INSULIN DOSING

• ACRONYMS AND DEFINITIONS

• ADA - American Diabetes Association
• Basal Insulin - Long- and Intermediate-acting insulins used to supply constant blood levels of insulin activity
• Carb- carbohydrate
• T1DM - Type 1 diabetes
• T2DM - Type 2 diabetes
• FDA - U.S. Food and Drug Administration
• Hypoglycemia - low blood sugar
• Multidose insulin regimen - Insulin regimens that involve a basal insulin and a premeal insulin given at meals
• Premeal Insulin - also called “prandial” insulin. Rapid and short-acting insulins given at mealtime for short burst of insulin.
• Total daily dose of insulin - Sum of premeal and basal insulin given in a day
• Units/kg/day - units of insulin per kilogram of body weight per day
• USDA - United States Department of Agriculture
• 1 kilogram = 2.2 pounds

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• IMPORTANT POINTS ABOUT DOSING INSULIN

• Overview
• There are a number of different ways to dose insulin
• The appropriate method for individual patients will depend on a number of factors including patient education, patient motivation, diabetes control, and resources


• Low blood sugar (Hypoglycemia)
• The main concern in most patients when initiating an insulin regimen is the occurrence of low blood sugars
• Patients need to understand that when they are starting and adjusting insulin, there is an increased risk for low blood sugars
• A number of things can affect this risk including variations in eating patterns, sensitivity to insulin, and variations in activity level


• Measures to help prevent low blood sugars
• Start low and go slow - patients naïve to insulin should start at the lower end of dosing ranges
• When using a multidose regimen, adjust only one of the regimens every 3 days and alternate between the two (see below for more)
• The correction factor can help to keep blood sugars from running too high while the insulin regimen is being adjusted
• Try to avoid insulin doses outside of the regimen as this may lead to overcorrections
• In a multidose regimen, it is important to consume a consistent diet of three meals a day while keeping the number of carbohydrates in each meal about the same

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• INSULIN CATEGORIES

• For dosing purposes, insulins can be divided into two categories:
• Basal insulins - provide a steady concentration of insulin in the bloodstream over a number of hours; do not act quickly.
• Premeal insulin (prandial insulin) - provide a burst of insulin that acts quickly; typically used 5 - 30 minutes before meals
• See insulin property chart for a review of available insulins including pharmacokinetics, dosage forms, storage, etc.

Basal insulins
Intermediate-acting insulins Humulin® N (NPH) Novolin® N (NPH) Long-acting insulins Basaglar® (insulin glargine) Lantus® (insulin glargine) Levemir® (insulin detemir) Toujeo® (insulin glargine) Tresiba® (insulin degludec)

Premeal insulins
Rapid-acting insulins Admelog® (insulin lispro) Afrezza® (inhaled insulin) Apidra® (insulin glulisine) Fiasp® (insulin aspart) Humalog® (insulin lispro) Novolog® (insulin aspart) Short-acting insulins Humulin® R (regular) Novolin® R (regular)

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• BLOOD SUGAR GOALS

• See ADA blood sugar goals in DM

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• INSULIN DOSING IN TYPE 2 DIABETES

• See ADA insulin recommendations in T2DM

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• STARTING INSULIN IN TYPE 1 DIABETES (T1DM)

ADA general treatment recommendations for T1DM
• T1DM patients should receive multidose injections (3 - 4 a day) of basal and premeal insulin, or insulin pump therapy
• Most individuals with T1DM should use rapid-acting insulin analogs to reduce hypoglycemia risk
• Patients should match premeal insulin to carbohydrate intake, premeal blood glucose levels, and anticipated activity [26]


• Starting therapy
• Insulin dosing in T1DM will vary based on patient's age, weight, and residual pancreatic insulin activity
• T1DM patients will typically require a total daily insulin dose of 0.4 - 1.0 units/kg/day
• A typical starting dose in metabolically-stable patients is 0.5 units/kg/day
• After calculating the total daily dose, it should be given as follows:
• Basal insulin - given as half of the total daily dose ^†
• Premeal insulin - half of the total daily dose divided into thirds and given before each meal
• ^† When first starting therapy, it is recommended that the initial basal dose be reduced by 20 - 30% to prevent hypoglycemia [11,19]
• T1DM patients may experience a "honeymoon phase" after starting insulin therapy where the initial effects of insulin are greater than what is seen later in the disease [7,13,26]


• Example
• Patient weighs 80 kg
• Total daily dose = 80 kg X (0.5 units/kg/d) = 40 units per day
• Basal insulin = 1/2 X 40 units = 20 units of basal per day^†
• Premeal Insulin = 1/2 X 40 units = 20 units / 3 = approximately 7 units before each meal
• ^† If patient is just starting therapy, the initial basal dose should be reduced by 20 - 30%. In our example: 20 units X 0.20 = 4 units, so initial basal dose would be 20 - 4 = 16 units

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• ADJUSTING BASAL INSULIN

• Overview
• There a number of ways to adjust basal insulin
• A common and straightforward method is presented below
• It may be used to adjust basal regimens in both T1DM and T2DM patients


• Steps for adjusting basal insulin:
• 1. Measure fasting blood sugar (no calories for 8 hours) for previous three consecutive days
• 2. Calculate the average of the three fasting blood sugars
• 3. Adjust basal insulin dose based on the table below
• 4. Repeat steps 1-3 until target range (80 - 99) is achieved

Reference [12]

Fasting blood sugar (mg/dl) average over 3 days	Adjustment to basal insulin dose (units of insulin)
≥ 180	add 8 units
160 - 179	add 6 units
140 - 159	add 4 units
120 - 139	add 2 units
100 - 119	add 1 unit
80 - 99	no change
60 - 79	subtract 2 units
< 60	subtract 4 or more units

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• ADJUSTING PREMEAL INSULIN (SCALE METHOD)

• Scale method
• With the scale method, premeal insulin is adjusted based on a scale
• Patients should try to consume the same amount of carbohydrates at each meal (a typical amount is about 60 grams a meal and 15 grams for a bedtime snack)
• Carbohydrate goals vary by individual (see carbohydrate information below)


• Steps:
• 1. Measure blood sugar fasting (pre-breakfast), pre-lunch, pre-dinner, and pre-bedtime snack for previous three consecutive days
• 2. Average the pre-lunch, pre-dinner and pre-bedtime values separately
• 3. Adjust the premeal insulin dose based on the table below
• 4. Repeat steps 1-3 until target range is achieved
• 5. A Correction Factor (see below) should also be incorporated when blood sugars are checked

Reference [12]

If pre-lunch average is not in desired range, adjust pre-breakfast dose If pre-dinner average is not in desired range, adjust pre-lunch dose If pre-bedtime snack average is not in desired range, adjust pre-dinner dose
Premeal blood sugar (mg/dl) average over 3 days	Adjustment to premeal insulin dose
≥ 180	add 3 units
160 - 179	add 2 units
140 - 159	add 2 units
120 - 139	add 1 units
100 - 119	maintain dose (desired range)
80 - 99	subtract 1 unit
60 - 79	subtract 2 units
< 60	subtract 4 or more units

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• ADJUSTING PREMEAL INSULIN (CARBOHYDRATE COUNTING)

• Carbohydrate counting
• In carbohydrate counting, premeal insulin is adjusted based on the amount of carbohydrates to be consumed in each meal
• The carbohydrate counting method is used to determine the amount of carbohydrates in a meal
• An insulin to carbohydrate ratio (ex. 1 unit/10g of carb) is used to calculate the premeal insulin dose
• A typical starting ratio is 1 unit of premeal insulin for every 10 grams of carbs to be consumed
• An individual may have different carbohydrate ratios for breakfast, lunch, and dinner because a person's response to insulin may vary throughout the day
• Example:
• 60 grams of carbs to be consumed for lunch
• Patient's ratio is 1 unit of insulin for every 10 grams of carbs
• Patient injects 6 units of premeal insulin before eating meal


• Steps for adjusting an insulin-to-carb ratio
• 1. Calculate the number of carbs to be consumed in a meal using carbohydrate counting
• 2. Dose premeal insulin based on number of carbs in a meal (typical starting point is 1 unit of premeal insulin for every 10 grams of carbs)
• 3. Measure blood sugar fasting (pre-breakfast), pre-lunch, pre-dinner, and pre-bedtime snack for previous three consecutive days
• 4. Average the pre-lunch, pre-dinner and pre-bedtime snack blood sugar values separately
• 5. Adjust the carbohydrate to insulin ratio as instructed in the table below
• 6. Repeat steps 1-5 until appropriate ratios are determined [3,4]
• 7. A Correction Factor (see below) should also be incorporated when blood sugars are checked

If pre-lunch average is not in desired range (80 - 120 mg/dl), adjust breakfast ratio If pre-dinner average is not in desired range (80 - 120 mg/dl), adjust lunch ratio If pre-bedtime snack average is not in desired range (80 - 120 mg/dl), adjust dinner ratio

If average blood sugar is > 120 mg/dl, adjust ratio by subtracting 2 - 3g of carbohydrate Example: Current ratio 1 unit / 10g of carb Pre-lunch average > 120 mg/dl Change breakfast ratio to 1 unit / 7g of carb

If average blood sugar is < 80 mg/dl, adjust ratio by adding 2 - 3g of carbohydrate Example: Current ratio 1 unit / 10g of carb Pre-bedtime snack average < 80 mg/dl Change dinner ratio to 1 unit / 13g of carb

If average blood sugar is 80 - 120 mg/dl, do not adjust ratio

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• ADJUSTING PREMEAL AND BASAL INSULINS CONCURRENTLY

• Overview
• When adjusting premeal and basal insulins concurrently, adjustments to one regimen may affect the other regimen. This can lead to overcorrections and hypoglycemia.
• Alternating between regimens may help prevent overcorrections


• Example:
• Day 3 - adjust basal
• Day 6 - adjust premeal
• Day 9 - adjust basal
• Day 12 - adjust premeal, and so on...

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• CORRECTION FACTOR

• Overview
• When premeal blood sugar checks are high, a correction factor should be used with premeal insulin
• The correction factor supplies supplemental insulin to account for the elevated blood sugar
• Insulin used in the correction factor should not be included in calculations for adjusting premeal or basal insulin
• There are several methods that can be used to determine the correction factor
• When first starting therapy, the ideal total daily insulin dose will not be known, so the flat method is preferred over the individual method

• Flat method
  • One unit of extra premeal insulin is added for every 25 mg/dl that blood sugar is above the upper limit of the desired range
  • Example:
  • Pre-lunch blood sugar is 200 mg/dl
  • upper limit of desired range is 120 mg/dl
  • 200 - 120 = 80 mg/dl above desired range
  • 80 mg/dl ÷ 25 mg/dl = approximately 3
  • add 3 extra units to premeal dose
  
  
• Individual method
• The individual method uses a patient's total daily insulin dose to calculate a correction factor
• The correction factor is calculated differently for regular insulins (Humulin R, Novolin R) and rapid insulins (Novolog, Humalog, Apidra, Fiasp)

Step 1 - calculate the correction factor For Regular insulin (Humulin R, Novolin R) 1. Divide 1500 by the patient's total daily dose of insulin 2. The result will equal the estimated drop in blood sugar (in mg/dl) from 1 unit of regular insulin For Rapid insulin (Novolog, Humalog, Apidra, Fiasp, Admelog) 1. Divide 1800 by the patient's total daily dose of insulin 2. The result will equal the estimated drop in blood sugar (in mg/dl) from 1 unit of rapid insulin [4,12] Example: Patient's total daily dose of insulin (premeal + basal) is 60 units Patient uses regular insulin as premeal insulin 1500/60 = 25 Patient can expect that for every 1 unit of regular insulin they inject, their blood sugar will come down 25 mg/dl

Step 2 - Once the correction factor is calculated, the patient can then figure out how much insulin to supplement Example: Patient from above: correction factor is 25 mg/dl Patient checks pre-lunch blood sugar and it is 175 mg/dl (desired range 80 - 120 mg/dl) 175 - 120 = 55 mg/dl 55/25 = approximately 2 Patient would add 2 extra units of regular insulin to premeal dose

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• EXERCISE AND INSULIN DOSING

• See exercise and insulin page

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• SLIDING SCALE INSULIN

• Sliding Scale Insulin involves checking the blood sugar and dosing the insulin (typically rapid or short-acting) based on the blood sugar value
• Doctors use a number of different regimens depending on the patient and their sensitivity to insulin. The example below is a common starting regimen.

Blood sugar (mg/dl)	Insulin dose in units of rapid or short-acting
< 150	0
150 - 200	2
201 - 250	4
251 - 300	6
301 - 350	8
351 - 400	10
401 - 450	12
> 450	14

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• CONVERTING BETWEEN INSULIN BRANDS AND TYPES

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• HYPOGLYCEMIA (LOW BLOOD SUGAR)

• See hypoglycemia

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• CARBOHYDRATE INFORMATION

• Carbohydrates and insulin
• It's important that diabetics who are taking insulin monitor their carbohydrate intake
• See the links below for more information on dieting and carbohydrates


• Carbohydrate counting - review of carbohydrate counting used in dosing premeal insulin
• Calories - review on calculating caloric requirements
• Diabetic diet - diabetic diet recommendations
• Carbohydrates - review of different carbohydrates found in foods

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• BIBLIOGRAPHY

• What is PMID?
• PI = Manufacturer's Package Insert

• #     PMID
  
• 1 - 18945920
• 2 - PMID: 10332663
• 3 - PMID: 18364392
• 4 - Braithwaite S: Case Study: Five Steps to Freedom: Dose Titration for Type 2 Diabetes Using Basal-Prandial-Correction Insulin Therapy. Clinical Diabetes Vol 23:1 p39-43 2005
• 5 - Kulkarni K: Carbohydrate Counting: A Practical Meal-Planning Option for People With Diabetes. Clinical Diabetes Vol 23:3 p120-122 2005
• 6 - PMID: 16915796
• 7 - PMID: 15616254
• 8 - PMID: 16921608
• 9 - PMID: 10378067
• 10 - PMID: 21193625
• 11 - PMID: 12734137
• 12 - PMID: 16847295
• 13 - Herbst K, Hirsch I Insulin Strategies for Primary Care Providers. Clinical Diabetes. Vol 20:1 p1-7 2002
• 14 - PMID: 17890232 - NEJM DM 2 study
• 15 - Hirsch I et al. A Real-World Approach to Insulin Therapy in Primary Care Practice. Clinical Diabetes. Vol 23:2 p78-86. 2005
• 16 - PMID: 18165339
• 17 - PMID: 12766131
• 18 - Glucagon PI
• 19 - Lantus PI
• 20 - Levemir PI
• 21 - Toujeo PI
• 22 - Tresiba PI
• 23 - Basaglar PI
• 24 - ADA 2015 Standards of Medical Care in Diabetes, Vol 38, Supplement 1, p. S46
• 25 - PMID 29222370 - ADA 2018 Standards of Medical Care in Diabetes
• 26 - ADA 2019 Standards of Medical Care in Diabetes