best practices … or suggestions on diabetes care what you should know jeff hitchcock children with...

Best Practices …Or Suggestions on Diabetes Care

What You Should Know

Jeff HitchcockChildren with Diabetes

October 2007

www.childrenwithdiabetes.com

Goals for Today

• Background … or Why This Matters• Overview of current tools and

techniques• It’s more than type 1 diabetes • Some science• Hints at the future• Mostly, reassurance


Knowledge is …

"...you shall know the truth, and the truth shall make you free."

-- John 8:32

Power-- Sir Francis Bacon

Life:The person with diabetes who knows the most lives the longest.

-- Elliott Joslin, M.D.


That was Then …

• Prior to 1980, 50% of people with type 1 diabetes would develop renal failure 10-20 years after onset of diabetes


This is Now

Age at Onset of Childhood-Onset Type 1 Diabetes and the Development of End-Stage Renal DiseaseSvensson, Diabetes Care 29:538–542, 2006


So, What’s Different?

• Home glucose monitoring• Insulin analogs• Insulin pumps• Blood ketone measurement• Continuous sensors• And more importantly …• … a realization that complications are

not inevitable and you can do something about it


Tools … or Diabetes Technology

• Glucose Meters• Other “Meters”• Lancing—Where the metal meets the

skin• Insulin delivery• Other drugs• Continuous sensors


What to Look for in a Glucose Meter

• Accuracy– Major brands make a difference– But technique matters

• Memory with PC download– Pattern analysis to reduce variability

• Intangibles– Lighting– Ease of use– On board data analysis


FreeStyle Flash / Lite

• Smallest meter• 0.3 microliter sample• 7+ second test time• 250 test memory• 14 day average• 4 built in alarms for

test reminders• Built in backlight and

test strip light• Interfaces with a PC• Most popular at CWD:

20% (Flash + Lite)Last poll:http://www.childrenwithdiabetes.com/poll/poll20070930.htm


ACCU-CHEK Compact Plus

• 17-test strip drum• 1.5 microliter blood

volume• 5 second test time• One handed testing• Could attach to car

dashboard and check while driving

http://www.childrenwithdiabetes.com/gifs/products/accuchek-compactplus1.jpg


OneTouch UltraSmart

• On board analysis and graphing

• 1 microliter sample• 5 second test time• 3,000 test memory• Tracks glucose,

insulin, food, and exercise

• Interfaces with a PC• Clinical trial shows

use can lower A1c


GlucoMON

• How do I know my child checked at … ?

• Wireless interface to a OneTouch Ultra• Remote oversight of glucose testing• Available in limited markets in the US


What we really need is …

• Biodegradable test strips


Other Meters: Ketone Testing

• Old Way: Urine– “Yucky”– 15 seconds– As low as 10¢ per

test– Accuracy issues– Force a child to pee?

• New Way: Blood– Familiar, easy– 10 seconds– 1.5 microliters– About $4 per test– Clinical benefits

Diabetic Medicine 23 (3), 278-284

http://www.childrenwithdiabetes.com/gifs/products/Precision_Xtra_New.jpg


Let’s save urine testing for …

Proving that beer is in fact just rented …

… and as a truth detector for athletes.


Other Meters: A1c Measurement

• Old way: venous blood draw, results long after the clinic visit

• Can be very stressful, sometimes painful• In 1999, study showed that discussing A1c at clinic

visit improved control• Enter the DCA2000 and A1cNow+

Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin-treated type 2 diabetic patients (Diabetes Care. 1999 Nov;22(11):1785-9)

New A1cNow+ has variance of around 3% and a blood volume of 5 microliters. About $10 per test. Available for home use.

DCA2000 is for office use. Finger stick sample, results in minutes.


Lancing

• Lancing is often overlooked, yet it’s a major reason people don’t check because it hurts

• Many people rarely change lancets– 25% report changing only

when painful or “bounces”

• MultiClix is the best lancing device for kids– No exposed sharp ever– 6 lancets on board– Very easy to use


How often …

• Number of blood glucose checks per day is increasing …

• … but changing lancets remains about the same – not often enough– 24% said change

due to excessive pain or when lancet “bounces”

– 23% change every time

http://www.childrenwithdiabetes.com/poll/BloodTestsPerDayB200611b.gif


Insulin Delivery – Some Science

• 65% of kids on pumps missed more than 1 meal bolus/week

• 2 missed meal bolus/week caused A1c to increase ½%

Mean Rate of Change of Glucose Values From Onset of Meal to Nadir

Breakfast Lunch Dinner Missed Meal Bolus

Mea

n

S

D (

mg

/dl-

min

)

0

1

2

3

4

5

“Insulin’s a great drug if you take it” -- Dr. Darrell Wilson, Stanford

Burdick, Chase, Pediatrics 113: e221, 2004


Insulin Delivery – Injection Devices

• Pens and pen-like devices becoming more common in the US; the norm elsewhere

• Dosing convenience the issue• Allows for very precise dosing that

cannot be matched with syringes• Downside is no mixing


Insulin Delivery – Insulin Pumps

• Studies show better A1c with lower risk of hypoglycemia, especially in grade school kids

• Studies show efficacy even in infants

• “Untethered Regimen” allows for pump breaks

Pumps not shown to scale


But how do kids choose a pump?

Color


Symlin—Another Drug

• Slows gastric emptying• Suppresses postprandial

glucagon secretion• Makes you feel full sooner• Can help you lose weight• But …

– Nausea at first– Must decrease insulin

because of delayed absorption of food

– Severe lows if not attentive

• Use in <18 off label


Diabetes Mixology

• Lantus– No change in A1c when

mixed and immediately injected

• Glucagon– Glucagon is effective for at

least 7 days once mixed and stored at room temperature

• Symlin– Anecdotal evidence shows

no difference via syringe– Some reports of mixing in

pumps

• This is all very off label

J Pediatr. 2006 Apr;148(4):481-4


Continuous Glucose Sensors

• Promises a revolution in diabetes care• Minute-by-minute glucose data has dramatic

clinical implications• Predictive alarming for impending lows and highs• Near Future: Sensor + Pump = Closed Loop (&

sleep)

MiniMed Paradigm® REAL-

Time System DexCom™Abbott

Freestyle Navigator™

http://www.childrenwithdiabetes.com/gifs/MonicaNavTra.jpg


It’s Not About Blood Anymore

• Continuous sensors look at interstitial fluid, not blood

• Blood has been easy to access, but …

• … interstitial might be the better compartment

• We really care about the brain, not the fingertip

• Danish pot belly pig study


CGMS Performance

From Use of Continuous Glucose Monitoring in the Detection and Prevention of Hypoglycemia by Howard A. Wolpert, M.D. (J Diabetes Sci Technol 2007; 1:146-150). Original from Evaluating the Clinical Accuracy of Two Continuous Glucose Sensors Using Continuous Glucose–Error Grid Analysis by William Clarke, et al (Diabetes Care 2005 28: 2412-2417)

Performance of two sensors during induced moderate hypoglycemia.


CGMS Accuracy

0%

5%

10%

15%

20%

25%

30%

35%

40%

0 50 100 150 200 250 300 350 400

Reference Glucose (mg/dL)

Median RAD

GWB

Original CGMS

Modified CGMS

Ultra

Freestyle% MAD of HGM 1989-1996

Diabetes Care 26:1176, 2003

From Bruce Buckingham, CWD FFL 2005


Sensor Summary

• Point accuracy not the same as finger stick glucose monitors, but …

• … interstitial fluid might be more relevant than finger stick blood

• Current point accuracy essentially the same as first generation blood glucose monitors

• Trend data has potential to improve care dramatically

• Low alarms


More than Diabetes—Celiac

• Allergy to gluten (wheat, barley, rye)

• Autoimmune disease• About 10% of people

with type 1 have celiac

• Can explain erratic control

• Testing is easy …• … Living with getting

easier


The Effects of Celiac

• Left: Healthy villi – increases the absorption area of the intestinal mucosa to ~ 250 square yards

• Right: Villi that have been destroyed by celiac antibodies – absorption area just ~ 2 square yards

• Enormous variability in nutrient absorption negatively impacts predictability of food and therefore diabetes control From Ragnar Hanas, CWD FFL 2006


Some Science– Risk for Retinopathy

0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

24 24

20 20

16 16

12 12

8 8

4 4

00

Conventional

Adapted from Diabetes 44:968-983, 1995From Irl Hirsch, DTM 2006

11%11%

Ra

t e P

er

Pa

tie

nt

Ye

ar

Ra

te P

er

Pa

tie

nt

Ye

ar 10%10%

9%9%

8%8%

7%7%

Time During Study (Years)Time During Study (Years)

Mean HbA1cMean HbA1c

0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9

Intensive

Ra

t e P

er

Pa

tie

nt

Ye

ar

Ra

te P

er

Pa

tie

nt

Ye

ar

9%9%8%8%7%7%

Time During Study (Years)Time During Study (Years)

24 24

20 20

16 16

12 12

8 8

4 4

00

Mean HbA1cMean HbA1c

Tight Control Matters More Than We Thought


Could it be Glucose Variability?

Cell death of human umbilical vein endothelial cells

“Variability in glycemic control may be more deleterious than a constant high concentration of glucose”

Am J Physiol Endocrinol Metab 281: E924-E930, 2001 From Irl Hirsch DTM2006

http://ajpendo.physiology.org/content/vol281/issue5/images/large/h11110562001.jpeg


OK, So Give Me a Goal

• What makes this hard to achieve?– Not taking enough insulin (check fasting)– Miscounting carbs (under or over bolusing)– Gastroparesis or celiac– Not pre-bolusing or missing meal boluses– Erratic snacking and not covering with

insulin– Absorption variability

• You’re not still using NPH are you?

SD X 2 < MEANSD X 2 < MEAN

From Irl Hirsch DTM2006


Hints at the Future—Closing the Loop

• Sensor + Pump = “Set it and forget it?”• Semi closed loop

– Pre-meal bolus, or at least partial pre-meal bolus– Even semi closed loop can provide essentially

normal blood sugars for at least 1/3rd of the day – at night

• Fully closed loop– Set it and forget it– Sensor lag (?) and kinetics of insulin action remain

a major challenge

• Is glucagon also needed?– At recent Diabetes Technology Meeting, 60% of

attendees decided yes after one presentation (vs. 47% pre)


Why Even Semi-Closed Loop Matters

Artificial External Insulin Pump

GARRY M. STEIL, Diabetes 53:A3, 2004

SLEEP!

This is relatively old data using older sensor technology


Sensor glucose levels during CL control vs. home open-loop pump therapy

8 3

5881

3315

0%

20%

40%

60%

80%

100%

Open Loop Closed Loop

> 18070-180< 70

p < 0.002

From Stu Weinzimer, DTM 2006


Comparing Closed vs. Semi Closed Loop:Single Meal Example

0 60 120 180 2400

20

40

60

80

100

Closed Loop

Hybrid CL

Time (min)

Pla

sma

Insu

lin

(

U/m

L)

From Stu Weinzimer, DTM 2006


Reference Glucose Levels in Closed Loop Versus Hybrid (Semi Closed)

16 18 20 22 24 26 28 30 32 34 36 38 40 420

100

200

300Closed Loop (N=8)

mealssetpoint

Hybrid Closed Loop (N=9)

Glu

co

se

(m

g/d

l)

Mean Daytime Peak PP

Full CL 149 57 160 59 226 51

Hybrid 140 46 149 47 197 47From Stu Weinzimer, DTM

2006


We Proudly Wear our Technology

Monicawith

Navigator(yes, in a study)

Kennywith

DexCom(yes, off label)

Hugh of Borgwith

Borg Drone Suit(not FDA

approved)


In Closing …

• The tools are good and getting better• Pump therapy has decided advantages• Don’t be afraid to mix• More data means better decision making

– Continuous sensing is real and makes a difference

• Variability might be as important as A1c• Get checked for celiac• The future looks very bright• The tools have made a dramatic impact

on reducing the risk of complications

best practices … or suggestions on diabetes care what you should know jeff hitchcock children with...

Documents

time slide

us slide

onset of diabetes slide

mixing slide

reassurance slide

lower a1c slide

test time

board data analysis