1. Demystifying Insulin The Science and The Art
Davida F. Kruger, MSN,APN-BC,BC-ADM
Certified Nurse Practitioner
Division of Endocrinology, Diabetes, Bone and Mineral Disorders
Henry Ford Health System
Detroit, Michigan
What I plan to do in this presentation is share our experiences in developing a different model of diabetes care delivery, using diabetes educators as care providers to a population of pts w/ poorly controlled type 2 diabetes.
This is not necessarily a new or unique process, as we will discover during the presentation.
This model gave diabetes educators the opportunity and responsibility of managing the care of pts under delegated prescribing authority from supervising senior staff physicians in our System.

2. Diabetes Today: An Epidemic
In 2005, 20.8 million Americans (7% of the population) were diagnosed with diabetes1
In 2008, 40% of Americans >age 20 have either pre-DM or DM
Complications of diabetes are a major cause of mortality and morbidity1
>224,000 deaths
82,000 lower-limb amputations
44,000 began treatment for end-stage kidney disease
12,000-24,000 new cases of blindness each year
Total cost in the United States in 2002: $132 billion1
Diabetes Today: An Epidemic
Review as stated.
1. ADA National Diabetes Fact Sheet. Available at: Accessed October 11, 2006.
2. ADA. The dangerous toll of diabetes. Available at: Accessed October 11, 2006.
References
ADA National Diabetes Fact Sheet. Available at: Accessed October 11, 2006.
ADA. The dangerous toll of diabetes. Available at: Accessed October 11, 2006.

3. ADA Glycemic Control Targets
A1C < 7%
Preprandial plasma glucose mg/dl
Postprandial plasma glucose (PPG) <180mg/dl
A1c goal must be customized for the individual patient, with consideration of numerous factors such as comorbid conditions, duration of diabetes, history of hypoglycemia, hypoglycemia unawareness, patient education, motivation, adherence, age, limited life expectancy, and use of other medications.

4. Most Patients on Diabetes Therapies not Meeting A1C < 7%
These are NHANES data from 1999 that show that pts with diabetes are not reaching goal whether they are receiving oral therapy or insulin.
42% of pts tx’d with oral agents have A1c’s >8% and 51% of pts tx’d with insulin are above 8% as well
This is especially troubling when we look at the insulin data, because there is no limit to the A1c lowering effect of insulin, so what’s wrong with this picture?

5. DCCT Results HbA1c and Relative Risk of Diabetic Complications
Title
Subtitle 15 13
Average US HbA1c Range % 11
Eye disease
Relative
Risk of
Complications 9
Kidney disease
AACE recommendation is 6.5% 7
Nerve damage 5 3
The landmark government study, the Diabetes Complications and Control Trial (DCCT) demonstrated that as you reduce your A1c, you can reduce the risk of complications. Participants in the study who followed a regimen of intensive insulin therapy – either multiple daily injections or pump therapy – reduced their risk for serious complications such as retinopathy (eye disease), nephropathy (kidney disease) and neuropathy (nerve damage) by up to 74%.
But as this graph shows, each time participants reduced their A1c by a percentage point, they reduce the risk of complications by up to 40%.
The mean A1C value in US patients with diabetes has been reported to range between 7.8 and 8.6%, with one third of all patients with diabetes having A1C levels greater than 9.5%. 1
6.5* 6 7 8 9 10 11 12
HbA1c
Skyler, J: Endo Met Cl N Am, vol 25, 2, p , June Adapted from DCCT Research Group: NEJM 1993;329:
Minshall M, et al. Clin Ther. 2005;27:940–950. 5

6. Most patients with T2DM will eventually require insulin therapy6

7. What are some of the obstacles?
Delayed diagnosis of diabetes Delay in starting insulin in patients failing oral agents
Weight gain with intensification of glycemic control
Hypoglycemia with intensification of glycemic control
Patient and provider resistance to starting insulin as well as clinical inertia
Inappropriate managed care practices

8. Normal Insulin Secretion70
Serum insulin 50
Insulin (mU/L) 30 10
First and 2d phase release
Rapid and complete return to baseline
9:00 AM
12:00 PM
3:00 PM
6:00 PM
9:00 PM
12:00 AM
3:00 AM
6:00 AM
Breakfast
Lunch
Dinner
Time of day
Polonsky. N Engl J Med. 1996;334:

9. Natural History of Type 2 Diabetes
Severity of Diabetes
Impaired Glucose Tolerance
Frank Diabetes
Insulin Resistance
Hepatic Glucose Production
Endogenous Insulin
Postprandial Blood Glucose
Fasting Blood Glucose
Asymptomatic
Stage
Microvascular Complications
Macrovascular Complications
Years to Decades
Time
Typical Diagnosis of Diabetes
Ramlo-Halsted and Edelman: Clinics of NA Vol. 26 P771, 1999

10. Insulin Secretion in Type 2 Diabetes Is Delayed and Blunted: Too Little, Too Late
The insulin response in Type 2 diabetes is delayed and blunted, reflecting the progressive dysfunction of the pancreatic beta cells.
Key words:
Type 2
Beta cell
Dysfunction
Polonsky KS, Sturis J, Bell GI. NIDDM – a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med. 1996;334:777–783.

11. Type 2 Diabetes Treatment Strategies: Stepwise Management
Advance treatment whenever glycemic targets are not met
Lifestyle modification
MNT, weight loss, physical activity
OADs
Monotherapy
Combination therapy
Glp-1 agonist
Addition of basal insulin therapy to OADs/exenatide
Basal insulin plus prandial insulin ± OADs/pramlintide
New Recommendation
Metformin
Plus:
T2DM Treatment Strategies: Stepwise Management
 Treatment of T2DM usually begins with lifestyle changes that address environmental factors with potentially adverse effects on disease progress, such as weight, diet, and physical activity.1 A low-calorie diet can lower plasma glucose levels, and even a small decrease in weight of 5 to 10 pounds can help a patient reach normative levels. The American Diabetes Association also recommends medical nutrition therapy (MNT), with input from a registered dietitian, for getting weight and diet under control2
 If patients cannot make or maintain appropriate lifestyle modifications, or if these interventions cannot achieve target plasma glucose levels, OADs are often prescribed—although continuing to make healthy lifestyle changes should simultaneously be encouraged. A variety of agents are available, either for monotherapy or combination therapy1
 To maintain the glycemic target when OAD therapy is no longer sufficient, insulin therapy can be added. Long-acting basal insulin added to OADs can be a very effective next step. If A1C levels are still not optimum, then prandial insulin can be added around mealtimes3
_________________________________________________________________________________________________________
1. Nathan DM. Initial management of glycemia in type 2 diabetes mellitus. N Engl J Med. 2002;347:
2. American Diabetes Association (ADA). Standards of medical care in diabetes. Diabetes Care. 2005;28(suppl 1):S4-S36.
3. Riddle MC. Making the transition from oral to insulin therapy. Am J Med. 2005;188(suppl 5A):14S-20S.
MNT=medical nutrition therapy; OADs= oral antidiabetic drugs.
Adapted from Nathan DM. N Engl J Med. 2002;347:

12. The Case For Insulin

13. By the Time of Diagnosis, Beta-Cell Decline Exceeds 50%
Data from the UKPDS trial in newly diagnosed diet-treated patients show that the patients’ beta-cell function was between 50% and 60% at the onset of the trial. This function then progressively declined during the trial.
In a further analysis, the authors have determined when the patients would have been at 100% function. The results of this extrapolation are shown here; the decline in beta-cell function began ~11–12 years prior to initiation of the study (diagnosis of diabetes).
Key words:
Type 2
Beta cell
Dysfunction
Beta-cell function was quantified by measuring insulin levels and blood glucose and then calculating the function based on what the level should be.
UKPDS. U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes. 1995;44:1249–1258.
Treatment should be predicated on the clinical condition of the pt, not because of the point at which diabetes is diagnosed.
In other words, let blood glucose levels determine mode of treatment, not when the pt was diagnosed (“we’ll start with diet,” but BG’s are persistently above 300 would be malpractice. 13

14. Indications for Insulin in T2DM
Symptomatic Hyperglycemia
BG > 250 mg/dL)
Inadequate glycemic control (patient specific (A1c >7%)
Oral agents cannot be tolerated/contraindicated
Longstanding Type 2 Diabetes/not responding to oral meds
Transient poor control
Intercurrent illness
Glucocorticoid therapy 14

15. Goals of Insulin Therapy
HbA1c < 7% (patient specific)
Fasting and pre-prandial: 70 – 130 mg/dL
2 hr after start of meal: < 180 mg/dL
Avoid frequent or severe hypoglycemia with physiologic insulin replacement therapies
Minimize weight gain
A1c goal must be customized for the individual patient, with consideration of numerous factors such as comorbid conditions, duration of diabetes, history of hypoglycemia, hypoglycemia unawareness, patient education, motivation, adherence, age, limited life expectancy, and use of other medications. 15

16. Mimicking Nature With Insulin Therapy Basal/Bolus Concept
Physiologic Insulin Secretion 50
24-hr profile
Basal insulin
Insulin (uU/mL) 25
Suppresses glucose production between meals and overnight
Nearly constant levels
50% of daily needs B L D
150
Mimicking Nature With Insulin Therapy
Basal/Bolus Concept
When considering glucose control, the focus must be on both postprandial and basal requirements. This slide illustrates the normal diurnal physiologic response, which highlights the need for both basal and meal insulin
Meal-insulin release occurs in response to nutrient ingestion
Basal insulin is continually secreted over a 24-hour period
In the past, insulin formulations did not have adequate pharmacokinetics to duplicate these profiles. However, within the past few years, new insulin analogs have been developed that provide more physiologic profiles
1. Bergenstal RM et al. In: DeGroot LJ, Jameson JL, eds. Endocrinology. 4th ed. Philadelphia, Pa: WB Saunders Co.; 2001:821
100
Glucose
(mg/dL) 50
Basal glucose
Insulin ( AM PM
Adapted with permission from Bergenstal RM et al. In: DeGroot LJ, Jameson JL, eds. Endocrinology. 4th ed. Philadelphia, Pa: WB Saunders Co.; 2001:821 16

17. TYPES OF INSULIN AND HOW THEY WORK17

18. Pharmacokinetic Profiles of Human Insulin and Insulin Analogs
Onset
Peak
Duration
Rapid-acting
10-15 mins
60-90 mins
4-5 hr
Regular
30-60 mins
2-4 hours
5-8 hr
Plasma Insulin Levels
0200
0400
0600
0800
1000
1200
1400
1600
1800
2000
2200
2400
Rapid-acting
NPH
1-3 hr
5-8 hours
12-18 hr
Detemir
90 mins
Relatively peakless
12-24 hr
Regular insulin
Glargine
90 mins
Peakless
24 hr
NPH
Detemir
Glargine
Lepore M et al. Diabetes. 2000;49: ; Howey DC et al. Diabetes. 1994;43: ; Plank J et al. Diabetes Care. 2005;28: ;; Wittlin SD et al. Insulin Therapy. Marcel Dekker, Inc.;2002:73-85.

19. BASAL INSULIN Intermediate Acting NPH Long-Acting Analogs
Glargine (Lantus)
Detemir (Levemir) 19

20. NPH Insulin Human Insulin Isophane Suspension Pharmacokinetics
Onset: hour
Peak: hours
Duration: hours
40% variance!!
Can be mixed with Regular and Rapid Acting insulin 20

21. Insulin Glargine (Lantus)
Recombinant human insulin analog
Pharmacokinetics
Onset: hour
Peak: Peakless
Duration: 24 hours
Administration:
Once Daily at anytime of day
When converting from once daily NPH, same dose used.
When converting from twice daily NPH, start with 20% less 21

22. Insulin Detemir (Levemir)
Recombinant human insulin analog
Pharmacokinetics
Onset: hour
Peak: Peakless
Duration: 12 hours
Administration:
Once or Twice Daily
Same dose as once daily NPH
20% less than twice daily NPH
May actually require more detemir than glargine
Shown to be associated with weight loss/less weight gain than other insulin 22

23. Insulin glargine (Lantus) Insulin detemir (Levemir)
Similar rates of absorption from abdominal, thigh and deltoid region
Cannot be mixed with any other form of insulin or IV solution
Incidence of nocturnal and severe hypoglycemia were less frequent compared to once-daily NPH insulin
CLEAR solution
Available in Pen Device 23

24. Basal Insulin Replacement Therapy
Normal Insulin Secretion
at Meal Time
Insulin Glargine/Detemir
NPH Insulin
Change in Serum insulin .
s.c. injection
Time (hours) 24

25. What is Going on in the Real World? Insulin Therapy Trends 2002–2006
Increasingly, patients are only taking a long acting insulin
Graph is the results of patient self-reported response
Percentage of insulin patients responding that they are taking only a long-acting insulin.
The market research study is a syndicated study of people with diabetes, not a study sponsored by Lilly.
The total number of patients who answered this question was 212.
* Statistically significant difference from prior wave.
** Includes Lantus (75%), Levemir (8%) and Ultralente (5%). Twelve percent (12%) report “don’t know.”
Source: 2006 Roper Survey of US Diabetes Patient Market, GfK Market Measures, N-705

26. PPG Contributes to 50% or More of Overall A1C When A1C Is 8.4 or Below
The choice of an initial insulin needs to be based on the pt’s curent state of glucose control.
This slides illustarates that when glycemic control is poor, correcting the fasting blood glucose would be the bettr strategy.
However, as A1c’s improve, and fall below 8.4%, then PPG becomes more significant
PPG Contributes to 50% or More of Overall A1C When A1C Is 8.4 or Below
In the past, the belief was that A1C levels were primarily dependent on FPG
However, postprandial hyperglycemia also is an important component of generating A1C
Postprandial glycemic excursions become more predominant in patients with good control of fasting plasma glucose. Therefore, treatment should focus on both FPG and PPG excursions to reach and maintain A1C targets.
Key words:
Diagnosis
Total glucose control
A1C
FPG
PPG
Postprandial glucose
Adapted from Monnier L, Lapinski H, Collette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of Type 2 diabetic patients: variations with increasing levels of HBA(1c). Diabetes Care. 2003;26:881–885. 26

27. BOLUS INSULIN Short Acting Regular Rapid- Acting Analogs
Aspart (Novolog)
Lispro (Humalog)
Glulisine (Apidra) 27

28. Regular Insulin Human Insulin (soluble) Pharmacokinetics
Onset: hour
Peak: hours
Duration: hours (as long as 8 hours)
Administration:
minutes BEFORE meals
Can be mixed with NPH insulin
Only insulin that can be given IV 28

29. Rapid-Acting Insulin Analogs
Equipotent to Regular Insulin
Products
Lispro (Humalog)
Aspart (NovoLog)
Glulisine (Apidra)
Goal: to mimic physiological prandial response 29

30. Rapid-Acting Insulin Analogs
Pharmacokinetics
Onset: < 0.25 – 0.5 hour
Peak: 0.5 – 1 hour (lispro 2.5 hour)
Duration: hours (lispro hours)
Administration:
Within 15 minutes BEFORE meals
Can be mixed with NPH insulin 30

31. Bolus Insulin Replacement Therapy
Normal Insulin Secretion
at Meal Time
Rapid-acting Analogue
Regular insulin
Change in Serum insulin .
s.c. injection
Time (hours)
Apidra
Humalog
Novolog 31

32. Why is Mealtime Control Important?
Patients with poorly controlled type 2 diabetes may spend much of their waking day with postprandial hyperglycemia1
99% of patients with A1Cs ≥7% have 2-hour postprandial glucose (PPG) levels ≥200 mg/dL2
Type 2 diabetes
Control
400
Plasma Glucose (mg/dL)2
300
Discussion points
Erlinger studied the prevalence of postchallenge hyperglycemia (PCH) in adults with type 2 diabetes who were not taking insulin.
PCH was defined as a 2-hour glucose ≥200 mg/dL.
Among those with diagnosed diabetes, 74% had PCH.
In patients with suboptimal glycemic control (A1C ≥7%), virtually all (99%) presented with PCH.
Glucose concentrations measured throughout the day from Polonsky show that in patients with poorly controlled type 2 diabetes (mean A1C ~10%), a postprandial state may be maintained from the first meal of the day (breakfast) through the evening.
In many patients with poorly controlled type 2 diabetes, postprandial hyperglycemia is a problem.
Erlinger TP, Brancati FL. Postchallenge Hyperglycemia in a National Sample of U.S. Adults With Type 2 Diabetes Diabetes Care 2001;24(10):
Polonsky KS, Given BD, Hirsch LJ, et al. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med. 1988;318(19):
200
100
Breakfast
Lunch
Dinner
6 AM
10 AM
2 PM
6 PM
10 PM
2 AM
6 AM
Time of Day
Polonsky KS, et al. N Engl J Med. 1988;318(19):
Erlinger TP, et al. Diabetes Care. 2001;24(10):

33. Relationship Between 2-Hour Plasma Glucose and All-Cause Mortality
Discussion points
Data from the DECODE study group showed that:
Fasting glucose is not by itself a good predictor of risk of death.
High 2-hour glucose is a better predictor of mortality than fasting glucose.
For any category of fasting blood glucose, an increase in 2-hour glucose was associated with a significant increase in risk of death.
The DECODE Study Group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria. Lancet. 1999;354(9179):

34. Basal-Bolus Insulin Therapy: Insulin Glargine at HS and Mealtime Lispro or Aspart
Insulin Effect
Slide 61
Basal-Bolus Insulin Therapy: Insulin Glargine at HS and Mealtime Lispro or Aspart
The slide depicts the profile of a “basal-bolus insulin” regimen, with insulin glargine at bedtime (HS) providing the basal component and prandial insulin lispro or insulin aspart providing the bolus component
This regimen affords the following advantages:
Provides flexibility for varying dietary habits
Less risk of nocturnal hypoglycemia due to the 24-hour near-constant effect of insulin glargine, making it an ideal basal insulin
Less risk of between-meal hypoglycemic episodes due to the short duration of the rapid-acting insulin analogs, which may also provide insulin coverage for snacks or extra meals with additional injections
Avoidance of mixing different insulin preparations in the same syringe as single insulins are administered with each injection. Insulin pens are suggested for maximal convenience and accuracy in dosing
1. Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002:87 B L D HS
Insulin lispro or aspart
Insulin glargine
Adapted with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York, NY: Marcel Dekker Inc.; 2002:87

35. Premixed Insulin HUMAN
70/30
70% NPH
30% REG
50/50
50% NPH
50% REG
Dual Peak
Administration:
Must be injected minutes before a meal
Once or twice daily dosing 35

36. Premixed Insulin HUMAN
Advantages:
Convenience
Accuracy
visually impaired
Manual dexterity challenges
Disadvantages:
Inability to adjust only one component
Nocturnal Hypoglycemia
MUST eat CONSISTENTLY timed meals 36

37. Premixed Insulin ANALOG
70/30 MIX (Novolog)
70% Aspart protamine
30% Aspart
75/25 (Humalog)
75% Lispro protamine
25% Lispro
One Peak followed by "long Tail” (No NPH)
Administration:
Must be injected within 15 minutes before a meal
Once, twice or three times daily dosing 37

38. Premixed Insulin ANALOG
Advantages:
Convenience
Accuracy
visually impaired
Manual dexterity challenges
Flexibility with meals
Less Nocturnal Hypoglycemia
Disadvantages:
Inability to adjust only one component 38

39. Mixed Insulin Replacement Therapy
Normal Insulin Secretion
at Meal Time
Analog Mix
PreMix 70/30
(NPH/REG)
Change in Serum insulin .
s.c. injection
Time (hours)
75/25 Humalog Mix
70/30 Novolog Mix 39

40. Now What ?

41. …then, Tackle Postprandial if A1C still >7%!
FIRST Correct FASTING
300
Time of Day
Uncontrolled A1C ~9%
“Controlled” A1C <7%
200
PG (mg/dL)
A1C ~6%
100
Normal A1C 5%–6%
0800
1200
1800
0800
…then, Tackle Postprandial if A1C still >7%!
Adapted with permission from Cefalu WT. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York: Marcel Dekker; 2002:1-11. 41

42. Possible Approaches for Adding Insulin
using a basal insulin with continued oral agents
using pre-mixed insulin with continued oral agents
stopping oral agents and initiating insulin using various regimens:
pre-mixed insulin
prandial insulin with a basal insulin once (or twice) daily 42

43. Start a Basal Insulin “Treat to Target”
Continue oral agent(s) at same dosage
Do NOT stop insulin secreting agent
Add single, evening insulin dose ( U/kg)
units
Glargine, Detemir or NPH (bedtime)
Increase insulin dose every 3-4 days as needed
Increase U if FBG >150 mg/dL
Increase U if FBG = >110,<150 mg/dL
Treat to target FBG (usually <120 mg/dL)
6-59

44. Traditional “Sliding Scale”
An arbitrary insulin dosing algorithm based only on pre-meal blood glucose values
Pre-Meal BG (mg/dl)
Insulin Dose (units)
Less than 151 2 4 6 8 10

45. Traditional “Sliding Scale”
Breakfast
Lunch
Dinner
Bedtime
Day 1
BG (mg/dl)
141
335 89
290
Insulin Dose 8 6
Day 2
381 76
261
121
Day 3 BG
>600

46. Adding a meal time bolus: Only Fasting BGs at target
Stop insulin secreting agent
Add Bolus insulin before meals (REG or analog)
Isocaloric meals
Add 10 units and redistribute total dose 50/50
Pt taking 30 units Lantus already
Add 10 units to a new total dose of 40 units
50% will be new basal (20 units)
50% in divided doses will be the meal time bolus (i.e. 7/6/7)
Carb counting and correction factors
BG checks a must! “blind leading the blind”
SAFETY

47. Total Daily Insulin
Total daily insulin requirement is calculated by body weight
T1: need about 0.6 units/kg (range )
T2: need about 1.2 units/kg (range 1 – 1.4)
BGs at goal without hypoglycemia.
40-50% basal (background)
50-60% bolus (meal doses)

48. Calculating “Basal–Bolus” Insulin
Calculate TDD
T1: need about 0.6 units/kg (range )
T2: need about 1.2 units/kg (range 1 – 1.4)
Basal dose: 40 – 50% of TDD
Bolus dose: 50-60% of TDD:
Divide equally for three meals OR
Sensitivity Factor = 1700/TDD
1 unit will drop BG by XX points
Carbohydrate Ratio = 500/TDD
1 unit for every XX gm carbs
(Pt BG – target) / (SF) = CORRECTION
Now add carb ratio for meal.

49. For Example 250 pound T2DM (114 kg)
Calculated TDD: 114 x 1.2 = 137 u/day
Basal Dose: 68 units a day (50% of TDD)
Bolus Dose: (other 50% of TDD)
Isocaloric meals:
68/3 = 23 units before each meal
Carbohydrate ratio: 500/137 = 3
1 unit for every 3 grams of carbs
Insulin Sensitivity: 1700/137 = 12
1 unit will lower BG 12 mg/dL

50. For Example: Above Target at Lunch
Pre meal target: 100
Pt BG before lunch: 160
Will be eating a meal of 65 gm CHO
160 – 100 = 60 points too HIGH before eating
Sensitivity Factor = 12
60/12 = 5 (will need 5 units to correct to target)
Carb ratio = 1 : 3
65 gm CHO / 3 = 21 (will need 21 units for the meal)
5 units +21 units = 26 units before lunch

51. For Another Example: Below Target at Lunch
Pre meal target: 100
Pt BG before lunch: 80
Will be eating a meal of 65 gm CHO
= - 20 points too LOW before eating
Sensitivity Factor = 12
-20/12 = -1.6 >> -2 (will need -2 units to correct to target)
Carb ratio = 1 : 3
65 gm CHO / 3 = 21 (will need 21 units for the meal)
21 units – 2 units = 19 units before lunch

52. Sliding scale: Correction
Correction Scales:
Helpful for sick days/NPO
Still need to calculate the TDD and the insulin sensitivity
Example: TDD = 137; SF 1:12
WILL NOT COVER FOR CARBS, ONLY TO CORRECT
< , no insulin
, 2 units ( )
, 4 units ( )
, 6 units ( )
, 8 units ( )
, 10 units, etc ( ) 52

53. Sliding scale: Correction + Carbs
Incorporates BOTH the correction and the meal requirements
Still need to calculate the TDD, sensitivity factor, and carbohydrate ratio
Works best for consistent carb intake (may have different scale for each meal)
Example: TDD = 137 units
SF = 1:12
CR = 1:3
Eats approx 65 gm carbs at each meal
<70, no insulin
71 – 125, 21 units
, 23 units
, 25 units
, 27 units
, 29 units
, 31 units 53

54. What’s the dose range? Type 2: 0.3 to 1.2 units/kg
“Thin type 2’s” are more insulin deficient
“Heavy type 2’s” are more insulin resistant
Most pts with T2DM need insulin doses of
1 to 1.2 units/kg to achieve an A1c <7%
(basal dose of 0.5 to 0.6 units/kg per day)

55. Lilly Pens: Memoir & Kwikpen
NovoNordisk: NovoPen 3
Insulin Pens
Lilly Pens: Memoir & Kwikpen
Convenient
Discreet
Protect Insulin from light, heat and agitation
Sanofi-Aventis: SoloStar

56. U-500 Insulin

57. History: Why U-500?
Main reason in early 1950s was for high insulin requirements in type 1 diabetes due to high levels of insulin antibodies developed from other animal insulins
Also used for severely insulin resistant type 2’s
Only developed as a regular insulin
Replaced by pork U-500 regular insulin in 1980
Replaced by human U-500 regular insulin in 1997

58. What About the Need for More CONCENTRATED Insulins?
For more resistant patients, U-100 insulin both impractical and inconvenient
When over 100 units (1mL) required at one time, would need more than one injection
Large volume of insulin painful
Large depot of insulin impedes absorption making it unpredictable (a more concentrated insulin should be more predictable at these doses)

59. Insulin Resistant Conditions to Consider U-500 Insulin
Non-Syndromic Insulin Resistance
Obesity with T2DM requiring > 200 u/day
Post-op or post-transplant state
High-dose steroids or pressors
Systemic infection
Pregnancy with underlying T2DM

60. Most Recent PK/PD U-500 Data
Duration of action was shown to be prolonged for U-500 vs. U-100; mean late tRmax50 was 3.4 hr longer than at the 100-U dose (p<0.001)
The longer duration of effect of U-500 compared to U-100 suggests that multiple daily injections of U-500 without use of a basal insulin may be a plausible treatment option for insulin-resistant patients with type 2 diabetes

61. So Is U-500 Regular Insulin a Basal or a Prandial Insulin?
It is BOTH!
Lag times never studied, but it only makes sense that when used as mealtime insulin timing between injection and eating is even more important than with U-100 regular (or analogue)
Main secret for success with U-500 insulin
FREQUENT SMBG!

62. Communicating U-500 Dosing
Two ways: “units” on a U-100 insulin syringe or volume (mL) on a tuberculin syringe
Ideally, would be nice if everyone used both; most patients will discuss this in units
My compromise with patients and in charting: always note U-500.

63. Example
Patient is taking 10 units of U-500 insulin at breakfast (the equivalent of 50 units of U-100 regular) and it is decided to increase the dose to 14 units U-500
I tell the patient to increase the dose to 14 units U-500 in his U-100 syringe
I chart the dose was increased to 14 units of U-500 (which is 70 units of U-100 regular)

64. Example
This can also be done in tuberculin syringes and only discussed in terms of volume of insulin
Problem: in the US tuberculin syringes only available in 27G needles
So 10 units of U-500 insulin would be 0.10 mL of insulin
An increase to 14 units would be 0.14 mL of insulin
My observation: patients and nurses prefer “units”

65. Implementing U-500 Insulin
units/day
U-500 has been shown effective with or without traditional basal insulin
Without basal insulin, U-500 can be split into ac breakfast and dinner shots (60/40) or ac TID (40/30/30 or 40/35/20)
Many continue basal insulin, esp. during transition from U-100
Like most insulin management, what we do with U-500 is generally anecdotal. The good news: these patients don’t generally get hypoglycemic!

66. Injection Problems Lipoatrophy (immune response) Lipohypertrophy
Breakdown (pitting) of fat tissue
Indentation in the skin
Lipohypertrophy
Thickening (lumps) of SQ fat
Causes: repeated injections same site, needle reuse
Delays insulin absorption
Bruising at Site:  technique 66

67. Insulin Delivery Systems
Insulin syringes
Know Needle Gauges (29-32), Lengths
Short Needle: 8mm, Longer: 12.7mm
Syringe size- 1/4ml, 3/10ml, 1/2ml,1ml
Insulin pens: Nano ® (4mm), mini (5mm), short (8mm), long (12.7mm) needles
Continuous insulin infusion pump
Uses bolus insulin only 67

68. Insulin Pen Once Opened
Humulin & Novolin R
28 days
Humalog®, Novolog®
Humulin & Novolin N
14 days
Humulin & Novolin 70/30®
10 days
Humalog Mix 75/25®
Novolog Mix 70/30®
Levemir®
Lantus®, Apidra®
42 days

69. Thank You
Many individuals freely shared their slides for this presentation:
Roger Austin
Steve Edleman
Irl Hirsch
Lucia Novak
Jane Seely
Geri Spollet
Virginia Valentine