Understanding Diabetes and First Line for T2DM Flashcards by Charmain Ng

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

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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

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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

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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.

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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

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What are the signs and symptoms of hyperglycemia?

Dry skin
Extreme thirst
Frequent urination
Drowsiness
Decreased healing
Hunger

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What are the signs and symptoms of hypoglycemia?

Shaking
Fast heartbeat
Dizziness
Sweating
Impaired vision
Weakness / fatigue
Headache
Anxious
Irritable
Hunger

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What are some monitoring parameters used to measure DM?

Fasting plasma glucose

Random plasma glucose

Postprandial plasma glucose

Hba1C

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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

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What is the relationship between Hba1c, FPG and PPG?

Hba1c = 3 months average of (FPG + PPG)

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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

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What is the purpose of glucometers?

Monitor hypo/hyperglycemia
Adjust medications, diet and exercise

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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

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How often should those with T2DM on multiple injections of insulin check their glucometer reading?

More than or equal 3 times daily

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When is the ideal time for patients to check their glucose reading?

Before breakfast

2h after largest meal

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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

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Patient comes in with HbA1c < 6.1-6.9%, what should you do?

Proceed to FPG or PPG

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What is the criteria to diagnose no diabetes?

Hba1C < 6.0%

FPG < 6.0 mmol/L

PPG < 7.8 mmol/ L

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When should pre diabetes be suspected?

FPG 6.1-6.9 mmol/L

PPG 7.8 - 11.0 mmol/L

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When should diabetes be suspected ?

FPG > 7.0mmol/L

PPG > 11.1 mmol/L

Hba1C > 7%

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Patient comes in with HbA1c > 7.0%, what does this mean?

No further test needed

Patient likely have diabetes

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Is Hba1C needed to diagnose those with diabetes?

2 abnormal readings of FPG and PPG are generally recommended

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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

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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

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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?

1. Competitively inhibit brush border alpha glucosidases enzymes 2. 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

Understanding Diabetes and First Line for T2DM Flashcards

(60 cards)