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. 2017 Dec;18(8):794-802.
doi: 10.1111/pedi.12485. Epub 2017 Jan 27.

Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls

Andrea K Steck  1 , Helena Elding Larsson  2 , Xiang Liu  3 , Riitta Veijola  4 , Jorma Toppari  5   6 , William A Hagopian  7 , Michael J Haller  8 , Simi Ahmed  9 , Beena Akolkar  10 , Åke Lernmark  2 , Marian J Rewers  1 , Jeffrey P Krischer  3 ; and the TEDDY Study Group
Affiliations

Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared to community controls

Andrea K Steck et al. Pediatr Diabetes. 2017 Dec.

Abstract

Objective: To explore whether children diagnosed with type 1 diabetes during islet autoantibody surveillance through The Environmental Determinants of Diabetes in the Young (TEDDY) study retain greater islet function than children diagnosed through the community.

Methods: TEDDY children identified at birth with high-risk human leukocyte antigen and followed every 3 months until diabetes diagnosis were compared to age-matched children diagnosed with diabetes in the community. Both participated in long-term follow up after diagnosis. Hemoglobin A1c (HbA1c) and mixed meal tolerance test were performed within 1 month of diabetes onset, then at 3, 6, and 12 months, and biannually thereafter.

Results: Comparison of 43 TEDDY and 43 paired control children showed that TEDDY children often had no symptoms (58%) at diagnosis and none had diabetic ketoacidosis (DKA) compared with 98% with diabetes symptoms and 14% DKA in the controls (P < 0.001 and P = 0.03, respectively). At diagnosis, mean HbA1c was lower in TEDDY (6.8%, 51 mmol/mol) than control (10.5%, 91 mmol/mol) children (P < 0.0001). TEDDY children had significantly higher area under the curve and peak C-peptide values than the community controls throughout the first year postdiagnosis. Total insulin dose and insulin dose-adjusted A1c were lower throughout the first year postdiagnosis for TEDDY compared with control children.

Conclusions: Higher C-peptide levels in TEDDY vs community-diagnosed children persist for at least 12 months following diabetes onset and appear to represent a shift in the disease process of about 6 months. Symptom-free diagnosis, reduction of DKA, and the potential for immune intervention with increased baseline C-peptide may portend additional long-term benefits of early diagnosis.

Keywords: HbA1c; pediatric diabetes; preservation of C-peptide; prospective study; type 1 diabetes.

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Conflict of interest statement

Duality of interest: The authors declare that there is no duality of interest associated with this manuscript.

Figures

Figure 1
Figure 1. Serum C-peptide AUC during MMTT in TEDDY cases and community controls during the first year follow-up after diagnosis of diabetes
Box plots with minimum, first quartile, median, third quartile, and maximum values. The line in the box plots indicates the median value, while the mean is denoted by + for cases and o for controls. Outliers are marked as ▪. Cases: continuous black line Controls: dotted black lines
Figure 2
Figure 2. HbA1c (A), insulin dose (B) and IDAA1C (C) in TEDDY cases and community controls during the first year follow-up after diagnosis of diabetes
Box plots with minimum, first quartile, median, third quartile, and maximum values. The line in the box plots indicates the median value, while the mean is denoted by + for cases and o for controls. Outliers are marked as ▪. IDAA1C: Insulin-dose adjusted A1c: calculated as A1c (%) + [4 × insulin dose (units/kg/day)] Cases: continuous black line Controls: dotted black lines
Figure 2
Figure 2. HbA1c (A), insulin dose (B) and IDAA1C (C) in TEDDY cases and community controls during the first year follow-up after diagnosis of diabetes
Box plots with minimum, first quartile, median, third quartile, and maximum values. The line in the box plots indicates the median value, while the mean is denoted by + for cases and o for controls. Outliers are marked as ▪. IDAA1C: Insulin-dose adjusted A1c: calculated as A1c (%) + [4 × insulin dose (units/kg/day)] Cases: continuous black line Controls: dotted black lines
Figure 2
Figure 2. HbA1c (A), insulin dose (B) and IDAA1C (C) in TEDDY cases and community controls during the first year follow-up after diagnosis of diabetes
Box plots with minimum, first quartile, median, third quartile, and maximum values. The line in the box plots indicates the median value, while the mean is denoted by + for cases and o for controls. Outliers are marked as ▪. IDAA1C: Insulin-dose adjusted A1c: calculated as A1c (%) + [4 × insulin dose (units/kg/day)] Cases: continuous black line Controls: dotted black lines
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