1. Insulin Initiation and Titration

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Teacher’s Room Code is:
DTCELUA8V

3. Insulin topics we will not cover today
Inhaled Insulin
Insulin Pump
Insulin management of the surgical and ICU patient
Insulin Requirements in Pregnancy

4. Goals for this session:
Know the indications for starting insulin
Know typical starting dose of Daily intermediate or long-acting insulin
Titrate the intermediate or long-acting insulin based on glucose readings
Be able to calculate starting doses based on weight for 70/30 insulin BID dosing
Titrate the 70/30 insulin based on glucose readings
Identify causes of hypoglycemia and hyperglycemia
Manage hypoglycemia and hyperglycemia

5. Complete 3 activities after this lecture
Calculating Insulin Starting Doses and Titration Case Studies
How to draw up and inject insulin
Hypoglycemia & Hyperglycemia identification & treatment. Glucose monitoring and the importance of the glucose logbook in titrating insulin doses.

6. Insulin types

7. Insulin Terms Basal Insulin Replacement
That insulin required to suppress hepatic glucose production overnight and between meals

8. Basal Insulin Action Product When to Take Onset Peak Duration
Intermediate
NPH (neutral protamine hagedorn)
BID
1-4 hours
4-12 hours
14-26 hours
NPL* (neutral protamine lispro)
1-2 hours
6 hours
15 hours
Long
Glargine (Lantus)
Determir (Levermir)
Usually bedtime**
Glargine No peak; determir 3-9 hours
Up to 24 hours
Ultra-long
Degludec
(Tresiba)
Once daily
No peak
Up to 42 hours
*In the US NPL is only available in combination with lispro (ie: Humalog mix)
**Long acting insulin may be given at any time of day because theoretically it does not peak. However, it must be given at the same time each day. Long acting insulin is usually given once a day, but may be given twice a day in rare instances.
NPH is usually given twice a day (except when adding to oral hypoglycemic medications – it is given once daily at bedtime).

9. Insulin Terms Bolus (prandial or mealtime) insulin replacement
That insulin required to utilize glucose after eating
Correction dose (also called supplement)
Additional insulin for pre-meal hyperglycemia
Can also be between-meal hyperglycemia
This insulin can only be regular, lispro, aspart, or glulsine

10. Bolus & Correction Insulin
Action
Product
When to Take
Onset
Peak
Duration
Rapid
Lispro
(Humalog)
Aspart (NovoLog)
Glulisine (Apidra)
0-15 minutes before a meal
10-30 minutes
30 minutes - 3 hours
3-5 hours
Short
Regular (R)
Human
30 minutes before a meal
30 minutes
1-5 hours
8 hours
With the exception of marked hyperglycemia (correction dose) do NOT administer bolus insulin (rapid or short acting) without the patient eating afterwards or hypoglycemia will occur.

11. Pre-mixed Humulin 70/30 Humalog Mix 75/25 Humulin 30/30
Rapid Acting with Intermediate
(NPL + Rapid)
Short Acting with Intermediate (NPH + Regular)
Humulin 70/30
Humulin 30/30
Novolin 70/30
Humalog Mix 75/25
Humalog Mix 50/50
Novolog Mix 70/30

12. What is the shelf-life of insulin after it is opened?
28 days
7-14 DAYS

13. Care of Insulin
Intermediate-acting insulins that are not refrigerated should be kept as cool as possible [<86°F], but not frozen.
Insulin glargine, once opened, should be stored in a refrigerator or kept as cool as possible.
Advise patients that all insulins need to be stored out of direct sunlight and kept from extremes of temperature.

14. When should you start insulin?
Type I Diabetes
Always

15. When should you start insulin in Type II Diabetes?
Glucose levels are so acutely elevated that immediate safety is a concern
Marked hyperglycemia OR Significant weight loss OR Severe/significant symptoms OR 2+ or greater ketonuria OR DKA/ hyperosmolar state OR Severe intercurrent illness or surgery
Chronic suboptimal control of glucose despite oral hypoglycemic medications/GLP-1 agonists/
Fasting Plasma Glucose > 140 OR 2 Hr Postprandial Plasma Glucose > 180 OR A1C > 7.0%

16. What fears do patients have about starting insulin?

17. Insulin Initiation Options for Type II Patients
It should be noted that there is great clinician variation when it comes to administering types and scheduling of insulin. The most important is to get the patient at goal without causing hypoglycemia.

18. Insulin options for patients with Type II DM
1) Continue PO medications & add nighttime basal insulin 2) Pre-mixed Insulin Program 3) Basal insulin + mealtime (bolus) insulin We will not cover this today

19. Option #1: Continue PO medications & add nighttime basal insulin
NOTE:
This is NOT an option for patients with Type II DM who have an A1c >8.5% on max oral hypoglycemics (they will never get to goal).
This is NOT an option for Type I diabetics

20. PO medications + Basal Insulin Initiation
Continue oral agents
Add single dose nighttime basal insulin (intermediate {NPH} or long acting insulin {glargine or determir})
Begin with a single dose of 10 Units at bedtime (or 0.2 Units/kg)….start with lower doses in elderly patients, severe CKD….

21. PO medications + Basal Insulin Titration
Check and log daily morning (fasting) blood glucose
Keep increasing the night time basal insulin by 2 units every 3 days until morning (fasting) blood glucose is consistently less than 130
If hypoglycemia occurs or AM blood glucose is <70 on any one reading, Decrease nighttime basal insulin by 4 units.

22. EXAMPLE
A 84 kg male has consistent elevated glucose readings, and A1C of 7.8 on Metformin 1g BID, Glyburide 10mg BID, and Pioglitazone 30mg daily. The patient has normal estimated CrCl.
Plan: Nighttime basal insulin: glargine or determir or NPH is added to the patient’s medications

23. EXAMPLE
Q: The patient was started on 10 Units of nighttime glargine in addition to his PO medications: glyburide 5mg BID, Metformin, 1g BID, and Pioglitazone 30mg daily. He checks his fasting glucose every morning and calls you with the following AM results from the past 4 days: 180, 160, 173. What should be done next? A:

24. EXAMPLE
Q: The patient calls you in 4 days with the following AM fasting readings: 136, 128, 134, What should you tell the patient? A:

25. EXAMPLE
Q: The patient calls you in 4 days with the following AM fasting readings: 102, 98, What should you tell the patient? A:

26. Option #2: Pre-mixed Insulin Program
70/30 or 75/25 or 50/50 insulin

27. Premixed Insulin Program
Taper and discontinue oral antihyperglycemic medications as insulin is initiated and adjusted, particularly if using short or rapid-acting + basal insulins (exception is METFORMIN - Type 2 diabetics on insulin can improve their glycemic control and lower their insulin dose with metformin.)
There is an increased risk for edema when insulin and a thiazolidinedione are used together. Rosiglitazone should not be used in combination with insulin.
I personally continue metformin (if the patient has no contraindications to this medication) and discontinue all other diabetic medications if I am switching entirely to insulin. Because you shouldn’t be giving a sulfonyurea with short-acting insulin & TZDs (ie rosiglitazone) may increase edema if given with all that insulin.

28. Pre-mixed Insulin Initiation
Calculate Total Daily Insulin Requirement = 0.5Units/Kg (consider lower if the patient is very active, elderly, has chronic kidney disease, or is taking Metformin)
70/3o insulin: give 2/3 QAM (before breakfast) and 1/3 QPM (before dinner) *** Do NOT administer pre-mixed insulin without eating afterwards – hypoglycemia will occur.
Short acting intermediate – give 30 minutes before breakfast and dinner
Rapid acting intermediate – give right before breakfast and dinner. “give the shot while the meal is hot”
Note: if a patient was started on insulin in the hospital via sliding scale – you may use the total amount of required insulin/day for the total daily insulin
* Give 2/3 insulin dose before breakfast as this will cover breakfast and lunch. 1/3 will cover dinner
Benefit – easy dosing, easy to administer (twice a day), easy to titrate based on twice a day glucose readings. Better control than once daily basal insulin.
Disadvantage – the patient has to eat consistent meals 3 times a day (and may require a bedtime snack). This regimen may not give as accurate control (as the last option that requires more # of shots a day).

29. PRACTICE
Calculate your own total starting dose of 70/30 insulin based on your weight in Kg.
Now divide total into 2/3 in the AM (pre-breakfast) and 1/3 in the PM (pre-dinner)

30. Example
Q: Calculate the insulin for a patient starting 70/30 insulin who is 200 lbs A:

31. Example
Q: Calculate the insulin for a patient starting 70/30 insulin who is 140 lbs (64 kg) A:

32. 70/30 Insulin Titration
Check glucose & log readings at least twice a day – pre breakfast and pre dinner (or with any signs of hyper or hypoglycemia)
*Important – pre breakfast glucose reading reflects the amount of insulin given pre dinner. Pre dinner glucose reading reflects the amount of insulin given pre breakfast.

34. 70/30 Insulin Titration
Monitor and log readings for 3 days: If pre breakfast glucose is >130 INCREASE pre dinner insulin by 2 units If pre dinner glucose is >130 INCREASE pre breakfast insulin by 2 units If pre breakfast glucose is >200 INCREASE pre dinner insulin by 4 units If pre dinner glucose is >200 INCREASE pre breakfast insulin by 4 units * If unexplained hypoglycemia (any reading <70), decrease the insulin by 4 units. (example – pre dinner glucose is 68 that is not explained by any change in eating/activity – decrease the pre-breakfast insulin by 4 units)

35. EXAMPLE – 70/30 insulin
Your patient is taking 70/30 insulin 20 Units before breakfast and 12 Units before dinner returns with the following glucose readings
Pre breakfast 20U Pre dinner 12 Units
Plan?

36. EXAMPLE – 70/30 insulin
For the next 2 days, the glucose readings on 24 units QAM & 16 units QPM are:
Pre breakfast Pre dinner
Plan?

37. EXAMPLE – 70/30 insulin
Now the patient has the following readings on 26 Units QAM and 16 Units QPM
Pre breakfast Pre dinner
60 (skipped dinner the night before) 220
Plan?
* High AM glucose readings in a patient taking NPH insulin may be due to the Somogyi effect. Having the patient randomly taking the 2am will diagnose this phenomenon: if glucose is 2am – decrease the pre dinner insulin (because of the Somogyi effect); if it is high (dawn phenomenon), then increase the pre dinner insulin

38. EXAMPLE 70/30 insulin titration
Now the patient has the following readings on 30 Units QAM and 16 Units QPM
Pre breakfast Pre dinner
Plan?

39. Option #3: Basal insulin + mealtime (bolus) insulin
For Type II patients who require insulin
For Type I patients

40. Step 1 Calculate Total Daily Insulin = 0.5 units x weight (kg).
EXAMPLE. If a patient weighs 100 kg, the total daily insulin = 50 units/day
If the patient is very active, has decreased creatinine clearance, or is on diabetic medications, then consider a lower weight dose (ie 0.3 units x weight (kg)). EXAMPLE 100 kg patient total insulin dose = 30 units/day.
* Note: if a patient was started on insulin in the hospital via sliding scale – you may use the total amount of required insulin/day for the total daily insulin

41. Step 2 Split Total Insulin dose 50:50 between basal and bolus insulin
50% of dose is basal
50% of dose is bolus
Further divide bolus insulin into 1/3 for 3 meal coverage.

42. Example using Glargine or Determire once daily dosing for Basal Insulin for a 100 kg person
Total Insulin Dose = 50 units
Mealtime or Bolus insulin (lispro, aspart, gluisine, regular)
25 Units
Breakfast
8 Units
Lunch
Dinner
Basal (Glargine or Determire) Insulin
Bedtime
Advantage – Tighter glucose control
Disadvantage – giving more # of shots a day and monitoring glucose (pricking finger) more frequently.

43. Question?
Calculate Insulin dosing for a 60 kg person using Glargine Basal Insulin and Regular Bolus insulin
Total Insulin Dose = 30 Units
Total Daily Glargine Insulin is 15 Units & Total Regular Insulin is 15 Units
Regular insulin: 5 Units before Breakfast, 5 Units before Lunch, 5U before Dinner. Glargine 15 Units at bedtime.
*Note: glargine should not be mixed in a syringe with other insulins.

44. Insulin Titration
Have the patient check glucose readings at least 3 times a day in the log book – goal (fasting ) and (3 hour post meal <160).
If fasting blood glucose is consistently > , increase the basal insulin (NPH or glargine, determir) by 2-4 units a week.
If 2-3 hour post meal is consistently > 160, increase bolus insulin (lispro, aspart, gluisine, regular) by 2-4 units
Example – if 3 hour post breakfast is consistently 200, however, all other glucose readings are well controlled…increase the pre-breakfast bolus insulin by 2-4 units

45. What about the high readings?

47. If the patient has persistent high glucose readings despite multiple titrations of insulin, think of:
Incorrect Insulin Administration (Watch the patient’s technique in your office)
Drawing up air and injecting it (instead of insulin)
Not injecting the insulin SC
Not rotating injection sites
Dietary Non-compliance, weight gain
Insulin Non-compliance/Skipping Doses
Infection
False readings – re-check glucometer & strips, check A1c and compare home glucose reading with clinic glucometer
Outdated insulin or insulin exposed to extreme temps.

48. And the low readings?

49. If the patient has low readings, think of
False readings – re-check glucometer & strips, check A1c and compare home glucose reading with clinic glucometer
Insulin overdose
No PO intake, change in eating habits
Weight loss (chronic low readings)
Renal failure (acute if sudden hypoglycemia on same dose of insulin)
***Rapid acting insulin and long acting insulin are both clear – have the patient label on with an elastic band or marker or store them separately to avoid medication errors.

50. Summary

51. Take Home Message Insulin Initiation Insulin Titration
Better to start lower and titrate upwards than have a patient experience hypoglycemia (especially in older patients)
Insulin Titration
It takes time and constant titration to get patient at goal
Follow patients closely (phone, ) for insulin titration.
Make sure the patient has a phone number to call with any questions or concerns.
Educate the patient on the sign/symptoms & treatment of hyper & hypoglycemia
Know when to refer the patient to a diabetes specialist

52. References
Joslin Diabetes Center & Joslin Clinic Clinical Guideline for Pharmacological Management of Type 2 Diabetes 1/09/
Joslin E-Z start Resource Manual for Primary Care Practices
Uptodate.com

53. Learning Outcomes for PD Lab Stations
Effectively dose and titrate insulin for the cases given
Demonstrate correct drawing up insulin and injection of insulin
Be able to instruct patients on this technique
Demonstrate correct technique of checking a capillary blood glucose
Identify the signs and symptoms of hyperglycemia and hypoglycemia