INITIATING INSULIN IN DM2: When Patient Fails Oral Rx
Patty Glatt, MD 10/09
I. INITIATING BASAL INSULIN
Describe to patient as insulin needed to run the fuel cells of their body's motor between meals; Bolus Mealtime insulin is the extra insulin needed to handle the calories eaten.
· Patient Selection: A1C> 7.5-8.0 or FBS> 130 on maximum oral regimen. Early use reduces CV/macrovascular complications.
· Advantage: Establish control FBS, transition to prandial and MDI insulin. Single basal dose sufficient when FBS elevated but orals control postprandial
· Oral DM agents: Continue MTF for weight control and insulin resistance. Caution w/TZD-may ↑CHF. SU: Usually ↓ reduce to ½ max dose or DC when 2 doses insulin or prandial added
TREAT TO TARGET (T2T) PROTOCOL WITH BASAL INSULIN
Why? Achieves quicker A1C control with patient-driven titration. Avoids hypoglycemia
What? Titrate to FBS 90-130 mg/dl. (May adjust to tighter goal ≤110 individually per MD outside of protocol)
How? Start 10 units once daily Lantus/Glargine®, or Levemir/Detemir® at HS, or patient preferred once a day time [or use alternate guideline outside of protocol. For 100kg, average 40-50 units ultimately. Some start at 50% calculated for T2T.]
↑ by 2 units until FBS <130; Option to ↑ by 4 units for FBS >180.
When? Adjust dose every 3-4 days (“twice a week- patient picks”)
Warn: Hypoglycemia: ↓ by 4U or 10% if pre-breakfast glucose <70 or 2AM < 100. If post meal hypoglycemia on SU, lower dose or stop SU.
BLOOD GLUCOSE GOALS ON HOME MONITORING
Before meals: 90-130: w/o significant hypoglycemia
120-180: for elderly or patients with hypoglycemic unawareness
70-100: for those desiring tighter physiologic control
2 hour after meals: under 180, recommended under or < 40 above premeal glucose
Bedtime: under 180; Recommended under 130
(ALTERNATIVE) STARTING BASAL INSULIN DOSE
(Usually dosed at bedtime)
0.2 U/kg if concerned about risk of hypoglycemia (elderly, impaired renal, cardiac or hepatic function)
0.5 U/kg normal weight
0.7 U/kg for presumed high insulin resistance (obesity, post-CABG, open wounds)
Alternative Basal Schedule:
Increase 1 unit per day until at goal <130 > 90
* Use of alternative schedules is outside of T2T Protocol and is managed by the clinician
II. Moving Beyond Single Basal Dosing: Premixed; Prandial; MDI
PREMIXED INSULIN GUIDELINES Humalog®75/25 or Novolog ®70/30
Patient Selection: HgbA1C remains >8.0 on Basal insulin, or TDD basal > 0.5 u/kg, start pre-meal "Prandial" insulin
PREMIXED INSULIN (Humalog ®75/25 or Novolog ®70/30):
Advantage of Premixed Insulin
· For patients unable to manage multiple dose injections for whatever reason
· Improved control when Basal insufficient
Disadvantages of Premixed Insulins
· Must eat at regular times and consistent calories; Skipping meals may lead to hypoglycemia
· Premixed insulin offers no flexibility in adjustment of rapid portion
PREMIXED INSULIN OPTIONS:
1.) Switch to single Premixed before dinner. Start 0.1-0.2 u/kg or 50% previous Basal dose.
Titrate Premixed T2T to fasting blood suger. Adjust according to SMBG.
2.) If starting Premix with no prior use, (If starting with premix, start with 10u.
3.) Advance to BID premixed. Calculate TDD(see box below) and divide equally split between prebreakfast and predinner. Advance →TID option if signif BMI. Adjust according to SMBG. Consider Humalog®50/50 for PM dose if more PM prandial insulin needed according to SMBG.
PATIENT SELF ADJUSTMENT FOR PREMIX AND MDI LISPRO
When? Every 3-4 days. Adjust one dose at a time, usually dinner dose first.
Target Goal: ↑ 1-3 units until at target goal 90-130 before meals.
WHEN? Uncontrolled SMBG Add/Adjust
Before Breakfast Glucose Bedtime Basal or before dinner premixed
Before lunch Before Breakfast Lispro or Breakfast premixed 2 hr after Lunch Before Lunch Lispro insulin or
Before Breakfast Premixed insulin
2 hr after Dinner Before Dinner Lispro or Before
Dinner premixed insulin
Bedtime Glucose Before Dinner Lispro or
Before Dinner premixed
HOW MUCH? If Blood Glucose Adjust Insulin 1-2 times per week
Target above goal ↑dose 1- 3 Units
At goal No Change
Target below goal ↓ dose 1 - 3 unit
Hypoglycemia <70 ↓ dose 4 units or 10%
TARGET GOALS:
FBS, PREMEAL ≤ 130 ≥90 , Recommended ˂100
2 HR POSTPRANDIAL ˂160; recommend goal ˂135
BEDTIME ˂130
HYPOGLYCEMIA ANY ˂70
http://care.diabetesjournals.org/content/32/1/193.full.pdf+html
http://clinical.diabetesjournals.org/content/23/2/78.full.pdf+html
http://care.diabetesjournals.org/content/31/7/1305.full.pdf+html
III. MDI (MULTI-DOSE INJECTION) BASAL +BOLUS REGIMEN:
Add pre-meal (Humalog®)Lispro, (Novolog®)Aspart, or (Apirdra)Glulisine® to single meal;
Start with largest meal. Gradually add additional largest meals, one at a time, until control.
Features:
· Test glucose before meal and 2 hours after meal (from first bite) being targeted. Adjust twice a week until readings are within 40mg/dl of each other or goal achieved
· Basal insulin Glargine usually given at bedtime. Adjust until FBS at target
· Rapid-acting Lispro (Humalog) before each meal. May start with highest meal.
· Add supplemental Lispro(Humalog) meal bolus insulin ( see Correction Factors below) if above target before giving prandial insulin
· Stop SU when advancing to Prandial insulin
Benefits
· Can be used with Type 2 DM and Type 1
· Assoc w/ improved glycemic control leading resulting in less microvascular ds
· Patient not tied to rigid eating schedule as with fixed-split
· Elimination of dietary restrictions for those who do CHO counting
Disadvantages
· Intensive management requires high level compliance and literacy to master
· Frequent testing required or learning Carb counting
Starting Basal/Bolus Insulin Regimen
1. Calculate TDD:
CALCULATE THE TDD: Calculate the TDD based on patient size for premixed insulin
Dialysis patient (regardless of BMI): 0.3 U/kg/d
Lean (BMI <25): 0.2- 0.4 U/kg/d
Overweight (BMI 25-30): 0.5 U/kg/d
Obese (BMI >30): 0.4-0.6 U/kg/d
2. Basal Dose =50% of TDD, usually at bedtime [alternatively 30% TDD as NPH pre-breakfast and 20% TDD as NPH pre-dinner]
3. Prandial (pre-meal) Dose =50% of TDD: 20% pre-breakfast, 10% pre-lunch, and 20% pre-dinner.
Alternative: Basal 40%; Premeal = 20% each
4. Alternative: Start 4 units qAC
5. Add supplemental insulin bolus according to Correction Factor if above target before giving
MISCELLANEOUS PRACTICE TIPS
· Adjust insulin in response to a pattern, not in response to a single abnormal value. Ask about skipped meals. Fix lows first.
· Fix lows first. Hypoglycemia: Review signs, symptoms, treatment, strategies to prevent
· Give patients early opportunity to try a “dry practice insulin injection”
· Offer pen devices when necessary for insulin acceptance; PAR or TAR as needed.
· Don’t underprescribe low dose syringes. Better to use 0.5cc syringes for T2T
· NEVER THREATEN A PATIENT WITH INSULIN
· Educate A1C is the damage assessment of diabetes, not a measure of average BS. Shared common value is motivation to live a long healthy life
· CCHP limits Lantus to 60 cc/month.
IV. Pens and Needles
PEN DEVICES
Patient Selection:
§ Poor Dexterity- OA, neuropathy - Approved indication
§ Mental or Cognitive impairment - Approved indication
§ Poor eyesight - Approved indication
§ Poor adherence –Requires explanation for authorization
§ Needle Phobia –Requires explanation for authorization
Manufacturer Product Timing Cost__ _Open
Aventis-Sanofi Solostar PrefilledPen Lantus (Glargine) *Once daily/ HS $195 28d
Solostar PrefilledPen Apidra (Glulisine)* 15 mins AC
Reusuable Opticlick* Most used in EU
*Order B-D Ultra Fine Needles 31g ,3/16"mini, 5/16"short; 29g 1/2" standard
Novo Nordisk Novolog® Mix 70/30 FLEXPENǂ 15 mins AC $195 14d
Reusable Novolog ® (Aspart) FLEXPENǂ 10 mins AC $195 28d
ǂOrder NovoFine 30,32 disposable needles or B-D Ultra Fine Needles 31g,3/16", 5/16";29g 1/2" standard
Lilly Humalog® Mix 75/25 Prefilled Pen 5 mins AC $195 10d
Humalog®Mix 50/50 Prefilled Pen 5 mins AC $195 10d
Humalog® (Lispro) Prefilled Pen 15 mins AC $195 28d
Humulin® N (NPH) Pen 30 mins AC $140 14d
Humulin® 70/30 (NPH/R) 30 mins AC $140 10d
*Order B-D Ultra Fine Needles 31g ,3/16", 5/16";[29g 1/2" original]
“Pre-filled” pens are disposable. All supplied 3ml. (hold 300 units) per pen/ 5 per box. Deliver up to 60 units max/ injection except Solostar Lantus and Opticlick with max 80 units per injection
[Innolet Device with large dial and numbers for use with Novolin ®(NPH/Reg) - soon to be discontinued]
All on CCHP and Medi-Cal with PAR & TAR. Good cost alternative are Prefilled Syringes for selective patients e.g. learning impaired, family members
Store all unopened cartridges in refrigerator until use or expiration date; Store open unrefrigerated pen cartridges for 10-14 days.
NEEDLES
Gauge: Thinness. Higher number refers to finer needle. Order highest gauge available for patient comfort
30, 31 (“microfine”) gauge: needles are painless (Not 29g)
Lengths: Thin patients can use shorter needles. Obese patients need longer needles.
1/2" Standard ( comes in 29, 30, 31 gauge) for more obese patients
5/16” Short ( comes in 28, 29, 20, 31 gauge) for thinner patients
3/16" Mini May be most comfortable for the
Volume: Don’t underprescribe. Patient may not exceed their monthly insurance allotment
0.3cc =Low dose - up to 30 units. Best visibility if low dose used. May exceed dose if T2T pt.
0.5cc = Low dose- up to 50 units. Best for starting T2T to avoid running out of syringes
1.0 cc = Standard- up to 100 units. Best if obeseT2T and likely will need high dose
V. Talking Points:
OVERCOMING BARRIERS TO STARTING INSULIN TX
· Using insulin does not mean failure. "You haven't failed' your pancreas has."
· Educate early that diabetes is a progressive disease; prepare your patient that most patients will eventually need insulin.
· Oral medication only work when the body makes enough insulin.
· Starting Insulin early is about reducing complications over 10 years (death, MI, Stroke, amputation). We can all agree on a goal to live a long healthy life.
· Insulin allows a person the freedom to eat a relatively “normal” diet again
The patient does not have to choose between good control and foods they enjoy
· Insulin is the only “natural therapy” we have
· Just one shot a day of insulin may be sufficient
· Insulin does not require refrigeration
· Starting insulin does not cause complications; untreated advanced disease does.
· INSULIN ALWAYS WORKS
VI. Addendum
Incretin: Alternatives to Basal Glargine
Analogs: Exenetide 5 mg SQ BID 4 wk →10 BID or 2mg qWK. Promotes wt.loss.
Enhancer-DPP4 inhibitor: Sitagliptin (Januvia) 100 mg.. weight neutral
Added to MTF or SU. No dose adjustment needed for BS or meals. Promote satiety, reduce appetite. Reduce glucagon secretion and hepatic gluconeogenesis. Common AE: Nausea mild-mod 43%; vomiting 10%; dropout rate 7%; PANCREATITIS: stop if persistent severe abdominal pain.$$$
Januvia and Byetta: $$. Not approved for use with insulin.
CALCULATED INSULIN CORRECTION FACTOR: "RULE OF 1800":
For patients reasonably controlled on known insulin regimen, calculate the Lispro needed to bring an elevated BG , down to target BG. Calculates the expected blood glucose drop for each unit of insulin. Varies depending on the patient characteristic.
“RULE OF 1800” INSULIN SENSITIVITY FACTOR:
1.) To calculate the Correction Factor: Divide 1800 by total current Total Daily Dose insulin (TDD)= glucose mg/dl point drop for every unit of Lispro insulin.
2.) Current BG – Target BG (e.g. 110)= # points over target.
3.) Divide this by “correction factor” (round # as needed).
BOLUS PRE-PRANDIAL INSULIN CORRECTION DOSE (Insulin Sensitivity Factor):
Adjust blood glucose before/between meals as needed for deviations from goal. Approximation if patient is not well controlled on current insulin regimen.
APPROXIMATION OF INSULIN CORRECTION FACTORS:
Patient Characteristic Amount ↓BG/1U Lispro Factor
Highly insulin sensitive and/or bad kidneys Lower 60-100 mg/dl 1:60 or more
Normally insulin sensitive Lower 50 mg/dl 1:50
Mild insulin resistance BMI> 25 Lower 30 mg/dl 1:30
Moderate insulin resistance BMI>30 Lower 20 mg/dl 1:20
Severe insulin resistance BMI>40 Lower <10 mg/dl 1:10 or less
INSULIN:CARBOHYDRATE CORRECTION FACTOR
§ To estimate the insulin required to cover the carbohydrate load of an upcoming meal. (CHO counting). Method used for intensive Bolus + 3X Prandial
§ Package labels and food lists with carbohydrate grams and portions sizes assist with this.
§ I:C ratio is the amount of carbohydrate covered by one unit of rapid-acting insulin analog (Lispro, Aspart). The insulin-to-carbohydrate ratio can be determined using the 500 rule (see below), in which the total daily dose of insulin (TDD) is divided by 500. Typically, insulin-to-carbohydrate ratios are in the range of 1U: 10-15 gram of carbohydrate.
§ This method can be modified for patients who prefer a simpler method of counting carbohydrates or food intake. Patients round their carbohydrate choices to a 15 g portion size and count their carbohydrates in denominations of portions rather than grams. An example would be 1 unit of insulin per 1 portion of carbohydrate.
The Carbohydrate Coverage “500 Rule”:
Gives an approximation for how many grams of CHO will be covered by 1U of Lispro insulin.
Divide 500 by the TDD of insulin (basal + bolus) to determine how many grams of carbohydrate will be covered by 1U of Lispro. This is this individuals “correction factor”.
EXAMPLES OF CORECTION FACTORS
Calculating Carbohydrate Coverage with “500 rule”
Example: Pt uses total 30 units per day (15 units Glargine and 15 units Lispro):
500/30= 17 grams carbohydrate covered by 1 unit of Lispro
Therefore, for this patient, there CHO: Lispro insulin ratio is 17:1
Calculating Insulin Sensitivity Factor- Example:
Joe typically uses 30 units of glargine at bedtime, 10 units of lispro at breakfast, 5 units at lunch, and 15 units at dinner.
TDD= 30glargine = 30lispro = 60 units insulin/day
1800/60 = 30
Therefore every 1 unit of Lispro should drop Joe’s blood glucose 30 mg/dl.
Or stated another way, for Joe, his insulin sensitivity correction factor is 30 mg/dl for each unit of Novolog (Lispro).This can be used to estimate what supplemental dose Joe will need for a pre-meal correction dose in addition to his usual dose if his pre-meal glucose value is exceeds target value.
Calculating Bolus- Example:
Joe has a tooth infection. His pre-lunch blood sugar has shot up to 240 from his usual 120. He needs a correction factor for 120mg/dl. Therefore, he needs 120mg/dl divided by 30mg/dl per 1 unit = 4 units Novolog for correction.. Therefore Joe’s dose will be his usual 5 + 4 = 9 units Novolog before eating lunch.