Autoantibody positive (Ab+) relatives of T1D patients have an increased risk for dysglycemia and progression to T1D. However, the occurrence of dysglycemia in Ab- relatives is not known. Thus, we compared the frequency and pattern of dysglycemia from oral glucose tolerance tests (OGTTs) between Ab- (n=101; mean age: 11.7± 3.6 years) and single Ab+ (n=977; mean age 10.4± 3.9 years) relatives in the TrialNet Pathway to Prevention study. Single Abs were ICA, GADA, IA-2A, mIAA, or ZnT8A. The glucose criteria for dysglycemia were: fasting 110-125 mg/dl; 30, 60, and/or 90-minutes glucose ≥ 200 mg/dl; and/or 120-minutes glucose 140-199 mg/dl. Of the Ab-’s, 29/101 (28.7%) had at least one dysglycemic OGTT at baseline or during follow-up, whereas 192/977 (19.7%) Ab+’s had a dysglycemic OGTT. At baseline, there were no significant differences in the proportions of dysglycemia [Ab-’s: 13/101 (12.9%) vs. Ab+’s: 114/977 (11.7%)]. Of those with normal OGTTs at baseline, the proportion progressing to dysglycemia was actually higher (p=0.007) in the Ab-’s (dysglycemia/total: [16/87 (18.4%) vs. 78/846 (9.2%)], but the hazard ratio for dysglycemia risk from a Cox regression analysis was not significant after adjustments for age, BMI%tile, relation to proband, and number of OGTTs performed. OGTT glucose and C-peptide at the first dysglycemic OGTT did not differ significantly between Ab-’s and Ab+’s after adjustments, except for a higher 90-minutes glucose in the Ab-’s (p=0.004). The early C-peptide response values (30-0 minutes C-peptide) did not differ significantly between the groups and were not indicative of overt insulin deficiency (Ab-’s: 5.6± 3.2 ng/ml vs. Ab+’s: 5.2± 3.3 ng/ml).

In summary, dysglycemia was as common in Ab- relatives as in single Ab+ relatives with similar dysglycemic OGTT patterns. These findings suggest that dysglycemia can precede Ab’s during the progression to T1D and/or an appreciable proportion of single Ab+ dysglycemic individuals do not develop T1D.


E.K. Sims: None. P. Xu: None. J.S. Skyler: Advisory Panel; Self; ADOCIA, Abvance. Consultant; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim GmbH. Advisory Panel; Self; Dance Biopharm. Consultant; Self; Diavacs, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Ideal Life Inc., ImmunoMolecular Therapeutics, Intrexon, Merck & Co., Inc.. Advisory Panel; Self; Orgenesis Inc.. Consultant; Self; Sanofi, Servier, VTV Therapeutics, Valeritas, Inc., Viacyte, Inc.. Board Member; Self; Dexcom, Inc.. Stock/Shareholder; Self; Dexcom, Inc.. Board Member; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc.. Board Member; Self; Moerae Matrix. Stock/Shareholder; Self; Moerae Matrix, Dance Biopharm, Ideal Life Inc., Intrexon, VasoPrep Surgical. A. Pugliese: None. J. Krischer: None. C. Greenbaum: Research Support; Self; Janssen Research & Development. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. J. Mahon: None. K.C. Herold: None. J.P. Palmer: None. J. Sosenko: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at