Insulin therapy: art of initiation and titration

Insulin Therapy-the Art Of Initiation and
Titration

Insulin is the body’s key to metabolism

Characteristics :
BASAL : 1u/hr between meals,through the night with fasting
» To restrict but not eliminate hepatic glucose
production which is necessary for cerebral
glucose metabolism
» Correlate highly with FPG
PRANDIAL : 5 to 10 times basal rate, peaks in ½ to 1 hr.
returning to base line in 2 to 4 hrs

Intiating insulin therapy
• In type 1 daibetes
– All patients
– In some patients like LADA who may be initially
responsive to to oral hypoglycemic agents later
require insulin

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

Advantages 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 HbA1c
– 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.

*Lower extremity amputation or fatal PVD
†P < 0.0001; ‡P = 0.035
Error bars = 95% CIs
Percentagereductioninrelativerisk
correspondingtoa1%fallinHbA1c
–50
–45
–40
–35
–30
–25
–20
–15
–10
–5
0
21%
Any
diabetes-related
endpoint
21%
Diabetes-
related
death
14%
All
cause
mortality
14%
Myocardial
infarction
12%
Stroke
43%
Peripheral
vascular
disease*
37%
Microvascular
disease
19%
Cataract
extraction
Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000;321:405–412.
UKPDS: Observational data for a
1% decrease in HbA1c
–55
†
†
†
† ‡
†
†
†

0 1 2 3 4 5
metformin
Sus
TZDs
EXENATIDE
INSULIN
9.5%HbA1c 6.5%HbA1c

Fears & concerns
about insulin therapy

Patient Concerns About Insulin
• Fear of injections(Trypanophobia)
• Perceived significance of need for insulin
• Worries that insulin could worsen diabetes
• Concerns about hypoglycemia
• Complexity of regimens
21

When to Start Insulin?
• Watch for the following signs
– Increasing BG levels
– Elevated A1C
– Unexplained weight loss
– Traces of ketonuria
– Poor energy level
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

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

Bolous insulins (Mealtime or prandial)
Insulin Type Onset of
action
Peak of
action
Duration of
action
Human
regular
Short acting 30-60 minutes 2-4 hours 8-10 hours
Insulin analogs
(Lispro,Aspart,
Glulisin)
Rapid acting 5-15 minutes 1-2 hours 4-5 hours
Inhaled insulin Rapid acting 10-20 minutes 2 hours 6 hours
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.

Basal Insulins
Insulin Type Onset of
action
Peak of
action
Duration
of action
NPH Intermediate
acting
1-2 hours 5-7 hours 13-18
hours
Glargine
(Lantus)
Aventis
Long
acting
1-2 hours Relatively
flat
Upto 24
hours
Detemir
(Levimir)Novo
Long
acting
2-4 hours 8-12 hours 16-20
hours
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.

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

The ADA Treatment
Algorithm for the Initiation
and Adjustment of Insulin

Initiating 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%...

Step One…
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 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

Step One: Initiating Insulin, 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 Insulin, cont’d
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

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

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.

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…

Step 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:
• 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

Making Adjustments
• Can usually begin with ~4 units and
adjust by 2 units every 3 days until blood
glucose is in range
When number of insulin Injections increase from 1-2
………..Stop or taper of insulin secretagogues (sulfonylureas).

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

Step Three:
Further 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

Premixed 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

• Choice of an insulin regime for initiation of therapy
has always been a matter of debate.
• There is no universal consensus for the optimal
method of starting insulin therapy in patients with
type 2 diabetes (T2DM) who do not respond to oral
anti-diabetic drugs (OADs).
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E,
Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR, American
Diabetes Association (ADA), European Association for the Study of
Diabetes (EASD) Diabetes Care. 2012 Jun; 35(6):1364-79.

• While the American Diabetes Association (ADA) and European
Association for study of Diabetes (EASD) suggest basal insulin
as an initial preferred strategy , the International Diabetes
Federation (IDF) recommends both premixed and basal insulin
• Many national guidelines, on the other hand, support the use
of premixed insulin as a preferred choice for initiation of
therapy. Intensive insulin therapy, too, is indicated as initial
line of management in a select group of patients

• The value 74 mg% is taken by calculating PPGE for the diagnostic cut offs
for diabetes (200 mg% and 126 mg%).
• The value 40 mg% is taken by calculating PPGE for the diagnostic cut offs
for prediabetic (impaired glucose tolerance 140 mg%, and impaired fasting
glucose 100 mg%).
Kalra and Gupta, Diabetes and Metabolic disorders 2015 vol 14:17

• Prandial: fasting index (PFI) = (PPG‐FPG) /FPG
• The value 0.6 is taken by calculating PFI for the diagnostic cut offs of
diabetes (200 mg%, 126 mg%).
• The value 0.4 is taken by calculating PFI for the diagnostic cut offs of
prediabetes.

• *The value 1.3 is calculated with the diagnostic cut offs of diabetes using
FPG (7.8 mmol/l) and HbA1c (6%).
• **The value 20 is calculated with the diagnostic cut offs for diabetes using
FPG (126 mg%) and currently accepted HbA1c (6.3%) levels.

• Use of sulfonylureas with insulin regimens ?

Insulin therapy: art of initiation and titration

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