Changes In Diabetes Care A History Of Insulin & Pumps Past, Present, and Future
John Walsh, P.A, C.D.E. jwalsh@diabetesnet.com
Online slide presentation
What We Will Cover
Early history of diabetes
Discovery of insulin
When insulin was found to not be the full answer
High glucose as the culprit
Lack of change in the A1c since the DCCT
Why the dumb insulin pump has not helped
What smart pumps offer
The promise of intelligent devices
The Super Bolus
How simple and intelligent timers can help
Screen shots from an intelligent device
In 1500 BC Diabetes First Described In Writing
Hindu healers wrote that flies and ants were attracted to urine of people with a mysterious disease that caused intense thirst, enormous urine output, and wasting away of the body
250 BC The Word Diabetes First Used
Apollonius of Memphis coined the name "diabetes” meaning "to go through" or siphon. He understood that the disease drained more fluid than a person could consume.
Gradually the Latin word for honey, "mellitus," was added to diabetes because it made the urine sweet.
Early Diabetes Treatments
In 1000, Greek physicians recommended horseback riding to reduce excess urination
In the 1800s, bleeding, blistering, and doping were common
In 1915, Sir William Osler recommended opium
Overfeeding was commonly used to compensate for loss of fluids and weight
In the early 1900s a leading American diabetologist, Dr. Frederick Allen, recommended a starvation diet
Early Research
In 1798, John Rollo documented excess sugar in the blood and urine
In 1813, Claude Bernard linked diabetes to glycogen metabolism
In 1869, Paul Langerhans, a German medical student, discovered islet cells in the pancreas
In 1889, Joseph von Mehring and Oskar Minkowski created diabetes in dogs by removing the pancreas
In 1910, Sharpey-Shafer of Edinburgh suggested a single chemical was missing from the pancreas. He proposed calling this chemical "insulin."
Near Miss
In 1908, a young internist in Berlin, Georg Ludwig Zuelzer created a pancreas extract named acomatrol.
After injecting acomatrol into a dying diabetic patient, the patient improved at first, but died when the acomatrol was gone
Zuelzer filed an American patent in 1911 for a "Pancreas Preparation Suitable for the Treatment of Diabetes”
Disappointing results, however, caused his lab to be taken over by the German military during WWI
Other “Pancreas Extractors”
American scientist E. L. Scott was partially successful in extracting insulin with alcohol
A Romanian, R. C. Paulesco, made an extract from the pancreas that lowered the blood glucose of dogs.
Some claim Paulesco may have been the first to discover insulin about 10 years before Banting and Best.
Before Insulin
Before insulin was discovered in 1921, everyone with type 1 diabetes died within weeks to years of its onset
1922 Leonard Thompson
In Jan, 1922, Banting and Best injected a 14-year-old "charity” patient who weighed 64 lb with 7.5 ml of a "thick brown muck" in each buttock
Abscesses developed and he became more acutely ill
However, his blood glucose had dropped enough to continue refining what was called "iletin” insulin
6 weeks later, a refined extract caused his blood glucose to fall from 520 to 120 mg/dL in 24 hours
Leonard lived a relatively healthy life for 13 years before dying of pneumonia (no Rx then) at 27
Insulin Production Begins
First produced as “Connaught” by the Univ of Toronto
On May 30, 1922, Eli Lilly signed an agreement to pay royalties to the University to increase production
First bottles contained U-10 insulin
3 to 5 cc were injected at a time
Pain and abscesses were common until purer U-40 insulin became available
Impact Of Insulin On Life Expectancy By The 1940’s
Not A Cure
Some early users died of hypoglycemia, but insulin seemed a remarkable cure.
By the 1940’s, however, diabetic complications began to appear
It became clear that injecting insulin was not the full answer
What Caused Complications? High Glucose Versus Genes
During the middle of the 20th century, it was unclear whether better glucose control could prevent diabetes complications
DCCT And Other Studies
Results
Better health
Fewer complications
Improved sense of well-being
More flexible lifestyle
Little Change In A1c Since DCCT
8.6% in 396 Canadian Type 1s in 19922
9.7% in 1,120 German children in 19963
9.7% in in U.S. in NHANES III, 1988 to 1994
8.6% in 2,873 European children and adolescents in 19971
9.2% in 62 Canadian Type 1s in 2004
We Know What Controls The A1c
Frequency of testing
378 pump (pre-smart) users Paul Davidson et al: Diabetes
Controls The A1c
Frequency of daily boluses
377 1-18 yo pump users, r = 0.068 TJ Battelino et al: Diabetes 2004
For injections: MP Garancini et al: Diabetes Care, 1997, 20, #11: 1659-1663
Controls The A1c
Recording of BGs
0.5% drop in A1c in several studies
Diet Approach1
CHO Counting
Regulated
WAG
Pre/Post DCCT A1c Results
What Causes High A1cs?
Inaccurate carb counting *
Insulin doses that are incorrect, misunderstood, or missed entirely *
Too hard to log all the data *
Not adapting to spontaneous events *
Complexity of the challenge *
Unclear accountability *
Noncompliance is not a patient problem. It is a system failure. Dr. Paul Farmer First to successfully use complex drug regimens to treat AIDs and TB in Haiti
Current Treatment Interval (CTI)
Unlike many other chronic diseases where CTI is not critical, the current treatment interval in diabetes with a doctor’s visit every 3 to 4 months does not work
Required Treatment Interval (RTI)
The required treatment interval in diabetes is every 2 to 5 hours rather than 3 to 4 months
This is the typical time interval between decisions that significantly affect glucose levels, such as BG monitoring, food intake, and activity
Only something that is both available and intelligent can assist the person with a chronic disease like diabetes
When a system is not working for patients, trying harder will not work. Only changing the care system or our approach to care will work.
Dumb Smart Intelligent Automatic
Today’s Smart Pumps
Carb boluses
Personalized carb factors for different times of day
Easy carb bolus calculations
Personalized carb database (soon)
Correction boluses
Personalized correction factors for different times
Easier and safer correction of high BGs
Reveal when correction bolus is high, ie > 8% of TDD
Combined carb/correction boluses
Automatic bolus reduction for Bolus On Board (BOB)
Today’s Smart Pumps
Track Bolus On Board
Improved bolus accuracy
Avoids stacking of bolus insulin
Helps prevent hypoglycemia
Requires BG reading for accuracy
Guide whether carbs or insulin are needed
Does not yet warn when carbs are needed
Today’s Smart Pumps
Reminders to
Test blood glucose after a bolus
Warn when bolus delivery was not completed
Test blood glucose following a low or high BG
Give boluses at certain times of day
Change infusion site
Direct BG entry from meter
Eliminates errors in data transfer
Ensures that all blood glucose data will be entered into a database or logbook format
Smart Pumps Do Not:
Today’s pumps collect the information needed (insulin doses, BGs, carb intake, and timing), but they do not:
Identify problem patterns
Automatically test basals and boluses or warn when they are out of balance
Suggest dose adjustments
Warn of pending lows or suggest carb intake needed for excess BOB
Warn when excess correction boluses are used
Account for GI differences between foods
Guarantee an improved outcome
Intelligent Devices
Today’s “smart” pumps are migrating to better pumps, pens, and PDAs
Calculus rather than formulas to set bolus amounts
Auto analysis of BG patterns
Fuzzy and artificial intelligence
Provide automatic (retrospective) carb/insulin balance
Use of A1c to focus therapy
The Intelligent Device Hypothesis
Intelligent devices:
provide meaningful advice, *
improve lifestyles, *
improve medical outcomes with diabetes.*
Smart Vs Intelligent Devices
Intelligent Devices
Pumps
Pens
PDAs
Smart Phones
Meters
A central reporting station where data is filtered for minor versus major problems and who is to be alerted (user, guardian, MD/RN)
Demands On Intelligent Devices
Intuitive interface and language
Must be impartial and fair
Outcome driven – user feels better and is more confident about control
Compatible with clinic workflow
Well funded
Able to rapidly evolve as errors appear
Must close the data loop between user and MD
Intelligent Device Ingredients
Automatic BG timer
Automatic basal decrease
Super Bolus
Automatic basal/bolus balancing
Automatic adjustment when correction boluses are overused
Carb list and carb counter
Exercise intensity and duration
Database intelligence
Intelligent Device Benefits
Provide immediate advice on situations
Identify common or infrequent patterns
Constant surveillance of data for changes
Provide real meaning to BG values
Integrate well with continuous monitoring and artificial intelligence
Smart Phones And PDAs
Fast internet & email communication
Convenient remote insulin delivery
Larger food and carb database
Better graphics for BG analysis, display of patterns, etc
Larger event database for long-term analysis
Intelligent Devices
300 personal carb selections with accurate carb counts
Carb factor (1:1 TO 1:100)
Correction factor (1:4 to 1: 400)
Thoughts And Developments For The Future
Old Basal/Bolus Concepts
Basal insulin
~ 50% of daily insulin need
Limits hyperglycemia after meals
Suppresses glucose production between meals and overnight
Bolus insulin (mealtime)
Limits hyperglycemia after meals
Immediate rise and sharp peak at 1 hour
10% to 20% of total daily insulin requirement at each meal
New: Rapid Basal Reduction
New: The Super Bolus
A Super Bolus helps cover high GI foods and prevent postmeal hyperglycemia. A 3 or 4 hour block of basal insulin is turned into a bolus to speed its effect.
New: The Super Bolus
To ensure safety and success, the Super Bolus will require some clinical testing:
How long can basal delivery be stopped or reduced without increasing the risk for clogging of the infusion line
How long (3, 4, 5 hours?) can the basal be lowered before a rebound high will occur once the Super Bolus is gone?
Is a reduction of the basal delivery rather than complete stoppage a better policy?
If a person sets their basal delivery too low or too high, will this affect a Super Bolus?
New: High BG Super Bolus
New: A Reminder Timer
A simple timer alerts the user 25 minutes after a bolus that it is safe to begin eating a high GI meal.
New: An Intelligent Reminder
New: Less Glucose Exposure
New: An Intelligent Reminder
Future Intelligent Devices
Useful reminders
Future Pattern Management
Finding problem patterns enables solutions
Set BG targets
Gather and record data
Analyze patterns in data
Assess factors that influence patterns
Recommend action
Only A Few Patterns
The relatively low number of BG patterns in diabetes makes them easy to identify:
High most of the time
Frequent lows
High mornings (lunches, dinners, bedtime)
Low mornings (lunches, dinners, bedtime)
Postmeal spiking
High to low
Low to high
Poor control with little or no pattern
Pattern Analysis: Low-High
Low High Pattern Alert
Insulin dose suggestions and an alert about past overtreatment of lows.
Low High Pattern Alert
An intelligent device can provide a person’s precise carb requirement when the blood glucose is tested.
Easy Analysis 2
Overnight Basal Patterns
User Interface – Critical Component
Despite 30 years of pump and meter development, device communication to the user is still in it’s infancy.
Future Intelligent Devices
Carb database for accurate carb counts.
Future Intelligent Devices
Suggestion for carb intake or to limit intake based on weight/calorie/carb goals
Future Intelligent Devices
A high glucose can be analyzed to determine the magnitude of the error
Future Intelligent Devices
Recommended carb intake (or insulin reduction) to balance activity.
Future Intelligent Devices
New dose recommendations based on A1c, % of TDD given as correction boluses, and frequency of hypoglycemia
Future Intelligent Devices
Pattern alerts and advice
Future Intelligent Devices
Fast lab results without calling. Messaging allows physician to make recommendations.
Pump Plus Continuous Monitor
Automatic basal and bolus testing
Trends allow exact short-term BG predictions for rapid recognition of pending highs or lows
Both user and device can relate problems to their source
Unfortunately, insulin delivery from an external pump is too slow to create an effective artificial pancreas with this combination
The Closed Loop Will Close Slowly
Patents impede device development
FDA is slow to allow medical care from a device or via telemedicine
Slow acceptance by medical personnel and people with diabetes
Liability issues
Large financial incentives in current meter and pump technology
