Objective: Identify predictors
of glycemic worsening among youth and adults with impaired glucose tolerance
(IGT) or recently-diagnosed type 2 diabetes in the RISE Study.
<p> </p>
<p>Research Design and Methods: Ninety-one
youth (10-19 years) were randomized 1:1 to 12 months of metformin (MET), or 3
months of glargine followed by 9 months of metformin (G-MET); 267 adults to
MET, G-MET, liraglutide plus MET (LIRA+MET) or placebo for 12 months. All
participants underwent baseline hyperglycemic clamp and 3-h oral glucose
tolerance test (OGTT) at baseline, month-6, month-12 and off treatment at month-15
and month-21. Cox models identified baseline predictors of glycemic worsening (HbA1c
increase ≥0.5% from baseline).</p>
<p> </p>
<p>Results: Glycemic worsening
occurred in 17.8% of youth vs. 7.5% of adults at month-12 (p=0.008), and 36% of
youth vs. 20% of adults at month-21 (p=0.002). In youth, glycemic worsening did
not differ by treatment. In adults, month-12 glycemic worsening was less on LIRA+MET
vs. placebo (HR 0.21, CI 0.05-0.96, p=0.044). In both age groups, lower baseline
clamp-derived β-cell responses predicted month-12 and month-21 glycemic
worsening (p<0.01); lower baseline OGTT-derived β-cell responses predicted month-21
worsening (p<0.05). In youth, higher baseline HbA1c and 2-h glucose predicted
month-12 and month-21 glycemic worsening and higher fasting glucose predicted month-21
worsening (p<0.05). In adults, lower clamp and OGTT-derived insulin
sensitivity predicted month-12 and month-21 worsening (p<0.05). </p>
<p> </p>
<p>Conclusions: Glycemic
worsening was more common among youth than adults with IGT or
recently-diagnosed type 2 diabetes, predicted by lower baseline β-cell responses
in both groups, hyperglycemia in youth and insulin resistance in adults. </p>
T-Cell Responses to Islet Antigens Improves Detection of Autoimmune Diabetes and Identifies Patients With More Severe β-Cell Lesions in Phenotypic Type 2 Diabetes