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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).
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.18
• 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):1963-72.19
• 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…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.20
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
Continue regimen; check
HbA1c 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 HbA1c ≤7%... If HbA1c ≥7%...
21
Step One…
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 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
Continue regimen; check
HbA1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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:
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.23
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
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.24
Insulin AdjustmentsInsulin 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):1963-72.25
• 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…
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.26
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 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
Continue regimen; check
HbA1c every 3 months
Target range:
3.89-7.22 mmol/L
(70-130 mg/dL)
If HbA1c ≤7%... If HbA1c ≥7%...
Step Two…
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.28
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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 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
Continue regimen; check
HbA1c every 3 months
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
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.30
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.
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.33
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
Key Take-Home MessagesKey Take-Home Messages
• Premixed insulin is not recommended
during dose adjustment.
49
Key Take-Home MessagesKey Take-Home Messages
• 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
Key Take-Home MessagesKey Take-Home Messages
• 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
Key Take-Home MessagesKey Take-Home Messages
• It is difficult to obtain optimal control
without occasional, mild episodes of
hypoglycemia.
52
53
Thanks to All

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Insulin initiation adjustment

  • 1. Insulin Therapy Initiation and Adjustment Dr Shahjada Selim Endocrinologist Registrar, Department of Medicine, ShSMCH 1
  • 2. 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. 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
  • 4. 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
  • 5. 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
  • 6. 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
  • 7. All type 1 diabetics should be on a Bolus-bolus insulin regimen to control glucose while minimizing hypoglycemia. 6-19
  • 8. However over time, most type 2 diabetics will also need both basal and mealtime insulin to control glucose. 6-19
  • 10. 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
  • 11. 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 --
  • 12. …..When Oral Medications Are Not Enough – Sleep disturbances – Polydipsia • Next steps – Make a decision to start insulin – Offer patient encouragement, not blame 12
  • 13. …..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
  • 14. ….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)
  • 15. ….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…
  • 16. The ADA TreatmentThe ADA Treatment Algorithm for the Initiation andAlgorithm for the Initiation and Adjustment of InsulinAdjustment of Insulin 16
  • 17. 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
  • 18. 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):1963-72.18
  • 19. • 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):1963-72.19
  • 20. • 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… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.20
  • 21. 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 Continue regimen; check HbA1c 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 HbA1c ≤7%... If HbA1c ≥7%... 21
  • 22. Step One… 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 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 Continue regimen; check HbA1c every 3 months Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c ≤7%... If HbA1c ≥7%... Nathan DM et al. Diabetes Care. 2006;29(8):1963-72. 22
  • 23. 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: Nathan DM et al. Diabetes Care 2006;29(8):1963-72.23
  • 24. 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 Nathan DM et al. Diabetes Care 2006;29(8):1963-72.24
  • 25. Insulin AdjustmentsInsulin 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):1963-72.25
  • 26. • 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… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.26
  • 27. 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 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 Continue regimen; check HbA1c every 3 months Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c ≤7%... If HbA1c ≥7%... Step Two… Nathan DM et al. Diabetes Care. 2006;29(8):1963-72. 27
  • 28. 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 Nathan DM et al. Diabetes Care 2006;29(8):1963-72.28
  • 29. Nathan DM et al. Diabetes Care. 2006;29(8):1963-72. 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 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 Continue regimen; check HbA1c every 3 months Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c ≤7%... If HbA1c ≥7%... Step Three… 29
  • 30. 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):1963-72.30
  • 31. Basal Insulins in Type 2 DM • NPH at HS - duration of action short: - usually need AM injection - nighttime hypoglycemia a problem 31
  • 32. 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
  • 33. 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. Nathan DM et al. Diabetes Care 2006;29(8):1963-72.33
  • 34. Upgrade and Intensification Selecting alternative insulin or altering the current treatment regimen (e.g. Increasing number of daily doses)
  • 35. Need of Changing Insulin Regimen • Failure to attain or maintain target glycemic status (FPG/PPG or HbA1C). • H/O repeated hypoglycemia • Lifestyle issues
  • 36. 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%
  • 37. 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.
  • 38. ………….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.
  • 39. 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.
  • 40. ………….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
  • 41. 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!
  • 42. A Quick Word on using Sliding Scale Insulin…. Don’t!
  • 43. 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…
  • 44.
  • 45. The Solution: • In acutely ill hospitalized diabetics: use continuous IV insulin
  • 46. ………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
  • 47. 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
  • 48. 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
  • 49. Key Take-Home MessagesKey Take-Home Messages • Premixed insulin is not recommended during dose adjustment. 49
  • 50. Key Take-Home MessagesKey Take-Home Messages • 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
  • 51. Key Take-Home MessagesKey Take-Home Messages • 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
  • 52. Key Take-Home MessagesKey Take-Home Messages • It is difficult to obtain optimal control without occasional, mild episodes of hypoglycemia. 52

Editor's Notes

  1. Slide 6-19 MIMICKING NATURE WITH INSULIN THERAPY Over time, most patients will need both basal and mealtime insulin to control glucose Since both fasting and postprandial glucose levels are abnormal in type 2 diabetes and the underlying insulin deficiency typically progresses, most patients will need both basal insulin and mealtime insulin if excellent glucose control is to be maintained. The goal of intensive insulin therapy is to delay the onset of microvascular complications and retard their progression once they occur.
  2. Slide 6-19 MIMICKING NATURE WITH INSULIN THERAPY Over time, most patients will need both basal and mealtime insulin to control glucose Since both fasting and postprandial glucose levels are abnormal in type 2 diabetes and the underlying insulin deficiency typically progresses, most patients will need both basal insulin and mealtime insulin if excellent glucose control is to be maintained. The goal of intensive insulin therapy is to delay the onset of microvascular complications and retard their progression once they occur.
  3. Slide 6-36 Overcoming Complexity by Starting With Basal Insulin One way to overcome the complexity of multiple daily insulin injection regimens is to start with basal insulin in patients with type 2 diabetes who are no longer responding adequately to oral agents.
  4. As described, patients often proceed from taking a single oral medication to taking 2 or more oral agents or a combination of oral medication with insulin. Commonly, insulin is initiated in a schedule with intermediate- or long-acting insulin at bedtime to control fasting glucose levels and oral medications to control daytime glucose levels.
  5. As described, patients often proceed from taking a single oral medication to taking 2 or more oral agents or a combination of oral medication with insulin. Commonly, insulin is initiated in a schedule with intermediate- or long-acting insulin at bedtime to control fasting glucose levels and oral medications to control daytime glucose levels.
  6. Key Point When initiating insulin, the ADA recommends beginning with either a bedtime intermediate-acting insulin or a bedtime or morning long-acting insulin. This can be initiated with 10 units or 0.2 units per kilogram. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  7. Key Points Fasting glucose should be checked daily via fingerstick and the dose should be increased, typically by 2 units every 3 days, until fasting levels are in the target range (i.e., 3.89-7.22 mmol/l or 70-130 mg/dl). If fasting glucose is over 10 mmol/l (i.e., over 180 mg/dl), doses can be increased in larger increments (for example, by 4 units every 3 days). All insulin regimens should be designed to take lifestyle and meal schedules into account. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  8. Key Points HbA1c should be re-checked within 2 to 3 months. If it is below 7%, the current regimen should be continued with re-evaluation of HbA1c levels every 3 months. If it is 7% or higher, physicians should move to Step Two of the algorithm. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  9. Key Points Although initial therapy is aimed at increasing basal insulin supply, usually with intermediate- or long-acting insulin, patients may also require prandial therapy with short- or rapid-acting insulin as well. The ADA algorithm has been created to help guide physicians in determining a patient’s optimal insulin regimen. There are three steps to the algorithm. Each will be reviewed in turn. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  10. Key Point Step one involves initiating insulin. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  11. Key Points If, after 2 to 3 months of initiating insulin therapy, fasting blood glucose levels are in target range but HbA1c is 7% or higher, the patient’s blood glucose should be checked before lunch, dinner, and bed, and a second injection should be added. If the patient’s pre-lunch blood glucose is out of range, rapid-acting insulin should be added at breakfast. If pre-dinner blood glucose is out of range, NPH insulin should be added at breakfast or rapid-acting insulin should be added at lunch. If pre-bed blood glucose is out of range, rapid-acting insulin should be added at dinner. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  12. Key Points If, after 2 to 3 months of initiating insulin therapy, fasting blood glucose levels are in target range but HbA1c is 7% or higher, the patient’s blood glucose should be checked before lunch, dinner, and bed, and a second injection should be added. If the patient’s pre-lunch blood glucose is out of range, rapid-acting insulin should be added at breakfast. If pre-dinner blood glucose is out of range, NPH insulin should be added at breakfast or rapid-acting insulin should be added at lunch. If pre-bed blood glucose is out of range, rapid-acting insulin should be added at dinner. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  13. Key Points Again, HbA1c should be re-checked within 2 to 3 months. If it is below 7%, the current regimen should be continued with re-evaluation of HbA1c levels every 3 months. If it is 7% or higher, physicians should move to Step Three of the algorithm. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  14. Key Point Step Two of the algorithm involves intensifying insulin therapy. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  15. Key Points If pre-meal blood glucose is out of range when rechecked, a third injection of insulin may be needed. If HbA1c is still 7% or higher, 2-hour postprandial levels should be checked and preprandial rapid-acting insulin adjusted. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  16. Key Point Step Three of the algorithm involves further intensifying insulin therapy. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  17. Key Points Premixed insulin is not recommended during dose adjustment. However, it can be used conveniently, usually before breakfast and/or dinner, if the proportion of rapid- and intermediate-acting insulin is similar to the fixed proportions available. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  18. Key Points Inhaled insulin was approved in the U.S. in 2006 for the treatment of type 2 diabetes. However, published clinical studies to date have not demonstrated whether inhaled insulin can lower HbA1c to 7% or lower, either as monotherapy or in combination with an injection of long-acting insulin. Reference: Nathan DM et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29(8):1963-72.
  19. Key Points In conclusion: Insulin is the oldest, most studied and most effective antihyperglycemic agent but can cause weight gain (2-4 kg) and, in rare instances, hypoglycemia Insulin analogues with longer, non-peaking profiles may decrease the risk of hypoglycemia compared with NPH insulin Published studies have not demonstrated whether inhaled insulin can lower HbA1c to 7% or lower Premixed insulin is not recommended during dose adjustment
  20. Key Points In conclusion: Insulin is the oldest, most studied and most effective antihyperglycemic agent but can cause weight gain (2-4 kg) and, in rare instances, hypoglycemia Insulin analogues with longer, non-peaking profiles may decrease the risk of hypoglycemia compared with NPH insulin Published studies have not demonstrated whether inhaled insulin can lower HbA1c to 7% or lower Premixed insulin is not recommended during dose adjustment
  21. Key Points (continued from previous): When initiating insulin, patients should start with bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin After 2 to 3 months, if fasting blood glucose levels are in target range but HbA1c is 7% or higher, blood glucose levels should be checked before lunch, dinner and bed, and, depending on the results, a 2nd insulin injection should be added. After 2 to 3 months, if pre-meal blood glucose is out of range, a 3rd injection may be needed. If HbA1c is still 7% or higher, 2-hour postprandial levels should be checked and preprandial rapid-acting insulin adjusted accordingly.
  22. Key Points (continued from previous): When initiating insulin, patients should start with bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin After 2 to 3 months, if fasting blood glucose levels are in target range but HbA1c is 7% or higher, blood glucose levels should be checked before lunch, dinner and bed, and, depending on the results, a 2nd insulin injection should be added. After 2 to 3 months, if pre-meal blood glucose is out of range, a 3rd injection may be needed. If HbA1c is still 7% or higher, 2-hour postprandial levels should be checked and preprandial rapid-acting insulin adjusted accordingly.
  23. Key Points (continued from previous): When initiating insulin, patients should start with bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin After 2 to 3 months, if fasting blood glucose levels are in target range but HbA1c is 7% or higher, blood glucose levels should be checked before lunch, dinner and bed, and, depending on the results, a 2nd insulin injection should be added. After 2 to 3 months, if pre-meal blood glucose is out of range, a 3rd injection may be needed. If HbA1c is still 7% or higher, 2-hour postprandial levels should be checked and preprandial rapid-acting insulin adjusted accordingly.