Diabetes Case Presentations

Irl B. Hirsch, MD-Disclosures

• Research: Sanofi Diabetes, Halozyme • Consulting: Abbott, Roche

Case 1 • An obese 40 year-old woman is admitted for asthma.

She received a dose of methylprednisolone in the ED at 7pm and will now be receiving 40 mg of oral prednisone daily in the AM. She had not been on any steroids for many years.

• Random finger-stick blood glucose when she gets to the floor at 10pm is 275 mg/dL. Her last meal was at 5pm.

• Her BMI is 25 m/kg2. Her last pregnancy was 10 years ago and she did not have gestational diabetes. She currently has no symptoms to suggest diabetes.

QUESTION 1

Besides Ordering a HbA1c and Low-Dose Correction Dose Insulin, What Will You Do for Her Hyperglycemia?

• A) Begin insulin glargine starting now at 10 units • B) Begin insulin glargine starting now at 10 units and

pre-meal insulin lispro between 0.05 and 0.10 u/kg/meal

• C) Begin AM NPH insulin at 10 units • D) Begin pre-mix 70% NPH 30% regular insulin before

breakfast and dinner at 0.2 units/injection • E) Begin insulin aspart between 0.05 and 0.10

u/kg/meal

HOW DO STEROIDS IMPACT BLOOD GLUCOSE?

Important Concepts

• Liver is responsible for fasting glycemia • Muscle is responsible for post-prandial glycemias

Effect of Single Dose of Dexamthasone in Normal

Persons (48 h)

Glucose Insulin Abdelmannan et al. Endo Practice, 2010;16:770-777

OGTT with 8 mg Dex in NGT Subjects* *all with at least one first degree releative with T2DM

GLUCOSE

INSULIN

DAY 2, DEX

DAY 2, DEX

Note the minimal change in fasting glucose and insulin levels on day 2

Taheri N: Endo Pract 2012;18:855-863

Bottom Line

• The Rx of steroid-induced hyperglycemia needs to focus on the post-prandial glucose levels

• Therefore, the emphasis for these patients needs to be with the use of prandial insulins

• Fasting hyperglycemia is generally seen with higher doses of steroids, often given long-term, and more often with previous histories of type 2 DM, pre-diabetes, or family history of DM

Prandial Insulin Pearls

What Is Duration of Action (Glucose Lowering Activity) of Our Current

Rapid-Acting Analogues? • A) 2 hours • B) 3 hours • C) 4 hours • D) 5 hours • E) 6 hours

Given in the typical doses of 0.1-0.2 units per injection

QUESTION 2

4

5

Seru

m in

sulin

leve

ls

(

ng/m

L)

Time (hours)

Insulin Lispro

3

2

1

0 1 2 3 4 5 6 7 8 9 10 11 12 0

Regular Human Insulin R

Lispro vs. Regular

Diabetes 43: 396-402, 1994

Time (hours)

insulin lispro regular human insulin

Glu

cose

Infu

sion

Rat

es

(mg

/mln

)

0 100

200

300

400

500

600

0 1 2 3 4 5 6 7 8 9 10 11 12

Lispro vs. Regular

Diabetes 43: 396-402, 1994

Glucodynamic Principles: Prandial Insulin: not as rapid acting as we thought!

Glucose Infusion Rate (mg/kg•min)

0.2 IU/kg SQ Time (minutes)

Insulin Aspart Regular Insulin

0 120 240 360 480 600

800 700 600 500 400 300 200 100

0

Euglycemic clamp profiles

0 1 2 3 4 5 6 7 8

% in

sulin

re

mai

ning

20

40

60

80

100

0

Insulin insulin aspart “insulin action” disappearance curves

Why in the Hospital We Don’t Use Between-Meal Insulin Routinely

♦ ACTIVE INSULIN (insulin remaining) ♦ The amount of insulin from the last bolus which has

not yet been absorbed based on pharmacodynamic (not pharmacokinetic) data

♦ INSULIN STACKING ♦ Using correction dose insulin to treat before-meal or

between-meal hyperglycemia in a situation when there is still significant active insulin

QUESTION 3

• A) 15 min after the meal is eaten • B) At the time the meal is eaten • C) 15 min before the meal is eaten • D) 30 min before the meal is eaten

For this woman on prednisone, and a pre-meal glucose of 180 mg/dL, when should the prandial insulin be injected in relation to when the food is eaten?

300

Timing of Rapid-Acting Analog Insulin Injection Alters PPG in T1DM

Rassam AG, et al. Diabetes Care. 1999;22:133-136. Cobry E, et al. Diabetes Technol Ther. 2010;12:173-177.

8.6 kcal/kg breakfast

Minutes

BG

Lev

el (m

g/dL

)

288

252

216

180

144

108

72

36

0 -30 0 30 60 240 90 270 120 150 180 210

–30 m –15 m 0 m

+15 m

Injection-Meal Interval (minutes)

Insulin Lispro

300

Standardized breakfast

Minutes

BG

Lev

el (m

g/dL

)

288

252

216

180

144

108

72

36

0 -30 0 30 60 240 90 270 120 150 180 210

–20 m 0 m

+20 m

Insulin Glulisine Injection-Meal Interval (minutes)

QUESTION 4 Case 2

• You are evaluating a 60 year-old man with aortic stenosis scheduled for aortic valve replacement within the week. You note a random glucose of 185 mg/dL but a HbA1c of 5.1% (normal <6%).

• How should you proceed?

Question 4: How To Proceed?

• A) Order a fructosamine level • B) Order a glycated albumin • C) Order a fasting glucose • D) Order a fasting insulin level • E) Order a 1,5 anhydroglucitol level

Don’t Believe Every Lab Test You Order

Circulation 1963;32:570-581

AD, AP, and multiple valve prosthesis with 25% reduction in RBC survival

What Alters A1C Hematologic conditions Anemia Accelerated erythrocyte turnover Thalassemia Sickle cell disease Reticulocytosis Hemolysis Physiologic States Aging Pregnancy Drugs/Medications Alcohol Opioids Vitamin C Vitamin E Aspirin Erythropoetin Dapsone Ribavirin

Disease States HIV infection Uremia Hyperbilirubinemia Dyslipidemia Cirrhosis Hypothyroidism* Medical Therapies Blood transfusion Hemodialysis Miscellaneous Glycation rate Protein turnover Race and ethnicity* Laboratory assay Glycemic Variability Smoking Mechanical heart valves Exogenous testosterone?

In a typical diabetes practice, 14% of A1C measurements are misleading

QUESTION 5

CASE 3

• It is midnight and you are called to the ER for a an 80 kg patient who 30 min previously accidently took 80 units of insulin lispro instead of his insulin glargine. His blood glucose at the time is 130 mg/dL.

• You order intravenous dextrose to maintain his blood glucose above 100 mg/dL

Question 5

• How long will this patient require intravenous dextrose?

• A) 5 hours • B) 6 hours • C) 7 hours • D) 8 hours • E) 12 hours

PK of Insulin Lispro

Gagnon-Auger M. Diabetes Care. 2010;33:2502-2507.

10 units, control

10 units, type 2 diabetes

30 units, type 2 diabetes

50 units, type 2 diabetes

8h

CASE 4 • You are caring for a 29 year-old woman with type 1

diabetes who was admitted due to an MVA. She required an exploratory laparotomy due to bleeding and is now slowing recovering. Her baseline Hct is 44% and it is now 25%.

• Her diabetes is complicated by advanced non-proliferative retinopathy and microalbuminuria. Her eGFR is 55. There has never been a concern of coronary artery disease and her EKG now is normal. She has never been a smoker.

• Besides insulin her home medications include lisinopril and an OCP

QUESTION 6

Question 6

• At this point what should you do? • A) Transfuse at least to a Hct of 30% • B) Increase the lisinopril to maintain a blood pressure

below 120 • C) Maintain goal glucose of 90-130 • D) Begin low-dose prednisone

Anemia and DR

• Acute anemia (not chronic) appears to result in worsening of diabetic retinopathy – Mechanism appears to be ischemia to retina

• No RCTs but if known retinopathy consensus is to transfuse to Hct of 30% if pre-event Hct known to be normal.

Case 5 • A 50 year-old man with type 2 diabetes is admitted

for a neuropathic foot ulcer. He also has severe non-proliferative retinopathy and a recent history of clinically significant macular edema

• His medications include metformin, glipizide, sitagliptin, atorvastatin, HCTZ, ramipril, and atenolol

• Pertinent lab includes a creatinine level of 1.0 and a HbA1c of 11.3%. He has no albuminuria

• You explain to him his diabetes is poorly controlled and he agrees it is time to start insulin therapy

QUESTION 7

Question 7

• His glycemic targets now and for the next few months should be:

• A) 80-110 • B) 110-140 • C) 140-180 • D) 180-220

What You Need To Know

• Abrupt normalization of glucose, generally when the HbA1c is > 10% and there is advanced non-proliferative retinopathy can lead to a worsening of the retinopathy (ischemic mechanism)

• If no retinopathy is present there is no concern about how quickly the glucose is normalized

• Unclear how slowly the HbA1c can be reduced but it should be done in conjunction with a retinal specialist (reports from the 1990s suggest 2% reduction per year)

Case 6

• You are caring for a patient who had a recent pancreatectomy without a previous history of diabetes.

QUESTION 8

Question8

• What insulin regimen should you provide? A) glargine/mealtime lispro; 0.7 units/kg B) glargine/mealtime lispro; 0.3 units/kg C) Twice daily NPH/Regular 0.7 units/kg D) Twice daily detemir with twice daily aspart 0.5

units/kg E) Twice daily detemir with mealtime aspart 0.5

units/kg with liraglutide

Case 7

• It is decided to begin nocturnal tube feeding on a patient with known type 2 diabetes, HbA1c 7%. At home he receives metformin, exenatide, and insulin glargine. He has been eating minimal food in the hospital receiving bedtime insulin glargine and postprandial lispro based on the amount of food he had consumed.

QUESTION 9

Question 9

• What is the best insulin regimen to use now, on top of the glargine/lispro – A) increase the bedtime glargine dose – B) increase the bedtime glargine dose and add a

dose of morning glargine – C) add a dose of bedtime NPH insulin – D) add a dose of bedtime NPH insulin with insulin

lispro – E) add bedtime metformin and morning

pioglitazone

Case 8

• A 45 year-old man s/p bone marrow transplant is receiving high-dose steroids. His appetite has improved on the steroids and he wants to eat. He had been receiving intravenous insulin requiring between 20-25 units/hour (480 to 600 units/day) to control his blood glucose when not eating.

• He is not in an ICU

QUESTION 10

Question 10 • Which insulin regimen will you order (which will also

control his blood glucose!)? – A) Increase the intravenous insulin 2X during his meal – B) Discontinue the intravenous insulin, convert his

basal insulin to insulin glargine given BID, and start premeal lispro at 0.1 units/kg

– C) Continue the intravenous insulin, begin SC insulin lispro before meals at 0.2 units/kg

– D) Convert the intravenous insulin dose to SC U-500 insulin to be giving in the AM with insulin lispro before meals at 0.2 units/kg