Changes In Diabetes Care a history Of Insulin & Pumps Past, Present, and Future

Changes In Diabetes Care A History Of Insulin & Pumps Past, Present, and Future

• John Walsh, P.A, C.D.E. [e-mail]

• 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

Questions ???