IC11 Diabetes Mellitus Management Part 1 Flashcards
What is diabetes?
Metabolic disorder characterized by insulin resistance or insufficiency or both
What is the pathogenesis of T1DM?
Autoimmune mediated destruction of pancreatic Beta cells due to positive antibodies resulting in insulin deficiency
What are the 3 stages of T1DM and how do they differ?
Stage 1: Presymptomatic Normoglycemia with positive Ab
Stage 2: Presymptomatic Dysglycemia with positive Ab
Stage 3: Symptomatic New onset Hyperglycemia with positive Ab
What is a surrogate measure of insulin and why is it used?
C peptide. It is a byproduct in the synthesis of insulin. If it is absent, it suggests deficiency in insulin production.
What is the pathogenesis of Type 2 DM?
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.
What is a characteristic of Type 2 DM in glucose and insulin levels in the blood?
Simultaneous elevations at early stage T2DM
What are 6 main differences between T1DM and T2DM?
- Age - Young < 30 y.o. vs Old > 40 y.o.
- Clinical presentation - Abrupt vs Gradual
- Insulin production - Absent vs Normal/Abnormal
- Primary cause - Autoimmune mediated vs insulin resistance
- Physical appearance - Thin vs Overweight
- Ketosis - Frequent vs Uncommon
Signs and Symptoms of Hypoglycemia
- Hunger, Fatigue, Weakness - No energy
- Headache, anxious, dizzy, irritable, tremor - Affect CNS
- Fast Heartbeat, sweating - Macrovascular effect (CV)
- Impaired vision - Affect eye
Signs and symptoms of hyperglycemia (3Ps and more)
Polyphagia (hungry), polyuria (frequent urination), polydipsia (extreme thirst, dry skin)
Others: Blurred vision (eye), drowsiness (CNS), reduced healing (immunity)
4 common Parameters used to measure DM
- Fasting Blood Glucose (FBG)
- Random / Casual Plasma Glucose
- Postprandial Glucose (PPG)
- HbA1c
Requirements for FBG
No calorie intake > 8h prior
Requirements for random plasma glucose
NIL, anytime of the day
Requirements for PPG
2h after meals
In clinical setting, a standardized 75g oral dose of glucose can be administered (OGTT)
When is HbA1c used? When is it not suitable?
Long term glucose monitoring as it measures the average blood glucose over 3-month period
Some anemia
At what end of the HbA1c range are contributed by basal and postprandial glucose
HbA1c at the lower end (7-8%) - Postprandial
HbA1c at the higher end (9-10%) - Basal
How frequent do you use glucometers for T1DM, T2DM and at practice setting?
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)
T2DM diagnosis requirement for sample
At least 2 abnormal test results from the same blood sample
Diagnostic criteria using measuring parameters
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
Associated Risks of Insulin Resistance (2 big categories)
Microvascular (Nephropathy, Neuropathy, Retinopathy)
Macrovascular (Cardiovascular disease)
What risks do antidiabetic therapy help to slow down the onset and progression? Which do not?
Microvascular complications
Macrovascular complications do not correlate with reduced HbA1c (U shaped relationship - Worsened CV outcomes)
What are some complications of DM?
- Micro and macrovascular
- Glucose toxicity - Progression of microvascular complications
- Degree of glucose control - Does not reduce risk for macrovascular CV events
Treatment targets of DM
HbA1c < 7% (7-8.5%) if vulnerable
FBG 4-7 mmol/L
PPG < 10 mmol/L
3 types of individualized HbA1c targets
- General < 7%
- Stringent 6-6.5% (Young, no significant CVD)
- Less stringent 7.5-8% (Elderly, comorbidites)
6 Monitoring parameters in T2DM and frequency
- Blood pressure - Every visit
- Eye exam - q6mth / q1yr
- Foot exam - self daily / q1yr (podiatrist)
- Lipid panel - q3-6mth / q1yr
- HbA1c - q3mth / q6mth
- Renal function (Albuminuria) - q6mth / q1yr
Non-pharmacological management of DM
Therapeutic Lifestyle Change (TLC)
1. Smoking
2. Weight loss
3. Diet
4. Exercise Moderate intensity / Muscle strengthening
Antidiabetic Drug classes
- Metformin (Biguanides)
- Glipizide (Sulfonylureas)
- Pioglitazone (Thiazolidinediones)
- Acarbose (Alpha Glucosidase Inhibitor)
- Incretins
- Liraglutide (GLP-1 Receptor Antagonists)
- Sitagliptin, Linagliptin (DPP-4 Inhibitors)
- Empagliflozin (SGLT2 Inhibitors)
Metformin MOA
Hepatic glucose output reduction
Peripheral/Muscle glucose uptake increase (sensitivity)
Metformin clearance
Renal clearance unchanged
Metformin max dosing
3g (One 1g tablet TDS)
Metformin comes in 500mg, 850mg, 1g
Metformin ADR
GI, anorexia, metallic taste, vitamin B12 deficiency (anemia, peripheral neuropathy), lactic acidosis (rare but severe)
Metformin Contraindications
- Renal impairment (Severe)
- Hypoxia / Hypoxemia risk (HF, sepsis, liver impaired)
- Alcoholism
Metformin DDI
- Alcohol (lactic acidosis risk)
- Iodinated contrast material / radiologic procedure
- Cationic drugs (Cimetidine, digoxin) affect renal tubular transport
Metformin use in renal insufficiency according to eGFR
eGFR > 60 - Monitor yearly
eGFR 45-60 - Monitor every 6 months
eGFR 30-45 - Halved max dose and do not start
eGFR < 30 - Stop
Metformin lowers HbA1c by
1.5%
Metformin benefits for place in therapy
- Negligible weight gain
- Low side effect incidence
- Positive effect of lipid profile
- CV event reduction (Possible)
- Prevent / Delay T2DM – BMI > 35 kg/m2, age < 60, women with prior gestational DM (Metformin + TLC)
- 1st line gestational diabetes (pregnant)
Name the first, second and third generation sulfonylureas. Why are first generations rarely used? Why is one of the 2nd generation SU preferred?
- Tolbutamide
- Glipizide, Gliclazide, Glibenclamide
- Glimepiride
1st Gen SU has more ADR except tolbutamide
Glipizide is hepatically cleared and preferred in renal impairment
Sulfonylurea MOA and what is required for it to work
- Acts on postprandial glucose
- Stimulate insulin secretion by blocking ATP-sensitive potassium channels of Beta cells
- Reduce hepatic glucose output
- Increase insulin sensitivity
- Needs functional beta cells
Sulfonylurea ADR
Hypoglycemia, weight gain, blood dyscrasias (Rare)
Sulfonylurea DDI
BB (Masks symptoms of hypoglycemia), alcohol, CYP2C9 inhibitors
Sulfonylureas’ place in therapy (HbA1c, line of use, benefits, caution, cost)
HbA1c lowering by 1.5% (Need functional Beta cells)
No other extra benefits
Caution with patient having irregular meals
Cost effective at initial stages
Thiazolidinediones include
Pioglitazone, Rosiglitazone
TZD MOA
Peroxisome proliferator activated receptor agonist ⇒ Promote cell glucose uptake
TZD elimination route
Hepatic CL
5 TZD ADR
Hepatotoxic – ALT > 3X ULN / Dysfunction = Do not use
Edema, Weight gain
Fracture
Bladder cancer (Pioglitazone)
LDL elevation (Rosiglitazone)
TZD Contraindications
Black Box Warning – NYHA III / IV HF, active liver disease
TZD place in therapy (HbA1c, benefits, risks)
HbA1c lowering by 0.5-1.4%
Benefits Fatty Liver Disease (Obese)
Consider HF risks
Fracture risks in women
Name of Alpha Glucosidase Inhibitors
Acarbose
When is acarbose used
In combination with other antidiabetics when diet alone cannot manage DM
Acarbose MOA
Delayed glucose absorption by competitive inhibition of the enzyme that digests complex carbohydrates (PPG reduced)
Acarbose elimination route
Fecal elimination
Acarbose dosing (initiation & uptitration)
Starting dose 25mg BD-TDS with meal, uptitrate 25mg/day q2-4wk to max dose 150mg/day (<60kg) / 300mg/day (>60kg)
Acarbose ADR
GI flatulence and diarrhea = Discontinuation
LFT raised by acarbose when >100mg TDS
Acarbose CI
Breastfeeding
GI obstruction, IBS
Acarbose DDI
Adsorbents, Digestive enzyme preparations
Acarbose place in therapy (HbA1c and others)
HbA1c lowering by 0.5-0.8%
PPG control
Carbohydrate rich diet (Useful)
