Post on 19-Aug-2015
Insulin TherapyInitiation and Adjustment
Dr Shahjada SelimDepartment of Endocrinology
Bangabandhu Sheikh Mujib Medical UniversityEmail: selimshahjada@gmail.com
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Issues in the Management ofType 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
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• 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.
*12 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)
57.2(90130)
<6 (<110)
<6 (<110)
Mean postprandial PG mmol/l (mg/dl)
<7.8 (<140)
<10* (<180)
<7.8** (<140)
<7.5** (<135)
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The Goal of Insulin Therapy:The Goal of Insulin Therapy:Attempt to Mimic Normal Pancreatic Function
Schade, Skyler, Santiago, Rizza, “Intensive Insulin Therapy,” 1993, p. 131.
0
60
30
100
60
140
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1930
HO URS
2330 0330 073015301130330
80
40
120
75
160
PLA SM AG LUC O SE
m g /d l
B L S HS
PLA SM A FREEIN SULIN
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
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All type 1 diabetics should be on aBolus-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.
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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
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When to Start Insulin?
• Watch for the following signs– Increasing BG levels– Elevated A1C– Unexplained weight loss– Traces of ketonuria– Poor energy level
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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
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…..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)
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….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, detemir, glargine
• Insulin mixtures (premixed) /coformulations
….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…
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The ADA Treatment Algorithm for The ADA Treatment Algorithm for the Initiation and Adjustment of the Initiation and Adjustment of
InsulinInsulin
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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.
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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.
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• 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.
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• 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.
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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%...
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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.
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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.
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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.
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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.
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• 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.
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 7A%...
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%...
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Step Two…
Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.
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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.
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%...
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Step Three…
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Premixed 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
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
Basal Insulins in Type 2 DM
• NPH at HS - duration of action short: - usually need AM injection - nighttime hypoglycemia is a
problem
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Basal Insulins in Type 2 DM
• Analogs - Degludec - true once daily
injection
- Glargin - likely to succeed as true
once daily injection- Detemir – Basal insulin
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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.
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 premeal Usually 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
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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.
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Key Take-Home MessagesKey Take-Home Messages
• Premixed insulin is not recommended during dose adjustment.
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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.
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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.
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Key Take-Home MessagesKey Take-Home Messages
• It is difficult to obtain optimal control without occasional, mild episodes of hypoglycemia.
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Thanks to All