<b>Objective:</b> To assess the progression of type 1
diabetes using time to peak glucose or C-peptide during oral glucose
tolerance tests (OGTTs) in autoantibody positive (Ab+) relatives of people
with type 1 diabetes.
<p><b>Methods:</b> We examined 2-hour OGTTs of participants
in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention
(PTP) studies. We included 706 DPT-1 participants (Mean±SD age: 13.84±9.53 years; BMI-Z-Score: 0.33±1.07; 56.1% male) and 3,720 PTP participants (age: 16.01±12.33
Years, BMI-Z-Score 0.66±1.3; 49.7% male). Log-rank
testing and Cox regression analyses with adjustments (age, sex, race,
BMI Z-Score, HOMA-IR and peak Glucose/C-peptide
levels, respectively) were performed. </p>
<p><b>Results:</b> In each of DPT-1 and PTP, higher 5-year
diabetes progression risk was seen in those with time to peak
glucose >30 min and time to peak C-peptide >60 min
(p<0.001 for all groups), before and after adjustments. In models examining
strength of association with diabetes development, associations were greater
for time to peak C-peptide versus peak C-peptide value (DPT-1: X<sup>2 </sup>= 25.76 vs. X<sup>2</sup>
= 8.62 and PTP: X<sup>2 </sup>= 149.19 vs. X<sup>2</sup> = 79.98; all p<0.001). Changes in the percentage of
individuals with delayed glucose and/or C-peptide peaks were noted over time.</p>
<p><b>Conclusions:
</b>In two independent at
risk populations, we show that those with delayed OGTT peak times for glucose
or C-peptide are at higher risk of diabetes development within 5 years, independent of
peak levels. Moreover, time to peak C-peptide appears more predictive than
the peak level, suggesting its potential use as a specific biomarker for diabetes
progression. </p>
β Cell death and dysfunction during type 1 diabetes development in at-risk individuals