37. Insulin Therapy in Type 1 and Type 2 Diabetes
Section 2
Insulin Therapy in Type 1
and Type 2 Diabetes

38. This slide summarizes the information in the new guidelines
This slide summarizes the information in the new guidelines. Note that information is provided for each drug option regarding efficacy, risk of hypoglycemia, effect on weight, major adverse effects, and relative cost. [Participants have a copy of this algorithm in their printed seminar materials.]
Review algorithm options with participants and respond to any questions.

41. Initiating Insulin Therapy
Add single dose of basal insulin
Glargine, detemir, or NPH
Usually administered at bedtime
Use conservative starting dose
10 units (empiric)
0.1 to 0.2 units/kg
0.3 to 0.4 units/kg if severe hyperglycemia
Review concepts in initiating basal insulin in patients with type 2 diabetes. (Points continue on next slide.)

42. Initiating Insulin Therapy
Adjust dose according to fasting SMBG
Typical titration 1–2 units every few days
Treat to target range for fasting glucose
ADA: 70–130 mg/dL
AACE: <110 mg/dL
May use product-specific titration instructions
Continue oral agent(s) at same dosage (eventually reduce)
Continue reviewing concepts in initiating basal insulin in patients with type 2 diabetes. (Points continue on next slide.)
American Diabetes Association Standards of Medical Care in Diabetes—2012
AACE Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan (2011)

43. Intensifying Insulin Therapy
A1C ≥7% after 2–3 months with fasting blood glucose in target range
Perform SMBG before meals, bedtime
Add prandial (bolus) insulin based on time of out-of-range result
Before lunch: add breakfast dose
Before dinner: add lunch dose
Before bedtime: add dinner dose
Review concepts in intensifying insulin therapy in patients with type 2 diabetes. (Points continue on next slide.)

44. Intensifying Insulin Therapy
Insulin options
Insulin aspart
Insulin glulisine
Insulin lispro
Regular insulin
NPH insulin
Dosing considerations
Typical initial dose: 4–5 units
Typical titration: 2–3 units every 2–3 days
Review common tactics for initiating basal insulin in patients with type 2 diabetes. (Points continue on next slide.)

45. Intensifying Insulin Therapy
Continue other agents?
Metformin
Thiazolidinediones (glitazones)
Sulfonylureas, glinides
α-Glucosidase inhibitors
DPP-4 inhibitors
GLP-1 receptor agonists
Colsevelam
Bromocriptine
Discuss which agents may be continued or should be discontinued as patients with type 2 diabetes advance to a basal-bolus regimen.
The new ADA/EASD guidelines provide the following information:
“Metformin is often continued when basal insulin is added, with studies demonstrating less weight gain when the two are used together. Insulin secretagogues do not seem to provide for additional A1C reduction or prevention of hypoglycemia or weight gain after insulin is started, especially after the dose is titrated and stabilized. When basal insulin is used, continuing the secretagogue may minimize initial deterioration of glycemic control. However, secretagogues should be avoided once prandial insulin regimens are employed. TZDs should be reduced in dose (or stopped) to avoid edema and excessive weight gain, although in certain individuals with large insulin requirements from severe insulin resistance, these insulin sensitizers may be very helpful in lowering A1C and minimizing the required insulin dose. Data concerning the glycemic benefits of incretin-based therapy combined with basal insulin are accumulating; combination with GLP-1 receptor agonists may be helpful in some patients. Once again, the costs of these more elaborate combined regimens must be carefully considered.”

46. Insulin Mini-Case 1 62-year-old Caucasian woman with type 2 diabetes
Weight: 219 lb
Medications
Insulin glargine (Lantus®) 42 units at bedtime
Metformin (Glucophage® XR) 1,000 mg twice daily
Pioglitazone (Actos®) 45 mg once daily
Let’s take a look at a mini-case of a patient with type 2 diabetes.
NOTE: Mini-cases are intended to be brief group discussions to apply concepts.
Refer participants to the printed materials for insulin mini-case #1. Quickly review the points on this slide.

47. Fasting Prelunch Presupper Bedtime
132
186
222
310
122
172
202
282
148
184
188
257
126
170
233
239
192
193
228
162
189
240
306
198
298
127
176
264
133
199
312
142
213
300
215
297
156
320*
387a
121
190
201
137
178
206
258
These are the patient’s SMBG results for the last 2 weeks. (Participants have a printed version of this table in their materials.)
Ask for some volunteers to describe what they see in these results.
NOTES FROM CASE AUTHOR
Readings for all three time points (pre-lunch, pre-supper, bedtime) are above target range ( mg/dL). On next slide, will need to discuss with participants considerations associated with best timing for added prandial dose.
aHad watermelon at lunch.

48. Insulin Mini-Case 1 How should insulin therapy be adjusted?
Continue current medications?
Lead a discussion with participants about what approach they would take to intensifying therapy, and whether they would continue therapy with metformin and pioglitazone.
NOTES FROM CASE AUTHOR
Suggested therapeutic options:
Add bolus insulin with meals. Since all three readings (pre-lunch, pre-supper, and bedtime) are out of range, can add bolus to all three meals. Some may choose to increase the Lantus dose in addition to the bolus doses, however, it’s always prudent to adjust one type of insulin at a time. In addition, by adding a bolus insulin at supper, this will likely lower the bedtime glucose levels, thus producing lower fasting levels.
Next question may become how much insulin do I initiate? This may be an initial dose of 2-5 units with each meal. At follow-up, use blood glucose diary in addition to determine adjustments in bolus doses that may be necessary.
Should Glucophage and Actos be continued or discontinued? Open for discussion.

49. Pattern Management Review SMBG data for general patterns
Identify trends
Three or more similar glucose values at the same time each day
Discuss with patient possible causes of values outside target
Food from previous meal?
Activity?
Insulin dose?
What we were doing in mini case 1 was looking for patterns in blood glucose and adjusting for those- that is pattern management

50. Pattern Management
Should changes in food/carbohydrate amount or timing of intake be made?
Should physical activity be more regular, increased, decreased?
Should the insulin regimen be adjusted?
When patterns in blood glucose results are detected, the next step is to evaluate the best possible action to bring the values into target range.

51. Insulin Mini-Case 2
54-year-old African American woman with type 2 diabetes
A1C: 9.2%
Medications
Humalog® Mix75/25TM (insulin lispro)
16 units each morning
10 units each evening
Metformin (Glucophage® XR) 1,000 mg twice daily
Now let’s take a look at another mini-case of a patient with type 2 diabetes who is using premixed insulin.
Refer participants to the printed materials for insulin mini-case #2. Quickly review the points on this slide.

52. Fasting Prelunch Bedtime Comments
310
176
198
Pizza for dinner last night
333
152
142
Walked after supper
289
133
199
256
Woke up late
202
165
201
148
205
286
163
189
292
161
200
301
145
212
277
158
209
162
177
197
284
149
303
159
182
These are the patient’s SMBG results for the last 2 weeks. (Participants have a printed version of this table in their materials.)
Ask for some volunteers to describe what they see in these results.
NOTES FROM CASE AUTHOR
Readings for all three time points (fasting, pre-lunch, bedtime) are above target range ( mg/dL)

53. Insulin Mini-Case 2 How should insulin therapy be adjusted?
Lead a discussion with participants about what approach they would take to adjusting this patient’s insulin regimen.
NOTES FROM CASE AUTHOR
Suggested adjustments:
Increase pre-supper dose by 4-5 units (~20% total dose increase)
Increase pre-supper dose as suggested and morning dose by 2 units

54. Multiple Injection Insulin Regimens
Basal-bolus therapy with multiple daily insulin injections is the most common approach to therapy for patients with type 1 diabetes. Many patients with type 2 diabetes also ultimately will require multiple daily injections of insulin.

55. Four injections per day
Review the various options for multiple injection insulin regimens, pointing out advantages and disadvantages (continues on the next slide).
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed

56. Initiating Insulin in Type 1 Diabetes
Typical starting dose: 0.5–0.7 units/kg/day
Basal insulin: ½ to ⅔ of total daily dose
Bolus insulin: ½ to ⅓ of total daily dose, divided among meals
Titrate doses as needed
Insulin therapy for patients newly diagnosed with type 1 diabetes typically is initiated empirically, with doses then titrated and adjusted as needed to reach target blood glucose levels.
Provide some detail about these common approaches to initiating basal-bolus insulin regimens in patients with type 1 diabetes.

57. Insulin Mini-Case 3a
19-year-old Caucasian man newly diagnosed with type 1 diabetes
Weight: 137 lb
A1C: 11.6%
Blood glucose: 256 mg/dL
Spilling ketones
Let’s take a look at a mini-case of a patient newly diagnosed with type 1 diabetes.
Refer participants to the printed materials for insulin mini-case #3 (first part of case). Quickly review the points on this slide.

58. Insulin Mini-Case 3a Determine total daily dose
0.6 units/kg/day
Determine individual doses
50% basal/50% bolus
Allow participants a few minutes to perform these calculations.
Provide the correct answers; lead a discussion about the responses if anyone failed to obtain the correct answers.
NOTES FROM CASE AUTHOR
Weight of 137 lb = 62 kg
Using 0.6 units/kg/day, the patient’s total daily dose (TTD) of insulin needed is about 37.
50% of this is 18.5, but unless using a specialty syringe, a pump, or a Jr. Pen device, you can’t reliably deliver 0.5 units of insulin. Can round to 18 or 19…for simplicity, choosing 18.
Therefore, 18 units will be given as the basal dose (Levemir or Lantus) and the remaining 18 units will be given as the bolus dose (regular or rapid). However, remember that the 18 units of bolus need to be divided further into meals; therefore if the patient eats 3 meals per day, he would inject 6 units per meal.
Please note that long-acting insulin was used here. NPH is more difficult to work with due to its peaks. Had NPH been chosen, NPH has to be dosed BID for T1DM. Thus the basal dose for NPH would be 9 units BID. Additionally, because NPH would peak around lunch time, the bolus only needs to be given BID rather than TID on initiation.

59. Adjusting Insulin Doses
Out-of-Range Result
Insulin Component to Adjust
Postbreakfast/prelunch
Prebreakfast rapid-acting/short-acting insulin
Postlunch/presupper
Prelunch rapid-acting/short-acting insulin
Morning NPH
Midafternoon
Long-acting insulin
Postsupper/bedtime
Presupper rapid-acting/short-acting insulin
Early morning
Evening NPH
Review the periods covered by each insulin dose, and how the timing of out-of-target blood glucose levels determines which component of the multiple injection regimen needs to be adjusted.
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed

60. Refining Insulin Doses
Correction insulin
Correction factor (insulin sensitivity factor)
Correction dose
Insulin-to-carbohydrate ratio
Insulin to cover ingested carbohydrate
Pattern management
Insulin doses determined or adjusted by trends in SMBG data
Multiple injection insulin regimens afford patients a great deal of flexibility for meal-to-meal adjustments of insulin doses based on preprandial blood glucose intake, carbohydrate intake, and activity. Over the next few slides, we’ll review a few of the concepts that are important to refining insulin doses for individual patients.

61. Correction Factor
Amount of rapid-acting or short-acting insulin needed to return an elevated blood glucose level to target level
Quantifies degree of change in blood glucose value expected with injection of 1 unit insulin
Explain what a correction factor is and why is it used.
In simple terms, the correction factor is a measure of how much the blood glucose value should change with the injection of 1 unit of insulin. The correction factor may also be known as the insulin sensitivity.

62. Correction Factor
For the average patient, 1 unit of insulin will lower blood glucose by 50 mg/dL
For insulin-sensitive individuals, 1 unit may lower blood glucose by as much as 100 mg/dL
For insulin-resistant individuals, 1 unit may lower blood glucose by as little as 25 mg/dL
On average, 1 unit of insulin lowers a patient’s blood glucose level by 50 mg/dL.
ADDITIONAL SPEAKING NOTES
Notice the change that can occur in different individuals with 1 unit of insulin. This is the reason that we have moved away from the traditional sliding scale insulin regimens. With the traditional sliding scale, patients with BG of were given 2 units of insulin, which is appropriate for the average individual. However, in a very insulin sensitive individual with a BG of 232, 2 units of insulin may leave them with a BG value of 32 mg/dL and then we’re fighting to get the level back up. Conversely, in an obese patient, the same 2 units may only decrease the blood glucose to 182 mg/dL and everyone is wondering why the sliding scale is not working. Thus the concept of a correction factor was formed that takes the patient’s weight into account.

63. Correction Factor 1800 rule Also 2000, 1700, 1500 rules
1800 ÷ total daily dose of insulin (TDD)
Example
1800 ÷ 50 units = 36
1 unit of rapid-acting or short-acting insulin will lower blood glucose by 36 mg/dL
Also 2000, 1700, 1500 rules
Higher rule value = lower risk of hypoglycemia
Review the common methods of determining a patient’s correction factor.

64. [Blood glucose now] − [Goal blood glucose]
Correction Dose
Current blood glucose − target blood glucose = amount of glucose over target
Amount of glucose over target ÷ correction factor = correction dose
[Blood glucose now] − [Goal blood glucose]
Correction factor
Explain how the correction factor is used to determine a specific correction dose of insulin.

65. Insulin Mini-Case 3b 19-year-old Caucasian man with type 1 diabetes
Experiencing unexpected elevations in blood glucose due to school-related stress
To illustrate the concepts of correction factor and correction dose, we’ll return to the mini-case of our patient newly diagnosed with type 1 diabetes.
Refer participants to the printed materials for insulin mini-case #3 (second part of case). Quickly review the points on this slide.

66. Insulin Mini-Case 3b Recall TDD Determine correction factor
37 units/kg/day
Determine correction factor
Use rule of 1800
Calculate correction dose
Current blood glucose: 320 mg/dL
Blood glucose goal: 120 mg/dL
Allow participants a few minutes to perform these calculations.
Provide the correct answers; lead a discussion about the responses if anyone failed to obtain the correct answers.
NOTES FROM CASE AUTHOR
Total daily dose (TDD) already was calculated in mini-case 2 part a as 37.
1800/37 = 48.6
Round down or up…doesn’t matter, just a starting point. So based on the patient’s weight, 1 unit of insulin should change his blood glucose by ~48 mg/dL.
Correction dose: [BG now − goal BG]/correction factor
[ ] ÷ 48 = 4.16
This means that if the patient injects 4 units of bolus insulin, his blood glucose level should decrease to approximately 120 mg/dL.
Remember that this is only a starting point…a best “guestimate.” The calculation will have to be redone if significant changes in weight occur, or at least once per year.

67. Insulin-to-Carbohydrate Ratio
Amount of rapid-acting or short-acting insulin needed to “cover” carbohydrates in meals and snacks
Patient may have different insulin-to-carbohydrate ratios for different meals
Explain what the insulin-to-carbohydrate is and why is it used.

68. Insulin-to-Carbohydrate Ratio
How to calculate
Determine average carbohydrate grams for each meal and snack
Divide carbohydrate grams by units of insulin administered (with appropriate glucose control)
Review the approach to calculating an insulin-to-carbohydrate ratio using actual carbohydrate intake data.

69. Insulin-to-Carbohydrate Ratio
Information needed
Detailed, accurate food records for at least 3 days
To determine total carbohydrate grams eaten at meals and snacks
Units of rapid-acting or short-acting insulin administered with each meal and snack
Premeal and postmeal blood glucose levels
Explain the information that is needed to use the calculation presented in the previous slide.

70. Insulin-to-Carbohydrate Ratio
Sample calculation
Average carbohydrate grams at dinner: 55 g
Administered 9 units rapid-acting insulin with appropriate return of glucose to baseline
55 g ÷ 9 units = 1 unit of insulin per 6 g carbohydrates
Insulin-to-carbohydrate ratio 1:6
Go over the sample calculation presented in this slide. Ask participants if they have any questions about this calculation.

71. Insulin-to-Carbohydrate Ratio
Rule of 500
Alternate method of calculating insulin-to-carbohydrate ratio
500 ÷ TDD
More simply, the insulin-to-carbohydrate ratio can be determined using the “rule of 500.” This is similar in concept to the “1800 rule” used to determine the correction factor.
Review the rule of 500 calculation.

72. Insulin Mini-Case 4 24-year-old Hispanic woman with type 1 diabetes
Weight: 118 lb
Uses insulin glargine (Lantus®) 22 units once daily
Guesses at prandial doses
Let’s take a look at a mini-case of a different patient with type 1 diabetes.
Refer participants to the printed materials for insulin mini-case #4. Quickly review the points on this slide.

73. Insulin Mini-Case 4 Calculate the insulin-to-carbohydrate ratio
Use rule of 500
Use 0.6 units/kg/day for insulin dose
Allow participants a few minutes to perform these calculations.
Provide the correct answers; lead a discussion about the responses if anyone failed to obtain the correct answers.
NOTES FROM CASE AUTHOR
First we have to determine the total daily dose of insulin:
118 lb = ~54 kg
54 kg × 0.6 = 32 units/day
Then plug total daily dose into the rule of 500:
500 ÷ 32 = 15
Thus 1 unit will cover approximately 15 g ingested carbohydrate. Note that the patient must understand carbohydrate counting to use this concept.

74. Patient Case Claire Green
Now we’ll try to pull all of these concepts together with our next patient, Claire Green.
Refer participants to the printed materials for the Claire Green case and have them answer the associated questions. Options include:
Participants complete worksheet alone, then discuss their findings with others at table.
Participants work in groups to complete worksheet (e.g., everyone seated at a table works together).

75. Claire Green What do Claire’s SMBG results tell you?
What changes (if any) should Claire make?
Review worksheet questions with participants. Ask for volunteers to offer responses, including their reasons for the responses.

76. Claire Green
How should Claire adjust her insulin regimen for her night out with the girls?
Review worksheet questions with participants. Ask for volunteers to offer responses, including their reasons for the responses.

77. Hypoglycemia
We will conclude our discussion of insulin therapy by reviewing the treatment of hypoglycemia.

78. Hypoglycemia Risk factors Symptoms Missed or irregular meals
Physical activity
Alcohol consumption
Symptoms
Review the risk factors and characteristic symptoms of hypoglycemia.

79. Hypoglycemia Management
CHECK
TREAT
CHECK
If hypoglycemia is suspected, check blood glucose. If confirmed by test, treat with 15–20 g glucose. Recheck in 15–20 minutes. If still low, retreat and check again. If blood glucose is normal, patient needs to eat a complex carbohydrate and protein-based meal or snack to maintain glucose levels.
Note: Newly diagnosed patients with type 2 diabetes who have been in a state of hyperglycemia for some time may feel hypoglycemic upon starting medications (even though blood glucose is within normal limits). Their bodies need to adjust to the new state of euglycemia. This is an important counseling and monitoring point.
EAT

80. Insulin Therapy Updates
This slide introduces a section in which news about insulin therapy can be presented and discussed briefly.

81. Emerging Insulin Regimens
Eli Lilly
Basal Insulin Peglispro: Phase III
Eli Lilly and Boehringer Ingelheim
Glargine biosimilar: Filed
Sanofi
Glargine U300: Phase III
Lixisenatide + glargine: Phase III
Basal insulin Peglispro: insulin lispro modified with a 20-kDa polyethylene glycol (PEG) moiety. increasing the hydrodynamic size of the insulin complex [20]. This large size delays insulin absorption and reduces clearance, resulting in a prolonged duration of action
IDegLiro: A fixed-ratio combination of insulin degludec and liraglutide intended to offer the benefits of the two components in a single preparation.
FIAsp: A faster-acting formulation of insulin aspart: Faster insulin aspart

82. Emerging Insulin Regimens
Novo Nordisk
Degludec + aspart (Ryzodeg): Filed
Degludec (Tresiba): Filed
Degludec + liraglutide (IDegLira): Phase III; Filed in Europe
Faster insulin aspart (FIAsp): Phase III
In a nutshell, insulin (and available diabetes treatments) is about to get really exciting!
Clipart: M word clipart
Insulin’s about to get really exciting!

83. Questions?
[Ask participants if they have any other questions about intensive insulin therapy or pattern management.]
LUNCH BREAK IS AFTER THIS SLIDE

84. Lunch