I

L Multiple Insulin Injection Therapy

I

N
I

N The presentation
S
Introduction:
U • Goals of multiple insulin injection.

L • High light of treatment method.

• Glycemic control effect.
I
• Diet treatment.
N
Type of insulin:
• Insulin preparation.
I
• What to mix and what not to mix.
N
Type of regimen:
J
• Western regimen.
E • Our regimen.
C • Future regimen.

T Important phenomena:
I • Somogyi phenomena.
• Dawn and predawn phenomena.
O

Multiple Insulin Injection Therapy

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N Goals
S

U Clinical Goals:
L • Elimination of ketosis.
• Elimination of hyperglycemia and it’s symptoms.
I • Prevention of chronic complications.

N
Additional Goals:
I • Maintaining desirable weight.
• Maintaining normal growth and sexual maturation.
N • Maintaining psychosocial well-being.
• Achieving normal fertility and pregnancy.
J • Sustaining normal family and sexual life.

E Control Goals:
C • HbA1c <7%.
• Pre-meal SMBG 80-120 mg/dl (4.4-6.7 mmol/l).
T • Bed time SMBG 100-140 mg/dl (5.6-7.8 mmol/l).
• No ketonuria.
I • Mean blood glucose level 120-160 mg/dl (6.7-8.9 mmol/l).

Multiple Insulin Injection Therapy

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N Highlights
S

U Insulin:
• Type 1 diabetes is dependent on insulin for survival.
• Insulin is classified by source or duration of action.
L • Human insulin has less allergy or lipoatrophy.
• More than one injection is needed and different types.
I • Proper action During honeymoon phase.
• The commonest side effect is hypoglycemia.
N
Nutrition:
• Enable near normal blood glucose level.
• Maintain a reasonable body weight.
I • Protein 10-20%, Fat 15-25%, Carbohydrate 65%.
• Fibers, vitamins, and minerals.
N • Food exchanges or carbohydrate counting.
• Total daily calorie intake adjustment.
J
Exercise:
E • Should be integrated.
• Weight control and improve well being.
• Pre-exercise medical evaluation.
C

T Monitoring:
• Glucometer use SMBG to monitor blood glucose level.
• Adjustment of insulin, diet, and exercise.
I • Urine testing for both glucose and ketones.
• HbA1c the best index for control.
O

Multiple Insulin Injection Therapy

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N Glycemic control
S

U
9
L

I Conventional
N 8
HbA1c (%)

I
Intensive
N 7

J
6.2% upper limit of normal range
E
6
C 0
0 3 6 9 12 15
T
Years from randomization
I

O
UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837–853.
N

Multiple Insulin Injection Therapy

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N Diet
S The total calories intake depends on patients age and activity but
have to related to the desirable body weight. 30 35 40
U Total daily calories = IBW X Estimated daily energy

Body weight
• Add 300 kcal/day during pregnancy.
L
• Add 500 kcal/day during lactation. 25 30 35
I Fibers, sweeteners, vitamins, and minerals.
20 25 30
N 25 years male IBW 60 kgm
Physical activity
I 60 Kg X 30 kcal = 1800 kcal

J Breakfast 600 kcal Lunch 800 kcal Dinner 400 kcal

Carbohydrate (65%) 390 Carbohydrate (65%) 520 Carbohydrate (65%) 260

E Protein (10%) 60 Protein (10%) 80 Protein (10%) 40
Fat (25%) 150 Fat (25%) 200 Fat (25%) 100
C
Carbohydrate 100 gm Carbohydrate 130 gm Carbohydrate 65 gm
Protein (10%) 15 gm Protein (10%) 20 gm Protein (10%) 10 gm
T Fat (25%) 17 gm Fat (25%) 22 gm Fat (25%) 11 gm

I Diet Carbohy. Protein Fat _ Diet Carbohy. Protein Fat _ Diet Carbohy. Protein Fat _
Arabian bread 30 gm --- --- Rice 80 gm --- 6 gm Tuna sandwich 45 gm 12 gm 10 gm
Cheese 5 gm 10 gm 10 gm chicken 5 gm 15 gm 12 gm Apple 15 gm --- ---
O Honey
Glass of milk
50 gm
10 gm
2 gm
5 gm
3 gm
5 gm_
Salad
Orange
30 gm
10 gm
4 gm
---
4 gm
---___
Tea
Total
---
95 gm
--- --- _
17 gm 18 gm
Total 95 gm 17 gm 18 gm Total 125 gm 19 gm 22 gm

Multiple Insulin Injection Therapy

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N Glucose sensor
S

U
The plan of insulin type and dose will
L
depend on:
I
- The shape of glucose curve.
N

- The diet and exercise.

I

J 20

E Day 1 Day 2 Day 3

C
10
T

O 0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Multiple Insulin Injection Therapy

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N Insulin Preparations
S

U
Action Name Onset Duration
Very rapid Lispro / Novo rapid 10-15 min 2-3 hrs
L
Rapid Crystalline zinc (CZI) 30-45 min 4-6 hrs
Intermediate Neutral Protamine
I
Hagedorn (NPH) 1-2 hrs 6-12 hrs
Lente zinc
N
Long acting Ultralente zinc 6-8 hrs 18 hrs
Lantus (glargine) 4-8 hrs 24 hrs
Premixed 80% NPH+20%CZI 30-45 min 6-12 hrs
I
70% NPH+30%CZI 30-45 min 6-12 hrs
50% NPH+50%CZI 30-45 min 6-12 hrs
N

C INSULIN TYPES DURATION OF ACTION

T

O
0 3 6 9 12 15 18 21 24
N

Multiple Insulin Injection Therapy

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N Insulin Mixing
S Action Name Mix (1)

U
(2)
Very rapid Lispro / Novo rapid Yes
L

I (2)
Rapid Crystalline zinc (CZI) Yes
N
(2)
Intermediate Neutral Protamine Yes
I (2)
Hagedorn (NPH) Yes
(2)
N Lente zinc Yes
J
Long acting Ultralente zinc No
E Lantus (glargine) No_
C
Premixed 80% NPH+20%CZI No
T 70% NPH+30%CZI No
I 50% NPH+50%CZI No_
(1) Mixing different type of insulin has to be fron the same source (ie same company)
O (2) Mixing different type of insulin has to be fron the same source (ie same company)

Multiple Insulin Injection Therapy

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N Pre-mixed insulin
S

U
10/90
L
Post- prandial hyperglycemia
I
20/80
N

Pre-prandial hyperglycemia
I

N 30/70
J

C 40/60

O 50/50

Multiple Insulin Injection Therapy

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N Western regimen
S

U 70
   Normal free insulin levels
(Mean)
L 60 Simulated s.c. injected
soluble human insulin +
Insulin (mU/l)
I
50 NPH
N Simulated s.c. injected
40 insulin aspart + NPH
I 30 Meal
N
20
J
10
E
0
C
0600 0900 1200 1500 1800 2100 2400 0300 0600
T Time of day
I

O Breakfast Lunch Dinner NPH

Adapted from Polonsky et al. 1988
N

Multiple Insulin Injection Therapy

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N Western regimen
S
Two doses: 150

U The usual dosing commonly used.

Initial insulin therapy
L 50

 
6 9 12 3 6 9 12 3

I
Three doses: 150

N Used for active patients.

Patients taking two main meals.
50

I 6 9 12 3 6 9 12 3

  
N Four doses: 150

Brittle diabetic patient.

J
Pregnant mothers specially type 1.
E
50

   
6 9 12 3 6 9 12 3

C
Four doses: 150

T Brittle diabetic patient.

Pregnant mothers specially type 1.
I Motivated patients. 50

6 9 12 3 6 9 12 3

O   
N 

Multiple Insulin Injection Therapy

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N Western regimen
S
Two doses: 150

U The usual dosing commonly used.

Initial insulin therapy
L 50

 
6 9 12 3 6 9 12 3

I
Three doses: 150

N Used for active patients.

Patients taking two main meals.
50

I 6 9 12 3 6 9 12 3

  
N Four doses: 150

Brittle diabetic patient.

J
Pregnant mothers specially type 1.
E
50

   
6 9 12 3 6 9 12 3

C
Four doses: 150

T Brittle diabetic patient.

Pregnant mothers specially type 1.
I Motivated patients. 50

6 9 12 3 6 9 12 3

O   
N 

Multiple Insulin Injection Therapy

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N Blood Glucose Curve

S Glucose variations in our culture:
Nondiabetic
U 250

L
150

N 50
1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

I 250
Diabetic week day

N
150

E 50
1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

C
Diabetic week end day
250

I 150

O
50

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

Multiple Insulin Injection Therapy

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N Insulin Use
S
• Regular and NPH use twice daily the commonest regimen used.
U • Premixed with different concentration (30/70, 40/60, 50/50).
L • Lunch is the biggest meal usually but no insulin dosing.

N 250

I 150

N
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

E Diabetic week day

250

T 150

I
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Multiple Insulin Injection Therapy

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N Hyper-glycemia window
S
Hyperglycemia
U Diabetic week day Window
250

I 150

N
50
6 7 8 9 10 11 12 1 2 3
Cause:
4 5 6 7 8 9 10 11 12 1 2 3 4 5

• Lack of insulin
I • Lunch effect
• afternoon snacks
N
Effect:
J • Pre-meal hyperglycemia
•  HbA1c by 1.7%
E

C
250

I 150

O
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Multiple Insulin Injection Therapy

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N Hyper-glycemia window
S
Treat by adding regular dose pre-lunch
U

I
Diabetic week day

N 250

I 150

N
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

E
250

T 150

I
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Multiple Insulin Injection Therapy

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N Hyper-glycemia window
S

U
Treat by adding regular dose pre-meals and small one before sleep
L

N
Diabetic week day
250

I
150

J 50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

C 250

T
150

O 50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Multiple Insulin Injection Therapy

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N Hypo-glycemia window
S

U Week end Problem

L

I 250
Diabetic week end day

Hypoglycemia
N Window
150

I
50

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

J
Cause:
E • NPH evening dose
250 • ? Late sleep

C Effect:
• Somogyi effect
T 150

I
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Multiple Insulin Injection Therapy

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N Hypo-glycemia window
S
Treat by moving am dose late and regular
U
dose pre-supper and NPH at night
L

I 250
Diabetic week end day

N
150

I
50

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

E
250

T 150

I
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Multiple Insulin Injection Therapy

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N Hypo-glycemia window
S
Treat by moving am dose late and regular
U dose pre-supper and another dose pre bed
L

I 250
Diabetic week end day

N
150

I
50

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

E
250

T 150

I
50
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Multiple Insulin Injection Therapy

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N Somogyi Phenomenon
S

U 20

I
10
N

I
0
N 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

E Cause: Treatment:
• Counter regulatory hormones response to • Decrease pre-supper intermediate insulin.
C
hypoglycemia at med-night.
• Defer the dose to 9 PM.
T • Increase in hepatic glucose production.
• Change or start pre-bed snack.
• Insulin resistance because of the Counter
I
regulatory hormones.
O

Multiple Insulin Injection Therapy

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N Dawn Phenomenon
S

U 20

I
10
N

I
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
N

E Cause: Treatment:
• Less insulin at bed time. • Use enough dose.
C
• More food at bed time. • Reduce bed time snack.
T
• Not using NPH at night. • Add NPH pre-supper.
I

Multiple Insulin Injection Therapy