It is known that individuals with a biphasic (BiP; two peaks) GRC during 2-hr oral glucose tolerance tests are at lower type 1 diabetes (T1D) risk than those with monophasic (MoP; one peak) and monotonic (MoT; continuous rise) GRCs. We hypothesized that GRC shapes during MMTTs in persons with newly-diagnosed T1D can predict response to intervention and that the shape may change in response to therapy. We performed an analysis to 1) Determine if the baseline GRC shape can predict response to intervention, and 2) Evaluate GRC changes in responders (R) vs. non-responders (NR) to interventions; response=AUC C-peptide (C-P) at 12 months not <5% of AUC C-P at baseline. Those with complete MMTT data at baseline (within 3 months of diagnosis) and at 12 months from all TrialNet intervention trials were included in the analyses (n=389, median (IQR) age 14.6 (8.1) years, BMI-z 0.6 (1.4), 56% male). At baseline, R had higher BiP GRCs [NR: 9.4% (25/227) vs. R: 20.6% (13/63); adjusted OR 2.92 (1.36-6.27); p=0.006)]. The overall shape distribution was significantly different between R and NR at 12 months (p=0.036) with a notable higher frequency of MoT GRCs in NR [NR: 30.1% (68/226) vs. R: 15.5% (9/58), p=0.031]. There were no differences between R and NR in the odds of changing from one GRC to another (p>0.05 for all).
In conclusion, the finding that a BiP GRC at baseline was more common in R than NR suggests that MMTT GRCs can be used to predict responses to interventions in those newly diagnosed with T1D. Further, the higher proportion of MoT GRCs in NR at 12 months suggests that MMTTs with MoT GRCs are indicative of metabolic decline.
N.N. Almutlaq: None. M.A. Cleves: None. S.E. Gitelman: Advisory Panel; Self; Avortes, Intermountain Therapeutics, Lilly Diabetes, Tolerion, Inc. Research Support; Self; Caladrius Biosciences, Inc., Janssen Research & Development. Other Relationship; Self; Novo Nordisk Inc. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J.M. Sosenko: None. H.M. Ismail: None.
National Institutes of Health