Dysglycemia Is as Common in Autoantibody-Negative Relatives as in Single-Autoantibody-Positive Relatives of Type 1 Diabetes (T1D) Patients
Authors: SIMS EMILY K. , XU PING , SKYLER JAY S. , PUGLIESE ALBERTO , KRISCHER JEFFREY , GREENBAUM CARLA , MAHON JEFFREY , HEROLD KEVAN C. , PALMER JERRY P. , SOSENKO JAY 
Published: June 2018

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.

Disclosure
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.