insulin initiation adjustment by dr shahjada selim

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Insulin TherapyInitiation and Adjustment

Dr Shahjada SelimDepartment of Endocrinology

Bangabandhu Sheikh Mujib Medical UniversityEmail: selimshahjada@gmail.com

1

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

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.

*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)

4

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

6

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.

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, 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…

16

The ADA Treatment Algorithm for The ADA Treatment Algorithm for the Initiation and Adjustment of the Initiation and Adjustment of

InsulinInsulin

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.

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.

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.

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.

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%...

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.

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.

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.

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.

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.

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%...

27

Step Two…

Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

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.

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%...

29

Step Three…

30

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

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

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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.

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.

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.

52

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

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