk of hypoglycaemia with insulin therapy
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73
Q

when should you not take Thiazolidinediones? (active or past)

A
  • Liver disease
  • Heart failure
  • Bladder cancer
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74
Q

what is Sulfonylureas used for?

A

Mono or in combi therapy

Can be used in renally impaired patients because not renally cleared

note: Require WORKING beta cells

  • Very potent: Decrease HbA1c by 1.5%
  • No other good outcomes apart from lowering blood glucose levels
  • Exercise to minimise weight gain
  • Cost effective cos subsidised by government
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75
Q

what are the 3 gens of Sulfonylureas?

A

1st gen: Shortest duration of action, need take most frequently

2nd gen
- Glipizide
- Gliclazide MR: Taken OD

3rd gen: Can take once daily (but higher cost)
- Glimepride

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76
Q

how does Sulfonylureas work?

A

Primary: Cause pancreas to release more insulin by blocking K+ channel (so need working beta cell, if not just give insulin directly)

Secondary: Decrease hepatic glucose output (to low extent) and increase insulin sensitivity

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76
Q

what is Sulfonylureas not safe for?

A

Not recommended for preggos, use metformin and insulin instead

Hypersensitivity to SUs

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77
Q

what are the adr for Sulfonylureas?

A
  1. Hypoglycemia (esp in elderly)
    • If nv eat sufficiently and drug too effective
  2. Weight gain
    • Not good for obese patients —> Exercise!!
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78
Q

when should you not take Sulfonylureas?

A

Beta blockers slow down HR —> Mask s/sx hypoglycemia (Palpitations, anxiety)

Disulfiram-like reactions (flushing, tremors) with alcohol esp with 1st gen
- But can still drink but wayyy lesser
- 2nd and 3rd gen preferred

CYP2C9 inhibitors which may increase potency

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79
Q

how to take Sulfonylureas?

A

Must be taken immediately before meals, do not miss or delay any meal
- Want to coincide with the spike —> Helps reduce risk of hypoglycaemia
- Use with caution if have irregularities in meal schedules

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80
Q

is DPP-4 Inhibitors popular like the rest?

A

Not very popular compared to the rest

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81
Q

what normally happens upon eating in relation to GLP-1 hormones? what happens to such hormones after eating?

A

Upon eating, stomach linings will release GLP-1 hormones to make you feel full to reduce food intake AND release insulin to work on glucose AND reduce glucagon AND helps intestine to slow mobility to feel full

  • Life span of GLP-1 is v short, only a few mins
  • DPP-4 enzyme rapidly degrades GLP-1 to inactive form
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82
Q

how does DPP-4 Inhibitors work?

A

DPP-4 inhibitors help to prevent the breakdown of GLP-1 to lengthen the effects of GLP-1

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83
Q

what are the 3 diff types of DPP-4 Inhibitors?

A
  1. Sitagliptin (Subsidised)
  2. Vildagliptin
  3. Linagliptin
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84
Q

what are the doses for the following DPP-4 inhibitors?

A
  1. Sitagliptin (Subsidised): 100mg OD
  2. Vildagliptin:
    50mg BD (with Met or TZD) or OD (with SU)
  3. Linagliptin; 5mg OD
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85
Q

what are the dose adjustments for the following DPP-4 inhibitors?

A
  1. Sitagliptin (Subsidised):
    eGFR <30 give 25mg
    eGFR <45 give 50mg
  2. Vildagliptin:
    CrCl not 50 give 50mg
  3. Linagliptin: nil
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86
Q

what are the ddis for the following DPP-4 inhibitors?

A
  1. Sitagliptin (Subsidised): Digoxin
  2. Vildagliptin: nil
  3. Linagliptin: CYP3A4 inducer
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87
Q

what are the adrs of DPP-4 Inhibitors?

A
  • Severe joint pain (may persist while on meds, not transient)
  • Headache: Most common
  • Rare: Acute pancreatitis
  • Hypersensitivity reaction
  • Rare: Bullous pemphigoid (skin rash with blisters) —> Need prednisolone
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88
Q

what is DPP-4 Inhibitors for?

A

Mild potency: Decrease HbA1c by 0.5-0.8% —> Good for SLIGHTLY elevated levels, or if have renal impairment

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89
Q

what are the adv of DPP-4 Inhibitors over GLP-1 agonists?

A
  • not SC injectables so cheaper!!, lower incidence of GI ADR
  • Mild ADR except joint pain
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90
Q

what are the disadv of DPP-4 Inhibitors over GLP-1 agonists?

A

No other good outcomes like ASCVD, HF, CKD (instead increase risk of Heart failure): So 2nd or third-line agent
- Does not increase weight unlike SUs

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91
Q

what is SGLT-2 Inhibitors?

A

Sodium–glucose cotransporter 2 that Works in the kidneys

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92
Q

why is SGLT-2 Inhibitors becoming more used?

A

due to good cardiovascular outcomes

Good for: (but costly!)
1. ASCVD (eg. MI): But only canagliflozin and empagliflozin
2. Heart failure: For dapagliflozin, empagliflozin
3. CKD: For dapagliflozin

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93
Q

how does SGLT-2 Inhibitors work?

A

Normal: As glucose passes through proximal tubules, SGLT-2 and 1 receptors reabsorb glucose
- If too much sugar aka DM, cannot reabsorb much —> Urine in sugar

Inhibit receptors so cannot reabsorb sugar —> increase renal glucose excretion —> Decrease blood glucose

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94
Q

what are the 3 types of SGLT-2 Inhibitors?

A
  1. Canagliflozin 100mg OD
  2. Empagliflozin 10mg OD
  3. Dapagliflozin 5mg OD
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95
Q

what are the dosing considerations for the following SGLT-2 Inhibitors?

A
  1. Canagliflozin:
    Do not initiate if eGFR <30ml/min and no other issues apart from high sugar
  2. Empagliflozin:
    Do not initiate if eGFR <45ml/min and no other issues apart from high sugar
  3. Dapagliflozin:
    Do not initiate if eGFR <45ml/min and no other issues apart from high sugar
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96
Q

when to initiate SGLT-2 Inhibitors?

A

if for Glycemic control ONLY (no other problems): eGFR > 45ml/min

if for Glycemic benefit and cardiorenal benefit: eGFR > 25 for dapagliflozin and > 20 for empagliflozin 10mg

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97
Q

when to discontinue SGLT-2 Inhibitors?

A

if for Glycemic control ONLY (no other problems): eGFR becomes persistently < 45 (from healthy to kidney failure) —> but for cardiorenal can continue

if for Glycemic benefit and cardiorenal benefit: Upon starting dialysis

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98
Q

whats the adr for SGLT-2 Inhibitors?

A
  1. Hypotension as push out sugar —> Decrease in water content
    • So check bp
      - Hypoglycaemia (not to a great extent as is based on how much one eats, unlike SUs)
  2. Renal impairment
  3. Female: Genital mycotic infection cause pee out sugar —> Higher risk of fungal infection —> increase risk of UTI
  4. Euglyemia (normal sugar levels) diabetic ketoacidosis (DKA)
    • Need insulin infusions as very serious, no longer can use SGLT-2 Inhibitors
    • Causes: Severe stress (sick, surgery, work), not eating well, severely dehydrated, alcohol abuse —> Once recover then give back
    • Quite prominent so in FDA warning
  5. Male: Fournier’s gangrene (infections on perineum)
    • Quite prominent so in FDA warning
  6. Only for Canagliflozin: Lower limb amputation, hyperkalemia, fractures
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99
Q

what is an impt adr to note for SGLT-2 Inhibitors?

A

Euglyemia (normal sugar levels) diabetic ketoacidosis (DKA)

- Need insulin infusions as very serious, no longer can use SGLT-2 Inhibitors
- Causes: Severe stress (sick, surgery, work), not eating well, severely dehydrated, alcohol abuse —> Once recover then give back
- Quite prominent so in FDA warning
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100
Q

who should not take SGLT-2 Inhibitors? any alternatives?

A

Dialysis patients (End-Stage Renal Disease) —> Use DPP-4 Inhibitors, SUs, Insulin instead

101
Q

what is SGLT-2 Inhibitors used for apart from its cvd benefits?

A

Mild potency: Decrease HbA1c by 0.8-1%
- Monotherapy (usually for other outcomes, intolerance to metformin) or with metformin

  • Doesnt cause hypoglycemia
  • Slight weight loss cause peeing out sugar
102
Q

is Alpha-Glucosidase Inhibitors getting rare?

A

Ye, Old agent, may slowly phase out

103
Q

can Alpha-Glucosidase Inhibitors be used alone?

A

No longer a monotherapy, but as an adjunct therapy

104
Q

how does Alpha-Glucosidase Inhibitors work?

A

Works on lining of GIT: Binds to receptor on GI —> prevent breakdown of complex carbohydrate to simple sugars —> reduction in postprandial glucose (PPG) levels as lesser glucose to be absorbed —> Reduce absorption of glucose

Acts locally so have a lot of side effects

105
Q

does Alpha-Glucosidase Inhibitors have a fast onset? if so, when to take to have optimal effects?

A

Rapid onset with each meal —> So take immediately or with meal for effects

106
Q

how is Alpha-Glucosidase Inhibitors excreted?

A

Half secreted via faeces as unabsorbed drugs

107
Q

what is a type of Alpha-Glucosidase Inhibitors?

A

Acarbose

25mg, 50mg, 100mg tablets
- Start low and titrate up
- Max daily dose is 150mg is <60kg or 300mg if >60kg

PPG dose-dependent, not fasting glucose

108
Q

does Alpha-Glucosidase Inhibitors have any good outcome? like cvd benefits?

A

Does not have any good impacts on other outcomes

109
Q

what are the adrs of Alpha-Glucosidase Inhibitors?

A

GI disturbances: Flatulence (fart alot —> number 1 reason for drug discontinuation… LOL), abdominal pain, diarrhoea

Renal impairement: CrCl <25ml/min cannot use

110
Q

hows the potency and what is Alpha-Glucosidase Inhibitors used for?

A

Mild potency: Decrease HbA1c by 0.5-0.8%

Mainly used to control postprandial blood glucose (can take during meals)

111
Q

what are the two types of injectable drugs for dm?

A
  1. Insulin agents: Exogenous Insulin
  2. Non-insulin agents: GLP-1 receptor agonists
  3. Combi therapy (Insulin and Non-insulin agents)
112
Q

whats so good about exogenous insulin?

A

Safest, first-line agent, easiest to titrate

113
Q

does insulin have the highest potency?

A

Highest potency: Decrease HbA1c up to 2.5%

If not effective, patient either not compensating or over-eating

114
Q

can insulin be used for preggos?

A

YESYESYES and for all types of DM

115
Q

how does insulin work?

A
  1. Carbohydrates
    • Increase uptake of glucose in muscles (utilise) & adipose tissue (store via lipogenesis: non-fats —> fats)
    • Inhibit hepatic glucose output
  2. Fats
    • Increase storage of glucose in the form of fats
    • Prevent lipolysis of fats into oxidised fatty acids for energy (as this causes ketone production)
  3. Proteins
    • Increase protein synthesis to build muscles
    • Inhibit proteolysis (break down of proteins) in muscle tissues
      • Muscle are primary site for glucose uptake
116
Q

how does insulin work on the liver?

A

Decrease gluconeogenesis

Increase glycogenesis for storage of glucagon

Decrease glycogenolysis

117
Q

how does insulin work on the pancreas?

A

Increase insulin secretion

118
Q

how does insulin work on the muscle?

A

Increase glucose utilisation

Increase glycogenesis

119
Q

how does insulin work on the adipocytes?

A

Increase glucose storage

Increase protein synthesis (for muscle health)

Increase lipogenesis (glucose or nonfats into fats)

Decrease lipolysis, so glucose is broken down instead of fats

120
Q

what is the onset of insulin?

A

High variable across individuals

More rapid and shorter for IV (if diabetic patient has surgery or toxicity due to Diabetic Ketoacidosis) >IM (seldom due to pain where there is a lot of nerves) > SC

121
Q

what is the absorption rate of insulin?

A

Rate-limiting step is the process where insulin moves from fat cells through layers of tissue into bloodstream

Other than RL step, absorption is quite fast

Onset depends on absorption

122
Q

how is insulin distributed in the body?

A

Injected into tissues —> Bloodstream —> Liver, fats, muscles, pancreas

123
Q

how is insulin metabolised and eliminated?

A

Exogenous insulin: Mainly via kidneys
- So if have CKD, exogenous insulin will accumulate in body —> Toxicity —> So need to dose titrate down

Endogenous insulin: Mainly via liver

124
Q

what to note when using syringes to inject insulin?

A

Use the smallest syringe possible, based on dose

125
Q

what are the types of needles and associated needle length to use when injected insulin?

A

Plastic, but still dont shake around as insulin is a large molecule and may denature

Pen needles: 4 - 12.7mm

Syringe needles: 6 - 12.7mm

  • Average skin thickness at insulin injection site is 2.4mm across age race BMI —> 4mm needle is sufficient to cross skin barrier to fats tissue
    • But if really very skinny, shorter needle is better to not risk injecting into muscles
    • NO medical reason for recommending needles >8mm
126
Q

whats the thickness of needle (gauge) using in injecting insulin?

A
  • 28-32 gauges
  • Higher the gauge number, the finer the needle, so lesser pain BUT greater needle weakness (if needle bend —> painful) and speed of giving is slower
127
Q

how to calculate the units for vial and pen when injecting insulin?

A

Vial only 1000 units = 10ml
Pen only 300 units = 3ml

  • U-100 = Each ml has 100 units —> Each vial is 10 units —> 100ml x 10 units = 1000 units of insulin
  • If need 80 units/day for 28days —> 80units x 28day = 2240 units total
  • Round up to the nearest number of vials required
128
Q

what to note when handling vial (glass bottles) when injecting insulin in terms of stability?

A
  • Stability (for vials!!! other devices like pens, refill cartridges need see insert)
    • Unopened vial: Good till expiration date if stored in refrigerator 2-8 deg —> if not stored appropriately, standardised to 28 days only (determir good for 42 days)
    • Opened vials: Good for 28days regardless of refrigeration
129
Q

what to take note of when deciding the insulin injection sites?

A

Fastest to slowest rate of absorption: Abdomen > Outer upper arms > Top and outer thighs > Buttocks

Rotate sites of the SAME location to prevent lipohypertrophy and retain consistency (1 rotation takes a month)

130
Q

what are the suggested injection sites for insulin?

A
  1. Abdomen (two fingers around naval)
    • All surrounding fatty areas
    • Most common area as can see and pinch
    • Preggos also can inject at abdomen
  2. Top and outer thighs
    • Avoid bony area above knees
  3. Outer upper arms (Back arm with fatty tissues)
  4. Buttocks
131
Q

how to prep insulin injection?

A
  1. Check the insulin label for insulin type and expiration date
    • Check if pre-mixed alr or need to mix two vials of insulin doses together
  2. Visually inspect the insulin vial for contamination or degradation
    (eg. white clumps or colour change)
  3. For all cloudy insulins, roll the vial gently back and forth between hands
    • Avoid vigorously shaking to prevent air bubbles from forming
    • To mix and warm it up
    • Only need to mix cloudy insulins, not clear insulins
  4. Wipe top of vial and injection site with alcohol swabs
  5. Remove protective covering (eg. cap) over the plunger and needle
  6. Draw up air equal to the insulin dose to be administered into the syringe
    • To remove vacuum in the syringe
  7. Inject the air into the insulin vial
  8. With the syringe still inserted, invert the vial and withdraw the insulin dose (the “bunny ears”)
    • Invert to ensure syringe is fully submerged in the insulin
    • Prevents air bubbles
  9. If bubbles are present, gently tap the syringe and remove syringe from vial
132
Q

what are the subcutaneous insulin injection skills to take note of?

A
  1. Pinch the area to be injected
    • Need to pinch for >6 mm needles
    • No need pinch for 4-5mm needles cos very short alr unless wna inject at arms or thighs
    • But anyway no harm pinching eitherways
  2. Insert the needle at a 90 degree angle to the skin in the center of the pinched area
    • BUT 45 degree angle for small children, very thin adults, elderly
  3. Release the pinch
  4. Press the plunger to inject insulin
  5. Hold the syringe or device in the area for 5-10 sec to ensure full delivery of insulin
  6. Remove the syringe or device and throw into a sharps container
133
Q

what are the factors affecting insulin absorption?

A
  1. Temperature
    • Hotter —> Faster absorption
  2. Massage —> Faster absorption
    • But leave it as it is, no need to massage
  3. Exercise —> Increase blood flow —> Faster absorption
  4. Jet injections
    • Pressure instead of needle to administer —> forceful delivery —> Faster absorption
    • Rarely used
  5. Lipodystrophy*****
    • Lipoatrophy: Concavity or pitting of adipose tissue due to an immune response (often assoc with pork and beef insulin) —> Faster absorption
      • Rare now with use of synthetic human insulin
    • Lipohypertrophy: Lumps/ Bulging of adipose tissue due to not rotating injection sites —> Slower absorption
  6. Others
    • Needle size/gauge: Larger gauge needles —> Create larger hole —> Faster absorption
    • Administration technique: SC injections slowest absorption
    • Insulin preparations: Varying absorption rates.
    • Mixtures: Both rapid- and longer-acting insulin have varying absorption rates
    • Concentration
    • Dose
    • Insulin stability: Insulin age, storage conditions
134
Q

what are the types of insulin? ><

A
  1. Ultra-short acting
  2. Rapid-acting
  3. Short-acting
  4. Intermediate-acting
  5. Long-acting
  6. Ultra-long acting
  7. Mixed insulin
135
Q

how to ensure stability while extending doa for ultra short acting insulin?

A

Add additional excipients to insulin to extend DOA while ensuring stability

136
Q

what are the types of ultra short acting insulin?

A
  • Insulin aspart (Fiasp)
  • Insulin lispro-aabc (Lyumjev): Not avail in SG
137
Q

what are the types of ultra-long acting insulin?

A

Insulin Deglgudec
- DOA up to 42h
- Inject SC OD at ANY time everyday

Insulin Glargine (U-300)
- More concentrated dose, so lesser amts needed for injection
- Inject SC OD at SAME time everyday
- NOT the same as glargine U-100

note: Lesser incidences of hypoglycemia compared to long-acting glargine (U-100)

138
Q

what are the two types of mixed insulin?

A
  1. Self-mixing: From ~5 to ~3 jabs
  2. Pre-mixed: Inject ~twice a day
139
Q

what is self mixing insulin used for?

A

To reduce frequency of doses
If not need inject before meals and before sleeping

140
Q

what are the two types of self-mixing insulin?

A
  1. stable mixes
  2. unstable mixes: not compatible!!!
141
Q

what are the two types of stable mixes for self-mixing insuliN?

A
  1. Regular + NPH
  2. Rapid-acting + NPH

note: If want to mix shorter-acting clear and longer-acting cloudy tgt, draw up clear first then cloudy (NPH)

142
Q

what are the three types of unstable mixes for self-mixing insuliN?

A

Glargine + others insulins —> pH incompatibility

Glulisine + insulins (other than NPH)

NOT RECO: Determir + other insulins

143
Q

whats pre-mixed insulin used for?

A

For meal/snack AND basal coverages

  1. Fast-acting insulin —> Cover peaks from eating meals
  2. Long acting insulin for long coverage —> Cover sugar made by liver throughout the 24h

note: 2 meals a day, meal pattern same, big meals —> Choose 50/50

breakfast, lunch, dinner —> novomix larger dose to cover bf and lunch and smaller dose for dinner

144
Q

what are the advantages of premixed insulin?

A
  • Beneficial for patients who have difficulty measuring and mixing insulin
  • Lesser jabs
  • Still retains PKPD profiles
145
Q

what are the disadvantages of premixed insulin?

A
  • Lesser flexibility in for titrate
    • Both basal and prandial coverage adjusted together
    • Easier to optimise drug therapy if do self monitoring of blood glucose at home
146
Q

when to admin premixed insulin?

A
  • If have longer acting like regular, give 30mins before meal
  • If have rapid acting, give within 15mins of meal
147
Q

what are the types of premixed insulin?

A
  • NovoMix: 30% short acting, 70% long acting —> Cloudy
  • Humalog Mix: 25% short, 75% long or 50/50
  • Mixtard: 30% short, 70% long
148
Q

why would dr continue oral therapies when starting injectables?

A

Sometimes done when obese patients want to reduce amt of insulin used, as want to sensitise body to insulin

149
Q

what if currently on oral metformin? then do i continue them when insulin injectables are started?

A

CONTINUE

150
Q

what if currently on oral TZDs? then do i continue them when insulin injectables are started?

A

Stop when initiate insulin or reduce TZD dose

151
Q

what if currently on oral SUs (Secrete out insulin from pancreas) ? then do i continue them when insulin injectables are started?

A

Stop or reduce SU dose by half when initiate basal insulin and titrate SU up again to prevent hypoglycemia

Stop SU when initiate basal + bolus or premix insulin as alr cover meal patterns so not necessary

152
Q

what if currently on oral SGLT-2i? then do i continue them when insulin injectables are started?

A

Continue

153
Q

what if currently on oral DPP-4i? then do i continue them when insulin injectables are started?

A

Stop DPP-4i when initiate GLP-1 agonists

154
Q

how to do insulin dosing conversions?

A

Most conversions are 1:1
- Mixtard or Insulatard to NovoMix: Both will give same dose regimen of 16u AM (bf and lunch) and 8u PM (dinner)
- Reduce dose by 10-20% if have renal failure, not eating well to prevent hypoglycemia —> Requires clinical judgement

Exceptions
- Switch NPH BD to Glargine/ Determir OD —> Need reduce dose by 20% as final dose will be very large since combine two doses
- 20units BD to 32units OD and titrate up
- Switch U-300 Glargine to other basal insulin which aint as concentrated —> Need reduce dose by 20%
- 40units to 32units

155
Q

how to initiate insulin injectables?

A

Normally will initiate with basal insulin which targets fasting blood glucose (basal sugars produced by liver)

10units at bedtime (esp if pt is vv big size and scared pt gets hypoglycemia) or 0.1-0.2u/kg/day then titrate up
- But for full-basal bolus regime start at 0.5/u/kg

NPH/Glargine/determir/degludec can but last 3 drugs VVV COSTLY

156
Q

what if hbA1c still uncontrolled after initiating with basal insulin? (initial uncontrolled)

A

continue to act on FPG

Uptitrate insulin 2units every 3 days until FPG goal (5-7mmol/L)
- There are days that are good and days that arent, so dont straightaway increase dose, only do so if consistency not good

Uptitrate insulin 4units every 3 days if FPG consistently >10mmol/L

Titrate downwards by 10-20% if got hypoglycemia risk

157
Q

what if hbA1c still uncontrolled after initiating with basal insulin? (after awhile still uncontrolled)

A
  • If HbA1c still too high (>8%) despite basal dose being ~maximised (>0.5u/kg) OR FPG at goal:
  1. To cover mealtimes: Add prandial coverage (either rapid (eg. aspart)/ regular (eg. actrapid insulin)
    - 1 dose with largest meal if only eat 1 meal
    - Dosage: 4u or 10% of basal
    - If HbA1c <8%, decrease basal dose by 4u or 10%
  2. To cover overnight: If on bedtime NPH, can split into two doses, 2/3 AM, 1/3 PM
    • Bc add prandial to NPH, can consider premix insulin or self-mixed to decrease number of injections
158
Q

Why need limit basal insulin dose? (bc there is an optimal basal insulin dose of 0.5u/kg)

A
  • Normally start with 0.2u/kg
  • Overbasalization
  • Ceiling effective dose where BG reductions become proportionally smaller with increasing doses
  • If not kena ADR
159
Q

why aim for 5-7mmol/L altho on paper says 4-7mmol/L? for dm patients

A
  • Hypoglycaemic risk is where BG <4.0 mmol/L (70mg/dL), so once BG is 4-5 mmol/L —> Tight glucose control
    • So just aim for 5-7 mmol/L, although on paper it says 4-7 mmol/L
160
Q

what are the adr of exogenous insulin?

A
  • Hypoglycemia
  • Weight gain
    • More than SUs!!!
    • So exercise and diet
  • Lipodystrophy
  • Local allergic reaction
    • Redness, swelling, itching at site
    • More common with beef or pork insulin (but phasing out)
  • Systemic allergic reaction (rare)
  • Insulin resistance (rare)
161
Q

when is glp-1 receptor agonist used?

A

Reco over insulin as first line injectable when greater glucose lowering is needed

162
Q

how does glp-1receptor agonist work?

A

Background: Incretins
- Once consume food, stomach linings will secrete incretins (aka GLP-1) —> Stimulate GIT to slowly push out food to feel full and cause pancreas to release more insulin —> Prevent overeating which reduces sugar intake
- Enzyme DPP-4 rapidly degrades to inactivate GLP-1 —> So introduce GLP-1 receptor agonists

MOA
- Acts like endogenous GLP-1 and binds to receptors on beta cells

163
Q

what are the advantages of GLP-1 receptor agonists over DPP-4i ?

A
  • DPP-4i only inhibits degradation and hence prolong activity of existing GLP-1
  • GLP-1 receptor increases supply of GLP-1 to work on GLP-1’s MOA
164
Q

what are the types of glp-1 agonist?

A
  1. Liraglutide (Victoza)
  2. Dulaglutide (Trulicity)
  3. Semaglutide (Ozempic)
  4. Semaglutide (Rybeisus)
165
Q

need to dose adj glp-1 agonist in renally impaired patients

A

No need to dose adj in renally impaired patients

166
Q

how to admin the diff types of glp-1 agonist?

A
  1. Liraglutide (Victoza): SC OD ANYTIME
  2. Dulaglutide (Trulicity): SC once weekly ANYTIME
  3. Semaglutide (Ozempic): SC once weekly ANYTIME
  4. Semaglutide (Rybeisus):
    PO OD 30mins before first meal
    - On empty stomach
    - No more than 120ml water
    - Due to coating which req alkaline environment to release drug (stomach becomes more acidic with food - can take with omeprazole which increases pH)
    - vvv low absorption rate 1% only, rest is excreted
167
Q

what are the dosing for the diff types of glp-1 agonist?

A
  1. Liraglutide (Victoza): 0.6mg then 1.2mg aft 1 week up to 1.8mg
  2. Dulaglutide (Trulicity): 0.75mg then 1.5mg aft 4 weeks up to 3 and 4.5mg
  3. Semaglutide (Ozempic): 0.25mg then 0.5mg after 4 weeks up to 1mg
  4. Semaglutide (Rybeisus): 3mg then 7mg after 30 days up to
168
Q

what are the adrs of glp-1 agonist?

A
  • Headache
  • N/v (common) - severe so start low
  • Acute pancreatitis
  • Acute cholecystitis
169
Q

what black box warning does glp-1 agonist have?

A

Black box warning: DONT USE IF HAVE THYROID CANCER

Not reco if have history of pancreatitis or fam history of thyroid cancer

170
Q

what good outcomes does glp-1 agonist have aside from lowering HbA1c?

A

ASCVD: Only injectables:
Liraglutide
Dulaglutide
SC Semaglutide

Heart Failure:
Nil unlike SGLT2i

CKD:
Only injectables reduces macroalbuminuria

171
Q

does glp-1 agonist have high potency?

A

yes, High potency: Decrease HbA1c by 1-2% (same as metformin and SUs)

172
Q

does glp-1 agonist cause weight loss?

A
  • Cause weight loss
173
Q

does glp-1 agonist cause hypoglycemia?

A
  • Does not cause hypoglycemia (like SGLT2-i) but costly
174
Q

what are the dm-related complications?

A
  1. blood pressure
  2. lipid
  3. atherosclerotic cardiovascular disease
  4. ckd
175
Q

how to manage bp to prevent dm related complications?

A

Recommended BP <130/80 mmHg
- Reduce CVD mortality
- Slow CKD progression

Preferred first line agents (with or without diabetic kidney disease): ACEi/ARB

176
Q

how to manage lipid to prevent dm related complications?

A

Secondary prevention
- Diagnosed with atherosclerotic cardiovascular disease (eg. Stroke, MI) : Undergo high-intensity statin therapy
- Add ezetimibe or a PCSK9 inhibitor if goal is not achieved
- Therapy goals
- Reduce LDL cholesterol by 50% from baseline
- Continue until LDL cholesterol of <55 mg/dL (1.4 mmol/L)
- 21% reduction in major cardiovascular events for every 39 mg/dL (1 mmol/L) of LDL cholesterol lowering, irrespective of baseline LDL cholesterol

Primary prevention
- Age 40-75 years: Take moderate-intensity statin
- High intensity statin if additional ASCVD
risk factors
- Therapy goals
- Reduce LDL cholesterol by 50% from baseline
- Continue until LDL cholesterol of <70 mg/dL (1.8 mmol/L)

177
Q

how to manage Atherosclerotic CardioVascular Disease to prevent dm related complications?

A

Anti-platelet agent: Aspirin
- Alternative if allergic to aspirin: Clopidogrel (75 mg/day)

Secondary prevention
- History of ASCVD: Aspirin recommended

Primary prevention
- <50 years old with no risk factors: Aspirin not recommended as low risk
- <50 years old with ≥ 1 risk factors, or older patients with no risk factors: Use clinical judgement as intermediate risk
- 50-70 years old with ≥ 1 risk factors: Aspirin recommended as high risk
- >70 years old with ≥ 1 risk factors: Aspirin not recommended as risk greater than benefit even though high risk

178
Q

how to manage ckd to prevent dm related complications?

A

Primary prevention
- Blood glucose and blood pressure control
- ACEi/ARB is not recommended for primary prevention for those with DM who have normal BP

179
Q

what are the risk factors of Atherosclerotic CardioVascular Disease in dm patients?

A
  • LDL cholesterol ≥ 2.6 mmol/L
  • High BP, smoking
  • Younger (<50 years old)
  • CKD
  • Albuminuria
  • Family history of premature ASCVD
180
Q

what are the risk factors of ckd in dm patients?

A

Long duration of diabetes

181
Q

what is the Clinical Presentation of Diabetic Kidney Disease (DKD)?

A
  • Presence of albuminuria without gross hematuria (blood in urine)
  • Absence of s/sx of other primary causes of kidney damage
  • Presence of retinopathy (more for T1DM, may not appear in T2DM)
  • Gradual decrease in eGFR
182
Q

how to treat Micro- or macro-albuminuria as a dm related complication?

A

Micro- or macro-albuminuria: ACEi/ ARB
- Reduce CKD progression
- Titrated to max tolerated dose based on BP and kidney function (eGFR, creatinine)
- Combi therapy with SGLT2i or Finerenone

183
Q

how to treat T2DM and diabetic kidney disease (DKD) and eGFR > 20 mL/min/1.73 m2 as a dm related complication?

A

SGLT2 inhibitor
- Reduce CKD progression and CVS risk
- Use concurrently with ACEi/ARB

184
Q

how to treat T2DM and diabetic kidney disease (DKD) and eGFR > 25 mL/min/1.73 m2 as a dm related complication?

A

Finerenone

Non-steroidal mineralocorticoid receptor antagonist (MRA)
- Block receptor to prevent aldosterone from binding —> Prevents reabsorption of Na —> Decrease in BP
- Exchange of Na with K so since Na does not get reabsorbed, K stays in body —> Hyperkalemia

Reduce CKD progression, reduce the risk of kidney failure, heart attack, heart failure hospitalisation, CVS death in adult patients

😖Side effects: Hyperkalemia, hypotension, lesser risk of gynecomastia compared to spironolactone

185
Q

how to monitor blood glucose via blood glucose monitoring machine (bgm)?

A

Via patient action only, finger-prick testing

186
Q

how to monitor blood glucose via Intermittently scanned CGM (isCGM)?

A

Via patient action through scanning of sensor, measure intestinal glucose

187
Q

how to monitor blood glucose via Real-time CGM (rtCGM)?

A

No patient action required, measure interstitial glucose

188
Q

how does blood glucose monitoring machine (bgm) detect hypoglycemia?

A

Proactive check when symptomatic or by direct action

189
Q

how does Intermittently scanned CGM (isCGM)? detect hypoglycemia?

A

Information recorded (retrospectively) and requires direct action every 8h

190
Q

how does Real-time CGM (rtCGM) detect hypoglycemia?

A

Automatically detected

191
Q

is there alarm/ warning for the following?

A
  1. Blood Glucose Monitoring (BGM): no
  2. Intermittently scanned CGM (isCGM): no
  3. Real-time CGM (rtCGM): yes
192
Q

what are the types of Continuous Glucose Monitoring (CGM)?

A
  1. Blood Glucose Monitoring (BGM)
  2. Intermittently scanned CGM (isCGM)
  3. Real-time CGM (rtCGM)
193
Q

what are some notes to take note of for Continuous Glucose Monitoring (CGM)?

A
  • Wearable device that measures glucose readings continuously
    • Even comes as a subcutaneous sensor
  • Measures interstitial glucose
  • Therapeutic goals
    • Improvement in HbA1c reduction
    • Reduction in hypoglycemia
  • Eliminates the use of a glucometer, lancet and blood test strip
    • Allows monitoring to be more discreet and regular
194
Q

what is considered a diabetic emergency?

A
  1. Diabetic ketoacidosis (DKA)
  2. Hyperglycaemic Hyperosmolar State (HHS)

note: Diabetic ketoacidosis is NOT the same as lactic acidosis

195
Q

what is the common underlying cause of DKA/ HHS?

A

infection!

others include myocardial infarction, stroke, inadequate insulin therapy, pancreatitis

196
Q

which type of dm is dka more common in?

A

type 1

197
Q

which type of dm is hhs more common in?

A

type 2

198
Q

what is dka?

A

Absolute/ relative insulin deficiency —> Lipolysis + metabolism of free fatty acids —> Formation of beta-hydroxybutyrate (measured to test for ketones), acetoacetic acid, acetone in liver

199
Q

what can contribute to ketones? and hence diabetic ketoacidosis?

A

Stress —> Stimulates insulin counter-regulatory hormones (Glucagon, catecholamines, glucocorticoids, growth hormone)
- Excess glucagon increases gluconeogenesis and decreases peripheral ketone utilisation

Ketones are by-products of fat metabolism
- Can be found in blood and urine
- Fruity breath odor
- Acidosis
- Usually still alert
- BG > 14 mmol/L

200
Q

why type 2 usually no dka?

A

Type 2 usually have some residual insulin production, so protected against excessive lipolysis and ketone production, and so no acidosis

201
Q

what happens when blood glucose is vv high? how can this cause hhs?

A
  • BG > 33 mmol (super super high!!! in crisis so need treat w IV insulin!!!!!!) —> Polyuria —> Extreme dehydration —> Stupor (altered mental status of confusion)

note: Osmolarity is to measure the solute within plasma: The more solutes (eg. glucose, urea, Na), the higher the osmolarity

202
Q

what is the somogyi effect vs dawn phenomenon?

A

take note if observe High BG when tested early in the morning, but reasonable BG before bedtime

Dawn phenomenon (NORMAL)
- Normal phenomenon where cortisol is released in the waking hours —> BG level rise sharply

Somogyi effect
- Miss bedtime snack, too much insulin —> BG level drops sharply at night —> Body responds by releasing glucagon —> BG level increases
- Can titrate dose to help with somogyi effect

203
Q

what is dm?

A
  • Cause hyperglycemia
    • Type 1: Pancreas no longer working, cannot produce insulin which regulates blood glucose levels
    • Type 2: Pancreas is working, can produce insulin, but blood glucose is still not well regulated
204
Q

what happens when blood glucose levels are not well controlled?

A

If blood glucose levels not well controlled —> fatigue, frequent urination, sudden weight loss, wound wont heal (esp at extremities), reduced libido, always hungry, blurry vision, numbness or tingling hands or feet aka extremities, always thirsty, increased chance of vaginal infections

205
Q

what is blood glucose test?

A

Blood glucose test: Fast —> consume one big bottle of glucose —> few hours later draw blood and measure

206
Q

what kind of meds are for dm type 2? what do they mostly act on?

A

Mostly oral drugs and small molecules except Liraglutide which is a peptide

Acts on pancreas except Empagliflozin which acts on kidney

207
Q

what are the main pharmacology for dm type 2?

A
  1. Metformin (Biguanide)
  2. Glipizide (sulphonylurea)
  3. Sitagliptin (DDP-4i)
  4. Liraglutide (GLP-1 agonist)
  5. Empagliflozin (SGLT-2i)
208
Q

what is metformin as a biguanide?

A

Biguanide that inhibits gluconeogenesis (non carbs to glucose) to decrease blood glucose levels

209
Q

How is blood glucose regulated?

A
  • Carbohydrate intake —> Absorption of glucose into GIT —> Excess glucose is stored in liver and skeletal muscles as glycogen
  • Regulator of blood glucose: Insulin
210
Q

how To INCREASE blood glucose levels when required?

A
  1. Increasing dietary carbohydrates for more absorption of glucose from GIT
  2. Breaking down of carbohydrates (glycogen) via glycogenolysis
    • Occurs in the liver and muscles
  3. Breaking down of non-carbohydrates substrate (amino acids from dietary carbs & muscles, glycerol from fats, lactic acid*) via gluconeogenesis!!!!! inhibited by metformin
    • Occurs mainly in the liver, lesser in the kidneys
    • *Esp during starvation and fasting need to rely on breaking down lactic acid produced during anaerobic metabolism (eg. intense exercise) —> BUT NEED TAKE NOTE OF TOXICITY OF LACTIC ACID ACCUMULATION
    • During prolonged starvation, body tends to conserve muscles and hence AA so rely more on fat stores for glucose via lipolysis
211
Q

how To DECREASE blood glucose levels when required?

A
  1. Inhibition of breakdown of glycogen to glucose
  2. Increase uptake and utilisation of glucose by tissues
  3. Increase glycogen synthesis via glycogenesis for storage in liver and muscles
212
Q

what is the moa of metformin?

A

Primary: Inhibits gluconeogenesis signalling pathway by activating AMP protein kinases which will phosphorylate enzymes used in gluconeogenesis —> Decrease production of glucose

Secondary: Enhance tissue sensitivity to insulin to increase glucose uptake by tissues

213
Q

how is the absorption properties like for metformin?

A
  • Oral tablet, so good bioavailability of 40-60%
  • Duration of action: 8-12h
214
Q

how is the distribution properties like for metformin?

A
  • Rapidly distribution
  • Minimum plasma protein binding so apparent volume of distribution is quite large (>5-8L cos distribute to other parts of the body)
  • t1/2 = 3h
215
Q

how is the metabolism and excretion properties like for metformin?

A
  • Not quite broken down by the body, so excreted unchanged mainly in urine through kidney
  • So avoid usage in patients with renal insufficiency if not level of metformin will remain high (t1/2 is higher) as cannot get rid of it fast enough —> Accumulation toxicity
216
Q

what is metformin used for?

A
  • Mono or combi therapy with other oral hypoglycemic agents
  • Useful in obese patients (and diabetes tend to be obese) as reduces appetite
  • Does not result in hyperinsulinemia or hypoglycemia (so esp good for elderly as they will still maintain their have energy to prevent fainting and giddiness)
  • Can help with weight loss and improve lipid levels
217
Q

what are the adrs for metformin?

A
  • Anorexia
  • GI disturbances (so take with or after meals)
    • Diarrhoea —> Weight loss
    • Vomiting
    • Indigestion
  • Increase risk of Vit B12 malabsorption —> Vit B12 deficiency
  • Use with caution in patients with renal problems or lactic acidosis
    • Inhibits gluconeogenesis so prevents breaking down of lactic acid into glucose —> Lactic acid conc increase —> Lactic acidosis (not good for patients having liver and CVS problems)
218
Q

what does glipizide (sulphonylurea) do?

A

Stimulate insulin release from pancreatic beta cells to decrease blood glucose levels

219
Q

what happens when there is high glucose levels?

A

note: Release of insulin is a calcium-dependent process

High glucose levels —> More glucose enter beta cells through GLUT-2 —> Metabolism of glucose produces ATP —> Increased ATP causes inhibition of ATP-sensitive potassium (KATP) channels on beta cell surface —> Inhibits efflux (pumping out) of potassium ions —> Causes membrane potential to be more positive (Depolarisation) —> Triggers opening of calcium channels —> Increase in intracellular Ca levels stimulates exocytosis (release) of insulin granules stored within beta cells’ secretory vesicles

Ca levels increase —> Insulin release to decrease blood glucose level

220
Q

how does glipizide (sulphpnylurea) help in aiding the relase of insulin?

A

ATP-sensitive potassium (KATP) channels on beta cell surface has sulfonylurea receptor subunit which binds to sulfonylureas —> Decrease efflux of potassium ions —> Depolarisation —> Ca levels increase —> Insulin release to decrease blood glucose level

221
Q

how is the absorption like for glipizide (sulphonylurea)?

A
  • Oral, bioavailability >95%
  • Absorption delayed with food, so dont take with meals
  • Onset of action is quite fast: 0.5h
  • Duration of action: Last 12-24h
222
Q

how is the distribution like for glipizide (sulphonylurea)?

A
  • Extensively binds to plasma protein (mainly albumin)
  • half life is ~4h
223
Q

how is the metabolism and excretion like for glipizide (sulphonylurea)?

A
  • 90% broken down in liver via hydroxylation —> Metabolite
  • <10% unbound, so remaining parent compound excreted unchanged in urine and faeces
  • If have renal disease, may reduce the excretion of parent compound, so plasma level of glipizide may increase —> So need monitor if not overdose!!! then cause side effects of over lowering of blood glucose
224
Q

does glipizide (sulphonylurea) have a lower risk for hypoglycemia than other sulphonylureas?

A

Lower risk of hypoglycemia compared to other sulphonylureas (so need monitor blood glucose closely by pricking yourself)

225
Q

what are the adr for glipizide (sulphonylurea)?

A
  • Overdose, or overregulate insulin production —> Hypoglycemia (esp in elderly due to kidney function being more compromised, DDI)
  • Weight gain (sad for obese patients)
226
Q

what is sitaglipitin (DDP-4i)?

A

Dipeptidyl peptidase-4 inhibitor

227
Q

what are incretinS?

A

Hormones Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon like peptide-1 (GLP-1)

they are Released by GIT cells in the intestines after eating —> Stimulates pancreas to release insulin in a glucose-dependent manner (aka only if hyperglycemia) —> Insulin mechanism by beta cells (so increases glucose uptake by fats and muscles) + Inhibits production of glucagon by alpha cells (so decreases glucose production in liver) —> Decrease blood glucose levels

228
Q

what is the moa of sitaglipitin (DDP-4i)

A

Inhibits DPP-4 from rapidly degrading incretins —> Prolongs action of incretins

229
Q

what are the ways to use sitagliptin (DDP-4i)?

A
  • Monotherapy: When patient finds metformin unsuitable
  • Combi therapy (More common): Sitagliptin + Metformin or Sulphonylurea or Thiazolidinediones
  • Triple therapy: Sitagliptin + Insulin + Metformin or Sulphonylurea or Thiazolidinediones
230
Q

how is the absorption like for sigtagliptin (DDP-4i)

A

Oral, so bioavailability is very good at 87%

231
Q

how is the distribution like for sigtagliptin (DDP-4i)

A

t1/2: 10-12h

232
Q

how is the metabolism and excretion like for sigtagliptin (DDP-4i)

A

Not much broken down in liver, so 80% excreted unchanged in urine, rest that are broken down (metabolites) is excreted in faeces

233
Q

what are the adrs for sigtagliptin (DDP-4i)

A
  • GI disturbances
  • Flu-like symptoms (headache, running nose, sore throat)
  • Skin reactions (rashes, itchiness)
  • Caution in patients with history of pancreatitis as works on pancreas to stimulate insulin
234
Q

what is liraglutide (glp-1 agonist)?

A

Better version of GLP-1 (mimics action so agonist)

  • Synthetic peptide (large molecule) derived from GLP-1(7-37) peptide
    • Acylated: Has an attached C16 fatty acid that allows it to bind to serum albumin to slow down clearance from body —> Increase half life —> Prolong action compared to GLP-1
235
Q

can liraglutide (glp-1 agonist) be used for preggos?

A

NONONONNONNONNONNONONO

236
Q

why is liraglutide (glp-1 agonist) long acting?

A

Resistant to degradation by DPP-4 —> Long acting

237
Q

how does liraglutide (glp-1 agonist) work?

A

Activates GLP-1 receptor (aka a membrane-bound G protein-coupled receptor (GPCR) on beta cells) —> Stimulates adenylate cyclase which increases production of cyclic AMP (cAMP) —> Increased cAMP levels activate protein kinase A (PKA) —> Activated PKA enhances insulin secretion and suppresses release of glucagon (just like Sitagliptin) —> Decrease blood glucose levels to euglycemia (normal levels)

238
Q

what is liraglutide (glp-1 agonist) used for?

A
  • Adjunct therapy for patients who are not achieving glycemic control with oral diabetes drugs
  • Delays gastric emptying and reduce appetite —> Weight loss (good for obese patients)
  • Reduces CVS death, non-fatal MI, heart failure among T2DM patients
239
Q

how is the absorption like for liraglutide (glp-1 agonist)

A
  • Only two products and all given SC (F = 55%, not IV) once daily at upper arm, abdomen or thigh
  • 5 week regime and beyond as per doctor instructed at 5th week’s dosage
240
Q

how is the distribution like for liraglutide (glp-1 agonist)

A

C16 fatty acid facilitates binding to plasma protein —> Prolongs half life to 13h

241
Q

how is the metabolism and excretion like for liraglutide (glp-1 agonist)

A
  • Endogenously broken down like any other polypeptides without a specific organ as a major route of elimination (blood, tissues etc as long as meet right enzyme)
  • Little or none excreted unchanged as peptide which is broken down anywhere appropriate into amino acids
242
Q

is liraglutide (glp-1 agonist) costly?

A

Very costly as SC injectable compared to oral drugs ($700/month)

243
Q

whats the adrs for liraglutide (glp-1 agonist) ?

A
  • N/v (improves when body adjusts to treatment, so only in the initial phase)
  • GIT: Diarrhea, constipation
  • CNS: Headache, tiredness
244
Q

what does empagliflozin (sglt-2i) do?

A

Decrease reabsorption of glucose back into bloodstream

  • SGLT-1 and SGLT2 (more effective): Responsible for reabsorbing glucose back into bloodstream from urine
    • Good for starvation and when glucose levels are too low
245
Q

how does empagliflozin (sglt-2i) work?

A
  • Inhibits sodium-glucose co-transporter-2 in proximal tubule of nephron in kidneys —> Decrease reabsorption of filtered glucose —> Decrease renal threshold for glucose so increase urinary glucose excretion at a lower blood glucose concentration
    • More glucose in urine —> Attracts more ants lol sad
246
Q

what is the absorption like for empagliflozin (sglt-2i)?

A
  • Oral, Good F
  • Reaches Cmax 1-2h
247
Q

what is the distribution like for empagliflozin (sglt-2i)?

A
  • t1/2=12h so once daily dose
  • Highly plasma protein bound
248
Q

what is the metabolism and excretion like for empagliflozin (sglt-2i)?

A
  • Little broken down in liver, the rest metabolised via phase 2 glucuronidation
  • Majority excreted in urine or faeces
249
Q

what are the adrs for empagliflozin (sglt-2i)?

A
  • Increased risk of UTI due to glucose in urine so drink more water
  • Increased urination due to increased urinary glucose excretion
  • Female genital mycotic (fungal) infection as glucose in urine creates a favourable environment for fungal overgrowth
  • Diabetic ketoacidosis (ketones in blood)
250
Q

what are the clinical benefits for empagliflozin (sglt-2i)?

A
  • Normally combi therapy with metformin or/and sulphonylurea OR insulin or/and metformin
    • Reduce risk of major cardiac event
    • Protects kidney function and reduce risk of kidney-related complications
      • Observed in patients with or without atherosclerotic CVD

finals (8 decks)

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