Nathan, Brandon M.

OBJECTIVE We assessed whether Index60, a composite measure of fasting C-peptide, 60-min C-peptide, and 60-min glucose, could improve the metabolic staging of type 1 diabetes for progression to clinical disease (stage 3) among autoantibody-positive (Ab+) individuals with normal 2-h glucose values (<140 mg/dL). RESEARCH DESIGN AND METHODS We analyzed 3,058 Type 1 Diabetes TrialNet Pathway to Prevention participants with 2-h glucose <140 mg/dL and Index60 <1.00 values from baseline oral glucose tolerance tests. Characteristics associated with type 1 diabetes (younger age, greater Ab+, higher HLA DR3-DQ2/DR4-DQ8 prevalence, and lower C-peptide) were compared among four mutually exclusive groups: top 2-h glucose quartile only (HI-2HGLU), top Index60 quartile only (HI-IND60), both top quartiles (HI-BOTH), and neither top quartile (LO-BOTH). Additionally, within the 2-h glucose distribution of <140 mg/dL and separately within the Index60 <1.00 distribution, comparisons were made between those above or below the medians. RESULTS HI-IND60 and HI-BOTH were younger, with greater frequency of more than two Ab+, and lower C-peptide levels, than either HI-2HGLU or LO-BOTH (all P < 0.001). The cumulative incidence for stage 3 was greater for HI-IND60 and HI-BOTH than for either HI-2HGLU or LO-BOTH (all P < 0.001). Those with Index60 values above the median were younger and had higher frequency of two or more Ab+ (P < 0.001) and DR3-DQ2/DR4-DQ8 prevalence (P < 0.001) and lower area under the curve (AUC) C-peptide levels (P < 0.001) than those below. Those above the 2-h glucose median had higher AUC C-peptide levels (P < 0.001), but otherwise did not differ from those below. CONCLUSIONS Index60 identifies individuals with characteristics of type 1 diabetes at appreciable risk for progression who would otherwise be missed by 2-h glucose staging criteria.

ObjectiveTo assess the safety and efficacy of short‐term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity.MethodsAdolescents (ages 12–18 years) with severe obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m2) were recruited for this double‐blind, randomized, placebo‐controlled trial. Participants completed 4 weeks of meal replacement therapy followed by randomization (1:1) to either 24 weeks of topiramate 75 mg/day or placebo. Mean changes were compared between groups.ResultsThirty adolescents (mean age 15.2 ± 1.7 years, mean BMI 40.3 ± 4.6 kg/m2) completed the meal replacement phase and were randomized; 21 completed the study. The difference in mean percent change in BMI between the topiramate and placebo groups was not significant (−1.9%; 95% CI: −5.2% to +1.5%; P = 0.291). Significant improvements in visceral fat and very‐low‐density lipoprotein cholesterol were observed in the topiramate compared with the placebo group. There were no concerning changes in neurocognitive function or bone health.ConclusionsIn this pilot study, 4 weeks of meal replacement therapy followed by 24 weeks of low‐dose topiramate compared with meal replacement therapy alone did not result in significant BMI reduction for adolescents with severe obesity.