Insulin initiation adjustment

Insulin TherapyInitiation and Adjustment

Dr Shahjada SelimEndocrinologist

Registrar, Department of Medicine, ShSMCH

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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:Attempt to Mimic Normal Pancreatic Function

Schade, Skyler, Santiago, Rizza, “Intensive Insulin Therapy,” 1993, p. 131.

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PLA SM AG LUC O SE

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B L S HS

PLA SM A FREEIN SULIN

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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

diabetes6

All type 1 diabetics should be on aBolus-bolus insulin regimen to control glucose while minimizing hypoglycemia.

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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

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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 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

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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,

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

Adjustment of InsulinAdjustment of Insulin

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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):1963-72.17

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%...

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Step One…






If HbA1c ≤7%...

Bedtime long-acting insulin (initiate with 10 units or 0.2 units per kg)


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)








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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:


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%...









Step Two…


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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








If HbA1c ≤7%...



If HbA1c 7%...









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


Basal Insulins in Type 2 DM

• NPH at HS - duration of action short: - usually need AM injection - nighttime hypoglycemia 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.


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 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.

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• Premixed insulin is not recommended during dose adjustment.

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

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Thanks to All

Insulin initiation adjustment

Health & Medicine

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