PRACTICAL INSULIN USE or, how to think like a pancreas

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PRACTICAL INSULIN USEor, how to think like a
pancreas

• Oliver Z. Graham, MD
• Department of Internal Medicine
• Virtual Endocrinologist

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Truly understanding issues such as when to use
regular insulin, when it would be better to use
insulin lispro or aspart simply requires a
great deal of experience. --Irl Hirsch, MD, UC
San Diego, Clinical Diabetes 2001
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It tends to be more difficult to manage a
patient on insulin if you dont really
understand what youre doing. --Oliver Z.
Graham, MD, reflecting on personal Experience,
Pittsburgh Health Center
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Types of Insulin
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Types of Insulin
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Types of InsulinLispro and Aspart
(Humalog/Novolog)

• Fast acting (works within 5 min)
• Better matches carbohydrate intake to insulin
  dose
• Can take right before meals

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Types of InsulinRegular

• Slower onset and later peaking
• Must take 30-45 min before meals
• Doesnt really match blood sugar levels,
  especially with high carbo meals
• May lead to hyperglycemia immediately after meals
  with hypoglycemia several hours thereafter

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Types of InsulinNPH

• Long acting, with peak at 6-10 hours
• May be used for AM dosing to cover midday meals,
  used in PM to cover overnight
• Commonly used BID as 70/30

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Types of InsulinGlargine (Lantus)

• A true basal insulin with a 24 hour, peakless,
  predictable effect
• Simulates basal pancreatic insulin secretion

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70/30 (NPH/Regular) BID
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2 Injections/day (ie 70/30)using regular/NPH

• Postprandial glucose levels for breakfast/dinner
  covered by short acting insulins, lunch and
  overnight sugars covered by NPH
• Advantage 2 Injections/day
• Disadvantage
• NPH given at supper does not last until
  breakfast, leading to high AM BS
• NPH in AM does not cover lunch BS well

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Lispro/Glargine
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4 Injections/day using Lispro/Glargine

• One dose basal insulin during day and overnight,
  with rapid/short acting insulin covering meals
• Advantage
• Allows for meal to meal adjustments of insulin in
  accordance to food intake, preprandial blood
  glucose levels, and exercise.
• With lispro, probably offers the tightest control
  of BS given its physiologic simulation of insulin
  secretion (the poor mans insulin pump)
• Disadvantage
• Its 4 injections

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Case Study 1

• See your handout for details

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Question 1

• How would you go about improving Johns glycemic
  control?

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Question 2

• If you choose insulin, should you start a long
  acting/short acting or both?

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Relative contribution of fasting and postprandial
glucose to A1C.
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Starting Insulin 101

• For HA1C gt 9, FIX FASTING FIRST
• Self monitoring on fasting glucose is easier for
  most patients
• Fasting glucose is primarily influenced by stage
  of disease and meds
• Diet and activity have limited influence on
  fasting BS
• Controlling postprandial BS is difficult with
  poorly controlled fasting sugars

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Starting Insulin 101

• As you near target A1C (lt7), post prandial
  control gets more important

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Question 3

• If basal insulin, how/which do you start?
• Lantus (glargine)?
• NPH?

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Lantus vs. NPH

• Equally efficacious when added to orals in
  achieving HA1c value
• Lantus associated with 41 lower risk of severe
  hypoglycemia (BS lt 51)

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How to start insulin gently

• Continue oral agents at same dosage
• Consider d/c sulfonyurea
• Add single dose at 10 U or 0.15 U/kg
• NPH at bedtime
• Glargine anytime

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How to start insulin gently, continued

• Have patient adjust dose by fasting BG every 3-5
  days
• Increase 4 U if FBG gt 140
• Increase 2 U if FBG 120-140
• No change if FBG lt 120
• Decrease dose by 2 U if FBG lt 72 or sx
  hypoglycemia
• Check in by phone in 1-2 weeks

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Question 3

• What about Byetta (exanatide)? Would that be a
  reasonable alternative to insulin?

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Byetta (exanatide)

• Naturally occurring component of Gila Monster
  Saliva
• Stimulates insulin release from pancreas, slows
  gastric emptying, inhibits glucagon release

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Why use Byetta?

• Most patients gain weight with DM tx
• Insulin tx? 4 lb increase for every 1 A1c
  reduction
• With Byetta ? WEIGHT LOSS
• 12 pound loss at 2 years tx
• A1c reduction about 1.1
• ? Animal studies suggest beta cell regeneration

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Why not use Byetta?

• Expensive (1 year -- 2700)
• Long term data not available (lessons from
  Avandia Rezulin)
• Nausea very common (50-60)
• Because slows gastric emptying CONTRAINDICATED in
  GASTROPARESIS
• 2 injections/day

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Who might get Byetta?

• Obese patients not at A1C target who are already
  on metformin, sulfonyurea or both or glitazone
  /- metformin
• Not FDA approved for pts on 3 oral agents or on
  insulin

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How to use Byetta

• Start 5 mcg BID prior to meals, titrate up to 10
  mcg BID as tolerated at one month

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Question 4

• Should John get Byetta?

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Case study, continued

• John has titrated up his Glargine to 40 U daily,
  and his A1c decreased to 7.8. He then missed
  his next appointment, and comes back 6 months
  later.

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Case study, continued

• Current meds
• Lantus 40 U daily
• Metformin 1000 BID
• Glipizide 10 mg BID
• HA1c 8.5
• What do you do now? Are lifestyle changes still
  worthwhile?

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Exercise and DM

• Studies show regular exercise
• reduced A1c from 8.3 ? 7.65

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Diet and DM

• Caloric restriction and weight loss (even 5-10
  of body weight) can lead to
• Improved glucose control
• Improved sensitivity to insulin
• Improved lipid profiles and BP

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Case study, continued

• Current meds
• Lantus 40 U daily
• Metformin 1000 BID
• Glipizide 10 mg BID
• HA1c 8.5
• He says his knees hurt and he doesnt want to
  start an exercise program. His diet is
  reasonable, but he is unable to lose more weight.
  How would you adjust his insulin at this time?

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How to initially dose prandial insulin

• 1 unit for every 10 g carb (needs to learn carb
  counting)
• OR
• 5 units for a small meal
• 8-10 units for a large meal
• OR
• Start with 4 units largest meal, titrate up every
  three days (see algorithm)
• OR
• Calculate insulin needs (0.1 U/kg prior to each
  meal)
• AND
• 1 unit additional correction factor for every
  30-50 mg/dl above 100 mg/dl preprandial (see
  handout)

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Case Study, continued

• John really doesnt want to do more than 2
  injections/day. How do you manage his insulin
  now?

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Insulin Regimens2 Injections/ day

• Postprandial glucose levels for breakfast/dinner
  covered by short acting insulins, lunch and
  overnight sugars covered by NPH
• Advantage 2 Injections/day
• Disadvantage
• NPH given at supper does not last until
  breakfast, leading to high AM BS
• NPH in AM does not cover lunch BS well

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Transition From One Regimen to Another
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Case continued

• John comes in two weeks later on the following DM
  meds
• 70/30 20 U BID
• Metformin 1000 BID
• Glipizide 10 mg BID
• AM BS 100, 90, 120, 111, 110
• PM BS -- 150, 144, 179, 180, 168
• What is your next step?

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70/30 (NPH/Regular) BID
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Dosage Titration for Once-Daily or Twice-Daily
Insulin Regimens
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Case Study 2

• RR is a 32 year old type I diabetic who was first
  diagnosed at age 12. Her HgA1c have ranged
  between 10-12 over the past ten years, and she is
  now legally blind from diabetic retinopathy and
  has a creatinine of 2.6. Her current insulin
  regimen is N 22 (AM) N 18 (PM) as well as sliding
  scale regular prior to meals. There have been 3
  episodes of hypoglycemia in the past 2 weeks.
  She now comes to your clinic for the first time
  in 6 months without a blood sugar log book and
  wants you to fix her diabetes as well as
  signing some paperwork for in home support
  services and giving her some vicodin for her
  neuropathy.
• What do you think her target blood sugars should
  be?

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Glycemic Goals forIntensive Insulin Therapy

• Preprandial 90-130
• 1-2 Hours Postprandial 160-180
• Target HbA1c lt 6.5 - 7

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Intensive Insulin TherapyRelative
Contraindications

• Individuals with hypoglycemia awareness
• Individuals with recurrent, severe hypoglycemic
  episodes
• Individuals with severe emotional disorders or
  psychosocial stressors
• Individuals with alcohol or drug abuse problems
• Individuals with advanced, end stage diabetic
  complications
• Individuals with medical conditions that can be
  aggravated by hypoglycemia, I.e. cerebrovascular
  disease, angina, or cardiac arrhythmia

Intensive Diabetes Management, 1998
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Intensive Insulin TherapyRelative
Contraindications, cont

• Individuals unable or unwilling to commit to the
  personal effort and involvement required for
  intensive diabetes management
• Individuals with concurrent illness and/or
  conditions that would functionally limit
  intensive management I.e. debilitating arthritis
  or severe visual impairment
• Individuals with a relatively short life
  expectancy
• Individuals who live alone

Intensive Diabetes Management, 1998
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Glycemic Goals for not-so-Intensive Insulin
Therapy

• Good control HbA1clt8
• Fair control pre-meal BGlt200
• Do no harm control Avoid hyper/hypoglycemic
  symptoms only
• One blood sugar target does not fit all

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Feel proud of any HgA1c reduction

• From horrible control to poor control pat
  yourself on the back!!

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Focus on the ABCs

• A1c
• Blood Pressure
• Cholesterol

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Organizational Guidelines the consensus.

• Per American Diabetes Association, JNC 7,
  California Department of Health Services,
  National Kidney Foundation, Singapore Ministry of
  Health, Scottish Intercollegiate Guidelines
  Network and many others
• IF DM GOAL BP lt 130/80

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Results From Statin Trials for Patients With
Diabetes
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ARE YOU LISTENING???Another Case Study

• A 29 year old patient has a very hectic life with
  two children and also works part time at a drug
  store. Her time of meals, length of workday and
  levels of physical activity are variable.

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• Her current insulin regimen is
• 4R 10N (8 AM), 8R 14 N (Before dinner)

What could account for the variability of the
readings?
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What affects Blood Sugars?Foods

• Inconsistent eating habits
• overeating or skipping meals
• Altering timing of meals when on a fixed dose
  insulin schedule
• variations in the carbohydrate load, glycemic
  index or fat content

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DM and carbohydrates

• The amount of carbohydrates directly affects
  post-prandial blood sugars. To achieve good
  control, patients either need to learn
• Carbohydrate Consistency Eat the same amount of
  carbs at every meal for predetermined insulin
  dosage
• Carbohydrate Counting Count up the amount of
  carbohydrates in the meal, and adjust insulin
  dosage accordingly

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DM Nutrition 101

• Increase activity
• Decrease calories for weight loss
• Whole grains instead of refined grains and
  starches
• Low saturated and hydrogenated fats
• Carb/meal consistency or carb counting

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ARE YOU LISTENING???A Case Study

• A patient who has been treated for type 1 DM for
  6 years is on N25 R10 (8 AM), N15 R10 (6 PM).
  His BS are

How would you change his regimen?
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Adjusting Insulin
If glucose levels are out of target at Check coverage provided by
Postbreakfast/prelunch Prebreak short insulin
Postlunch/presupper Prelunch short insulin and/or AM NPH
Postsupper/bedtime Presupper short insulin
Midafternoon Morning NPH or long acting insulin
Early morning Evening NPH or long acting insulin
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ARE YOU LISTENING???A Case Study

• A patient who has been treated for Type I DM for
  14 years has the following regimen N42 R12 (8
  AM), N21 R 15 (6 PM)

How would you change his insulin regimen? How do
you account for the blood sugar outliers?
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ARE YOU LISTENING???A Case Study

• His regimen N42 R12 (8 AM), N21 R 15 (6 PM)

Avg AM 172 (excluding 95) Avg lunch 172 Avg
dinner 129 (excluding 275) Avg QHS 225 Change
evening to N24 R18, should improve daytime
values
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Adjusting insulin

• Insulin adjustments should be based on average
  blood glucose readings, not the outliers
• Changes should be made based on numbers over
  several days to over 1-2 weeks
• Except for severe hypo/hyperglycemia, changes
  should be made in 10-20 increments (about 1-5U
  at a time)