1. Common Errors in Insulin
Therapy
Anil Bhansali
Department of Endocrinology
PGIMER, Chandigarh

2. Insulin Therapy
1. Alternative therapy to insulin in T1DM
2. Delay in initiating insulin therapy
3. Pre-injection assessment
4. Insulin injection techniques
5. Regimens of insulin treatment
6. Insulin analogues
7. Consequences of Insulin Therapy
-Short term
-Long term

3. Alternative therapy to insulin in T1DM!

4.  Omission of insulin in T1DM is
SUICIDAL
 Never stop insulin even during
sickness
 Follow sick day guidelines

5. Delay in Initiation of Insulin Therapy

6. The 2 Defects of T2DM
 Insulin resistance
 Insulin deficiency
Insulin resistance alone cannot produce
T2DM
AJM 2000

7. Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(Suppl.):S21–S25

8. Previous Algorithm – Type 2
Inadequate non-
pharmacologic therapy
2 Oral 3 Oral 4 Oral*
Oral agent agents agents agents
Add insulin
Adapted from Mudaliar S et al. In: Ellenberg and Rifkin’s Diabetes Mellitus, 6th ed. New York, NY:
Appleton and Lange; 2003:531-557.
*-Indian scenario

9. Standard Approaches to Therapy Result in
Prolonged Exposure to Elevated Glucose
10% Diet/Exercise Sulfonylurea or Combination Insulin
Metformin Therapy
Monotherapy 9.6%
Mean A1C at Last
9%
9.0%
8.6%
Visit
8%
7%
ADA
Goal
<7%
6%
Diagnosis 2 3 4 5 6 7 8 9 10
Years
At insulin initiation, the average patient had:
 5 years with A1C >8%
 10 years with A1C >7%
Psychological Insulin Resistance(PIR)
Brown JB, et al. Diabetes Care. 2004;27:1535-1540.

10. ADA 2012 Algorithm for T2DM

11. American Association of Clinical Endocrinologists:
algorithm for patients with T2DM
Drug-naïve patients Initiate monotherapy
HbA1c 6%–7% Metformin, TZD, secretagogues,
DPP-4 inhibitors, α-glucosidase inhibitors
HbA1c 7%–8% Initiate combination therapy
Secretagogue + metformin, TZD, or α-glucosidase inhibitor
Lifestyle Changes
TZD + metformin
DPP-4 + metformin or TZD
Secretagogue + metformin + TZD
Fixed-dose combinations
Insulin
HbA1c 8%–10% Intensify combination therapy
To address fasting and postprandial glucose levels
HbA1c >10% Initiate / intensify insulin therapy
Patients currently As above
pharmacologically Exenatide may be combined with oral therapies in patients
treated not achieving goals
DPP-4=dipeptidyl peptidase-4; T2DM=type 2 diabetes mellitus; TZD=thiazolidinedione
AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007; 13 (Suppl 1): 16–34.

12. When to Add insulin?
 At the initial diagnosis
 Failure of maximal doses of monotherapy
 Failure of submaximal doses of 2 OHA’s
 Failure of maximal doses of 2 OHA’s
 Failure of submaximal doses of triple therapy

13. At the Diagnosis of T2DM
 Severely symptomatic
 FPG>250 mg/dl
 RPG >300mg/dl
 HbA1c >10%
 Presence of ketosis
 BMI < 23 Kg/m2
 Cardiac / renal / hepatic dysfunctions
 Critically ill patients

14. ORIGIN study
N Engl J Med 2012; 367:309-318

15. Add Insulin
Patient on two OHA’s
 FPG > 130 mg/dl
 PPG > 180 mg/dl
 HbA1c >8.5%
 Tighter control is desired
 Contraindication/intolerant to other
OHA’s

16. Pre-injection Assessment is Not
Done!

17. Pre- injection Assessment
 Injection-related concerns
 Psychological insulin resistance
(personal failure, anticipated pain,
once on insulin always on insulin)

18. Pre-injection Assessment
-Dexterity problems
-Cognitive capacity
-Health literacy
-Numeracy skills
-Visual impairment
-Local infections, ulcers and scars

19. How insulin should be stored ?

20. Injection Storage
 Store insulin in use at room
temperature (15-25oC) and discard 30
days after initial use
 Short acting analogue,Lispro, in use
should be stored at 40 C after use
 Currently unused vials/refill cartridges
should be refrigerated
 Never freeze the insulin

21. Injection Technique is not Properly Advised!

22. Injection Technique
 Re-suspension of cloudy insulin is
essential (Rolled 20 cycles)
 Needle length 4-6 mm
 Site of injection should be looked for
lipohypertrophy or any bruise/blisters
 Recommend use of alcohol swabs or
cotton ball dipped in water for cleaning
 Injection site : Abdomen < thigh <arm

23.  Ensure the correct insulin syringe with
correct strength of insulin (40U vial
with 40U syringe)
 Insulin pen should be primed with two
units of insulin as the first step
 Insert the needle at 90o to the skin fold
and count till 10 before pulling the
needle out
 Needle site should not be massaged
 Injection site should be rotated

24. Insulin Dose Prescription is not Properly Written!

25.  Inadvertent use of abbreviations
 Inj Reg insulin 4U
 Route of administration is not
mentioned
 Site of administration is not written
 Time of administration is missing
 Premixed insulin strengths are not
mentioned (25:75, 30:70, 50:50)

26. Insulin is administered through clothing
!

27.  Pre- and post-injection site
assessment is not possible
 The needle becomes unsterile and
can cause infection
 Skin pinch-up may not be correct
through clothing
 Fiber from the cloth could enter the
skin and cause irritation

28. Insulin is Administered just Prior to
Meal!

29.  Lag time between insulin administration
and meal
-30-45 min for conventional insulin
(Hexamer to monomer)
-5-10 min for short acting analogues
 Time of administration of long acting
analogues
-Preferably at bed time, usually at fixed
time
-If early morning hypoglycemia, then
administer in morning

30. Short acting insulin is used twice or
thrice a day without intermediate or
long acting insulin!

31. This strategy will never control fasting
hyperglycemia as short acting insulin acts only for
4-6 hrs.

32. Characteristics of Currently
Available Insulin
Insulin Onset of Peak action(h) Duration(h)
action(h)
NPH 1-3 4-10 10-20
Glargine 2-4 No peak 20-24
Detemir 2 No peak 16-24
Regular 0.5-1 2-3 5-8
Lispro/aspart 0.1-0.25 0.5-1.5 3-5
Lispro 25/75 0.25-0.5 5.8 12-24
Aspart 30/70 0.17-0.33 2.4 ± 0.8 12-24

33. Insulin Regimens
 Basal-bolus
(3 prandial and one/two NPH or Glargine)
 Only Basal
(NPH or Glargine or Detemir)
 Premixed twice a day
(30:70 either conventional or analogues)
 Premixed twice a day + one regular insulin at
Lunch
 One regular or short acting analogues to
control post-prandial hyperglycemia
 One dose of premixed insulin before major
meals

34. Insulin Regimens
 Fasting hyperglycemia
-NPH
-Glargine at bed time
-Detemir
 Post-prandial hyperglycemia
-Regular insulin
-Short acting analogues
-Premixed
 Predinner hyperglycemia
-NPH, Glargine, Detemir at morning
-Premixed before lunch, if it is a major meal
 ‘Global hyperglycemia’
-Basal and bolus

35. What should be targeted?
-FPG, PPG, HbA1c or all three
-Which should be the first?

36. Basal vs Post-Prandial
Hyperglycemia – A1c
Uncontrolled Diabetes HbA1c 8%
Basal hyperglycaemia
300 contributes ~2%
Post-prandial
Plasma glucose (mg/dL)
hyperglycaemia
contributes HbA1c ~1%
200 Post-prandial
hyperglycaemia
Fasting
hyperglycaemia
100
Normal
HbA1c ~5%
0   
6 B 12 L 18 D 24 6
Time of day (h)
B=breakfast; L=lunch; D=dinner.
Adapted from Riddle MC. Diabetes Care. 1990;13:676-686.

41. HbA1c: Limitations
 Does not detect glycemic excursions
 Does not reveal hypoglycemia
 Cautions:
◦ Anemia
◦ Uremia
◦ EPO therapy

42. Short acting and Long acting Analogues
are Indiscriminately Used!

43.  Short acting analogues used as i.v
infusion for the treatment of
hyperglycemic emergencies
 Use of short acting analogues with
premixed conventional insulin
 Mixing of glargine with short acting
insulin
 Premixed insulin twice a day and
glargine at bedtime

44. Distinctive Uses of Analogues
 Short acting analogues
-School going children
-Pregnancy with diabetes
-Busy executives
-Gastroparesis
 Long acting analogues
-Elderly subjects
-Targeting HbA1c <6.5%
-Inability to inject multiple injections

45. Somogyi phenomenon is not
Recognized?

46. Somogyi Phenomenon
 Post-hypoglycaemic hyperglycemia
 Wide swings in blood glucose profile
 Common cause of fasting
hyperglycemia
 Perform 4am BG level (<80mg/dl)

47. Dawn Phenomenon is usually
Missed!

48. Dawn Phenomenon
 Early morning hyperglycemia
(nocturnal GH surge, increased insulin
clearance)
 Perform BG at 4 am >80mg/dl

49. Use of Biosimilars!

50.  These preparations are structurally
similar but pharmacokinetics and
therapeutic efficacy are variable
 Biosimilars with suboptimal efficacy
may induce DKA

51. Consequences of Insulin Therapy

52. Immediate
 Hypoglycemia
Short term
-Weight gain
-Worsening of retinopathy and
neuropathy
Long term
-Malignancy

53. Insulin-Induced Hypoglycemia
 Major barrier
 Common with
-Advanced duration of disease
-Concurrent OHA’s
-Older age, DKD

54. Conclusions
 Diabetes is an insulin deficient
disorder, hence it should be repleted
 Insulin administration is a state-of-art
 The time of initiation may be variable
but delay should be avoided
 Close monitoring should be done for
hypoglycemia and weight gain

55. Thank you