FP18-2 HbA1c and OGTT Plasma Glucose Levels Start to Rise During the Last Year Before Diagnosis in Children With Multiple Autoantibodies and Increased Genetic Risk for Type 1 Diabetes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP18-Diabetes: Glycemia & Insulin Sensitivity
Basic/Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:50 AM
Room 304 (Moscone Center)

Poster Board SUN-785
Olli Helminen1, Susanna Aspholm2, Milla-Riikka Hautakangas1, Tytti Pokka1, Jorma Ilonen3, Olli Simell3, Mikael Knip4 and Riitta Veijola*1
1University of Oulu, Oulu, Finland, 2Tampere University Hospital, Tampere, Finland, 3University of Turku, Turku, Finland, 4Univ of Helsinki, Helsinki, Finland
Background and aims: Few data is available on the development of glucose intolerance before diagnosis of type 1 diabetes (T1D).
Materials and methods: Children with increased HLA-conferred risk of T1D have participated in the Type 1 Diabetes Prediction and Prevention (DIPP) Study in Finland. The subjects have been screened for islet cell (ICA), glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and insulin autoantibodies (IAA) at ages of 3, 6, 12, 18 and 24 months and annually thereafter. Children seroconverting positive for autoantibodies were seen at 3 month (0.25 yr) intervals including HbA1c measurements. When multiple positive autoantibodies appeared oral glucose tolerance tests (OGTT) were performed annually. We included children who had progressed to multiple autoantibody positivity before Jan 1, 2012. At least one HbA1c measurement was available from 485 children, and at least one OGTT had been tested from 410 children. A total of 216 children were diagnosed with T1D (case group), and 269 children were positive for multiple autoantibodies but remained disease free until the end of follow-up (control group).
Results: Children who developed T1D turned positive at younger age for single autoantibody when compared to the control group (2.60 yrs, SD 1.99 vs. 3.96 yrs, SD 2.83; p<0.001) and for multiple autoantibodies (3.03 yrs, SD 2.16 vs. 5.26 yrs, SD 3.44; p<0.001). In the case group HbA1c started to rise significantly towards diagnosis. Mean HbA1c of the cases was 5.45% (SD 0.32) 1-5yrs before diagnosis, 5.65% (SD 0.43) 0.75-1 yrs before diagnosis, 5.73% (SD 3.78) 0.5-0.75 yrs before diagnosis and 7.84% (SD 1.82) at diagnosis, whereas the mean HbA1c in the controls was 5.43% (SD 0.25) throughout the follow-up. OGTT 0 hour and 2 hour glucose levels also rose before diagnosis in the case group. Mean 0 (2) hour glucose level 1-5 yrs before diagnosis was 4.55 mmol/l, SD 0.611 (5.87 mmol/l, SD 1.35), 0.5-1 yrs before 4.83 mmol/l, SD 0.73 (6.70 mmol/l, SD 1.80), 0.05-0.5 yrs before 4.74 mmol/l, SD 0.78 (7.05 mmol/l, SD 2.18) and at diagnosis 6.17 mmol/l, SD 1.49 (17.76 mmol/l, SD 4.48). Paired samples t-test showed significant rise in both HbA1c and OGTT starting 1 year before diagnosis when comparing to the previous time period, p<0.001 in HbA1c and p=0.015 in 0 hour glucose and p=0.046 in 2 hour glucose.
Conclusions: Rise of HbA1c and plasma glucose levels in OGTT starts as early as one year before the diagnosis of T1D.

Nothing to Disclose: OH, SA, MRH, TP, JI, OS, MK, RV

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Juvenile Diabetes Research Foundation (DIPP, Finland, Awards 4-1999-731 and 4-2001-435)