changes in diabetes care a history of insulin & pumps past, present, and future john walsh, p.a,...

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 Cover

Early 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


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


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.


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


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 ResearchIn 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

JL on 12/15/22 and 2 mos later


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


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 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


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

ResultsBetter health

Fewer complications

Improved sense of well-being

More flexible lifestyle

StudiesDCCT 1984-1992

EDIC 1996

UKPDS 1978-1998

Kumamoto 1992-2000

Research studies between 1970 and 2000 showed that complications could be prevented by lowering high glucose levels


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

1. HB Mortensen et al: Diabetes Care. 1997 May;20(5):714-20

2. Diabetes Care. 1997 May;20(5):714-20

3. Horm Res 1998;50:107–140

GOAL: A1c < 6.5%


We Know What Controls The A1c

Frequency of testing378 pump (pre-smart) users Paul Davidson et al: Diabetes


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


Controls The A1c

Recording of BGs

0.5% drop in A1c in several studies

Diet Approach1

CHO Counting

Regulated

WAG

1. Bode et al: Diabetes, 1999, 48 Suppl 1: 264

7.2%7.5%8.0%


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


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


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


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 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


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.


Convergence Toward Automation

Insulin

Monitoring

HCP Self Management Automation

Insulin & syringes

Pumps

Pens

Connectivity

Clinic Monitoring

Home Monitors

Data ManagementAdvice/Feedback

Open Loop

Delivery

Closed Loop

You are here


DumbSmart

IntelligentAutomatic

Results over Features!

Do not judge a device by how cool it is, but by whether it lowers the A1c.


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)



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



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


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


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.**

Made byMade byUnidentified company hereUnidentified company here

* Yet to be proven* Yet to be proven


Smart Vs Intelligent Devices

Feature Smart IntelligentCarb list Alphabetic By recent use

Basal 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


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 timerAutomatic basal decreaseSuper BolusAutomatic basal/bolus balancingAutomatic adjustment when correction boluses are overusedCarb list and carb counterExercise intensity and durationDatabase 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 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


Thoughts And Developments For The Future


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


New: Rapid Basal Reduction

A rapid basal reduction offsets excess BOB and eliminates the need to eat at bedtime.


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


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?


New: High BG Super Bolus

If a pumper misjudges the carb content of a meal, a super bolus enables a faster, safe correction.


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

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.


New: Less Glucose Exposure

The lower the blood glucose is at the start of a meal, the less exposure to glucose there will be.


New: An Intelligent Reminder

An intelligent pump alerts the user when their blood glucose is low enough to begin eating


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 timeFrequent lowsHigh mornings (lunches, dinners, bedtime)Low mornings (lunches, dinners, bedtime)Postmeal spikingHigh to lowLow to highPoor control with little or no pattern


Pattern Analysis: Low-High

.

3810 pm

320

.Overtreated low


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

232194217243178263222

Breakfast

Breakfast highs


Overnight Basal Patterns

bedtime 2 am breakfast

100

200

300basal too low Dawn

Phenomenon

just right

too high

Goal for overnight BG change = +/- 30 mg/dl

just right


User Interface – Critical Component

Despite 30 years of pump and meter development, device communication to the user is still in it’s infancy.



Carb database for accurate carb counts.



Suggestion for carb intake or to limit intake based on weight/calorie/carb goals



A high glucose can be analyzed to determine the magnitude of the error



Recommended carb intake (or insulin reduction) to balance activity.



New dose recommendations based on A1c, % of TDD given as correction boluses, and frequency of hypoglycemia



Pattern alerts and advice



Fast lab results without calling. Messaging allows physician to make recommendations.


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


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

Even so, truly intelligent and helpful devices could be created soon.


Questions???

changes in diabetes care a history of insulin & pumps past, present, and future john walsh, p.a,...

Documents

future john walsh

insulin production

chemical insulin

bc diabetes

john rollo

available slide

extracting insulin

impact of insulin