IC11 Diabetes Mellitus Management Part 1

Question 1

What is diabetes?

Answer 1

Metabolic disorder characterized by insulin resistance or insufficiency or both

Question 2

What is the pathogenesis of T1DM?

Answer 2

Autoimmune mediated destruction of pancreatic Beta cells due to positive antibodies resulting in insulin deficiency

Question 3

What are the 3 stages of T1DM and how do they differ?

Answer 3

Stage 1: Presymptomatic Normoglycemia with positive Ab

Stage 2: Presymptomatic Dysglycemia with positive Ab

Stage 3: Symptomatic New onset Hyperglycemia with positive Ab

Question 4

What is a surrogate measure of insulin and why is it used?

Answer 4

C peptide. It is a byproduct in the synthesis of insulin. If it is absent, it suggests deficiency in insulin production.

Question 5

What is the pathogenesis of Type 2 DM?

Answer 5

Progressive and gradual loss of adequate Beta cell insulin secretion due to insulin resistance

Insulin resistance results when glucose utilization is impaired and hepatic glucose output increases despite the presence of insulin.

Question 6

What is a characteristic of Type 2 DM in glucose and insulin levels in the blood?

Answer 6

Simultaneous elevations at early stage T2DM

Question 7

What are 6 main differences between T1DM and T2DM?

Answer 7

1. Age - Young < 30 y.o. vs Old > 40 y.o.
2. Clinical presentation - Abrupt vs Gradual
3. Insulin production - Absent vs Normal/Abnormal
4. Primary cause - Autoimmune mediated vs insulin resistance
5. Physical appearance - Thin vs Overweight
6. Ketosis - Frequent vs Uncommon

Question 8

Signs and Symptoms of Hypoglycemia

Answer 8

1. Hunger, Fatigue, Weakness - No energy
2. Headache, anxious, dizzy, irritable, tremor - Affect CNS
3. Fast Heartbeat, sweating - Macrovascular effect (CV)
4. Impaired vision - Affect eye

Question 9

Signs and symptoms of hyperglycemia (3Ps and more)

Answer 9

Polyphagia (hungry), polyuria (frequent urination), polydipsia (extreme thirst, dry skin)

Others: Blurred vision (eye), drowsiness (CNS), reduced healing (immunity)

Question 10

4 common Parameters used to measure DM

Answer 10

1. Fasting Blood Glucose (FBG)
2. Random / Casual Plasma Glucose
3. Postprandial Glucose (PPG)
4. HbA1c

Question 11

Requirements for FBG

Answer 11

No calorie intake > 8h prior

Question 12

Requirements for random plasma glucose

Answer 12

NIL, anytime of the day

Question 13

Requirements for PPG

Answer 13

2h after meals

In clinical setting, a standardized 75g oral dose of glucose can be administered (OGTT)

Question 14

When is HbA1c used? When is it not suitable?

Answer 14

Long term glucose monitoring as it measures the average blood glucose over 3-month period

Some anemia

Question 15

At what end of the HbA1c range are contributed by basal and postprandial glucose

Answer 15

HbA1c at the lower end (7-8%) - Postprandial

HbA1c at the higher end (9-10%) - Basal

Question 16

How frequent do you use glucometers for T1DM, T2DM and at practice setting?

Answer 16

Frequency varies
- T1DM pregnancy: 4x/day before meals/bed/3 am (Higher risk of hypoglycemia, more frequent)
- T2DM: > 3X/day for multiple injection insulin
- Non-insulin injection patients: Self-monitoring blood glucose guides success therapy
- Practice setting: Before breakfast and 2h after largest meal (2X/day)

Question 17

T2DM diagnosis requirement for sample

Answer 17

At least 2 abnormal test results from the same blood sample

Question 18

Diagnostic criteria using measuring parameters

Answer 18

HbA1c ≤ 6% = No diabetes

HbA1c ≥ 7% = Diabetes

HbA1c 6.1-6.9% = Require further diagnostic test
- FBG ≤ 6 mmol/L OR OGTT < 7.8 mmol/L = No DM
- FBG 6.1-6.9 mmol/L OR OGTT 7.8-11 mmol/L = Pre-DM
- FBG ≥ 7 mmol/L OR OGTT ≥ 11.1 mmol/L = DM

Question 19

Associated Risks of Insulin Resistance (2 big categories)

Answer 19

Microvascular (Nephropathy, Neuropathy, Retinopathy)

Macrovascular (Cardiovascular disease)

Question 20

What risks do antidiabetic therapy help to slow down the onset and progression? Which do not?

Answer 20

Microvascular complications

Macrovascular complications do not correlate with reduced HbA1c (U shaped relationship - Worsened CV outcomes)

Question 21

What are some complications of DM?

Answer 21

1. Micro and macrovascular
2. Glucose toxicity - Progression of microvascular complications
3. Degree of glucose control - Does not reduce risk for macrovascular CV events

Question 22

Treatment targets of DM

Answer 22

HbA1c < 7% (7-8.5%) if vulnerable
FBG 4-7 mmol/L
PPG < 10 mmol/L

Question 23

3 types of individualized HbA1c targets

Answer 23

1. General < 7%
2. Stringent 6-6.5% (Young, no significant CVD)
3. Less stringent 7.5-8% (Elderly, comorbidites)

Question 24

6 Monitoring parameters in T2DM and frequency

Answer 24

1. Blood pressure - Every visit
2. Eye exam - q6mth / q1yr
3. Foot exam - self daily / q1yr (podiatrist)
4. Lipid panel - q3-6mth / q1yr
5. HbA1c - q3mth / q6mth
6. Renal function (Albuminuria) - q6mth / q1yr

Question 25

Non-pharmacological management of DM

Answer 25

Therapeutic Lifestyle Change (TLC) 1. Smoking 2. Weight loss 3. Diet 4. Exercise Moderate intensity / Muscle strengthening

Question 26

Antidiabetic Drug classes

Answer 26

1. Metformin (Biguanides) 2. Glipizide (Sulfonylureas) 3. Pioglitazone (Thiazolidinediones) 4. Acarbose (Alpha Glucosidase Inhibitor) 5. Incretins 6. Liraglutide (GLP-1 Receptor Antagonists) 7. Sitagliptin, Linagliptin (DPP-4 Inhibitors) 8. Empagliflozin (SGLT2 Inhibitors)

Question 27

Metformin MOA

Answer 27

Hepatic glucose output reduction Peripheral/Muscle glucose uptake increase (sensitivity)

Question 28

Metformin clearance

Answer 28

Renal clearance unchanged

Question 29

Metformin max dosing

Answer 29

3g (One 1g tablet TDS) Metformin comes in 500mg, 850mg, 1g

Question 30

Metformin ADR

Answer 30

GI, anorexia, metallic taste, vitamin B12 deficiency (anemia, peripheral neuropathy), lactic acidosis (rare but severe)

Question 31

Metformin Contraindications

Answer 31

1. Renal impairment (Severe) 2. Hypoxia / Hypoxemia risk (HF, sepsis, liver impaired) 3. Alcoholism

Question 32

Metformin DDI

Answer 32

1. Alcohol (lactic acidosis risk) 2. Iodinated contrast material / radiologic procedure 3. Cationic drugs (Cimetidine, digoxin) affect renal tubular transport

Question 33

Metformin use in renal insufficiency according to eGFR

Answer 33

eGFR > 60 - Monitor yearly eGFR 45-60 - Monitor every 6 months eGFR 30-45 - Halved max dose and do not start eGFR < 30 - Stop

Question 34

Metformin lowers HbA1c by

Answer 34

1.5%

Question 35

Metformin benefits for place in therapy

Answer 35

1. Negligible weight gain 2. Low side effect incidence 3. Positive effect of lipid profile 4. CV event reduction (Possible) 5. Prevent / Delay T2DM – BMI > 35 kg/m2, age < 60, women with prior gestational DM (Metformin + TLC) 6. 1st line gestational diabetes (pregnant)

Question 36

Name the first, second and third generation sulfonylureas. Why are first generations rarely used? Why is one of the 2nd generation SU preferred?

Answer 36

1. Tolbutamide 2. Glipizide, Gliclazide, Glibenclamide 3. Glimepiride 1st Gen SU has more ADR except tolbutamide Glipizide is hepatically cleared and preferred in renal impairment

Question 37

Sulfonylurea MOA and what is required for it to work

Answer 37

1. Acts on postprandial glucose 2. Stimulate insulin secretion by blocking ATP-sensitive potassium channels of Beta cells 3. Reduce hepatic glucose output 4. Increase insulin sensitivity 5. Needs functional beta cells

Question 38

Sulfonylurea ADR

Answer 38

Hypoglycemia, weight gain, blood dyscrasias (Rare)

Question 39

Sulfonylurea DDI

Answer 39

BB (Masks symptoms of hypoglycemia), alcohol, CYP2C9 inhibitors

Question 40

Sulfonylureas' place in therapy (HbA1c, line of use, benefits, caution, cost)

Answer 40

HbA1c lowering by 1.5% (Need functional Beta cells) No other extra benefits Caution with patient having irregular meals Cost effective at initial stages

Question 41

Thiazolidinediones include

Answer 41

Pioglitazone, Rosiglitazone

Question 42

TZD MOA

Answer 42

Peroxisome proliferator activated receptor agonist ⇒ Promote cell glucose uptake

Question 43

TZD elimination route

Answer 43

Hepatic CL

Question 44

5 TZD ADR

Answer 44

Hepatotoxic – ALT > 3X ULN / Dysfunction = Do not use Edema, Weight gain Fracture Bladder cancer (Pioglitazone) LDL elevation (Rosiglitazone)

Question 45

TZD Contraindications

Answer 45

Black Box Warning – NYHA III / IV HF, active liver disease

Question 46

TZD place in therapy (HbA1c, benefits, risks)

Answer 46

HbA1c lowering by 0.5-1.4% Benefits Fatty Liver Disease (Obese) Consider HF risks Fracture risks in women

Question 47

Name of Alpha Glucosidase Inhibitors

Answer 47

Acarbose

Question 48

When is acarbose used

Answer 48

In combination with other antidiabetics when diet alone cannot manage DM

Question 49

Acarbose MOA

Answer 49

Delayed glucose absorption by competitive inhibition of the enzyme that digests complex carbohydrates (PPG reduced)

Question 50

Acarbose elimination route

Answer 50

Fecal elimination

Question 51

Acarbose dosing (initiation & uptitration)

Answer 51

Starting dose 25mg BD-TDS with meal, uptitrate 25mg/day q2-4wk to max dose 150mg/day (<60kg) / 300mg/day (>60kg)

Question 52

Acarbose ADR

Answer 52

GI flatulence and diarrhea = Discontinuation LFT raised by acarbose when >100mg TDS

Question 53

Acarbose CI

Answer 53

Breastfeeding GI obstruction, IBS

Question 54

Acarbose DDI

Answer 54

Adsorbents, Digestive enzyme preparations

Question 55

Acarbose place in therapy (HbA1c and others)

Answer 55

HbA1c lowering by 0.5-0.8% PPG control Carbohydrate rich diet (Useful)