Browsing by Author "Cleves, Mario A."

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    Associations of HbA1c with the Timing of C‐peptide Responses during the Oral Glucose Tolerance Test at the Diagnosis of Type 1 Diabetes
    (Wiley, 2019) Ismail, Heba M.; Evans-Molina, Carmella; DiMeglio, Linda A.; Becker, Dorothy J.; Libman, Ingrid; Sims, Emily K.; Boulware, David; Herold, Kevan C.; Rafkin, Lisa; Skyler, Jay; Cleves, Mario A.; Palmer, Jerry; Sosenko, Jay; Pediatrics, School of Medicine
    Background In new onset type 1 diabetes (T1D), overall C‐peptide measures such as area under the curve (AUC) C‐peptide and peak C‐peptide are useful for estimating the extent of β‐cell dysfunction, and for assessing responses to intervention therapy. However, measures of the timing of C‐peptide responsiveness could have additional value. Objectives We assessed the contribution of the timing of C‐peptide responsiveness during oral glucose tolerance tests (OGTTs) to HbA1c variation at T1D diagnosis. Methods We analyzed data from 85 individuals <18 years with OGTTs and HbA1c measurements at diagnosis. Overall [AUC and peak C‐peptide] and timing measures [30‐0 minute C‐peptide (early); 60 to 120 minute C‐peptide sum‐30 minutes (late); 120/30 C‐peptide; time to peak C‐peptide] were utilized. Results At diagnosis, the mean (±SD) age was 11.2±3.3 years, BMI‐z was 0.4±1.1, 51.0% were male and the HbA1c was 43.54±8.46 mmol/mol (6.1±0.8%). HbA1c correlated inversely with the AUC C‐peptide (p<0.001), peak C‐peptide (p<0.001), early and late C‐peptide responses (p<0.001 each), and 120/30 C‐peptide (p<0.001). Those with a peak C‐peptide occurring at ≤60 minutes had higher HbA1c values than those with peaks later (p=0.003). HbA1c variance was better explained with timing measures added to regression models (R2=11.6% with AUC C‐peptide alone; R2=20.0% with 120/30 C‐peptide added; R2=13.7% with peak C‐peptide alone, R2=20.4% with timing of the peak added). Similar associations were seen between the 2‐hr glucose and the C‐peptide measures. Conclusions These findings show that the addition of timing measures of C‐peptide responsiveness better explains HbA1c variation at diagnosis than standard measures alone.
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    Early and late C-peptide responses during oral glucose tolerance testing are oppositely predictive of type 1 diabetes in autoantibody-positive individuals
    (Wiley, 2020-01-31) Ismail, Heba M.; Becker, Dorothy J.; Libman, Ingrid; Herold, Kevan C.; Redondo, Maria J.; Atkinson, Mark A.; Cleves, Mario A.; Palmer, Jerry; Sosenko, Jay; Pediatrics, School of Medicine
    We examined whether the timing of the C-peptide response during an oral glucose tolerance test (OGTT) in relatives of patients with type 1 diabetes (T1D) is predictive of disease onset. We examined baseline 2-h OGTTs from 670 relatives participating in the Diabetes Prevention Trial-Type 1 (age: 13.8 ± 9.6 years; body mass index z score: 0.3 ± 1.1; 56% male) using univariate regression models. T1D risk increased with lower early C-peptide responses (30–0 min) (χ2 = 28.8, P < 0.001), and higher late C-peptide responses (120–60 min) (χ2 = 23.3, P < 0.001). When both responses were included in a proportional hazards model, they remained independently and oppositely associated with T1D, with a stronger overall association for the combined model than either response alone (χ2 = 41.1; P < 0.001). Using receiver operating characteristic curve analysis, the combined early and late C-peptide response was more accurately predictive of T1D than area under the curve C-peptide (P = 0.005). Our findings demonstrate that lower early and higher late C-peptide responses serve as indicators of increased T1D risk.