Insulin initiation adjustment

Insulin Therapy
Initiation and Adjustment
Dr Shahjada Selim
Endocrinologist
Registrar, Department of Medicine, ShSMCH
1

Issues in the Management of
Type 2 Diabetes
• Type 2 DM is a chronic condition with
progressive loss of beta-cell function over time
• Increasing prevalence with obesity
• Hyperglycemia affects morbidity, mortality
• Tight glycemic control with insulin may reduce
costly complications
2

3
• 30% to 40% of patients ultimately require
insulin.
• Newer semisynthetic or analog insulins
and delivery systems may improve
compliance and achieve better glycemic
control with less hypoglycemia.
…………………Conted

Defined glycemic targets in T2DM
PG=plasma glucose.
1. American Diabetes Association. Diabetes Care 2005;28(suppl 1):S14—36.
2. American Association of Clinical Endocrinologists. Endocr Pract 2002;8(suppl 1):43—84.
3. International Diabetes Federation. Diabet Med 1999;16:716—30.
*1−2 hours postprandial; **2 hours postprandial.
Glucose control Healthy ADA1
AACE2
IDF3
HbA1c (%) <6 <7 ≤6.5 ≤6.5
Mean FPG
mmol/l (mg/dl)
<5.6
(<100)
5−7.2
(90−130)
<6
(<110)
<6
(<110)
Mean
postprandial PG
mmol/l (mg/dl)
<7.8
(<140)
<10*
(<180)
<7.8**
(<140)
<7.5**
(<135)
4

The Goal of Insulin Therapy:
Attempt to Mimic Normal Pancreatic Function
Schade, Skyler, Santiago, Rizza, “Intensive Insulin Therapy,” 1993, p. 131.
0
6 0
3 0
1 0 0
6 0
1 4 0
1 5
1 9 3 0
H O U R S
2 3 3 0 0 3 3 0 0 7 3 01 5 3 01 1 3 03 3 0
8 0
4 0
1 2 0
7 5
1 6 0
P L A S M A
G L U C O S E
m g / d l
B L S H S
P L A S M A F R E E
IN S U L IN
u / m l

Purpose of Insulin Therapy
• Prevent and treat fasting and postprandial
hyperglycemia
• Permit appropriate utilization of glucose and
other nutrients by peripheral tissues
• Suppress hepatic glucose production
• Prevent acute complications of uncontrolled
diabetes
• Prevent long term complications of chronic
diabetes 6

All type 1 diabetics should be on a
Bolus-bolus insulin regimen to
control glucose while minimizing
hypoglycemia.
6-19

However over time, most type 2
diabetics will also need both basal
and mealtime insulin to control
glucose.
6-19

Initiating Insulin Therapy
6-36

Patient Concerns About Insulin
• Fear of injections
• Perceived significance of need for insulin
• Worries that insulin could worsen diabetes
• Concerns about hypoglycemia
• Complexity of regimens
10

When to Start Insulin?
• Watch for the following signs
– Increasing BG levels
– Elevated A1C
– Unexplained weight loss
– Traces of ketonuria
– Poor energy level 11
When OHAs are not enough to achieve
target glycemic status --

…..When Oral Medications Are Not Enough
– Sleep disturbances
– Polydipsia
• Next steps
– Make a decision to start insulin
– Offer patient encouragement, not blame
12

…..Initiating Insulin Therapy in Type 2 Diabetes
• Let blood glucose levels guide choice
of insulins
– Select type(s) of insulin and timing
of injection(s) based on pattern of
patient’s sugar (fasting, lunch,
dinner, bedtime)
13

….Initiating Insulin Therapy in Type 2 Diabetes
• Choose from currently available insulin
preparations
– Rapid-acting (mealtime): lispro, aspart,
glulisine
– Short-acting (mealtime): regular insulin
– Intermediate-acting (background): NPH,
lente
– Long-acting (background): degledec,
ultralente, glargine
– Insulin mixtures (premixed)

….Initiating Insulin Therapy in Type 2 Diabetes
• Provide long-acting or intermediate-
acting as basal and rapid-acting as bolus
• Titrate every week
Goal: to approximate endogenous insulin secretion…

The ADA TreatmentThe ADA Treatment
Algorithm for the Initiation andAlgorithm for the Initiation and
Adjustment of InsulinAdjustment of Insulin
16

Step One: Initiating InsulinStep One: Initiating Insulin
• Start with either…
– Bedtime long-acting/intermediate acting
insulin
Insulin regimens should be designed taking
lifestyle and meal schedules into account
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.17

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).

• 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

• If HbA1c is <7%...
– Continue regimen and check HbA1c every
3 months
• If HbA1c is ≥7%...
– Move to Step Two…
After 2-3 Months…After 2-3 Months…

Initiating and Adjusting InsulinInitiating and Adjusting Insulin
Continue regimen; check
HbA1c 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 HbA1c continues to be out of range, check 2-hr postprandial levels
and adjust preprandial rapid-acting insulin
If HbA1c ≤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 HbA1c ≥7%...
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
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
If HbA1c ≤7%... If HbA1c ≥7%...
21

Step One…
If HbA1c ≤7%...
Bedtime long-acting insulin
If HbA1c ≥7%...
Hypoglycemia
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
22

Step Two: Intensifying InsulinStep Two: Intensifying Insulin
If fasting blood glucose levels are in target
range but HbA1c ≥7%, check blood glucose
before lunch, dinner, and bed and add a
second injection:

Step Two: Intensifying InsulinStep Two: Intensifying Insulin
• 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

Insulin AdjustmentsInsulin Adjustments
• Can usually begin with ~4 units and
adjust by 2 units every 3 days until
blood glucose is in range.

• If HbA1c is <7%...
– Continue regimen and check HbA1c every
3 months
• If HbA1c is ≥7%...
– Move to Step Three…
After 2-3 Months…After 2-3 Months…

If HbA1c ≤7%...
If HbA1c ≥7%...
Hypoglycemia
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
Step Two…
27

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 HbA1c is still ≥ 7%
–Check 2-hr postprandial levels
–Adjust preprandial rapid-acting insulin

If HbA1c ≤7%...
If HbA1c ≥7%...
Hypoglycemia
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
Step Three…
29

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

Basal Insulins in Type 2 DM
• NPH at HS - duration of action short:
- usually need AM injection
- nighttime hypoglycemia a
problem
31

Basal Insulins in Type 2 DM
• Analogs
- Degludec - true once daily injection
- Glargin - likely to succeed as true once
daily injection
- Detemir – Basal insulin
32

Inhaled InsulinInhaled Insulin
• Approved in the U.S. in 2006 for the
treatment of type 2 diabetes and then had
been withdrawn from the market.
• In June, 2014 another inhaled insulin
(Afreeza) got US FDA approval and Aventis
bought the patent of it for commercial
production and marketing.

Upgrade and Intensification
Selecting alternative insulin or altering
the current treatment regimen (e.g.
Increasing number of daily doses)

Need of Changing Insulin Regimen
• Failure to attain or maintain target
glycemic status (FPG/PPG or HbA1C).
• H/O repeated hypoglycemia
• Lifestyle issues

Changing from Other regimens to
Basal/Bolus Insulin
~50%
Basal*
Total Daily DoseTotal Daily Dose
(~70-75% of prior insulin regimen TDD)(~70-75% of prior insulin regimen TDD)
~50%
Bolus*
Usually divided into 3 premealUsually divided into 3 premeal
dosesdoses*Range: 40 to 60%*Range: 40 to 60%

An Example:
• Mr. M: 58 yrs with history type 2 diabetes for
8 years
– In addition to OHAs, he is on 70/30 premixed
insulin: 30 u AM and 15 u PM
– Current Total Daily Dose = 45 u of 70/30
– However, he has been having difficulty with
wide glycemic excursions.

………….An Example:
• After discussing his options in detail, he
is willing to begin with basal/bolus
regimen:
• New TDD= 45 u x .75 = 33.75 = 34 u
– Basal = 17 u Degludec at bedtime
– Bolus = 17 u total / 3 = 5.6 u = 5 u
aspart/Glulisine immediately before meals.

Another method
• Same patient: Mr. M on 70/30 insulin:
30 u AM and 15 u PM
– Current Total Daily Dose = 45 u of 70/30
• Instead, some clinicians prefer to
instead calculate the new basal/bolus
doses independently of each other
– Current Basal= 0.70 x 45 u TDD = 31.5 u N
– Current Bolus= 0.30 x 45 u TDD = 13.5 u.

………….Another method
• Then, use 70 to 75% of prior NPH,
but divide prior short acting into 3
premeal doses
– New Basal= 0.75 x 31.5 u N = 24 u
Degludec, Glargine, Detemir.
– New Bolus= 13.5 u R / 3 = 4.5 u (round up
or down) Aspart or Glulisine

So which method is best?
• This is where the “Art of Medicine”
comes in:
– If patient has been having difficulty with
hypoglycemia, then start any new insulin
regimen with conservative doses.
– If patient, on the other hand, has been having
hyperglycemia, then one can be more
aggressive.
Remember: every patient is an individual!

A Quick Word on using Sliding
Scale Insulin….
Don’t!

Instead of Sliding Scale....
• Basal insulin is necessary even in the fasting
state
• Sliding scales do not provide physiologic insulin
needs
• Sliding scales often result in “chasing” of
blood sugars
• There can be wide glycemic excursions
Remember: Just because a diabetic’s FBG is <150 does not mean
that they need no insulin!
Think Supplementation or Correction Scale…

The Solution:
• In acutely ill hospitalized diabetics:
use continuous IV insulin

………The Solution:
• If one must use an insulin scale in an outpatient or
stable inpatient setting:
• Insulin scale should only supplement a routine
scheduled regimen of basal and premeal insulin
• May use to correct for hyperglycemia between
scheduled doses of insulin
• It should NEVER be ordered such that the scale is
the only source of insulin for the patient

Drawbacks of intensive
insulin regimens
• Requires frequent monitoring of glucose
• Multiple daily injections of insulin
• Requires intensive patient education/on-
going support
• Newer insulin analogues require less
injections a but are more expensive 47

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.
48

• Premixed insulin is not recommended
during dose adjustment.
49

• When initiating insulin, start with bedtime
or morning long-acting insulin.
• After 2-3 months, if FBG levels are in
target range but HbA1c ≥7%, check BG
before lunch, dinner, and bed,
and, depending on the results, add 2nd
injection.
50

• After 2-3 months, if pre-meal BG out of
range, may need to add a 3rd
injection; if
HbA1c is still ≥7% check 2-hr postprandial
levels and adjust preprandial rapid-acting
insulin.
• Adjust one insulin at a time. Begin with the
insulin that will correct the first problem
blood glucose of the day.
51

• It is difficult to obtain optimal control
without occasional, mild episodes of
hypoglycemia.
52

Insulin initiation adjustment

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