Mealtime Glycemic Excursions in Mealtime Glycemic Excursions in Pediatric Subjects with Type 1 Diabetes: Pediatric Subjects with Type 1 Diabetes:

Results of the Diabetes Research in Results of the Diabetes Research in Children (DirecNet) Accuracy StudyChildren (DirecNet) Accuracy Study

Study Group

BackgroundBackground

• The Diabetes Research in Children Network (DirecNet) is a multi-center group whose aim is to study the accuracy and practicability of glucose sensor systems in children with type 1 diabetes (T1DM)

• Meal-related hyperglycemic excursions contribute greatly to difficulty in optimal diabetes control

• Continuous glucose monitoring systems provide the opportunity to study meal-related glucose excursions

ObjectivesObjectives

• To describe meal-related glycemic excursions in children and adolescents with T1DM

• To determine the accuracy of the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Inc.) and the GlucoWatch® G2™ Biographer (GW2B, Cygnus, Inc.) under rapidly changing glucose levels

MethodsMethods

• 82 children with T1DM admitted to 5 CRCs• CGMS, GW2B, blood-drawing IV inserted• Short-acting or meal-related bolus insulin omitted • Standard liquid carbohydrate meal administered, 1.75

gm/kg (max 75 gm)• Reference venous blood glucose (BG) measured at

baseline and every 5 min for up to 60 min• Sensor glucose (SG) levels compared to reference BG

Subject DemographicsSubject Demographics

Gender F / M 41 / 41

Age mean ± SD (y) 10.4 ± 4.1

Race / Ethnicity N(%)

White 73 (89)

Hispanic or Latino 4 (5)

African-American 3 (4)

Other 2 (2)

BMI percentile mean ± SD (%) 67 ± 23

Clinical CharacteristicsClinical Characteristics

Duration of T1DM mean ± SD (y)

All ages 4.9 ± 3.3

1 - < 7 (n = 23) 3.2 ± 1.0

7 - < 12 (n = 27) 3.8 ± 2.4

12 - < 18 (n = 32) 7.0 ± 3.9

Insulin Route N (%)

Pump 38 (46)

Multiple daily injection 44 (54)

HbA1c mean ± SD (%) 7.7 ± 1.1

BG Distribution at each 5-minute interval BG Distribution at each 5-minute interval during meal-induced Hyperglycemia testduring meal-induced Hyperglycemia test

Time since start of test (min)

0

100

200

300

400

500

Glu

cose

(m

g/d

L)

0 5 10 15 20 25 30 35 40 45 50 55

Baseline and Peak Glucose Levels Baseline and Peak Glucose Levels by Age and Treatment Modality*by Age and Treatment Modality*

0

50

100

150

200

250

300

350

400

Overall 1 - < 7 7 - < 12 12- < 18 CSII MDI

Blo

od

Glu

cose

(m

g/d

L)

Baseline Peak *Height of bar = mean Whisker = mean + 1 SD

Tim

e to

pea

k B

G (

min

)

30

40

50

60

70

Overall 1 - < 7 7 - < 12 12- < 18 CSII MDI

2

2.5

3

3.5

4

4.5

5

5.5

6

Rate

of C

han

ge (m

g/d

L-m

in)

Time Course of Glucose Excursion Time Course of Glucose Excursion by Age and Treatment Modality*by Age and Treatment Modality*

Restricted to n=62 subjects in whom hyperglycemia was successfully induced (increase of 100 mg/dL or doubling from baseline)

*Height of bar = mean Whisker = mean + 1 SD

Sensor Accuracy According to Rate Sensor Accuracy According to Rate of Glucose Change During Test of Glucose Change During Test

0%

5%

10%

15%

20%

25%

Overall < 0 0 - < 2.0 2.0 - < 4.0 > 4.0

CGMS GW2B

Me

dia

n R

ela

tiv

e A

bs

olu

te D

evi

ati

on

Rate of Change* (mg/dL per min)

Accuracy did not vary by rate of change.

*Calculated from the previous reference glucose value (drop in BG divided by minutes between values)

Fulfillment of ISO Criteria* According to Fulfillment of ISO Criteria* According to Rate of Glucose Change During Test Rate of Glucose Change During Test

0%

20%

40%

60%

80%

Overall < 0 0 - < 2.0 2.0 - < 4.0 > 4.0

CGMS GW2B

Accuracy did not vary by rate of change

*ISO criteria: for reference BG ≤75 mg/dL, SG within ±15 mg/dL for reference BG >75 mg/dL, SG value within ±20%

% M

eeti

ng

ISO

Cri

teri

a

Rate of Change (mg/dL per min)

ConclusionsConclusions

• Magnitude, timing, and rate of meal-related hyperglycemic excursions were consistent across all age groups

• Sensor accuracy was not affected by rapid increases in BG levels

• Sensor performance during rapid glucose changes met ISO criteria for 51-72% of SG readings

• Barbara Davis Center

– H. Peter Chase– Rosanna Fiallo-Scharer– Jennifer Fisher

• University of Iowa– Eva Tsalikian– Michael Tansey– Linda Larson

• Nemours Children’s Clinic– Tim Wysocki– Nelly Mauras– Kristen Gagnon

• Stanford University– Bruce Buckingham– Darrell Wilson– Jennifer Block

• Yale University– William Tamborlane– Stuart Weinzimer– Elizabeth Boland

• Jaeb Center for Health Research– Roy Beck– Katrina Ruedy– Craig Kollman– Andrea Booth– Gladys Bernett

AbstractAbstractMealtime Glycemic Excursions in Pediatric Subjects with Type 1 Diabetes Mellitus (T1DM): the DirecNet ExperienceStuart Weinzimer1, Roy Beck2, Katrina Ruedy2, Andrea Booth2, Elizabeth Boland1, and the Diabetes Research in Children Network (DirecNet) Study Group. 1Department of Pediatrics, Yale University School of Medicine, New Haven, CT and 2Jaeb Center for Health Research, Tampa, FL. Background: DirecNet is a multi-center network whose aim is to study glucose sensing systems in children with T1DM. A meal protocol, in which a standard carbohydrate load was administered to test the accuracy of these sensors during changing blood glucose (BG) conditions, provided the opportunity to study the magnitude and timing of hyperglycemic excursions in children with T1DM. Objective: To describe the BG excursions in children with T1DM after a standard meal challenge and determine their relationship to patient factors. Design/Methods: 82 subjects with T1DM (41F, 41M, mean age 104 y [range 3-17 y]) were admitted to the CRC for metabolic monitoring. After oral ingestion of a standard liquid simple carbohydrate meal (1.75 gm/kg, maximum 75 gm), venous BG measurements were obtained at baseline and every 5 minutes for up to 60 minutes. Subjects using multiple daily injections (MDI) delayed their insulin injection, and pump subjects continued basal insulin delivery but delayed bolus insulin, until meal test completion. Results: BG increased from a mean baseline of 14865 mg/dL to a peak of 28378 mg/dL. Mean time to peak BG was 569 min. Among subjects who increased at least 100 mg/dL or 100% from baseline (N=62), mean rate of rise of BG was 3.41.1 mg/dL-min from start of increase to peak glucose. Magnitude of time to glucose peak, and rate of change of blood glucose were similar comparing the MDI and insulin pump-treated subjects. Conclusions: This standardized carbohydrate load induced a large hyperglycemic excursion, which was relatively consistent across all age groups and treatment modalities. Notably, the timing of BG rise was slower than anticipated, particularly in the first 15 minutes, which has important therapeutic implications regarding conventional treatment of hypoglycemia in T1DM with oral carbohydrates.