Diabetes (including Pharmacology) Flashcards
(140 cards)
1
Q
Describe the etiology/ pathogenesis of T1DM
A
Caused by absolute deficiency of pancreatic β-cell function due to immune mediated destruction of β-cells
2
Q
Describe the pathogenesis of T2DM.
A
Progressive loss of adequate β cell insulin secretion on the background of insulin resistance
o Insulin resistance = glucose utilisation is impaired and hepatic glucose output ↑ despite presence of insulin -> simultaneous elevations in both glucose and blood insulin levels at early stage
o Once pancreas slows down, can have impaired insulin secretion -> somewhat similar to Type 1
3
Q
State the differences between T1 and T2DM (7 differences)
A
1) C-peptide (byproduct from formation of insulin in pancreas) absent in T1DM, usually normal in T2DM but can be abnormal at later stages
2) Autoantibody positive in T1DM
3) T1DM has younger age of onset (usually < 30 y.o), T2DM usually > 40 y.o
4) Etiology (T1DM is autoimmune, T2DM insulin resistance)
5) Onset of symptoms is abrupt in T1, gradual in T2
6) Physical appearance usually thin for T1, usually obese for T2DM (insulin resistance often lead to obesity)
7) T1DM more prone to ketosis
4
Q
What are the common signs of both hyper and hypoglycemia? (6 total)
A
1) Shaking
2) Dizziness
3) Hunger (Polyphagia)
4) Impaired/blurred vision
5) Drowsiness
6) Weakness/fatigue
5
Q
What are the symptoms unique to hyperglycemia? (4 total)
A
- Extreme thirst (Polydipsia)
- Dry skin (from dehydration)
- Frequent urination (Polyuria)
- Decreased wound healing (from high blood glucose)
6
Q
What are the unique symptoms of hypoglycemia?
A
- Tachycardia (fast heartbeat)
- Sweating
- Anxiousness
- Headaches
- Irritable
7
Q
What are the various diagnostic tests available to diagnose diabetes?
A
HbA1c, FPG or 2hOGTT
8
Q
At what HbA1c level would a person be considered diabetic?
A
HbA1c ≥ 7.0%
9
Q
At what HbA1c level would a person be considered to have no diabetes?
A
HbA1c ≤ 6.0%
10
Q
At what FPG level would a person be considered to have diabetes?
A
FPG ≥ 7.0mmol/L
11
Q
At what FPG level would a person be considered to have no diabetes?
A
FPG ≤ 6.0mmol/L
12
Q
At what 2hOGTT level would a person be considered to have diabetes?
A
2hOGTT ≥ 11.1mmol/L
13
Q
At what 2hOGTT level would a person be considered to have no diabetes?
A
2hOGTT < 7.8mmol/L
14
Q
Assuming that a person has a HbA1c level of 6.1-6.9%, state the number of further tests required to make a diagnosis on whether person has diabetes or not
A
1 test (either FPG or 2hOGTT)
15
Q
State the number of abnormal results required to diagnose diabetes if HbA1c is not used
A
2 abnormal results
16
Q
List the complications of diabetes
A
o Microvascular:
1) Retinopathy, blindness
2) Nephropathy, kidney failure
3) Neuropathy, amputation
* Occurs in 60-70% of patients
o Macrovascular:
1) Cardiovascular Disease
* Risk increases by 2-4 times
o Life expectancy ↓ by 5-10 years
17
Q
State how HbA1c lowering affects the progression of microvascular and macrovascular complications respectively
A
Microvascular: The more lowered the HbA1c is, the slower the onset and progression of microvascular complications
Macrovascular: CV outcomes improve as HbA1c decreases but eventually worsens as HbA1c continues to drop
18
Q
What are suitable measures to prevent diabetes in pre-diabetic patients?
A
o Lifestyle interventions:
- Achieve and maintain 7% loss of initial body weight
- Increase moderate intensity physical activity to at least 150 mins/week
o Metformin therapy
- Especially for those with BMI > 35 kg/m2, those aged < 60 years, and women with prior gestational diabetes mellitus (particularly high risk for progression to T2DM)
19
Q
When is Metformin especially indicated in preventing/ delaying T2DM?
A
1) BMI > 35 kg/m2,
2) those aged < 60 years, and
3) women with prior gestational diabetes mellitus (particularly high risk for progression to T2DM)
20
Q
What is the general HbA1c target for general population?
A
HbA1c ≤ 7.0%
21
Q
In what group of patients would more stringent HbA1c target be acceptable?
A
Patients with:
1) Short disease duration
2) Long life expectancy
3) No significant CVD (lower the HbA1c, higher the risk of CVD)
22
Q
In what group of patients would less stringent HbA1c target be acceptable?
A
Patients with:
1) History of severe hypoglycemia
2) Limited life expectancy
3) Advanced complications
4) Extensive comorbid conditions
5) Those whose target is difficult to attain despite intensive Self-Monitoring of Blood Glucose (SMBG), repeated counselling, and effective pharmacotherapy
23
Q
What is the general FBG target for general population?
A
4.0-7.0 mmol/L
In practice: 5.0 -7.0 mmol/L targeted instead
24
Q
What is the general PPG target for general population?
A
< 10 mmol/L
25
What is the MOA of Metformin?
* Primary: ↓ hepatic glucose production
* Secondary: ↑ peripheral/muscle glucose uptake and utilization (i.e↑ insulin sensitivity) via activation of AMPK (AMP-activated protein kinase)
26
What are the maximal doses of Metformin?
Maximum doses: 3 x 850mg or 3 x 1g (1 tab TDS basically)
27
What are the ADRs of Metformin?
* Common:
o GI side effects (vomiting, diarrhea, indigestion), Anorexia, Weight loss, Metallic taste (usually transient; take with food to alleviate)
* Long term use:
o ↓ serum B12 concentrations
(May lead to anemias e.g Megaloblastic anemia; Greater risk in malnourished patients)
* Rare but fatal:
o Lactic acidosis (signs: shallow/ laboured breathing, nausea, mental confusion)
28
Patient who was started on Metformin 1 week ago presents today with shortness of breath, nausea and mental confusion. Explain the possible pathogenesis of the patient's symptom.
Metformin decreases metabolism of pyruvate by inhibiting certain enzymes -> ↑ pyruvate -> ↑ lactate (causing lactic acidosis)
29
What are the contraindications of Metformin?
1) Severe renal impairment (< 30ml/min)
2) Hypoxic states or at risk for hypoxemia
o Heart failure, sepsis (severe hypotension due to infection), liver impairment (cannot clear pyruvate), alcoholism (usually have malnutrition), ≥ 80 yo (not a hard contraindication)
30
What are the DDIs of Metformin?
1) Ethanol: ↑ risk for lactic acidosis
2) Iodinated contrast material/radiologic procedure -> risk of AKI (renal impairment) which will lead to ↑ metformin concentration
o Temporarily hold metformin for ≥ 48 hrs after contrast administration; restart when renal function returns to normal post procedure
3) Cationic drugs (e.g. Dofetilide, cimetidine, digoxin) may ↑ metformin by competing for renal tubular transport -> less metformin gets secreted
31
List the key points for Metformin use in renal impairment
o GFR < 60ml/min/m^2: Increase monitoring of renal function (every 3-6 months instead of once a year)
o GFR < 45ml/min/m^2: Halve Metformin dose
o GFR < 30ml/min/m^2: Stop Metformin
32
What is the place in therapy for metformin? (When is it used, benefits, disadvantages)
First-line (DOC) for T2DM and gestational diabetes
Prevention and delay of T2DM onset
Benefits:
- Good HbA1c reduction (1.5-2%)
- Weight loss
- Positive effects on lipid profile (TG, Total C, LDL)
- Positive CV effects
- Cheap
- Minimal adverse effects
33
What other off-label uses does Metformin have?
1) PCOS
2) Weight loss
34
What is the MOA of Sulfonylureas?
* Primary: stimulate insulin secretion by binding to SU receptors -> blocks K+ channel of the β cells -> membrane depolarisation -> Ca influx -> exocytosis of insulin granules in vesicles within the β cells
* Secondary: ↓ hepatic glucose output and ↑ insulin sensitivity
35
Which are the preferred SU(s) if patient is renally impaired?
Tolbutamide or Glipizide
36
List the duration of action of the various SUs.
Tolbutamide: 6-12 hours
the rest: 12-24 hours
37
Need to avoid co-administration of renally cleared drugs for which sulfonylureas?
Glibenclamide, Gliclazide, Glimepride
38
What are the ADRs of Sulfonylureas?
* Hypoglycemia (especially in elderly due to reduced kidney and/or liver function)
* Weight gain (~2-5 kg) -> happens with drugs that ↑ insulin secretion
* Blood dyscrasias (rare)
39
Which sulfonylurea needs to be avoided in renal impairment. State the CrCl at which its use needs to be avoided
Glibenclamide
CrCl < 50ml/min
40
What administration instructions would you give a patient who is going to start on Sulfonylurea?
Take 15-30mins before food. Should you skip meals, also skip your sulfonylurea dose to avoid hypoglycemia (supposed to target PPG).
41
Which sulfonylurea has the lowest risk of hypoglycemia?
Glipizide
42
What are the DDIs of Sulfonyureas?
1) β blockers may mask signs and symptoms of hypoglycemia
o Symptoms like tremors, fast heartbeat may be masked
o Only symptom that cannot be masked is sweating
2) Disulfiram like reaction with Ethanol (1st gen>>2nd/3rd gen)
o “Alcohol-like” reaction -> symptoms include drunkenness, nausea, vomiting
3) CYP2C9 inhibitors (e.g. amiodarone, 5-FU, fluoxetine) may ↑ glimepiride, glipizide
o Affects those Sulfonylureas that are hepatically eliminated
43
What is/are the contraindication(s) of Sulfonylureas?
Hypersensitivity
44
How is Glipizide metabolised?
* Mainly liver (~90%) -> Undergoes Phase I Hydroxylation
45
What is SU's place in therapy? (When is it typically used, What are the benefits and disadvantages)
2nd-line antidiabetic for T2DM, uncontrolled with diet and exercise OR in combination with other antidiabetics
No effect for T1DM (requires functioning beta-cells)
Benefits:
- Good HbA1c reduction (1.5%)
- Cost (at early stages of therapy)
Downsides:
- Weight gain
- Risks of hypoglycemia
- Efficacy wears off in long-term (15-20y)
46
What is the MOA of Thiazolidinediones (TZD)?
Peroxisome proliferator activated receptors (PPAR) agonist -> binding to and activation of PPAR promotes glucose uptake into target cells (skeletal muscle/adipose) by:
o ↓ insulin resistance; ↑ increase insulin sensitivity
* Note: No effects on insulin secretion but dependent on insulin presence for activity
47
Which TZD is the only one approved for use in combination with insulin?
Pioglitazone
48
What are the contraindications for TZDs?
1) Active liver disease (TZDs are hepatically cleared)
2) NYHA Class III or IV HF
49
What are the ADRs of TZDs? (6)
1) Hepatotoxicity
2) Edema (caution in NYHA Class I or II HF) -> from increased sodium and fluid retention
3) Increased risk of fractures (more likely in women)
4) Weight gain -> associated with edema
5) Increased risk of Congestive Heart Failure (HF)
6) Bladder cancer (Pioglitazone)
7) Elevated LDL (Rosiglitazone)
50
When should a patient on TZDs discontinue/ consider to discontinue TZD
1) ALT > 3x UNL (discontinue)
2) Signs and symptoms of hepatic dysfunction (regardless of ALT level)
3) Pt develop confirmed SnS of HF (consider dose reduction or discontinue)
51
Other than blood glucose levels, what else need to be monitored after starting TZDs?
- ALT level
(if ALT > 1.5 UNL during therapy, repeat LFTs weekly until normal; Discontinue if ALT >3x UNL)
- Signs and symptoms of HF
52
TZDs should not be initiated if ALT > ___ UNL
3x
53
What are TZDs place in therapy? (When is it used, benefits, disadvantages)
(T2DM) Monotherapy or in combination with other antidiabetics
Benefits:
- Moderate reduction in HbA1c (0.5-1.4%)
- Some benefits in fatty liver disease
Downsides:
- Weight gain (from edema)
- Hypoglycemia
- Numerous adverse effects (including hepatotoxicity and increased risk of HF and fracture)
54
What is the MOA of alpha-glucosidase inhibitor?
* Delay glucose absorption and ↓ PPG by competitively inhibiting brush border α-glucosidases enzyme required for breakdown of complex carbohydrates (i.e prevents breakdown of complex sugars)
* Acts locally in GIT
55
Comment on the pharmacodynamics of Acarbose (e.g onset of action, dose based on what)
* Rapid onset with each meal
* PPG lowering effect is dose related (↑ dose, ↑ PPG lowering)
* Dosing is weight-based
56
What are the ADRs of Acarbose? (2)
* GI: flatulence, abdominal pain, osmotic diarrhea (most common cause of drug discontinuation; glucose present in water pulls water into large intestine)
* ↑ LFT (specific for acarbose; ↑ risk at dose >100 mg TDS)
57
What are the contraindications of Acarbose?
* Breastfeeding
* GI disease (obstruction, IBD)
58
What are the DDIs of Acarbose?
Intestinal adsorbents and digestive enzyme preparations (e.g Yakult) may ↓ effects of α-Glucosidase inhibitors
59
What is Acarbose's place in therapy? (When is it used, benefits, disadvantages)
• Management of T2DM when hyperglycemia cannot be managed by diet alone (usually NOT used as monotherapy)
• Off label use: treatment in patients with T1DM who are on insulin therapy but require additional control in PPG level
Benefits:
- Good to be taken after heavy, high-carb meals (to control PPG)
Downsides:
- Poor HbA1c reduction (0.5-0.8%)
- Adherence issues (due to GI effects)
60
What is the MOA of GLP-1 Agonist? (3 ups and 2 downs)
Binds to GLP-1 receptors on β-cells and activate them (↑ adenylate cyclase -> ↑cAMP -> ↑PKA) leading to:
o Decreased gastric emptying
o Increased glucose-dependent insulin biosynthesis and secretion
o Decreases glucagon secretion
o Improve β-cell function
o Decreased food intake (from decreased gastric emptying)
61
What are the ADRs of Liraglutide? (3 total)
1) GI side effects:
o N/V (less for longer acting agents)
o Diarrhea (more for longer acting agents)
o Weight loss
2) Acute pancreatitis
3) Risk of thyroid cancer
o Counsel patients regarding the risk of medullary thyroid carcinoma and the symptoms of thyroid cancers
62
State how Liraglutide is administered.
SC injection once daily regardless of meals
63
What is the dosing of Liraglutide?
Initiate at 0.6mg once daily then titrate to 1.2mg once daily after 1 week. Can increase to 1.8mg
64
Which GLP-1 agonist can be taken orally?
Semaglutide
65
Does Liraglutide need dose adjustment in renal impairment?
No
66
What are the contraindication of GLP-1 Agonists?
Thyroid cancer
67
Which GLP-1 agonists are indicated for weight loss?
Liraglutide and Semaglutide
68
What are GLP-1 agonists place in therapy? (When is it used, benefits, disadvantages)
Recommended as first-line injectable over insulin, when insufficient glycemic control from oral therapy in T2DM
Benefits:
- Moderate reduction in HbA1c (0.7-1.5%)
- Weight loss
- ASCVD benefits (neutral for HF)
Downsides:
- Injectable (patient acceptability) [except Semaglutide]
69
What is the MOA of DPP-4 inhibitors?
Inhibit DPP-4 enzyme, preventing the degradation of GLP-1 -> leading to increased endogenous concentrations of Incretins, Incretins (e.g GLP-1) bind to their receptors and activate them -> longer stimulation of β-cell + ↓ glucagon secretion from pancreatic alpha cells -> ↑ glucose stimulated insulin release + ↓ glucagon secretion results in decreased hepatic glucose production -> ↓ blood glucose level
70
What are the names of Incretins and which cells release them?
Incretins are GIP (released from K cell) and GLP-1 (released from L cell)
71
What are Incretins?
Incretins: a group of metabolic hormones that are released post meal which increase insulin secretion from β-cell in a glucose dependent manner (only in presence of hyperglycemia)
72
What are the ADRs of Linagliptin?
- Nasopharyngitis
- Runny nose, sore throat
- Severe joint pain
73
What are the ADRs of Sitagliptin?
- Acute pancreatitis (unique to Sitagliptin)
- Headache
- N/V, abdominal pain
- Skin reaction
- Angioedema
- Severe joint pain
74
Which DPP-4 does not require dose adjustment and which one does? State the dose adjustment required
Linagliptin don't need
Sitagliptin need adjust. Normal dose = 100mg OD. Half when CrCl below 50ml/min, half again when below 30ml/min
75
What are DPP-4 inhibitors place in therapy? (When is it usually used, benefits and disadvantages)
2nd or 3rd line antidiabetic in T2DM, usually used in combination with other agents (rarely monotherapy)
Benefits:
- Less side effects than GLP-1A
- PO route compared to SC for most GLP-1As
Downsides:
- Poor HbA1c reduction (0.5-0.9%)
- Neutral effect on weight
- No apparent ASCVD, HF or CKD benefits
76
What component/ molecule present in Liraglutide (GLP-1 agonist) is proposed to offer protection from cleavage by DPP4?
C16 fatty acid
77
What is the MOA of SGLT2 inhibitor?
Inhibits SGLT2 transporter which leads to ↓ reabsorption of filtered glucose and ↓ renal threshold for glucose (kidney start to remove glucose at lower plasma glucose Cmax) -> ↑ urinary glucose excretion
78
What is the place in therapy for SGLT2 inhibitor? (When is it usually used, benefits and disadvantages)
Monotherapy or combination with other antidiabetics for T2DM
Benefits:
1) Slight weight loss benefits
2) Mild BP lowering effect (good for hypotensive patients)
3) Has many benefits besides glucosuria effects however costs remain a limitation
o ASCVD benefit (only Canagliflozin and Empagliflozin so far)
o Heart failure benefit (class effect) -> Dapa and Empa was approved for HF for general population
- Better use of ketone and fatty acid oxidation is the purported mechanism of SGLT2i that improve cardiac function [↑ Cardiac energy (ATP) production relative to untreated diabetic hearts].
o CKD benefit (class effect) -> Dapa approved for CKD for general population
- Renal function dips by ~5mL/min/1.73m2 during initiation and reach lowest by 1-2 weeks, after that GFR slowly returns to pre-treatment values over next 6-9 months and after that rate of decline of GFR is slower than in untreated individuals
Disadvantage:
4) ↓ HbA1c by 0.8%-1.0% (quite weak; ~ same as DPP4i)
79
What are the side effects specific to Canagliflozin? (3)
Amputations, hyperkalemia, fractures
80
What are the ADRs of SGLT2i?
1) Hypotension, hypoglycaemia, urinary urgency and increased urine
o Risk of volume depletion increased with N/V/D
2) Renal impairment
3) ↑ LDL
4) Genital mycotic infection/UTI (>5%)
o Most common in first months after initiation
o More common in women and those with prior GMI
5) Increased risk of diabetic ketoacidosis
o Especially euglycemic DKA -> usually sugar level is high when people get DKA; but euglycemic DKA is harder to detect
o T1DM > common than T2DM
o Risk factors:
- >20% insulin dose reduction (esp in patients dependent on high dose insulin at baseline), lean body habitus, women, surgical stress, trauma, intercurrent illness (e.g sepsis, pneumonia), alcohol abuse, and patients with latent autoimmune diabetes of adulthood (T1DM)
6) Fournier’s gangrene
o Potentially life threatening
o More common in males
81
How would you counsel patient regarding management of ADRs with SGLT2i use? (ADRs: fungal infx, DKA, increased urine)
1) Mycotic infx/UTI
- Maintain genital hygiene, including keeping the
genital region dry. Applicable to Fournier’s Gangrene
2) DKA
- Avoid >20% reduction in insulin dose, careful monitoring following insulin dose changes
- Discontinue SGLT2 inhibitors during episodes of acute illness, vomiting, diarrhea, or inability to eat or drink (does not include Ramadan fasting)
- Hold 2 to 3 days prior to scheduled surgery.
3) ↑ Pee
- Patients should be provided with sick day advice, whereby patients are advised to hold their SGLT2 inhibitor until resolution of symptoms. Remember to restart when better.
- Some patients including those with heart failure may require liberalization of fluid intake if they are euvolemic when initiating SGLT2 inhibitors.
82
What are the contraindications of SGLT2i?
1) ESRD or dialysis
2) Hypovolemia (only start when hemodynamically stable)
83
Summarise the key points for SGLT2i use in a person with CKD
< 30ml/min cannot start
Can start treatment if patient is GFR ≥ 30ml/min and can continue even if GFR falls below 30ml/min unless not tolerated or kidney replacement therapy initiated
84
How is GLP-1 Agonist metbolised?
Endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination
85
What is the target LDL for a patient with only diabetes and no other additional ASCVD risk?
< 2.6 mmol/L (DM treated as CV high risk equivalent)
86
What is the target LDL for patient with diabetes and other ASCVD risk (very high risk)?
< 2.1mmol/L
87
State when fibrates are to be added on in TG management and which fibrate is preferred
o If TG > 4.5 mmol/L or TG level still high even with optimal LDL from statin, consider adding on fibrate
- Use fenofibrate (gemfibrozil has DDI with statin and increases risk of rhabomyolysis)
88
Describe lipid profile in diabetic patients
* HDL ↓
* LDL marginally ↑
* TG ↑
89
Which of the following non-pharmacological measures is most effective in reducing LDL?
a) Reduce saturated and trans fatty acid consumption
b) Increase consumption of unsaturated fat rich oils e.g vegetable oil, olive oil
c) 10kg weight loss
d) Body weight reduction and regular exercises
e) Consume less Alcohol, carbo rich food and fructose
a) Reduce saturated and trans fatty acid consumption
90
Which of the following non-pharmacological measures is most effective in reducing TG and increasing HDL?
a) Reduce saturated and trans fatty acid consumption
b) Increase consumption of unsaturated fat rich oils e.g vegetable oil, olive oil
c) 10kg weight loss
d) Body weight reduction and regular exercises
e) Consume less Alcohol, carbo rich food and fructose
d) Body weight reduction and regular exercises
91
What are the non-pharmacological management of diabetes? (Total 9)
1) Quit smoking
2) Weight Reduction (7% loss of initial body weight + better if lose weight quicker)
3) Exercise
* 150 min/week, spread into at least 3 days per week with no more than 2 consecutive days without exercise
o Moderate intensity -> anything that increases HR above baseline; anything that after done, you can still talk but cannot sing
* Include muscle strengthening activities at least 2 days per week
o Carry things heavier than you would normally carry
* If older (> 55 yo):
o Incorporate balance and functional training
- E.g standing on one foot, stretching, taichi etc
4) Diet Modification
* Fruit, vegetables, grains, cereals, legumes
* Skinless poultry, fish, lean meats
* Low fat dairy products
* Restrict alcohol and simple carbohydrates (mainly ↓ TG)
5) Skin care
6) Foot care
7) Eye care
8) Dental and oral care -> high sugar level increase risk of cavities
9) Identification tags
* More for T1DM who are children and cannot take care of themselves
92
What are some methods for prevention and management of DM complications? (6 total)
o Low-dose aspirin/clopidogrel
o Smoking cessation
o Blood pressure control
o Lipid profile control
o Vaccination (E.g influenza, pneumococcal vaccines)
o Metabolic Syndrome (treat each risk factor)
93
State when Aspirin should and should not be used in diabetes
SHOULD:
- Use as a secondary prevention strategy in those with diabetes and history of ASCVD
- Aspirin therapy may be considered as a primary prevention strategy in those with diabetes who are at increased CV risk, after a discussion with the patient on the benefits vs increased risk of bleeding
SHOULD NOT:
- Aspirin is not recommended for those at low risk of ASVCD
- For older patients >70 years, risk > benefit, generally do not start aspirin
• Note: ASCVD risk factors include LDL cholesterol ≥ 2.6 mmol/L, high blood pressure, smoking, chronic kidney disease, albuminuria, and family history of premature ASCVD.
94
What are the indications for insulin?
- Treatment of all types of DM
- DOC in pregnant patients with DM
95
What are the various mechanisms of action of insulin?
- Facilitate uptake of glucose by muscle and adipose tissue
- Inhibit hepatic glucose output (glycogenolysis and gluconeogenesis)
- Enhance fat storage (lipogenesis)
- Inhibit mobilization of fat for energy in adipose tissue (lipolysis, FFA)
- Increase protein synthesis; inhibit proteolysis in muscle
96
How is insulin metabolised?
- Exogenous insulin: mainly via kidneys
- Endogenous insulin: mainly via liver
97
What are the recommended needle lengths for insulin products?
Generally advocate for shorter needles.
Pen: 4mm, Vial: 6mm
No more than 6-8mm, as average skin thickness at insulin injection sites is 2.4mm, which does not vary significantly across different patient groups
98
What are some considerations for syringe size to be used?
- Generally, use the smallest syringe possible for the dose involved (to draw up a more accurate amount for each injection)
99
What are some considerations for the storage of insulin products?
Unopened insulin vials:
- Not refrigerated: good for 28d
- Refrigerated: good till expiration date
Opened insulin vials:
- Good for 28d regardless of refrigeration
- Exception is opened detemir (good for 42d)
See package insert for other insulin-containing devices (e.g. pens)
100
What are some of the areas where insulin can be administered?
- 2-inch circle around navel (abdomen)
- Outer upper arms
- Top and outer sighs (avoid bony areas around knees)
- Buttocks
Above arranged in decreasing rate of absorption
101
List the factors that affect insulin absorption
- Temperature (higher, more absorption)
- Massage (inc)
- Exercise (inc)
- Jet injectors (inc)
- Lipoatrophy (inc)
- Lipohypertrophy (dec)
- Others [needle size/gauge, administration technique (IM increases absorption), insulin preps, mixtures, conc, dose, insulin stability etc]
102
State the various rapid-acting insulin preparations, their onset, peak effect, duration of action and administration.
Rapid-acting insulin preps: Aspart, Lispro, Glulisine
Onset: 5-15min
Peak: 1-2h
Duration: 3-5h
Administer 15 mins before meals (1 injection per meal)
103
State the various short-acting insulin preparations, their onset, peak effect, duration of action and administration.
Short-acting prep: Regular insulin
Onset: 30-60min
Peak effect: 2-4h
Duration: 6-8h
Administer 30 mins before meals (1 injection per meal)
104
State the various intermediate-acting insulin preparations, their onset, peak effect, duration of action and administration.
Intermediate-acting preps: NPH
Onset: 1-2h
Peak: 6-12h
Duration: 10-16h
2 injections for 24h coverage, Inject at same time everyday regardless of meals
105
State the various long-acting insulin preparations, their onset, peak effect, duration of action and administration.
Long-acting preps: Detemir and Glargine
Onset: 0.8-2h; 1.5h
Peak: Hill; peakless
Duration:
(Detemir) 12h for 0.2U/kg; 20-24h for 0.4U/kg (2 injections for better coverage)
(Glargine) ~24h (1 injection for 24h coverage)
Inject at same time everyday regardless of meals
106
List the various ultra long-acting insulin preparations, their duration of actions, administration, and their considerations for use.
1) Degludec
- Peakless with a duration of action of 42h
- Inject (SC) once daily at any time of day
2) Glargine (U-300)
- Peakless, duration of action of 36h
- Once daily at same time every day
- NOT bioequivalent to glargine U-100
Both have seemingly lower rates of hypoglycemia than Glargine U-100
107
List the stable insulin mixes.
1) Regular + NPH
2) Rapid-acting + NPH
3) Rapid-acting (Aspart) + Degludec [mix right before administration]
108
List the unstable insulin mixes.
1) Glargine and other insulins (incompatible pH)
2) Detemir and other insulins (formulation)
3) Glulisine and other insulins (except NPH)
109
List the pre-mixed insulin preparations and their general dosing regimen.
1) NovoMix 30 (30% Aspart, 70% Aspart protamine)
2) Humalog Mix (25% Lispro, 75% Lispro protamine)
3) Mixtard 70/30 (70% NPH, 30% regular)
4) Mixtard 50/50 (50% NPH, 50% regular)
Due to the NPH-like component in all preps, these products are given twice daily.
Those containing rapid acting (e.g Novomix and Humalog) given within 15 mins of meal
Those containing regular insulin (Mixtards) given 30mins before meals
110
What are some of the pros and cons of pre-mixed insulin preparations?
Pros:
- Meal/snack (PPG) and basal (FPG) coverages
- Beneficial for those who have difficulty measuring and mixing insulin
- Less injections
Cons:
- Challenging to titrate and adjust dose (need to adjust basal and prandial coverage tgt)
111
List the general approach to dosing conversion for insulin. And state when must dose be decreased during conversion.
- Generally, most conversions are 1:1
1) Switch from twice daily NPH to once daily Glargine/Detemir -> decrease total daily dose by 20%
- Other exceptions:
2) Switch from U-300 glargine to alternative basal insulin analogue -> dec dose by 20% (FYI)
3) Switch from U-100 to U-300 glargine -> inc dose by 14% (to achieve similar glycemic control) (FYI)
112
List the various adjustments to oral therapies when antidiabetic injectables are initiated. (Metformin, SU, TZD, SGLT2i, DPP4i)
- Metformin: continue
- TZDs: discontinue or reduce dose (only pioglitazone can use with insulin)
- SU: discontinue/halve dose if initiating basal insulin; discontinue if initiating prandial insulin
- SGLT2i: continue
- DPP-4i: discontinue if GLP-1 initiated
113
List the adverse effects of insulin.
1) Hypoglycemia (BG 4.0mmol/L or less)
2) Lipodystrophy
(lipohypertrophy > atrophy; atrophy due to pork/beef insulin but phasing out)
3) Insulin resistance (rare)
4) Local allergic reactions (redness, swelling, itching at injection site) or systemic allergic reactions (both rare)
5) Weight gain (more than SUs)
- Type 1: +4.6kg over 5y
- Type 2: +4kg over 10y
114
Describe the management of hypoglycemia (15-15-15 rule).
15g of fast-acting carbohydrates (1/2 cup fruit juice, glucose tabs/gel, soft drinks, 1 tbsp honey etc)
Wait for 15 minutes
If BG is still <4mmol/L, take another 15g of fast-acting carbs
115
List the general approach to initiating insulin in a T2DM patient.
- Generally start with basal insulin (High HbA1c predominantly contributed by FPG)
- NPH <10 units at bedtime
- ~0.1IU/kg/d
116
List the various dose adjustments if HbA1c continues to be uncontrolled after initiation of insulin (when increase, when decrease).
- Increase dose if FPG is out of range for 3 consecutive days
- Increase dose by 2 units every 3 days till FPG is at goal
- Increase dose by 4 units every 3 days if FPG is consistently >10 mmol/L (Maximum rate of increase)
- Decrease dose by 10-20% if there is no clear reason for hypoglycemia
117
List the various adjustments that can be made to insulin regimen, if HbA1c levels are still elevated despite
1) FPG at goal; or
2) Basal insulin >0.5IU/kg/d
- Possible overbasalisation -> monitor for weight gain, hypoglycemia, or post-prandial hyperglycemia.
- Add PPG coverage -> 1 dose with largest meal of the day. 10% of basal insulin dose OR 4IU.
* If A1c < 8%, to also decrease basal dose by 4 IU or 10% if prandial coverage is increased -> prevent hypoglycemia
OR
- If patient does not want PPG insulin, can divide basal insulin (NPH) into 2 unequal doses. 2/3 given in the morning, and 1/3 given at night.
118
Which antidiabetic is the DOC for patients newly-diagnosed w T2DM?
Metformin (assuming no CI)
119
When should early combination therapies be considered?
If HbA1c levels are considerably elevated
120
State various modifications that can be done to antidiabetic therapy for the following:
- ASCVD
- HF
- CKD
- ASCVD: Add SGLT-2i or GLP-1 Agonist
- HF: Add SGLT-2i
- CKD: SGLT-2i > GLP-1 agonist
This is done without regard to HbA1c levels.
121
What can be done if patient is on metformin and A1c is still not at goal if:
a) Want to minimise hypoglycemia?
b) Want to promote weight loss?
c) Patient is poor?
d) patient has fatty liver disease (e.g NASH/NAFLD)?
a) Avoid SUs and insulin (if hypoglycemia risks)
b) Add SGLT2i or GLP-1A to promote weight loss
c) Consider SUs > TZD > DPP-4i if there are cost considerations
d) TZD
122
What can be done if A1c is not at target despite optimized oral therapy?
- Initiate GLP-1A.
- GLP-1A preferred over insulin as first-line injectable.
123
What are some compelling indications for starting insulin rather than GLP-1? (4 total)
- Severe symptoms of hyperglycemia
- Ongoing catabolism (weight loss)
- BG > 16.7 mmol/L
- HbA1c > 10%
124
Describe Diabetic Ketoacidosis (DKA), and its pathophysiology.
DKA occurs when the body does not have enough insulin for glucose uptake into target cells.
The body compensates by increasing the metabolism of fat as fuel, which results in the production of ketones.
Stress from insulin insufficiency also lead to increased glucagon secretion leading to increased gluconeogenesis and decreased ketone utilisation.
Occurs more commonly in T1DM.
125
Describe Hyperglycemic Hyperosmolar Syndrome (HHS), and its signs and symptoms.
Marked elevation in BG levels (up to >33mol/L).
Often characterised by severe dehydration (extreme thirst), and a drunken stupor (confused state).
Occurs more often in T2DM.
126
Describe the Dawn Phenomenon.
Production of cortisol in early morning, which causes a sharp increase in BG levels
127
Describe the Somogyi Effect.
Decline in BG levels at night due to 1) no night snack or 2) too much insulin. Body responds by increasing glucagon secretion, causing BG levels to sharply rise in early morning.
128
How do you differentiate between the Dawn Phenomenon and Somogyi Effect?
Wake patient in the middle of the night (2-3am) to measure blood glucose levels.
129
How may culture/race influence diabetes risk?
Genetics
- genetic (asian less muscle, more abdominal fat, higher insulin resistance, higher T2DM risk)
Environment
- stress level (more stress, more binge eating, less exercise)
- poor health literacy (eg carb make us full)
- language barrier
Food
- diet (asian more carb heavy)
130
How may ramadan affect DM management?
fasting abstains from food, drink, meds from dawn to sunset
1) no food in the day cause risk of hypoglycemia, lack of exercise, binge eating for Iftar (sunset meal)
2) no water in the day causes risk of dehydration, thrombosis, acute diabetes
3) no meds in the day increases risk of hyperglycemia, acute diabetes (HHS/DKA)
Overall: leads to unpredictable blood glucose levels in individuals with differing baseline glycemic control in an ethnic minority group who may be reluctant to seek professional advice as they are worried HCP do not understand
131
List some general ways to adjust medications during ramadan (4 points)
1) TDS to BD dosing
2) reduce med with high hypoglycemia potential e.g insulin, SU
3) Evening dose higher than morning (sunset meal heavier than predawn meal)
4) Lower overall potency of medications during Ramadan (compared to pre-Ramadan periods) as overall patients eat lesser
132
tips to address cultural differences
culturally specific diabetes support
understand patient views (listen, explain, acknowledge, recommend, negotiate)
133
What are risk factors for diabetic foot infection (5 total) ?
1) poor glycemic control
2) peripheral artery disease
3) peripheral neuropathy
4) visual impairment (cannot see feet)
5) smoking
134
What are some education pointers for diabetic foot infection patients (5)
1) Foot protection (Do not be bare footed even at home, at least wear socks. Do not wear too tight or loose shoes to prevent poor circulation or abrasion)
2) Nail, foot care and hygiene (Soak foot in water, wash foot with soap and dry after washing. Use moisturiser but not apply between toes or will grow fungus. Cut nails straight to prevent ingrown toenails and leave abit of gap)
3) Annual foot examination (vascular assessment of pedal pulse to ensure no peripheral artery disease. neurologic exam to ensure no peripheral neuropathy)
4) Self examination of foot daily (check for dryness, cracks or new injuries starting to form, remember to check base of feet as well)
5) Minimise risk factors eg control blood glucose, smoking cessation
135
State the monitoring parameters for a patient with DM and when to monitor (6 total)
Hint: think of complications
1) HbA1c (q3mth, q6mth if stable)
2) BP (every visit)
3) Lipid panel (q3-6mth after initiation/ titration i.e poor control, once a year if controlled)
4) Eye exam (q6mth if not controlled, once a year if stable)
5) Renal function (6 mth or annually depending on presence of proteinuria)
6) Foot exam (daily by patient, annually by podiatrist)
136
State the maximum basal insulin dose above which, basal insulin should not be increased any further
0.5 IU/kg
137
What are the symptoms of nocturnal hypoglycemia? (4 total)
Nightmares, restless sleep, profuse sweating, morning headache
138
What are signs and symptoms of DKA?
Signs and Symptoms:
- Ketones in blood and urine
- Acidosis (presence of anion gap, low bicarb, low blood pH)
- Fruity breath and odor
- Confusion (in severe cases)
139
Compare and contrast DKA and HHS (4 main differences)
1) DKA got ketones and acidosis (presence of anion gap, low bicarb, low blood pH). HHS less likely to have ketones and acidosis (normal anion gap, normal-ish bicarb, normal blood pH)
2) DKA onset more gradual vs HHS more abrupt
3) Both have high blood glucose level (but HHS > DKA) -> serum osmolarity in HHS > DKA
4) DKA patient usually still alert (unless severe) while HHS patient usually coma/stupor
140
What is the usual size of insulin vial?
10mL
