Clinical Case: Starting a Prednisone-Using Patient on Insulin


#1

Patient Background

John is a 55 year-old Caucasian man with diabetes and asthma. He teaches math at a local high school in New York City. He was diagnosed with type 2 diabetes on blood tests performed when he applied for life insurance at age 51. At the time, he was obese, weighing 220 pounds at 5 feet, 10 inches height (BMI = 31.6).

He stopped smoking at age 46 and he does not consume alcohol.

John lost 20 pounds with a strict diet and daily exercise and started metformin, which was titrated up to 1000 mg twice-daily. His glucose levels improved and his A1c declined from 7.2% to 6.2% within 4 months.

At age 53 glimepiride (Amaryl®) was added at a dose of 2 mg daily due to a rise in A1c to 7.3%. His A1c rose to 6.6%, and he gained 5 pounds.

John controls his asthma with inhaled medications, including fluticasone propionate and salmeterol inhalation powder (Advair®) 250/50 mcg, and montelukast sodium (Singulair®) 10 mg daily.

Last year John’s asthma worsened. In addition to inhaled medications, he has intermittently required Prednisone in doses up to 40 mg daily. Exercise has been less regular and he has gained a further 10 pounds in weight. HbA1c has risen to 8.5%, corresponding to an overall average blood glucose of 220 mg/dL.

Clincal Profile

Age: 55
Weight: 215 lbs.
Height: 5’ 10"
BMI: 31

Blood Glucose
Last A1C: 8.5% (overall
average 220 mg/dL)

Fasting: 94-135 mg/dL
Post-breakfast: 250-340 mg/dL

Pre-lunch: 200-300 mg/dL
Post-lunch: 220-310 mg/dL

Pre-dinner: 125-180 mg/dL
Bedtime: 164-234 mg/dL

Lipid Profile
Total: 194 mg/dL
LDL: 120 mg/dL
HDL: 31 mg/dL
Triglycerides: 210

Kidney Profile
Creatinine: 1.2 mg/dL
Microalbuminuria:

Liver Function
ALT: 27
AST: 39

Blood Pressure
Normal: 135/90 mmHg

Cardiovascular profile
High cholesterol, low HDL, no history of chest pain or known CHD

Eye Exam
Background diabetic retinopathy

Foot Exam
n/a

Lifestyle

Compliance with meal plan?
Less compliant with diabetes meal plan
than he used to be.

Compliance with exercise plan?
Limited activity.

Current Medications

For blood glucose:

Metformin 1000 mg bid

Glimepiride 2 mg qd

For other conditions:

prednisone (Sterapred®) 40 mg qd

fluticasone propionate and salmeterol (Advair Diskus®) 250/50 mcg qd

montelukast sodium (Singulair®) 10 mg qd

What lifestyle changes could John make to improve his glucose levels?
a) Reduce the carbohydrate content in his meals
b) Exercise after breakfast
c) Skip dinner
d) a and b above
e) All of the above


#2

d) a and b above

I think this is the best option


#3

Preferred Answer: (d) reduce carbohydrate content of meals and exercise after breakfast

Glucocorticoids, like Prednisone, have their greatest impact on post-prandial glucose excursions, yielding peak glucose levels after breakfast. Carbohydrates have the greatest effect on post-prandial glucose levels. By morning, fasting glucose levels are frequently at the lowest levels of the day. This patient’s lowest glucose levels are before breakfast.

Reducing breakfast carbohydrates and exercising after breakfast both may help to reduce the post-breakfast glucose excursions that this patient is experiencing. Depending on his schedule, he can exercise before or after breakfast. Exercise increases insulin sensitivity, and the effect lasts for several hours.

Patients should avoid skipping a meal altogether, which has been found to be associated with weight gain. Skipping dinner would lower mostly bedtime and overnight glucose levels and would not address the patient’s post-prandial excursions. In patients on sulfonylureas such as glimepiride, this might increase the risk of hypoglycemia overnight.

After consulting with a registered dietitian, he reduced his breakfast carbohydrates by eating less cereal and reducing the quantities of milk and juice. His physician also advised him to try exercising before or after breakfast to try to reduce the high blood sugar levels he has been having between breakfast and lunch, and between lunch and dinner.

Would you propose changing John’s blood glucose medications?
a) Yes
b) No


#4

a) Yes

I want to change


#5

Preferred Answer: Yes, consider changing his blood glucose medications

John’s glucocorticoid therapy for asthma is raising his blood glucose beyond what the current metformin and glimepiride regimen can control. The metformin is already at its maximum effective dose of 1000 mg, bid.

What medication changes would you propose to John?

a) Add an alpha-glucosidase inhibitor such as acarbose (Precose®) with each meal

b) Increase glimepiride to 8 mg daily

c) Add long-acting insulin such as glargine (Lantus®) or detemir (Levemir®) at bedtime

d) Add a TZD (thiazolidinedione) such as Actos® (pioglitazone) or Avandia® (rosiglitazone)

e) Add premixed insulin before breakfast


#6

e) Add premixed insulin before breakfast


#7

Preferred Answer: e) add premixed insulin before breakfast). An alternative choice might be (a) add alpha-glucosidase inhibitor with each meal

Higher doses of glucocorticoids generally require insulin. Pre-mixed insulin at breakfast is an easy and effective way to manage this. Pre-mixed insulin combines intermediate and short- or rapid-acting insulin in different ratios: 75/25, 70/30 and 50/50. The rapid-acting component addresses post-prandial glycemic excursions due to the carbohydrates eaten at breakfast. Since John’s highest blood glucose levels are from morning to mid-day, a 50/50 mix that contains relatively more short-acting insulin is preferred. The effect of the pre-mixed insulin diminishes by evening, as does the effect of the glucocorticoid, so there is less risk of hypoglycemia.

John is prescribed 15 U of premixed human insulin (e.g. Humulin® 50/50) at breakfast. He is taught to titrate his insulin dose based on his blood glucose readings after breakfast and before lunch.

Alpha-glucosidase inhibitors delay the entry of carbohydrates and can reduce post-prandial rises in glucose. They may be adequate to correct the glucose abnormalities seen with low-dose glucocorticoids, but generally not at the higher doses taken by this patient (40 mg). Alpha-glucodisase inhibitors are not commonly prescribed in the U.S. because many patients experience distressing GI side effects such as bloating, cramps and flatulence. A trial could be undertaken with this patient to see if he can tolerate this drug.

These medication choices would be considered less effective in John’s case:
Increasing the sulfonylurea (e.g. glimepiride) dose is generally not adequate to prevent the hyperglycemia resulting from glucocorticoid therapy, and can result in nocturnal hypoglycemia in such patients.

Long-acting insulins (such as Levemir® and Lantus®) can lower glucose levels effectively, especially fasting glucose. However, this patient’s fasting blood glucose is not significantly elevated. Long-acting insulin can result in nocturnal hypoglycemia (when the effect of prednisone wanes during the night). Patients who take insulin and Prednisone should be instructed to lower their insulin doses when their Prednisone doses are reduced, in order to avoid hypoglycemia.

TZD’s are effective in reducing glucose levels in most patients with type 2 diabetes. However, in a patient taking prednisone, they offer no real advantages. While TZDs have been viewed as safe and effective in most patients with type 2 diabetes, a recent publication has raised concerns about the cardiovascular risk profile of rosiglitazone, particularly in patients at high risk of coronary heart disease, although other reports do not confirm the apparent risk.With diabetes, obesity, elevated blood pressure and lipids, John is at increased CVD risk.


#8

Visit 2, Two Weeks Later

In the second week, John titrates his pre-mixed insulin dose up to 18 U at breakfast. At the end of the second week, his blood glucose ranges are shown below. After 2 weeks on insulin, the patient’s blood glucose levels have improved, but are still not at goal:

Communication between his primary physician and pulmonologist is essential to understand how long the patient will be on this dose of prednisone. If the prednisone will be continued for some time, he can continue titrating his breakfast insulin upward to lower his post-breakfast and pre-lunch blood glucose levels without inducing a risk of hypoglycemia.

Visit 3, Two Weeks Later

At the third visit, John indicates that his asthma is responding to the prednisone but he is still taking 40 mg daily. He has titrated his pre-breakfast mixed insulin to 22 U.

The table below lists the patient’s blood glucose ranges. The fasting blood glucose is in the target range, with little variability. His breakfast and lunch readings are improved, although still elevated. He still has post-prandial hyperglycemia in mid-morning, and his bedtime readings are elevated.

An evening injection of pre-mixed insulin is not advised because his fasting blood glucose is already close to target, and an evening dose of pre-mixed insulin raises the risk of nocturnal hypoglycemia.

What option would you choose to further lower his blood glucose?

a) Add acarbose before breakfast and dinner

b) Add Regular insulin before breakfast and dinner

c) Increase the glimepiride dose

d) Add long-acting insulin such as glargine (Lantus®) or detemir (Levemir®) at bedtime

e) Add exenatide injection (Byetta®)


#9

a) Add acarbose before breakfast and dinner


#10

Preferred Answer: Either (a) add acarbose or (b) add Regular insulin are effective choices

Adding Regular insulin before breakfast and dinner will address his late morning and bedtime hyperglycemia. However, if the patient continues to use pre-mixed insulin before breakfast, he would need to inject a second time using a Regular-only insulin pen. An alternative is to teach the patient how to draw a custom mix of NPH and Regular using vials and an insulin syringe.

Acarbose is also a viable choice to treat post-prandial hyperglycemia. Acarbose is a pill with modest efficacy at lowering A1c in clinical trials. However, alpha glycosidase inhibitors rarely lower A1c by more than a half point and often have unpleasant GI side effects such as diarrhea and flatulence, so many patients do not tolerate them.

Increasing the patient’s glimepiride dose is unlikely to have a noticeable effect on blood glucose, and raises the patient’s risk of nocturnal hypoglycemia.

Adding a long-acting insulin at bedtime is not advised because the patient’s fasting blood glucose is close to target.

Exenatide is not advised in this regimen because it is not FDA-approved for use with insulin or to control glucocorticoid-induced hyperglycemia.

The patient and physician discuss the two first medication options, and decide to use NPH and Regular insulin in vials, using an insulin syringe to mix the custom ratio. This situation illustrates the limitations of pre-mixed insulin. As the patient’s metabolic functions change, his ability to titrate the pre-mix is more difficult. Generally, pre-mixed insulin is excellent for patients whose blood glucose levels are relatively stable, with little day-to-day fluctuation.

Using a custom mix in the morning, and Regular insulin in the evening helps to introduce the patient to the concept of basal-bolus insulin therapy.

The patient is asked to call his physician when the prednisone dose is reduced, so that an adjustment to his insulin doses can be made. A follow-up visit is scheduled for 2 weeks later.


#11

Visit 4, Two Weeks Later

At the fourth visit, the patient reports that he is taking 15 U NPH and 14 U Regular before breakfast, and 6 U Regular before dinner.

His latest blood glucose ranges are shown in the table.

Some of the readings are a still bit high, but overall, they are much improved.
This glycemic control regimen will be maintained for another 12 weeks, assuming that his prednisone dose remains the same, at which time the patient’s A1c will be checked.

Is there anything else that you want to change in John’s overall care?

a) Continue diet adjustments: reduce saturated fats and further reduce carbohydrates
b) Begin statin therapy
c) Begin fibrate therapy
d) Add low dose aspirin
e) Combination of a, b and d above
f) All of the above


#12

e) Combination of a, b and d above


#13

Preferred Answer: (e) Combination of diet changes, statin and low-dose aspirin

Statin therapy is recommended for this patient because his diabetes puts him at greater risk of coronary heart disease.

His LDL-C is 120 mg/dL; the target for patients with diabetes without known CHD is <100 mg/dL

His HDL is below 40

His triglycerides are mildly elevated

Statins have cardioprotective benefits

Low-dose aspirin therapy is also recommended for people who are at increased risk for coronary heart disease.

John’s elevated blood pressure is another risk factor that should be watched closely. It may be necessary to add an ACE inhibitor to his regimen in the future.

Is there anything else that you would recommend to this patient?

a) Refer patient to an ophthamologist for annual dilated eye examinations

b) Conduct a careful evaluation of his lower extremities including his feet. Check pulses, skin condition, neurological condition)

c) Collect a urine specimen for an assessment of his renal function

d) All of the above


#14

d) All of the above

I think this is the best


#15

Preferred Answer: (d) All of the above

This patient already has background diabetic retinopathy, so he should be monitored closely for signs of other diabetes complications such as neuropathy and nephropathy.


#16

I agree with you! Good case


#18

d) appears the most suitable life style change.


#19

d) is appropriate answer.


#20

choice D( a and B above)