DM - Therapeutics - Dr. Frye

Question 1

Trials:
IMPROVE-IT
DCCT

Answer 1

IMPROVE-IT - ezetimibe addition to statin therapy may help with recent coronary syndrome
DCCT - Tighter control increases the rate of hypoglycemia

Question 2

If a patient has normal kidney function but is diabetic, should they be on an ACE or ARB?

Answer 2

No

Question 3

What are FDA approved drugs to treat diabetic neuropathy? Off-label?

Answer 3

Duloxetine
Pregabalin
Tapentadol

Gabapentin
TCAs
Venlafaxine
Valproate

Question 4

When is metabolic surgery recommended?

Answer 4

T2DM with BMI of >40 regardless of hyperglycemic control
T2DM with BMI 35-39 with inadequate control despite optimized lifestyle and meds
T2DM with BMI 30-34.9 with poor hyperglycemic control with optimized meds

Question 5

Term:
Uncontrolled hyperglycemia, metabolic acidosis, increased total body ketone concentration, decreased bicarbonate (<15-18)

Answer 5

DKA

Question 6

Term:

Severe hyperglycemia, hyperosmolarity, dehydration in absence of ketoacidosis

Answer 6

HHS (hyperosmolar hyperglycemic state)

Question 7

What can cause DKA?

Answer 7

Missed insulin doses or acute infection

Question 8

Which type of diabetes is more common in DKA?

Answer 8

Type I

Question 9

Which type of diabetes is more common in HHS?

Answer 9

Type II. No absolute insulin deficiency, so little ketogenesis.

Question 10

What are the treatments of DKA and HHS?

Answer 10

Fluids to correct dehydration
Insulin (IV first then SQ) to correct hyperglycemia
Potassium repletion and other interventions as necessary

Question 11

Where is the line for critically significant hypoglycemia?

Answer 11

<54mg/dL

Question 12

In hypoglycemia, what symptoms are the first seen? What type are they?

Answer 12

The autonomic/neurogenic symptoms are first seen in hypoglycemia. These are tremors, anxiety, sweating, irritability. These are related to the secretion of epinephrine.

Question 13

In hypoglycemia, what symptoms are caused by deprivation of glucose to the brain? What are these called?

Answer 13

Confusion, lethargy, loss of consciousness and seizures are neuroglycopenic.

Question 14

What is the treatment for hypoglycemic unawareness? How does this work?

Answer 14

Less tight A1C control. Increase epinephrine response to low blood sugar. Decrease sensitivity to glucose.

Question 15

What is the adult dose of glucagon?

Answer 15

1.0mg

Question 16

How many glucose tabs should be used to treat mild hypoglycemia?

Answer 16

3-4

Question 17

Why should foods high in protein or fat be avoided when trying to treat hypoglycemia?

Answer 17

Because they will take longer to work.

Question 18

What is CGM?

Answer 18

Continuous glucose monitoring.
Useful in T1DM
Can see trends, help people nervous about highs and lows. 
Cost is an issue.
Need robust diabetes education.

Question 19

How often should A1C be checked in those who are at goal? Not at goal?

Answer 19

In those at goal, check 2 times a year. In those not at goal, check 4 times a year at least.

Question 20

What is fructosamine?

Answer 20

Measures glycated albumin, but not well standardized.

Indicated for pregnancy and hemoglobinopathies, and those with discordant A1C and CBC results.

Question 21

What A1C does a 126 mg/dL average glucose reading indicate?

Answer 21

6%

Question 22

What is the general rule for conversion of A1C to glucose?

Answer 22

A1c-2 x 30
(so an A1C of 7.5: 7.5-2 = 5.5
5.5 x 30 = 150 + 15 = 165

Question 23

What is a reasonable A1C goal for a healthy adult?

Answer 23

<7%
This is associated with a reduction in microvascular complications
If implemented soon after diagnosis it is also associated with reduction of microvascular complications

Question 24

What are the glycemic goals for the ADA?
A1C
Pre-prandial
Post-prandial
For the AACE?

Answer 24

A1C <7%
Pre-prandial 80-130
Post-prandial <180

A1C <6.5%
Pre-prandial <110
Post-prandial <140

Question 25

How was the ACCORD trial different than the others, such as UKPDS, ADVANCE, VADT, and DCCT/EDIC?

Answer 25

It found that there was increased mortality with more stringent A1C goals.

Question 26

Generally, when did trials find microvascular benefits with more stringent A1C goals?

Answer 26

With initial trial and long-term follow-up.

Question 27

Generally, when did trials find CVD benefits with more stringent A1C goals?

Answer 27

Some CVD benefits seen in follow-up

Question 28

Generally, when did trials find mortality benefits with more stringent A1C goals?

Answer 28

No change at all, too late.

Question 29

Why is lower A1C associated with a greater increase of mortality?

Answer 29

Higher A1C is associated with a greater risk of death, but the hypoglycemia associated with lower A1C contributed.

Question 30

What did the ACCORD trial find about the risks of hypoglycemia?

Answer 30

That hypoglycemia was associated with all sorts of negative outcomes.

Question 31

What are some potential mechanisms that hypoglycemia can increase CVD risk?

Answer 31

Cardiac arrhythmias Increased thrombotic tendency Cvd changes induced by catecholamines

Question 32

Metformin | a biguanide

Answer 32

MOA - Decreases liver gluconeogenesis and improves insulin sensitivity. 1st line low cost weight neutral No hypoglycemia Disadvantages: GI intolerance, B12 deficiency, increased risk of lactic acidosis Continue use unless eGFR is <30. Don't start metformin if eGFr is less than 45.

Question 33

Sulfonylureas

Answer 33

MOA - increases insulin secretion by acting in the K channels of beta cells Low cost Effective Generally well-tolerated Disadvantages: Risk of hypoglycemia, weight gain 1st gen - Achexamide, Tolubutamide, Chloropropamide, Tolazamide 2nd gen - Glimipiride, glipizide, glyburide

Question 34

Which drug class is SIADH associated with?

Answer 34

Syndrome of Inappropriate Antidiuretic hormone... associated with 1st gen sulfonylureas

Question 35

Meglitinides

Answer 35

MOA - Increase insulin secretion by binding to the sulfonylurea receptor Decrease postprandial glucose Disadvantages: hypoglycemia, weight gain, frequent dosing, only modest efficacy, expensive, CYP 3A4 interactions Repaglinide, nateglinide If you miss a meal, skip the dose too

Question 36

TZDs

Answer 36

MOA - PPAR agonist, which increases sensitivity to insulin Efficacious Cheap Disadvantages: 8-12 weeks for full effect, weight gain, edema (HF CI), bladder cancer, risk of fractures no hypoglycemia, CVD benefits (PROactive trial), lipid benefits "glitizones"

Question 37

Alpha-glucosidase inhibitors

Answer 37

MOA - Delays intestinal carb digestion by inhibiting enzymes in the small intestine No hypoglycemia, reduces post-prandial hyperglycemia, decreases CVD events Disadvantages: Flatulence, diarrhea, bloating/gas, modest efficacy Acarbose, miglitol LFTs needed for monitoring, initially every 3 months Avoid use if SCr is >2mg/dL

Question 38

DPP4 inhibitors

Answer 38

MOA - increases insulin secretion (glucose dependent) and decrease glucagon secretion by inhibiting DPP4, increasing post-prandial incretin (GIP and GLP-1) No hypoglycemia, well-tolerated, weight neutral Disadvantages: Expensive, moderate efficacy, pancreatitis, joint pain, HF risk with saxagliptan Sitagliptan, Saxagliptan, Linagliptan, Alogliptan

Question 39

What does GLP-1 do?

Answer 39

``` Decreases appetite Slows gastric emptying Increases insulin secretion Decreases glucagon secretion Increases B-cell proliferation Decreases B-cell apoptosis Decreases glucose production ```

Question 40

Which DDP-4 inhibitor does not require renal or hepatic adjustment?

Answer 40

Linagliptan

Question 41

SGLT2 I's

Answer 41

MOA - Blocks glucose reabsorption in the kidney, resulting in increased glucose excretion Advantages: Weight loss, low hypoglycemia risk, modest BP lowering, CVD benefit (empagliflozin) Disadvantages: All CI w/ renal dysfunction, UTIs, genital mycotic infections, euglycemic ketoacidosis, modest efficacy, high cost, bone fracture with canagliflozin Canagliflozin, dapagliflozin, empagliflozin

Question 42

GLP-1 agonists

Answer 42

MOA - Increase insulin secretion, decrease glucagon secretion, slows gastric emptying, increases satiety Efficacious, no hypoglycemia, weight reduction, improved beta-cell mass, Cvd benefit with liraglutide (LEADER trial) Disadvantages: GI side effects, increased pancreatitis risk, high cost, no long term safety data Black box warnings for all but exanitide for thyroid C cell tumors Exanitide, liraglutide, albiglutide, dulaglutide

Question 43

Amylin analog

Answer 43

MOA - slows gastric emptying, decreases glucagon secretion, increases satiety Adjunct to mealtime insulin only, moderately efficacious, decreases postprandial glucose, weight loss Disadvantages: GI effects, no long term safety, frequent dosing, hypoglycemia potential with insulin use, high cost. (Decrease insulin dose by 50% when taking)

Question 44

Insulin

Answer 44

MOA - facilitates cellular uptake of glucose, and reduces hepatic glucose production Universally effective, unlimited efficacy, decreases microvascular complications Disadvantages: weight gain, hypoglycemia, injectable, SMBG required, cost

Question 45

Human insulin vs insulin analogs:

Answer 45

Human: identical to endogenous insulin. Protamine and zinc can be added to create NPH, which has delayed peak and duration. Insulin analogs are created by genetic engineering, which alters pharmacokinetics.

Question 46

When is U-500 insulin useful?

Answer 46

For when daily injections total 200 units or more

Question 47

What are the rapid-acting insulins?

Answer 47

Humalog Novolog Apidra Take immediately before a meal

Question 48

What are the short-acting insulins?

Answer 48

Regular (R) Novolin R HUmulin R Take 30 minutes before a meal

Question 49

What are the intermediate-acting insulins?

Answer 49

NPH Novolin N Humulin N (The only cloudy insulins)

Question 50

What are the long-acting insulins?

Answer 50

detimir glargine degludec

Question 51

What is Afrezza?

Answer 51

Inhaled insulin. Administer before meals. Warnings of acute bronchospasm in patients with chronic lung disease

Question 52

What combos of split-mixed insulins can you use?

Answer 52

NPH and glassine, aspart, or lispro NPH and regular NO glargine, deter, or degludec