Utility of CGMS as a Measure of Glycemic Control in Children with

Type 1 Diabetes (T1DM)

Rosanna Fiallo-Scharer, MDfor

Background: DirecNet

• Diabetes Research in Children Network• NIH funded collaborative study group• 5 clinical centers, central laboratory,

coordinating center, and representatives from NICHD and NIDDK

• Objective: to critically evaluate the clinical usefulness of current and future glucose sensors in children and adolescents

DirecNet Outpatient Randomized Clinical Trial (RCT)

6-month RCT to assess the merits of the GlucoWatch G2® Biographer (Cygnus Inc.; Redwood City, CA) in children ages 7-17 years with type 1 diabetes

• Initial outpatient evaluations of glycemic control prior to randomization included:

– 48-72 hr CGMS (Medtronic MiniMed) profile.– 8-point SMBG testing while simultaneously wearing a CGMS

for 2-3 days using the One Touch UltraSmart (Life scan) meter.

– HbA1c measured by HPLC in a central laboratory.

• Purpose: To examine and compare the results obtained by these baseline measures of glycemic control in a large sample of children and adolescents with T1DM.

Methods• Analysis included 183 patients who completed the following:

– At least 10 Ultra measurements during 2 days of 8-point testing.– 40 total hours of CGMS use.– At least one day of overlap between 8-point testing and CGMS use.

• Ultra plasma glucose levels used as reference values for assessment of accuracy of hypoglycemic detection by the CGMS.

Demographic and Clinical Characteristics of 183 Subjects

Male/Female 52%/48%

Age 12.5 ± 2.8 years

Minorities 14%

Duration of Diabetes 5.4 ± 3.3 years

Injections/Pump 54%/46%

Number of Glucose Measurements

Ultra 3,408

CGMS 170,381

0

50

100

150

200

Mea

n G

luco

se (

mg/

dl)

Ultra CGMS

Mean Ultra and CGMS glucose values

Mean (± SD) A1c value was 8.0% ± 0.9%

Results were similar for pre- and post-prandial and bedtime.

Percent Glucose Values in Range, Below Range and Above Range

0%

10%

20%

30%

40%

50%

<60 mg/dl 61-180 mg/dl >180 mg/dl

8 Point TestingCGMS

Mean Glucose Values by Time of Day

0255075

100125150175200225250275

Pre-prandial Post-prandial Bedtime 12-4 am

Mea

n G

luco

se (

mg/

dl)

Ultra

CGMS

Mean ± 1 SD

Mean Ultra Glucose Values by A1c With regression line and 95% confidence limits

0

50

100

150

200

250

300

350

6 7 8 9 10 11 12

A1c (%)

Mea

n G

luco

se (

mg/

dl)

Spearman correlation = 0.44P-value < 0.001

Mean CGMS Glucose Values by A1c With regression line and 95% confidence limits

0

50

100

150

200

250

300

350

6 7 8 9 10 11 12

A1c (%)

Mea

n G

luco

se (

mg/

dl)

Spearman correlation = 0.44P-value < 0.001

Slopes of Regression Lines

• 8-point testing: – 26 mg/dl per 1.0% change in A1c

• CGMS: – 22 mg/dl per 1.0% change in A1c

0%

20%

40%

60%

80%

100%

Sensitivity=90% False Positive Rate=32%

CGMS and Ultra During Hypoglycemia

Ultra > 70

Ultra 61-70

Ultra ≤ 60

136 CGMS hypoglycemia episodes* Hypoglycemia = two values 60 mg/dl without

an intermediate value >70 mg/dl

80 ULTRA hypoglycemia episodes* Hypoglycemia = BG value 60 mg/dl

CGMS ≤ 60

CGMS > 70

CGMS 61-7032%

33%

35%

Sensitivity defined as CGMS ≤ 70 within ± 30 minutes; False positive defined as Ultra > 70.

10%

11%

79%

0%

20%

40%

60%

80%

100%

Sensitivity=60% False Positive Rate=59%

CGMS and Ultra During Overnight Hypoglycemia

Ultra > 70

Ultra 61-70

Ultra ≤ 60

17 CGMS episodes* Hypoglycemia = two values 60 mg/dl without

an intermediate value >70 mg/dl

5 ULTRA episodes* Hypoglycemia = BG value 60 mg/dl

CGMS ≤ 60

CGMS > 70

CGMS 61-70

59%

29%

12%

Sensitivity defined as CGMS ≤ 70 within ± 30 minutes; False positive defined as Ultra > 70.

40%

20%

40%

Summary

• 8-point testing and CGMS were similar in detection of hyperglycemia and normoglycemia, and in their correlation to A1c values.

• One-third of CGMS defined hypoglycemia episodes overall and over half overnight could not be confirmed by the home glucose meter.

Conclusions

• 8-point testing and the CGMS provide useful short-term measure of glucose control in youth with type 1 diabetes

• Both methods have limitations for determining the true rate of hypoglycemia in these patients

Conclusions

• Limitations of 8-point testing: – Compliance– Limited number of values

• Limitations of CGMS– Retrospective data– Inaccuracy of low glucose measurements

• Barbara Davis Center

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

• University of Iowa– Eva Tsalikian– Michael Tansey– Linda Larson– Julie Coffey– Amy Sheehan

• Nemours Children’s Clinic– Tim Wysocki– Nelly Mauras– Larry Fox– Keisha Bird– Kelly Lofton

• Stanford University

– Bruce Buckingham– Darrell Wilson– Jennifer Block– Paula Clinton

• Yale University– William Tamborlane– Stuart Weinzimer– Elizabeth Doyle– Kristin Sikes– Amy Steffen

• Jaeb Center for Health Research– Roy Beck– Katrina Ruedy– Craig Kollman– Dongyuan Xing– Cynthia Silvester