GeneralResearch & Publications

Rationale and Design for a GRADE Substudy of Continuous Glucose Monitoring

By December 1, 2019September 24th, 2020No Comments


Diabetes Technology & Therapeutics

Mary E Larkin 1 ,
David M Nathan 1 ,
Ionut Bebu 2 ,
Heidi Krause-Steinrauf 2 ,
William H Herman 3 ,
John M Higgins 4 5 ,
Margaret Tiktin 6 ,
Robert M Cohen 7 ,
Claire Lund 2 ,
Richard M Bergenstal 8 ,
Mary L Johnson 8 ,
Valerie Arends 9 ,
GRADE Research Group

Background: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study has enrolled a racially and ethnically diverse
population with type 2 diabetes, performed extensive phenotyping, and
randomly assigned the participants to one of four second-line diabetes
medications. The continuous glucose monitoring (CGM) substudy has been
added to determine whether there are racial/ethnic differences in the
relationship between average glucose (AG) and hemoglobin A1c (HbA1c). CGM
will also be used to compare time in target range, glucose variability, and
the frequency and duration of hypoglycemia across study groups. Methods: The observational CGM substudy will enroll up to 1800 of the 5047 GRADE
study participants from the four treatment groups, including as many as 450
participants from each of 4 racial/ethnic minority groups to be compared:
Hispanic White, non-Hispanic White, non-Hispanic African American, and
non-Hispanic Other. CGM will be performed for 2 weeks in proximity to a
GRADE annual visit, during which an oral glucose tolerance test will be
performed and HbA1c and glycated albumin measured. Indicators of
interindividual variation in red blood cell turnover, based on specialized
erythrocyte measurements, will also be measured to explore the potential
causes of interindividual HbA1c variations. Conclusions: The GRADE CGM substudy will provide new insights into whether differences
exist in the relationship between HbA1c and AG among different
racial/ethnic groups and whether glycemic profiles differ among frequently
used diabetes medications and their potential clinical implications.
Understanding such differences is important for clinical care and
adjustment of diabetes medications in patients of different races or


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