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PowerPoint Presentation - Insulin Past, Present, and Future
Transcript of PowerPoint Presentation - Insulin Past, Present, and Future
Changes In Diabetes CareA History Of Insulin & PumpsPast, Present, and Future
John Walsh, P.A, [email protected]
Online slide presentation
© 2004, John Walsh, P.A., C.D.E.
What We Will CoverEarly history of diabetesDiscovery of insulinWhen insulin was found to not be the full answerHigh glucose as the culpritLack of change in the A1c since the DCCTWhy the dumb insulin pump has not helpedWhat smart pumps offerThe promise of intelligent devicesThe Super BolusHow simple and intelligent timers can helpScreen shots from an intelligent device
© 2004, John Walsh, P.A., C.D.E.
In 1500 BCDiabetes 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
© 2004, John Walsh, P.A., C.D.E.
250 BCThe 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.
© 2004, John Walsh, P.A., C.D.E.
Diabetes is a wonderful affection, not very frequent among men, being a melting down of the flesh and limbs into urine…The flow is incessant, as if from the opening of aqueducts…it takes a long period to form, but the patient is short-lived…for the melting is rapid, the death speedy.
Moreover, life is disgusting and painful; thirst unquenchable; excessive drinking…and one cannot stop them either from drinking or making water... they are affected with nausea, restlessness, and a burning thirst; and at no distant term they expire.
150 BC Aretaeus the Cappadocian
© 2004, John Walsh, P.A., C.D.E.
Early Diabetes Treatments
In 1000, Greek physicians recommended horseback riding to reduce excess urinationIn the 1800s, bleeding, blistering, and doping were commonIn 1915, Sir William Osler recommended opium Overfeeding was commonly used to compensate for loss of fluids and weightIn the early 1900s a leading American diabetologist, Dr. Frederick Allen, recommended a starvation diet
© 2004, John Walsh, P.A., C.D.E.
Early ResearchIn 1798, John Rollo documented excess sugar in the blood and urineIn 1813, Claude Bernard linked diabetes to glycogen metabolism In 1869, Paul Langerhans, a German medical student, discovered islet cells in the pancreasIn 1889, Joseph von Mehring and Oskar Minkowski created diabetes in dogs by removing the pancreasIn 1910, Sharpey-Shafer of Edinburgh suggested a single chemical was missing from the pancreas. He proposed calling this chemical "insulin."
© 2004, John Walsh, P.A., C.D.E.
Near MissIn 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
© 2004, John Walsh, P.A., C.D.E.
Other “Pancreas Extractors”
American scientist E. L. Scott was partially successful in extracting insulin with alcoholA 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.
© 2004, John Walsh, P.A., C.D.E.
Before Insulin
Before insulin was discovered in 1921, everyone with type 1 diabetes died within weeks to years of its onset
JL on 12/15/22 and 2 mos later
© 2004, John Walsh, P.A., C.D.E.
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 buttockAbscesses developed and he became more acutely illHowever, 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 hoursLeonard lived a relatively healthy life for 13 years before dying of pneumonia (no Rx then) at 27
© 2004, John Walsh, P.A., C.D.E.
Insulin Production Begins
First produced as “Connaught” by the Univ of TorontoOn May 30, 1922, Eli Lilly signed an agreement to pay royalties to the University to increase productionFirst bottles contained U-10 insulin 3 to 5 cc were injected at a timePain and abscesses were common until purer U-40 insulin became available
© 2004, John Walsh, P.A., C.D.E.
Impact Of Insulin OnLife Expectancy By The 1940’s
Age at start of diabetes 50 30 10
Avg. age of death in 1897 58.0 34.1 11.3
Avg. age of death in 1945 65.9 60.5 45.0
Years Gained 8 26 34
© 2004, John Walsh, P.A., C.D.E.
Not A Cure
Some early users died of hypoglycemia, but insulin seemed a remarkable cure.By the 1940’s, however, diabetic complications began to appearIt became clear that injecting insulin was not the full answer
© 2004, John Walsh, P.A., C.D.E.
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
© 2004, John Walsh, P.A., C.D.E.
DCCT And Other Studies
ResultsBetter healthFewer complicationsImproved sense of well-beingMore flexible lifestyle
StudiesDCCT 1984-1992EDIC 1996UKPDS 1978-1998Kumamoto 1992-2000
Research studies between 1970 and 2000 showed that complications could be prevented by lowering high glucose levels
© 2004, John Walsh, P.A., C.D.E.
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 19948.6% in 2,873 European children and adolescents in 19971
9.2% in 62 Canadian Type 1s in 2004
1. HB Mortensen et al: Diabetes Care. 1997 May;20(5):714-202. Diabetes Care. 1997 May;20(5):714-203. Horm Res 1998;50:107–140
GOAL: A1c < 6.5%
© 2004, John Walsh, P.A., C.D.E.
We Know What Controls The A1c
Frequency of testing378 pump (pre-smart) users Paul Davidson et al: Diabetes
© 2004, John Walsh, P.A., C.D.E.
Controls The A1c
Frequency of daily boluses377 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
© 2004, John Walsh, P.A., C.D.E.
Controls The A1c
Recording of BGs0.5% drop in A1c in several studies
Diet Approach1
CHO CountingRegulated WAG
1. Bode et al: Diabetes, 1999, 48 Suppl 1: 264
7.2%7.5%8.0%
© 2004, John Walsh, P.A., C.D.E.
Pre/Post DCCT A1c Results
1992 2003
On 4 inj. 27.8% (0.4%) 72.6% (6.4%) or a pump
Median A1c 8.3% 8.3%
18,403 German childrenW Hecker et al: 2004 ADA, poster 22B
© 2004, John Walsh, P.A., C.D.E.
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 *
* handled by well-designed intelligent device
© 2004, John Walsh, P.A., C.D.E.
Noncompliance is not a patient problem.It is a system failure.
Dr. Paul FarmerFirst to successfully use complex drug regimens to treat AIDs and TB in Haiti
Our Current Diabetes Approach Does Not Work
© 2004, John Walsh, P.A., C.D.E.
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
© 2004, John Walsh, P.A., C.D.E.
Required Treatment Interval (RTI)
The required treatment interval in diabetes is every 2 to 5 hours rather than 3 to 4 monthsThis is the typical time interval between decisions that significantly affect glucose levels, such as BG monitoring, food intake, and activityOnly something that is both available and intelligent can assist the person with a chronic disease like diabetes
© 2004, John Walsh, P.A., C.D.E.
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.
© 2004, John Walsh, P.A., C.D.E.
Convergence Toward Automation
Insulin
Monitoring
HCP Self Management Automation
Insulin & syringes
PumpsPens
Connectivity
Clinic Monitoring
Home Monitors
Data Management Advice/FeedbackOpen Loop
Delivery
Closed Loop
You are here
© 2004, John Walsh, P.A., C.D.E.
DumbSmart
IntelligentAutomatic
Results over Features!Do not judge a device by how cool it is,
but by whether it lowers the A1c.
© 2004, John Walsh, P.A., C.D.E.
Today’s Smart Pumps
Carb bolusesPersonalized carb factors for different times of dayEasy carb bolus calculationsPersonalized carb database (soon)
Correction bolusesPersonalized correction factors for different times Easier and safer correction of high BGsReveal when correction bolus is high, ie > 8% of TDD
Combined carb/correction bolusesAutomatic bolus reduction for Bolus On Board (BOB)
© 2004, John Walsh, P.A., C.D.E.
Today’s Smart Pumps
Track Bolus On BoardImproved bolus accuracyAvoids stacking of bolus insulin Helps prevent hypoglycemiaRequires BG reading for accuracy
Guide whether carbs or insulin are needed
Does not yet warn when carbs are needed
© 2004, John Walsh, P.A., C.D.E.
Today’s Smart Pumps
Reminders toTest blood glucose after a bolusWarn when bolus delivery was not completedTest blood glucose following a low or high BGGive boluses at certain times of dayChange infusion site
Direct BG entry from meterEliminates errors in data transferEnsures that all blood glucose data will be entered into a database or logbook format
© 2004, John Walsh, P.A., C.D.E.
Smart Pumps Do Not:Today’s pumps collect the information
needed (insulin doses, BGs, carb intake, and timing), but they do not:Identify problem patternsAutomatically test basals and boluses or warn when they are out of balanceSuggest dose adjustmentsWarn of pending lows or suggest carb intake needed for excess BOBWarn when excess correction boluses are usedAccount for GI differences between foodsGuarantee an improved outcome
© 2004, John Walsh, P.A., C.D.E.
Intelligent Devices
Today’s “smart” pumps are migrating to better pumps, pens, and PDAsCalculus rather than formulas to set bolus amounts Auto analysis of BG patternsFuzzy and artificial intelligenceProvide automatic (retrospective) carb/insulin balanceUse of A1c to focus therapy
© 2004, John Walsh, P.A., C.D.E.
The Intelligent Device Hypothesis
Intelligent devices:provide meaningful advice, ** improve lifestyles, ** improve medical outcomes with diabetes.**
Made byMade byUnidentified company hereUnidentified company here
* Yet to be proven* Yet to be proven
© 2004, John Walsh, P.A., C.D.E.
Smart Vs Intelligent Devices
Feature Smart IntelligentCarb list Alphabetic By recent useBasal testing By user Automatic
Bolus testing By user Automatic
Exercise NA Automatic
Timer Manual Automatic
Corr. bolus Ignored Redistributed
Super Bolus None Automatic
# of hypos By user Automatic
Communication Verbal Bidirectional
© 2004, John Walsh, P.A., C.D.E.
Intelligent Devices
PumpsPensPDAsSmart PhonesMetersA central reporting station where data is filtered for minor versus major problems and who is to be alerted (user, guardian, MD/RN)
© 2004, John Walsh, P.A., C.D.E.
Demands On Intelligent Devices
Intuitive interface and languageMust be impartial and fairOutcome driven – user feels better and is more confident about controlCompatible with clinic workflowWell fundedAble to rapidly evolve as errors appearMust close the data loop between user and MD
© 2004, John Walsh, P.A., C.D.E.
Intelligent Device Ingredients
Automatic BG timerAutomatic basal decreaseSuper BolusAutomatic basal/bolus balancingAutomatic adjustment when correction boluses are overusedCarb list and carb counterExercise intensity and durationDatabase intelligence
© 2004, John Walsh, P.A., C.D.E.
Intelligent Device Benefits
Provide immediate advice on situationsIdentify common or infrequent patternsConstant surveillance of data for changesProvide real meaning to BG valuesIntegrate well with continuous monitoring and artificial intelligence
© 2004, John Walsh, P.A., C.D.E.
Smart Phones And PDAs
Fast internet & email communicationConvenient remote insulin deliveryLarger food and carb databaseBetter graphics for BG analysis, display of patterns, etcLarger event database for long-term analysis
© 2004, John Walsh, P.A., C.D.E.
Intelligent Devices
300 personal carb selections with accurate carb countsCarb factor (1:1 TO 1:100) Correction factor (1:4 to 1: 400)
5 sec microdraw BG meter0.1 unit precision motorNon-volatile memory3,000 eventsBluetooth data transfer
© 2004, John Walsh, P.A., C.D.E.
Thoughts And Developments For The Future
© 2004, John Walsh, P.A., C.D.E.
Old Basal/Bolus ConceptsBasal insulin
~ 50% of daily insulin needLimits hyperglycemia after mealsSuppresses 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
© 2004, John Walsh, P.A., C.D.E.
New: Rapid Basal Reduction
A rapid basal reduction offsets excess BOB and eliminates the need to eat at bedtime.
© 2004, John Walsh, P.A., C.D.E.
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.
A Super Bolus can be activated at a user-selected quantity, such as 40 or 50 grams
© 2004, John Walsh, P.A., C.D.E.
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 lineHow 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?
© 2004, John Walsh, P.A., C.D.E.
New: High BG Super Bolus
If a pumper misjudges the carb content of a meal, a super bolus enables a faster, safe correction.
© 2004, John Walsh, P.A., C.D.E.
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.
© 2004, John Walsh, P.A., C.D.E.
New: An Intelligent Reminder
An intelligent pump alerts the user when their BG is likely to cross a selected threshold value, such as 120 mg/dl. They can then eat without exposure to extremely high readings.
© 2004, John Walsh, P.A., C.D.E.
New: Less Glucose Exposure
The lower the blood glucose is at the start of a meal, the less exposure to glucose there will be.
© 2004, John Walsh, P.A., C.D.E.
New: An Intelligent Reminder
An intelligent pump alerts the user when their blood glucose is low enough to begin eating
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
Useful reminders
© 2004, John Walsh, P.A., C.D.E.
Future Pattern Management
Finding problem patterns enables solutionsSet BG targetsGather and record dataAnalyze patterns in dataAssess factors that influence patternsRecommend action
© 2004, John Walsh, P.A., C.D.E.
Only A Few PatternsThe relatively low number of BG patterns in
diabetes makes them easy to identify:High most of the timeFrequent lowsHigh mornings (lunches, dinners, bedtime)Low mornings (lunches, dinners, bedtime)Postmeal spikingHigh to lowLow to highPoor control with little or no pattern
© 2004, John Walsh, P.A., C.D.E.
Pattern Analysis: Low-High
.
3810 pm
320
.Overtreated low
© 2004, John Walsh, P.A., C.D.E.
Low High Pattern Alert
Insulin dose suggestions and an alert about past overtreatment of lows.
© 2004, John Walsh, P.A., C.D.E.
Low High Pattern Alert
An intelligent device can provide a person’s precise carb requirement when the blood glucose is tested.
© 2004, John Walsh, P.A., C.D.E.
Easy Analysis 2
232194217243178263222
Breakfast
Breakfast highs
© 2004, John Walsh, P.A., C.D.E.
Overnight Basal Patterns
bedtime 2 am breakfast
100
200
300 basal too low Dawn Phenomenon
just right
too high
Goal for overnight BG change = +/- 30 mg/dl
just right
© 2004, John Walsh, P.A., C.D.E.
User Interface – Critical Component
Despite 30 years of pump and meter development, device communication to the user is still in it’s infancy.
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
Carb database for accurate carb counts.
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
Suggestion for carb intake or to limit intake based on weight/calorie/carb goals
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
A high glucose can be analyzed to determine the magnitude of the error
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
Recommended carb intake (or insulin reduction) to balance activity.
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
New dose recommendations based on A1c, % of TDD given as correction boluses, and frequency of hypoglycemia
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
Pattern alerts and advice
© 2004, John Walsh, P.A., C.D.E.
Future Intelligent Devices
Fast lab results without calling. Messaging allows physician to make recommendations.
© 2004, John Walsh, P.A., C.D.E.
Pump Plus Continuous Monitor
Automatic basal and bolus testingTrends allow exact short-term BG predictions for rapid recognition of pending highs or lowsBoth 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
© 2004, John Walsh, P.A., C.D.E.
The Closed Loop Will Close Slowly
Patents impede device development FDA is slow to allow medical care from a device or via telemedicineSlow acceptance by medical personnel and people with diabetesLiability issuesLarge financial incentives in current meter and pump technology
Even so, truly intelligent and helpful devices could be created soon.
© 2004, John Walsh, P.A., C.D.E.
Questions???