There are different kinds of insulin that people with diabetes can use every day to help them stay healthy. This booklet gives some basic facts about insulin. Use this booklet to help you talk to your healthcare provider about

2. Insulin and Insulin Pumps
Dr Waqar Malik
Consultant Diabetologist
Blakesley Hall, Blakesley Road, Birmingham
9th Jan. 2017

3. Lay Out
• Why glycaemic control is important and what role insulin plays
• Different insulins old and new
• Some tips about dose titration
• Different devices
• Continuous subcutaneous insulin infusion (CSII or 'insulin pump')

4. 1
3
5
7
9
11
13
15
6 7 8 9 10 11 12
Retinop
Neph
Neurop
DCCT Research Group, N Engl J Med 1993, 329:977-986.
RELATIVE
RISK
Mean A1C

5. 15.3 years
5.1 years
DCCT Study Group, JAMA 1996, 276:1409-1415.

6. Effect of A1C On Complications in the UKPDS Study
A1C
Stratton IM et al. BMJ 2000;321:405
0
10
20
30
40
50
60
Myocardial Infarction Microvasc Disease
5.5%
6.5%
7.5%
8.5%
9.5%
10.5%

7. Lessons from the DCCT and UKPDS:
Sustained Intensification ofTherapy is Difficult
DCCT EDIC
(Type 1)
UKPDS (Type 2),
Insulin Group
DCCT/EDIC Research Group. New Engl J Med 2000; 342:381-389
Steffes M et al. Diabetes 2001; 50 (suppl 2):A63
UK Prospective Diabetes Study Group (UKPDS) 33
Lancet 1998; 352:837-853
4
6
8
10
9.0
8.1
7.3
7.9
0 6.5 + 4 + 6 yrs
DCCT EDIC
0
6
7
8
0 2 4 6 8 10 yrs
A1C (%)
Normal
Baseline
A1C (%)

8. 0
2
4
6
8
10
12
14
16
<150 150-175 175-200 200-225 225-50 >250
Mortality
Average Post-operative glucose (mg/dl)
Cardiac-related mortality
Noncardiac-related mortality
Mortality of DM Patients Undergoing CABG
Furnary et al JThoracCardiovasc Surg 2003;123:1007-21

9. 0
5
10
15
20
25
30
35
40
45
0 50 100 150 200 250
Days after inclusion
Cumulative
%
Mortality
(in
hospital
death)
P=0.0009
P=0.026
BG<110
110<BG<150
BG>150
Surgical ICU Mortality
Effect of Average BG
Van den Berghe et al (Crit Care Med 2003; 31:359-366)

10. 0
5
10
15
20
25
30
35
40
45
80-99 100-
119
120-
139
140-
159
160-
179
180-
199
200-
249
250-
299
>300
Average ICU glucose (mg/dl)
Mortality
%
Hyperglycemia and Hospital Mortality
1826 consecutive ICU patients 10/99 thru 4/02, Stamford CT
Krinsley JS: Mayo Clin Proc 78: 1471-1478, 2003

12. Patient J.L., December 15, 1922 February 15, 1923

13. Adapted from: Atkinson. Lancet. 2002;358:221-229.
Age (y)
Precipitating Event
Beta-cell
mass Genetic
predisposition
Normal insulin
release
Glucose
normal
Overt diabetes
No C-peptide
present
Progressive loss
of insulin release
C-peptide
present
Antibody

16. b-cell
(genetic background)
Hyperglycaemia
(glucose toxicity)
Protein
glycation
Amyloid
deposition
Insulin resistance
“lipotoxicity”
elevated FFA,TG

17. Adapted from Type 2 diabetes in
adults: management. NICE
Clinical guideline update (NG28)
2015 [Accessed Dec 2015].
a. When prescribing pioglitazone, exercise particular caution if the person is at high risk of the adverse effects of the drug. Pioglitazone is associated with an increased risk of heart failure, bladder cancer and bone fracture. Known risk factors for these conditions, including
increased age, should be carefully evaluated before treatment: see the manufacturers’ summaries of product characteristics for details. Medicines and Healthcare products Regulatory Agency (MHRA)guidance (2011) advises that ‘prescribers should review the safety and
efficacy of pioglitazone in individuals after 3–6 months of treatment to ensure that only patients who are deriving benefit continue to be treated’.
b. Treatment with combinations of drugs including sodium–glucose cotransporter 2 inhibitors may be appropriate for some people at first and second intensification; see NICE technology appraisal guidance 288, 315 and 336 on dapagliflozin, canagliflozin and empagliflozin
respectively. All three SGLT-2 inhibitors are recommended as options in dual therapy regimens with metformin under certain conditions. All three are also recommended as options in combination with insulin. At the time of publication, only canagliflozin and empagliflozin
are recommended as options in triple therapy regimens. The role of dapagliflozin in triple therapy will be reassessed by NICE in a partial update of TA288. Serious and life-threatening cases of diabetic ketoacidosis have been reported in people taking SGLT-2 inhibitors
(canagliflozin, dapagliflozin or empagliflozin)or shortly after stopping the SGLT-2 inhibitor. MHRA guidance (2015) advises testing for raised ketones in people with symptoms of diabetic ketoacidosis, even if plasma glucose levels are near normal.
c. Only continue GLP-1 mimetic therapy if the person has a beneficial metabolic response (a reduction of HbA1c by at least 11 mmol/mol [1.0%] and a weight loss of at least 3% of initial body weight in 6 months).
d. Be aware that, if metformin is contraindicated or not tolerated, repaglinide is both clinically effective and cost effective in adults with type 2 diabetes. However, discuss with any person for whom repaglinide is being considered, that there is no licensed non-metformin-
based combination containing repaglinide that can be offered at first intensification.
e. Be aware that the drugs in dual therapy should be introduced in a stepwise manner, checking for tolerability and effectiveness of each drug.
f. MHRA guidance (2011) notes that cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for the development of cardiac failure. It advises that if the combination is used, people should be
observed for signs and symptoms of heart failure, weight gain, and oedema. Pioglitazone should be discontinued if any deterioration in cardiac status occurs.
g. The recommendations in this guideline also apply to any current and future biosimilar product(s) of insulin glargine that have an appropriate Marketing Authorisation that allows the use of the biosimilar(s) in the same indication.
h. A consultant-led multidisciplinary team may include a wide range of staff based in primary, secondary and community care.
- Recommendations that cover
dipeptidyl peptidase-4 inhibitors (DPP-
4i), glucagon-like peptide-1 (GLP-1)
mimetics and sulfonylureas (SUs) refer
to these groups of drugs at a class level
- SGLT-2, sodium-glucose
cotransporter-2

18. 18

19. 19

20. Insulin
Aspart or
Lispro
Regular
Human
Insulin
PeakTime = 80-120 min
PeakTime = 40-50 min
Capillary
Membrane
Subcutaneous
Tissue

21. 400
350
300
250
200
150
100
Meal
SC injection
50
0
0 30 60
Time (min)
90 120 180 210
150 240
Regular
Lispro
500
450
400
350
300
250
150
50
200
100
0
0 50 100
Time (min)
150 200 300
250
Plasma
insulin
(pmol/L)
Plasma
insulin
(pmol/L)
Meal
SC injection
Heinemann, et al. Diabet Med. 1996;13:625–629; Mudaliar, et al. Diabetes Care. 1999;22:1501–1506.
Regular
Aspart

22. Lepore, et al. Diabetes. 1999;48(suppl 1):A97.
6
5
4
3
2
1
0
0 10
Time (h) after SC injection
End of observation period
20 30
Glargine
NPH
Glucose
utilization
rate
(mg/kg/h)

23. 4:00
25
50
75
8:00 12:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
Plasma
insulin
(
µ
U/ml)
Time
8:00

24. 4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:00
12:00
8:00
Time
Glargine
Lispro Lispro Lispro
Aspart Aspart Aspart
or or
or
Plasma
insulin

27. 6-37

31. Rosenstock J, Riddle M, HOE901/4002 StudyGroup. Diabetes 2002;51(suppl 2):A482.Abstract 1982-PO
Results

32. Riddle et al, Diabetes June 2002,Abstract 457-p

34. Morning vs Bedtime Insulin
Baseline: 9.11.0
Morning
Glargine
Bedtime
Glargine
Bedtime
NPH
-2
-1
0
A1C
Change
From
Baseline
(%)
–1.24
–0.96
–0.84
P<0.001
P=0.008
Adapted from Fritsche A et al, and the 4001 Study Group. Ann Intern Med. 2003:138:952

39. Large push button with low
resistance
Large-scale numbers
1 unit increments
Support shoulder
Maximum dose 50 units
Clear & uncomplicated dial,
dials forward and back
Contains 300 units Novolin®
70/30, NPH, or R
Audible clicks
NovoFine®
disposable needle
Needle storage
compartment

45. Intermediate
NPH/Isophane insulins
Insulatard
Humulin-I
Insuman Basal
Never withdraw insulin from a prefilled pen. Use 50unit (0.5mL) insulin syringes or
attach a safety needle to the insulin pen to administer insulin to patients.
Short-acting
Soluble insulins
Actrapid
Humulin-S
Insuman Rapid
Insulin analogues
Novorapid (insulin aspart)
Apidra (insulin glulisine)
Humalog (insulin lispro)
Long-acting
Abasaglar (insulin glargine)
Lantus (insulin glargine)
Levemir (insulin detemir)
Tresiba (insulin degludec)
Pre-mix/biphasic
Biphasic
NovoMix30
Humalog Mix25
Humalog Mix50
Humulin-M3
Insuman Comb15
Insuman Comb25
Insuman Comb50
INSULIN GUIDE
Combination: Xultophy (liraglutide + degludec)
Standard strength insulin: 100 units/ml. High strength insulin:
Humalog (lispro) 200units/ml and Toujeo (glargine) 300units/ml

48. Time (h)
Baseline
level
Regular insulin
Premix 70/30
SC injection
Normal insulin secretion
at mealtime
NPH insulin
Change
in
serum
insulin

49. Analog Mix 70/30:
Serum Insulin Levels inType 2 Diabetes
Breakfast Lunch
0
6:00 PM 10:00 PM 8:00 AM 6:00 PM
1:00 PM
Dinner
Cmax
Serum
insulin
(mU/L)
100
Time
80
40
20
60
* * NovoLog® Mix 70/30
70/30 Premix
McSorley. ClinTher. 2002;24(4):530-539.
*P<0.05.

50. Analog Mix 70/30 vs 75/25 vs 70/30 Premix:
Serum Insulin Levels inType 2 Diabetes
Lispro Mix 75/25
70/30 Premix
Aspart Mix 70/30
0 1 2 3 4 5
0
80
Time (h)
Serum
insulin
(mU/L)
60
40
20
Hermansen. Diabetes Care. 2002;25(5):883-888.

51. Aspart Mix 70/30:
Serum Glucose Levels inType 2 Diabetes
Aspart Mix 70/30
70/30 Premix
Dinner Breakfast Lunch
*
0
300
200
150
250
Serum
glucose
(mg/dL)
6:00 PM 10:00 PM 8:00 AM 6:00 PM
1:00 PM
*
*
*Glucose excursions 0-4 h, P<0.05.
McSorley. ClinTher. 2002;24(4):530-539.

52. 4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:00
12:00
8:00
Time
Basal infusion
Bolus Bolus Bolus
Plasma
insulin

53. Photograph reproduced with permission of manufacturer.

55. Bode, et al. Diabetes 52,(Suppl 1), 2003 Abstract 438.
Mean ± 2 SEM
200
160
140
120
100
180
Self-
monitored
BG
(mg/dL)
BB AB BL AL BD AD Midnight 3 AM
CSII (n=93)
MDI (n=91)

56. n=63 in each treatment
0
500
1000
1500
2000
2500
3000
CSII MDI
p = 0.0027
Novo Nordisk, data on file (Study 2155/US)
Measurement of AUC(glu) ≥80 mg/dL
during the 48-hour continuous glucose
monitoring period
†
AUCglu
(mg•hr/dL)
†

57. 6
6.5
7
7.5
8
8.5
9
Baseline 4 weeks 8 weeks 12 weeks 16 weeks
Glargine (n=16)
CSII (n=14)
Boland, E. Diabetes 52,(Suppl 1), 2003 Abstract 192.

58. Continuous subcutaneous insulin infusion (CSII or 'insulin
pump') therapy is recommended as a treatment option for
adults and children 12 years and older with type 1 diabetes
mellitus provided that:
attempts to achieve target haemoglobin A1c (HbA1c) levels
with multiple daily injections (MDIs) result in the person
experiencing disabling hypoglycaemia. For the purpose of this
guidance, disabling hypoglycaemia is defined as the repeated
and unpredictable occurrence of hypoglycaemia that results in
persistent anxiety about recurrence and is associated with a
significant adverse effect on quality of life
or
HbA1c levels have remained high (that is, at 8.5% [69
mmol/mol] or above) on MDI therapy (including, if
appropriate, the use of long-acting insulin analogues) despite a
high level of care.
NICE GUIDANCE

59. CSII therapy is recommended as a treatment option for
children younger than 12 years with type 1 diabetes mellitus
provided that:
MDI therapy is considered to be impractical or inappropriate,
and
children on insulin pumps would be expected to undergo a trial
of MDI therapy between the ages of 12 and 18 years.