Understanding Diabetes and First Line for T2DM Flashcards
Describe the pathophysiology behind Type 1 Diabetes
Absolute deficiency of pancreatic B-cell function
Pancreas unable to produce insulin due to immune mediated destruction and positive antibodies
What are the different stages of T1DM?
Stage 1: Autoimmunity (Positive antibodies), Normoglycemia and presymptomatic
Stage 2: Autoimmunity (positive antibodies), Dysglycemia and presymptomatic
Stage 3: Autoimmunity, new onset of hyperglycemia and symptomatic
What are the types pf positive antibodies present? HINT: List all 5
Insulin
Islet cell autoantibodies
Autoantibodies to GAD
Tyrosine phosphatases IA-2 and IA-2b
Zinc transporter 8
Describe the pathogenesis of Type 2 DM.
Progressive loss of adequate B-cells insulin secretion on the background of insulin resistance
In presence of insulin, glucose utilization is impaired and hepatic glucose output increased.
Name the differences between T1DM and T2DM.
Primary causes
- T1: autoimmune mediated pancreatic beta cell destruction; positive antibodies
- T2: insulin resistance, impaired insulin secretion and negative antibodies
Insulin production
- T1: Absent
- T2: Normal/ Abnormal
Age
- T1: Usually < 30
- T2: > 40y; increased in obese children and young adults
Onset of clinical presentations
- T1: Abrupt
- T2: Gradual
Physical appearance
- T1: Thin
- T2: Overweight
Proneness to ketosis
- T1: Frequent
- T2: Uncommon
What are the signs and symptoms of hyperglycemia?
Dry skin
Extreme thirst
Frequent urination
Drowsiness
Decreased healing
Hunger
What are the signs and symptoms of hypoglycemia?
Shaking
Fast heartbeat
Dizziness
Sweating
Impaired vision
Weakness / fatigue
Headache
Anxious
Irritable
Hunger
What are some monitoring parameters used to measure DM?
Fasting plasma glucose
Random plasma glucose
Postprandial plasma glucose
Hba1C
Define the following monitoring parameters. (FPG, PPG, Hba1c)
FPG: No calorie intake for more than 8 hours
PPG: Glucose level measured after meal, usually after 2h
- Use standardized 75g oral glucose tolerance test
Hba1c: average amount of glucose in blood over past 3 months
What is the relationship between Hba1c, FPG and PPG?
Hba1c = 3 months average of (FPG + PPG)
Why is Hba1c not often used to diagnose DM? Which is a better parameter? (ref slide 17)
Hba1c provide a range of basal and postprandial contributions.
Better indicator would be basal hyperglycemia since it contributes a larger proportion at high Hba1C
What is the purpose of glucometers?
Monitor hypo/hyperglycemia
Adjust medications, diet and exercise
What is the frequency of use of glucometers in T1DM? When should glucose monitoring be done?
What other populations also following the T1DM regime?
More than 4 times daily
To do glucose reading:
- Before meals
- At bedtime
- At 3AM
Pregnant, insulin pump users
How often should those with T2DM on multiple injections of insulin check their glucometer reading?
More than or equal 3 times daily
When is the ideal time for patients to check their glucose reading?
Before breakfast
2h after largest meal
Patient comes in with HbA1c < 6.0%, what is the clinical susceptibility of diabetes? What should you advice a patient and when should the next test be done?
No diabetes
To maintain a healthy lifestyle and weight. Repeat test in 3 years
Patient comes in with HbA1c < 6.1-6.9%, what should you do?
Proceed to FPG or PPG
What is the criteria to diagnose no diabetes?
Hba1C < 6.0%
FPG < 6.0 mmol/L
PPG < 7.8 mmol/ L
When should pre diabetes be suspected?
FPG 6.1-6.9 mmol/L
PPG 7.8 - 11.0 mmol/L
When should diabetes be suspected ?
FPG > 7.0mmol/L
PPG > 11.1 mmol/L
Hba1C > 7%
Patient comes in with HbA1c > 7.0%, what does this mean?
No further test needed
Patient likely have diabetes
Is Hba1C needed to diagnose those with diabetes?
No
2 abnormal readings of FPG and PPG are generally recommended
What are the potential complications associated with diabetes? Categorize them according to microvascular and macrovascular complications.
Microvascular:
Retinopathy, blindness, Nephropathy, kidney failure, Neuropathy, Amputation
Macrovascular: CVD
How are macrovascular and microvascular outcomes related to the lowering of Hba1c?
Decrease in Hba1c can help lower risk of microvascular complications
Relationship not clear between degree of glucose control and risk of macrovascular CV events
What is the general target goal of Hba1c, FPG and PPG?
Hba1c < 7.0%
FPG: 5.0 - 7.0
PPG: < 10
When should more stringent Hba1c goals (3) be set? Define the more stringent Hba1c goal.
Hba1c: 6.0-6.5%
Shorter disease duration
Longer life expectancy as patient is young
No significant CVD
When should less stringent Hba1c goals (5) be set? Define the less stringent goals.
Hba1c: 7.5-8.0%
History of severe hyperglycemia
Limited life expectancy
Advanced complications
Extensive comorbidities
Target difficult to attain despite intensive SMBG, repeated lifestyle changes and effective counselling
How frequent should the following parameters be monitored for stable DM patients?
HbA1C
Lipid
BP
Eye Exam
Renal function test
Foot Exam
Hba1c: Every 6 months
Lipid panel: 1 year
BP: Every visit
Eye exam: 1 year
Renal function test: every 6 months/ annually
Foot exam: annually by podiatrist
Which are the parameters to be monitored more frequently and how frequent should they be monitored?
Hba1c: every 3 months
Lipid panel: 6 months
Eye exam: 6 months
What are the nonpharmacological advice to give patients with diabetes?
Quit smoking
Weight reduction by 7% of initial body weight
Exercise about 150min/ week and spread into at least 3 days a week
Balanced diet
Restrict alcohol and simple carbs
How can T2DM be prevented or delayed?
Lifestyle intervention through weight loss and physical activity
Initiating metformin for those BMI > 35, aged < 60 years and women with prior gestational diabetes mellitus
What is the indication for use of metformin?
Monotherapy with diet and exercise
Combination therapy with other antidiabetic agents and/or insulin
What is the mechanism of action of metformin?
Decreases hepatic glucose production
Increase peripheral glucose uptake and utilization and hence, increases insulin sensitivity
How is Metformin excreted?
Renally
What are some adverse drug events associated with the use of Metformin?
Diarrhea
Anorexia
Metallic tase
Decrease serum B12 concentration hence to check hemolytic anemia
Lactic acidosis
How does lactic acidosis occur?
Lactic acidosis occurs when
1. Glucose broken down in pyruvate
2. Pyruvate breaks down to lactate and H+ in the presence of no oxygen which can be caused by metformin
What are some contraindicated group of patients where Metformin use should be reconsidered to prevent lactic acidosis?
Heart failure
Sepsis
Liver impairment
Alcoholism
More than 80 years old
What are some drug drug interactions of Metformin and how do they affect its efficacy?
Alcohol: increase patient risk of lactic acidosis
Iodinated / contrast media
Cationic drugs such as cimetidine and digoxin: Increase metformin by competing for renal tubular transport
How is dose adjustment done for patients with renal insufficiency?
eGFR
> 60: no dose adjustment
45 - 60: continue but monitor renal function every 3-6 months
30-45: use lower dose and monitor every 3 months; do not initiate metformin for those not started
< 30: stop
What are the benefits of using Metformin?
Decrease A1c level by 1.5%
Negligible weight fain and hypoglycemia
Low incidence of side effect
Helps prevent T2DM
What are the types of sulfonylureas? HINT: Generations
First Gen: Tolbutamide
Second Gen: Glipizide, Gliclazide, Glibenclamide
Third Gen: Glimepride
What is the preferred drug for those renally impaired?
Glipizide
Describe the mode of action for sulfonylureas
Stimulates insulin secretion by blocking K+ channel of B cells
Decreases hepatic glucose output and increase insulin sensitivity
What is a strict criteria for sulfonylureas to work?
Functional beta cells
What are the adverse effects of sulfonylureas?
Hypoglycemia (NOTE: Prevalent in elderly)
Weight gain
Blood dyscracia
What are the drug-drug interactions of sulfonylureas?
Alcohol
Beta blockers: Mask effect of hypoglycemia
CYP2C19 inhibitors (e.g. Amiodarone, 5-FU; Fluoxetine): increase conc of sulfonylureas
What advice should be given for those on sulfonylureas?
Take 15-30 minutes before meal to allow drug to work post-meal (CAUTION those with irregular meals)
Name the drugs that are TZD
Pioglitazone
Rosaglitazone
What is the mode of action of TZDs?
Perioxidase proliferator activates receptors by acting as agonist
Promoting glucose uptake into target cells
Decrease insulin resistance and increase insulin sensitivity
How are TZDs eliminated?
Liver
Benefit patients with NAFLD or NASH
What are the adverse drug events related to TZD?
Hepatotoxicity
Edema
Fractures: Increased risk in women
Weight gain
Pioglitazone: bladder cancer
Rosaglitazone: increase LDL
How is ALT used to guide the initiation / continuation of TZD?
> 3 ULN OR symptoms of hepatic dysfunction: discontinue/ do not initiate
> 1.5 ULN: continue and repeat LFT until normal
What are the contraindications of TZD?
Acute Liver Disease
HF Class III and IV
What are the indications to use alpha glucosidase inhibitors?
Act as adjunct therapy with other agents when hyperglycemia cannot be managed by diet alone
What is the mode of action of alpha glucosidase inhibitors?
- Competitively inhibit brush border alpha glucosidases enzymes
- Delaying glucose absorption
Name the alpha glucosidase inhibitor
Acarbose
What are the adverse effects of acarbose?
GI: Flatulence, abdominal pain and diarrhea
Increases LFT at high doses
Who are contraindicated from the use of acarbose?
Breastfeeding
GI diseases such as obstructive IBD
Name the DDI associated with acarbose
Intestinal adsorbants e.g. charcoal
Digestive enzymes preparations
What advice should you give patients who intend to take alpha-glucosidase inhibitors?
Take with large meal
