305-OR: Glycemic Variability and Progression of CKD: PERL Substudy

Abstract

To test the hypothesis that glucose variability may impact the progression of kidney disease in type 1 diabetes (T1D), we studied a subgroup of the Preventing Early Renal Loss (PERL) study population with T1D and mild to moderate diabetic kidney disease, using blinded continuous glucose monitoring (CGM) for up to 14 days for each wear period. We studied 175 participants wearing 366 blinded FreeStyle Libre CGMs on one to five occasions between weeks 96 and 164 of the follow-up in the parent study. The mean age of the population was 52.2 ± 10.9 (mean ± SD) years, mean duration of T1D was 36.1 ± 12.2 years. Baseline BMI, A1C, and iothalamate GFR (iGFR) were 29.9 ± 6.3 kg/m2, 8.2 ± 1.2%, and 67.5 ± 17.2 ml/min/1.73m2 respectively. During the study, mean glucose (MG) and coefficient of variation glucose (CV) were 174.5 ± 41.4 mg/dL and 44.5± 8.8% respectively. Mean amplitude of glycemic excursions (MAGE) was 146.0 ± 43.9 mg/dL while time-in-range (TIR) was 50.5 ± 16.1%. A 10% increase in the mean CV was associated with a 1.4 ml/min/1.73m2 decrease in iGFR at the end of the study [95%CI (-3.33, 0.44); p=0.13] while a 10 mg/dL increase in MAGE was associated with a 0.01 ml/min/1.73m2 decrease [95%CI (-0.41, 0.38); p=0.95]. For those with CV >36, iGFR was 2.56 ml/min/1.73m2 lower compared with those with CV <36 [95%CI (-7.44, 2.31); p=0.30]. Low blood glucose index, high blood glucose index, MG, and TIR were not significantly associated with iGFR. Given the non-significant associations between CGM metrics and iGFR, we conclude in this study of a population with T1D and mild to moderate kidney disease that there is no evidence that glycemic variability or glucose control impacts the rate of loss of iGFR. Limitations of the study include the observational study design, the relatively small sample size, the variability of how frequently CGM data were collected, and the short duration of observation. A larger prospective study using real-time CGM to improve glycemic parameters and reduce glycemic variability is required to answer this question definitively. Disclosure J.B. McGill: Advisory Panel; Self; Aegerion Pharmaceuticals, Bayer AG, Lilly Diabetes, Novo Nordisk A/S. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc. Research Support; Self; Medtronic, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; Aegerion Pharmaceuticals, Dexcom, Inc., Janssen Pharmaceuticals, Inc. I.B. Hirsch: Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care. Research Support; Self; Medtronic, Omnipod. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. A. Galecki: None. K. Ruedy: None. C. Wu: None. A. Doria: Research Support; Self; Sanofi. Funding The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-TD1014); National Institute of Diabetes and Digestive and Kidney Diseases (R03DK094484, R34DK097808, UC4DK101108); JDRF (17-2012-377)