Insulin Therapy in DM

1. First step into insulin
therapy
(How to start insulin in a patient not controlled on OADs)
By
Dr.Muhammad Tahir Chaudhry
B.Sc.M.B;B.S(Pb).C.diabetology(USA)

2. The breakthrough: Toronto 1921 – Banting & Best

24. Fears & concerns
about insulin therapy

29. Normal physiologic patterns of
glucose and insulin secretion in
our body

30. How Is Insulin Normally Secreted?

31. The rapid early rise of insulin secretion in
response to a meal is critical,
because
 it ensures the prompt inhibition of endogenous
glucose production by the liver
disposal of the mealtime carbohydrate load, thus
limiting postprandial glucose excursions.

34. Bolous insulins (Mealtime or prandial)
6 hours2 hours10-20 minutesRapid actingInhaled insulin
4-5 hours1-2 hours5-15 minutesRapid actingInsulin
analogs
(Lispro,Aspart,
Glulisin)
8-10 hours2-4 hours30-60 minutesShort actingHuman
regular
Duration of
action
Peak of
action
Onset of
action
TypeInsulin
The time course of action of any insulin may vary in different individuals, or
at different times in the same individual. Because of this variation, time
periods indicated here should be considered general guidelines only.

35. Pre-mixed Insulins
Humulin 70/30
Dongsulin 70/30
Mixtard 70/30
70% NPH
30% Regular
NPH-Regular
ExamplesCompositionInsulin
30% rapid acting aspart
+70 % intermediate
acting aspart(IAA)
Rapid acting
aspart
(Free and soluble)
+
Intermediate acting
aspart(protaminated-
crystallized
ExampleCompositionInsulin
NovoMix 30
Humolog Mix 25
Humolog Mix 50
(25% lispro75%IAA)
(50% lispro 50%IAA)

36. Basal insulins
NPH
•Humulin N (Eli Lilly)
•Insulatard (Novo)
(also available as insulatard Novolet pen)
•Dongsulin N (Highnoon)
•Insuget N (Getz)
===========================================
Analogs
Glargine (Lantus)
Lantus Solostar Pen (Sanofi Aventis)
Detemir (Levimir) by Novo

37. Basal Insulins
16-20
hours
8-12 hours2-4 hoursLong
acting
Detemir
(Levimir)Novo
Upto 24
hours
Relatively
flat
1-2 hoursLong
acting
Glargine
(Lantus)
Aventis
13-18
hours
5-7 hours1-2 hours
Intermediate
acting
NPH
Duration
of action
Peak of
action
Onset of
action
TypeInsulin
The time course of action of any insulin may vary in different individuals, or at different times in
the same individual. Because of this variation, time periods indicated here should be considered
general guidelines only.

38. Bolous insulins
(Mealtime or prandial)
Human Regular
•Humulin R (Eli Lilly)
•Actrapid (Novo)
(Also available as Actrapid novolet pen)
•Dongsulin R (Highnoon)
•Insuget R (Getz)
==========================================
Analogs
•Lispro (Humolog) by Eli Lilly
•Novorapid by Novo
•Aspart
•Glulisine (Apidra) by Sanofi Aventis

39. Bolous insulins
(Mealtime or prandial)
4-5 hours1-2 hours5-15 minutesRapid actingInsulin
analogs
(Lispro,Aspart,
Glulisine)
8-10 hours2-4 hours30-60 minutesShort actingHuman
regular
Duration of
action
Peak of
action
Onset of
action
TypeInsulin
The time course of action of any insulin may vary in different individuals, or at
different times in the same individual. Because of this variation, time periods
indicated here should be considered general guidelines only.

40. Pre mixed
70/30 (70% N,30% R)
•Humulin 70/30 (Eli Lilly)
•Mixtard 30 (Novo)
(Also available as Mixtard 30 Novolet Pen)
•Dongsulin 70/30 (Highnoon)
•Insuget 70/30 (Getz)
===================================
Analogs
•Novomix 30 (Novo)
•Humolog Mix 25(Lilly)
•Humolog Mix 50(Lilly)

41. Types of InsulinTypes of Insulin
1. Rapid-acting
2. Short-acting
3. Intermediate-acting
4. Premixed
5. Long-acting
6. Extended long-acting
(Analogs)
(Regular)
(NPH)
(70/30)
(Lantus)

43. Indications for Insulin Use in Type 2 Diabetes
Pregnancy (preferably prior to pregnancy)
Acute illness requiring hospitalization
Perioperative/intensive care unit setting
Postmyocardial infarction
High-dose glucocorticoid therapy
Inability to tolerate or contraindication to oral antiglycemic agents
Newly diagnosed type 2 diabetes with significantly elevated blood
glucose levels (pts with severe symptoms or DKA)
Patient no longer achieving therapeutic goals on combination
antiglycemic therapy

44. Inadequate
Non pharmacological
therapy
1oral agent
2 oral
agents
3 oral
agents
Add Insulin Earlier in the Algorithm
•Severe symptoms
•Severe
hyperglycaemia
•Ketosis
•pregnancy
Proposed Algorithm of therapy for Type 2
Diabetes

45. First step into
Insulin therapy

46. What we have in our
pockets?
•Basal Insulins (NPH,Lantus)
•Bolus Insulins(Human Regular)
•Premixed (Human 70/30)

47. The ADA
Recommendations
on the Use of
Insulin
in Type 2 Diabetes

48. Touch Pad QuestionTouch Pad Question
Currently, roughly ____ of my patients with type Currently, roughly ____ of my patients with type
2 diabetes are taking some form of insulin.2 diabetes are taking some form of insulin.
1. >80%
2. 60-80%
3. 40-60%
4. 20-40%
5. 0-20%

49. Touch Pad QuestionTouch Pad Question
When it comes to first-line insulin, I tend to
prescribe:
1. An intermediate-acting insulin with
fast-acting insulin as needed
2. A long-acting or extended long-acting
insulin with fast-acting insulin as needed
3.A premixed insulin

50. Rapid Acting
(e.g., aspart, lispro,
glulisine)
Short Acting
(e.g., regular insulin)
Onset10-15 mins 30-60 mins
Peak 60-90 mins 2-4 hrs
Duration4-5 hrs 5-8 hrs
Types of InsulinTypes of Insulin

51. Intermediate Acting
(e.g., NPH,
lente)
Premixed
(e.g., 75% NPL / 25% lispro,
70% APS / 30% aspart,
70% NPH / 30%
regular/NPH)
Onset 1-3 hr(s)
One vial or cartridge
with a fixed ratio of
rapid- or short-acting
to intermediate-acting
insulin
Peak 5-8 hrs
DurationUp to 18 hrs
Types of InsulinTypes of Insulin

52. Long Acting
(e.g., ultralente)
Long-Acting
Analogues
(glargine, detemir)
Onset 3-4 hrs 1.5-3 hrs
Peak 8-15 hrs No peak with glargine,
dose-dependent peak
with detemir
Duration22-26 hrs 9-24 hrs (detemir);
20-24 hrs (glargine)
Types of InsulinTypes of Insulin

53. Inhaled InsulinInhaled Insulin
•Approved in the U.S. in 2006 for the treatment
of type 2 diabetes
•However, published studies to date have not
demonstrated whether inhaled insulin can lower
HbA
1c
to ≤7%, either:
–As monotherapy or
–In combination with an injection of long-acting
insulin
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
Inhaled InsulinInhaled Insulin

54. Advantages of Insulin TherapyAdvantages of Insulin Therapy
•Oldest of the currently available
medications, has the most clinical
experience
•Most effective of the diabetes medications
in lowering glycemia
–Can decrease any level of elevated HbA
1c
–No maximum dose of insulin beyond which a
therapeutic effect will not occur
•Beneficial effects on triglyceride and
HDL cholesterol levels
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

55. Effect of Insulin on Triglyceride Effect of Insulin on Triglyceride
and HDL-C Levels and HDL-C Levels
Adapted from Nathan DM et al. Ann Int Med 1988;108:334-40.
1
1.1
1.2
1.3
1.4
1.5
Baseline Month 9
1
1.2
1.4
1.6
1.8
2
Baseline Month 9
Tryglyceride level (mmol/l)
HDL-C (mmol/L)
0.22 mmol/l
(19.4mg/dl)
p=0.07
n=15
1.85
1.17
1.51
1.39
HDL-CTriglycerides
0.34 mmol/l
(30mg/dl)
p=0.07
n=15

56. Disadvantages of Insulin TherapyDisadvantages of Insulin Therapy
•Weight gain ~ 2-4 kg
–May adversely affect cardiovascular health
•Hypoglycemia
–However, rates of severe hypoglycemia in
patients with type 2 diabetes are low…
Type 1 DM: 61 events per 100 patient-yearsType 1 DM: 61 events per 100 patient-years
Type 2 DM: 1-3 events per 100 patient-yearsType 2 DM: 1-3 events per 100 patient-years
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

57. Balancing Good Glycemic Control with Balancing Good Glycemic Control with
a Low Risk of Hypoglycemia… a Low Risk of Hypoglycemia…
Hypoglycemia
Glycemic
control

58. Rates of Hypoglycemia Rates of Hypoglycemia
for Premixed vs. Long-Acting Insulinfor Premixed vs. Long-Acting Insulin
Adapted from Raskin P et al. Diabetes Care 2005;28(2):260-5.
0
0.5
1
1.5
2
2.5
3
3.5
BIAsp 70/30
(n=117)
0
5
10
15
20
25
30
35
40
45
Glargine
(n=116)
BIAsp 70/30
(n=117)
Glargine
(n=116)
Episodes per patient-year
% of subjects
p<0.05 p<0.05
3.4
0.7
43
16

59. HbAHbA
1c1c ££7% Without Hypoglycemia (Composite 7% Without Hypoglycemia (Composite
Endpoint) in Two Treat-to-Target StudiesEndpoint) in Two Treat-to-Target Studies
Hypoglycemia definition: glucose levels
≤4 mmol/L (72 mg/dL) or requiring assistance
1. Riddle M et al. Diabetes Care 2003;26:3080-6.
2. Hermansen K et al. Diabetes Care 2006;29:1269-74.
0
5
10
15
20
25
30
35
Once-daily dosing
1
Twice-daily dosing
2
p<0.05
Percentage of patients
achieving HbA
1c
£
7%
33.2
26.7
Insulin
glargine
NPH NPHInsulin
detemir
0
5
10
15
20
25
30
35
Percentage of patients
achieving HbA
1c
£
7%
p=0.008
26.0
16.0

60. Rates of Hypoglycemia for Premixed Rates of Hypoglycemia for Premixed
vs. Long-Acting Insulin + OADvs. Long-Acting Insulin + OAD
Adapted from Janka et al. Diabetes Care 2005;28:254-9.
Mean number of confirmed hypoglycemic events
per patient-year in a 28-week study
0
1
2
3
4
5
6
Symptomatic Nocturnal Severe
Premixed insulin
Insulin glargine + OADs
5.73
2.62
1.04
0.51
0.050.00
Events per patient-year
p=0.0009
p=0.0449 p=0.0702

61. Rates of Hypoglycemia for Premixed Rates of Hypoglycemia for Premixed
vs. Long-Acting Insulin + OAD in Elderly Patientsvs. Long-Acting Insulin + OAD in Elderly Patients
Adapted from Janka HU et al. J Am Geriatr Soc 2007;55(2):182-8.
R
a
t
e

o
f

e
v
e
n
t

p
e
r

p
a
t
i
e
n
t
-
y
e
a
r
p=0.01
p=0.008
p=0.06
0
2
4
6
8
10
12
Premixed (n=63)
Glargine + OAD (n=69)
All episodes of
hypoglycemia
All confirmed
episodes of
hypoglycemia
Confirmed
symptomatic
hypoglycemia

62. Rates of Nocturnal Hypoglycemia for Rates of Nocturnal Hypoglycemia for
NPH vs. Long-Acting InsulinNPH vs. Long-Acting Insulin
Adapted from Rosenstock J et al. Diabetes Care 2001;24(4):631-6.
HbA
1c
and rates of nocturnal hypoglycemia at Week 28
NPH (n=259)
Insulin glargine (n=259)
4
3
2
1
0
-1
-2
40
30
20
10
0
Adjusted mean change

from baseline
Patients (%)
p<0.01 for both
treatments vs.
baseline
p<0.02
glargine
vs. NPH
HbA
1c
(%) Nocturnal
hypoglycemia
(Month 2 to
endpoint)

63. The ADA Treatment The ADA Treatment
Algorithm for the Initiation Algorithm for the Initiation
and Adjustment of Insulinand Adjustment of Insulin

64. Initiating and Adjusting InsulinInitiating and Adjusting Insulin
Continue regimen; check
HbA
1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA
1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA
1c
≤7%...
Bedtime intermediate-acting insulin, or
bedtime or morning long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA
1c
³7%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA
1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
If HbA
1c
≤7%... If HbA
1c
³7%...

65. Step One…
Continue regimen; check
HbA
1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA
1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA
1c
≤7%...
Bedtime intermediate-acting insulin, or
bedtime or morning long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA
1c
³7%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA
1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA
1c
≤7%... If HbA
1c
³7%...
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

66. Step One: Initiating InsulinStep One: Initiating Insulin
•Start with either…
–Bedtime intermediate-acting insulin or
–Bedtime or morning long-acting insulin
Insulin regimens should be designed taking
lifestyle and meal schedules into account
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

67. Step One: Initiating InsulinStep One: Initiating Insulin, cont’d, cont’d
•Check fasting glucose and increase dose until
in target range
–Target range: 3.89-7.22 mmol/l (70-130 mg/dl)
–Typical dose increase is 2 units every 3 days, but if
fasting glucose >10 mmol/l (>180 mg/dl), can
increase by large increments (e.g., 4 units every 3
days)
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

68. •If hypoglycemia occurs or if fasting glucose
< 3.89 mmol/l (70 mg/dl)…
–Reduce bedtime dose by ≥4 units or 10%
if dose >60 units
Step One: Initiating InsulinStep One: Initiating Insulin, cont’d, cont’d
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
Reduction in overnight and fasting glucose levels achieved
by adding basal insulin may be sufficient to reduce
postprandial elevations in glucose during the day and
facilitate the achievement of target A1C concentrations.
While using basal insulin alone,never stop or reduce ongoing oral
therapy

69. •If HbA
1c is <7%...
–Continue regimen and check HbA
1c
every 3 months
•If HbA
1c is ≥7%...
–Move to Step Two…
After 2-3 Months…After 2-3 Months…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

70. With the addition of basal insulin and titration
to target FBG levels, only about 60% of
patients with type 2 diabetes are able to achieve
A1C goals < 7%.
[36]
In the remaining patients
with A1C levels above goal regardless of
adequate fasting glucose levels, postprandial
blood glucose levels are likely elevated.

72. Continue regimen; check
HbA
1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA
1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA
1c
≤7%...
Bedtime intermediate-acting insulin, or
bedtime or morning long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA
1c
³7%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA
1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA
1c
≤7%... If HbA
1c
³7%...
Step Two…
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

73. Step Two: Intensifying InsulinStep Two: Intensifying Insulin
If fasting blood glucose levels are in target range but
HbA
1c
≥7%, check blood glucose before lunch, dinner,
and bed and add a second injection:
•If pre-lunch blood glucose is out of range,
add rapid-acting insulin at breakfast
•If pre-dinner blood glucose is out of range,
add NPH insulin at breakfast or rapid-acting insulin at
lunch
•If pre-bed blood glucose is out of range,
add rapid-acting insulin at dinner
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

74. Making AdjustmentsMaking Adjustments
•Can usually begin with ~4 units and
adjust by 2 units every 3 days until blood
glucose is in range
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
When number of insulin Injections increase from
1-2………..Stop or taper of insulin secretagogues
(sulfonylureas).

75. •If HbA
1c
is <7%...
–Continue regimen and check HbA
1c
every
3 months
•If HbA
1c
is ≥7%...
–Move to Step Three…
After 2-3 Months…After 2-3 Months…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

76. Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
Continue regimen; check
HbA
1c every 3 months
If fasting BG in target range, check BG before lunch, dinner, and bed.
Depending on BG results, add second injection
(can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range)
Recheck pre-meal BG levels and if out of range, may need to add another
injection; if HbA
1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA
1c
≤7%...
Bedtime intermediate-acting insulin, or
bedtime or morning long-acting insulin
(initiate with 10 units or 0.2 units per kg)
Check FG and increase dose until in target range.
If HbA
1c
³7%...
Hypoglycemia
or FG >3.89 mmol/l (70 mg/dl):
Reduce bedtime dose by ≥4 units
(or 10% if dose >60 units)
Pre-lunch BG out of range: add
rapid-acting insulin at breakfast
Pre-dinner BG out of range: add NPH insulin at
breakfast or rapid-acting insulin at lunch
Pre-bed BG out of range: add
rapid-acting insulin at dinner
Continue regimen; check
HbA
1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA
1c
≤7%... If HbA
1c
³7%...
Step Three…

77. Step Three: Step Three:
Further Intensifying InsulinFurther Intensifying Insulin
•Recheck pre-meal blood glucose and if out of
range, may need to add a third injection
•If HbA
1c
is still ≥ 7%
–Check 2-hr postprandial levels
–Adjust preprandial rapid-acting insulin
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

78. Premixed InsulinPremixed Insulin
•Not recommended during dose adjustment
•Can be used before breakfast and/or dinner if the
proportion of rapid- and intermediate-acting
insulin is similar to the fixed proportions
available
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

79. Key Take-Home MessagesKey Take-Home Messages
•Insulin is the oldest, most studied, and most effective
antihyperglycemic agent, but can cause weight gain
(2-4 kg) and hypoglycemia
•Insulin analogues with longer, non-peaking profiles
may decrease the risk of hypoglycemia compared
with NPH insulin
•Premixed insulin is not recommended during dose
adjustment

80. Key Take-Home Messages, cont’dKey Take-Home Messages, cont’d
•When initiating insulin, start with bedtime intermediate-
acting insulin, or bedtime or morning long-acting insulin
•After 2-3 months, if FBG levels are in target range but HbA
1c

≥7%, check BG before lunch, dinner, and bed,and, depending
on the results, add 2
nd
injection (stop sulfonylureas here)
•After 2-3 months, if pre-meal BG out of range, may
need to add a 3
rd
injection; if HbA
1c
is still ≥7% check
2-hr postprandial levels and adjust preprandial
rapid-acting insulin.

81. Regimen # 2

82. First calculate total
daily dose of insulin
Body weight in kgs / 2
•e.g; an 80 kg person will require roughly about
40 units / day.

83. Dose calculation……..contd
Split the total calculated dose into 4 (four) equal s/c
injections.
–¼ of total dose as regular insulin s/c half-hour
( ½ hr ) before the three main meals with 6 hrs
gap in between.
–¼ total calculated dose as NPH insulin s/c at
11:00 p.m. with no food to follow.

84. Dose calculation: example
For example in an 80-kg diabetic requiring 40 units per
day, start with:
•08:00 a.m. --- 10 units regular insulin s/c ½ hr before
breakfast.
•02:00 p.m. --- 10 units regular insulin s/c ½ hr before lunch.
•08:00 p.m. --- 10 units regular insulin s/c ½ hr before dinner.
•11:00 p.m. --- 10 units NPH/ lantus insulin s/c

85. Dose adjustment
•For adjustment of dosage, check fasting
blood sugar the next day and adjust the
dose of night time NPH Insulin
accordingly i.e. keep on increasing the
dose of NPH by approximately 2 units
daily until you achieve a normal fasting
blood glucose level of 80-110 mg/dl.

86. Control BSF by adjusting Control BSF by adjusting
the prior the dose of NPHthe prior the dose of NPH

87. Dose adjustment….contd.
•Remember that the BSL (Blood Sugar Level)
at any given time reflects the insulin / meal
taken before the reading, and therefore, a
raised level of fasting blood sugar requires a
change in the dose of previously
administered night time insulin and will NOT
be controlled by adjusting the next insulin
injection.

88. Dose adjustment…contd.
•Once the fasting blood glucose has been
controlled, check 6-Point blood sugar as
follows:
–Fasting.
–2 hours after breakfast.
–Before lunch (and noon insulin)
–2 hours after lunch.
–Before dinner (AND EVENING INSULIN)
–2 hours after dinner

89. Control random sugar level by Control random sugar level by
adjusting the prior dose of adjusting the prior dose of
regular insulinregular insulin

90. Dose adjustment…contd.
•Now control any raised random reading by
adjusting the dose of previously
administered regular insulin.
•For example: a high post lunch reading will
NOT be controlled by increasing the dose
of next insulin (as in sliding scale), rather
adjustment of the pre-lunch regular
insulin on the next day will bring down
raised reading to the required levels.

91. Examples
•For the following profile:

–Blood sugar fasting = 180 mg/
dl
–Blood sugar after breakfast =
250 mg/dl.
–Blood sugar pre lunch = 190
mg/dl
–Blood sugar post lunch 270 =
mg/dl
–Blood sugar pre dinner = 200
mg/dl
–Blood sugar post dinner 260 =
mg/dl
•We need to increase the dose
of NPH at night to bring
down baseline sugar level
(BSF) to around 100 mg/dl
after which the profile should
automatically adjust as
follows:
–Blood sugar fasting = 100
mg/dl
–Blood sugar 02 hrs after
breakfast = 170 mg/dl
–Blood sugar pre-lunch =
110 mg/dl
–Blood sugar 2 hrs. after
lunch = 190 mg/dl
–Blood sugar pre-dinner =
120 mg/dl
–Blood sugar 2 hrs. post
dinner = 180 mg/dl

92. Examples……contd.
•Blood sugar fasting = 130 mg/dl
•Blood sugar after breakfast = 160 mg/dl
•Blood sugar pre-lunch = 130 mg/dl
•Blood sugar post lunch = 240 mg/dl
•Blood sugar pre-dinner = 180 mg/dl
•Blood sugar 2 hrs. post dinner = 200 mg/dl
•This patient needs adjustment of pre-lunch regular
Insulin which will bring down post lunch and pre dinner
readings within normal limits.
•2 hrs post dinner blood sugar(200 mg/dl) will be
brought down by adjusting pre dinner regular insulin.

93. Combinations
•In types 2 subjects, once the blood
sugar profile is normalized and the
patient is not under any stress, the
total daily dose (morning + noon +
night + NPH at 11 p.m) may be
divided into two 12 hourly injections
of premixed Insulin

94. Examples….contd.
•e.g-1; If a patient is
stabilized on
•10U R + 12U R +
10U R + 12U NPH;
•then he may be
shifted to
• 44/2 = 22 units of
70/30 Insulin 12
hourly s/c ½ hr before
meal.
•e.g-2; If the
adjusted Insulin is
•14U R+16U R+12U
R+8U NPH,
•then split the total
dose:
30 U 70/30 before
breakfast and 20U
70/30 before dinner
to compensate for the
high morning and lunch
Insulin.

95. Combinations………contd.
•Problem: Remember that BD dosing usually fails to
cover lunch, especially if it is heavy. So:
•Always check for post lunch hyperglycemia when using
this regimen.
•Solution:
•Patients can be advised to take their lunch (heavier
meal) at breakfast; and breakfast (lighter meal) at
lunch.
•Adding Glucobay with lunch some times provides a
reasonable control.
•An alternate combination to overcome the problem is
regular insulin for morning and noon, with premixed
insulin at night.

96. Example
•10U R before breakfast + 12U R
before lunch + 22U 70/30 before
dinner.
• Insulin will be injected exactly 6 hrs
apart as in the QID regimen.

97. Choice of regimens
R+ R+ R+ L****
R+ R+ R+ N ***
R+ R+ premixed insulin**
BD premixed insulins*

98. Regimen # 3
(Pre mixed)

99. Adding basal insulin to oral agents is simple to implement, well tolerated,
and highly effective -- particularly for patients with A1C levels between 7.0%
and 10.0%

100. The dose of this basal insulin should be adjusted
every 3-5 days to reach a target fasting glucose level
of ≤ 120 mg/dL, provided that nocturnal
hypoglycemia does not occur. Reduction in overnight
and fasting glucose levels achieved by adding basal
insulin may be sufficient to reduce postprandial
elevations in glucose during the day and facilitate the
achievement of target A1C concentrations

104. This should also be adjusted every 3-5 days to target FBG.

106. Theoretically, people with type 2 diabetes have a predominance of postprandial
hyperglycemia, which may increase macrovascular risk. Thus, there is a rationale
for early initiation of prandial coverage as well. However, with patient and
caregiver reluctance to utilize injected insulin before meals, this approach is not
often taken. However, once a patient develops clear insufficiencies in insulin
secretory capacity, full-day insulin coverage is clearly required.
This circumstance raises a philosophical question about taking the next step in
treatment design. When converting from bedtime insulin treatment, one option
would be to start with a conventional insulin program using a twice-daily
premixed insulin or a custom-designed split mix. This will often eventually evolve
into a full physiologic program. Or, it is also possible to go right to the full
physiologic coverage approach, using a long-acting insulin at bedtime to provide
basal coverage plus premeal rapid-acting insulin. At the crux of this decision is
whether or not the patient is willing to take the additional premeal injections and
monitoring in exchange for more lifestyle flexibility. The more physiologic
approach has many advantages, but the frequent injections are often a deterrent.
Thus, at this juncture, a clinician should determine the patient's interest, and if
they are willing to move to a physiologic program right away, it is the best option
medically.
While the more conventional therapies are simpler, they do not optimally mimic
natural patterns of insulin release, and postprandial coverage is often suboptimal.
Hypoglycemia is more likely because insulin levels do not match the glucose
levels from food intake. They are also less flexible if there are alterations to meal
times or amounts.

109. The prandial insulins

111. Limitations of Regular Human Insulin

•Slower onset of activity that requires injections to be
given 30 to 45 minutes before meals
• Patient inconvenience
• Safety concerns if the meal is not eaten when scheduled
• A prolonged duration of action (up to 12 hours of activity)
• Late postprandial hypoglycemia (4 to 6 hours after a meal)
• Risk of hyperinsulinemia

113. How to add and titrate prandial
insulins?
(Starting Insulin in Patients With A1C > 10.0%)

114. Regular insulin and Rapid
acting analogues(Lispro)

115. 1.Pre-meal plasma glucose levels
and
2. meal size
(carbohydrate content)
prandial insulin dosing depends upon

116. A usual starting dosage for patients with type 2
diabetes is 1 U of rapid-acting insulin for every 10
g of carbohydrate eaten plus an additional 1 U for
every 30 mg/dL above the target self-monitoring
blood glucose level of 100 mg/dL.
For example, a patient who had a premeal self-
monitoring blood glucose level of 160 mg/dL, and
was planning to eat a meal containing 30 g of
carbohydrate, would take a prandial insulin dose
of 5 U .

117. If the patient is uncomfortable counting
carbohydrates, the physician can recommend a
range of insulin dosages empirically based on the
size of the meal I.e,
5 U of a rapid-acting analog for a small meal
and
8-10 U for a large meal
plus additional units of insulin, if needed, based on
the pre -meal self-monitoring blood glucose level
reading

118. A simple way to introduce prandial
insulin is to start with 1 dose at the
main meal (ie, 5-10 U).

119. Titration of regular insulin and
analogues

120. You can increase or decrease the dose
of regular insulin and analogues
by 20 % i.e
If the patients is using,
1-10 units…………….+/- 2 unit
11-20 units……………+/- 4 units
21-30 units……………+/- 6units
31-40 units……………+/- 8 units…………………..

121. How to start pre mixed (70/30)
Insulin

122. For pre mixed insulins(70/30 preparations)
Step1:First calculate the total daily starting requirement
of insulin;
body weight(kg)/2
eg, For a 60kg patient,total daily dose =30 units
Step 2:Then devide this dose into 3 equal parts;
10+10+10
Step 3:Give 2 parts in the morning and 1 part in the
evening;
Morning=20U Evening=10 U

123. Dose titration of Pre-mixed(70/30)
preparations

124. You can increase or decrease the dose of
pre-mixed insulin by 10 % i.e
If the patients is using,
1-10 units…………….+/- 1 unit
11-20 units……………+/- 2 units
21-30 units……………+/- 3 units
31-40 units……………+/- 4 units…………………..

125. Advantages and disadvantages
of pre- mixed insulins

126. Advantages:
Easy to administer for the
physician.
Easy to fill and inject by the
patient.
Provides both basal and bolus
coverage with fewer number of
injections.

127. Disadvantage:
No dose flexability
If u increase/decrease the dose of one
component ,the dose of other
component is also changed un desirably

128. How to solve the problem of
dosage flexibility

129. Regimen # 4

131. Disadvantage of split- mixed regimen
Mid-night hypoglycemia

132. How to solve the problem of
nocturnal hypoglycemia

133. Somogyi phenomenon
•Due to
– excess dose of night time insulin, or
–Night insulin taken early
•Peaks at 3:00 a.m: hypoglycemia
•Counter regulatory hormones released in excess:
•Resulting in over correction of hypoglycemia:
•Fasting hyperglycemia
•Solution:
–Check BSL AT 3 :00 a.m
–Give long acting at 11:00 p.m so peak comes
later
–Reduce dose of night time insulin

135. Dawn phenomenon
•Growth hormone surge at dawn raises insulin
requirement.
•Night time insulin taken early, fades out before
dawn.
•Fasting hyperglycemia
Solution
•Give long acting insulin not before 11 :00 p.m
•May need to increase dose of night time insulin

136. More physiologic regimens

142. Remember
•Insulin
–No miracle drug
–Has definite indications
As delivery route follows reverse
physiology:
–Good control is achieved only if residual
pancreatic function is preserved to a
certain extent i-e:
–Starting insulin on time is vital
(Concept of early insulinization)

143. Pearls for practice
Never try to control diabetes with oral hypoglycemic drugs /
insulin without first ensuring strict diet control.
Always bring fasting sugar to normal before trying to control
post prandial / random blood sugar.
Control any underlying infection/stressful condition
vigorously.
Keep meal timings regular with 6 hrs between the three
meals.
Do not inject NPH before 11 p.m.
Keep number of calories during the meals same from day to
day. The quantity and quality of diet should be same at same
timings.
Do not use sliding scale to calculate the dose of insulin.
Use proper technique to inject s/c insulin.
Ensure proper storage of insulin.

144. Common Problems

145. Problems can be avoided
•Adherence to time table is all that is
required to avoid problems:
–Regular meals
–Regular injections
–Regular excercise

146. Choosing an Insulin with a Choosing an Insulin with a
Lower Risk of Lower Risk of
HypoglycemiaHypoglycemia
•Insulin analogues with longer, non-peaking
profiles may decrease the risk of
hypoglycemia…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

147. Injection Techniques

148. Sites of injection
•Arms 
•Legs 
•Buttocks 
•Abdomen 

149. Sites of injection…….contd.
•Preferred site of injection is the
abdominal wall due to
•Easy access
–Ample subcutaneous tissue
•Absorption is not affected by exercise.

150. Injection technique

151. Technique
•Tight skin fold
•Spirit…. X
•Appropriate needle size
•90 degree angle
•Change site to avoid lipodystrophy

152. Injection
technique…….contd.
INSTRUCTIONS:
Keep the needle perpendicular to skin in order to
avoid variability in absorption (fig-A)
Insert needle upto the hilt (fig-A)
Distribute daily injections over a wide area to avoid
lipodystrophy and other local complications (fig-B)

153. Storage
•Injections: refrigerate
•Pens: do not refrigerate

154. Shelf life
•One month
once opened

155. Thank you all
For
Sparing your valuable time
&
Patient listening