Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention.
OBJECTIVE
Non-diabetic children with multiple islet autoantibodies were recruited to a secondary prevention trial. The objective was to determine the predictive value of baseline (1) HbA1c and metabolic variables derived from intravenous (IvGTT) and oral glucose tolerance tests (OGTT), (2) insulin resistance and (3) number, type and levels of islet autoantibodies, for progression to type 1 diabetes.


METHODS
Children [n = 50, median 5.1 (4-17.9) years] with autoantibodies to glutamate decarboxylase (GAD65A) and at least one of insulinoma-associated protein 2 (IA-2A), insulin or ZnT8 transporter (ZnT8RA, ZnT8WA, ZnT8QA) were screened with IvGTT and OGTT and followed for a minimum of 2 years.


RESULTS
Baseline first phase insulin response (sum of serum-insulin at 1 and 3 min during IvGTT; FPIR) ≤3 μU/mL [HR 4.42 (CI 1.40-14.0) p = 0.011] and maximal plasma glucose ≥11.1 mmol/L measured at 30, 60 and/or 90 min during OGTT [HR 6.13 (CI 1.79-21.0) p = 0.0039] were predictors for progression to diabetes. The combination of FPIR from IvGTT and maximal plasma glucose during OGTT predicted diabetes in 10/12 children [HR 9.17 (CI 2.0-42.0) p = 0.0043]. High-level IA-2A, but not number of autoantibodies, correlated to dysglycemia during OGTT (p = 0.008) and to progression to type 1 diabetes [HR 4.98 (CI 1.09-22.0) p = 0.039].


CONCLUSIONS
Baseline FPIR, maximal plasma glucose ≥11.1 at 30, 60 or 90 min during OGTT and high-level IA-2A need to be taken into account when randomizing islet autoantibody positive non-diabetic children to secondary prevention.
Department of Clinical Sciences Malmö/Pediatric Endocrinology, Skåne University Hospital SUS, Lund University, Jan Waldenströms gata 35, CRC 60:11, 20502, Malmö, Sweden, helena.larsson@med.lu.se.
Helena
H
Elding Larsson
Christer
C
Larsson
Åke
Å
Lernmark
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000097:blood; D012307:Risk Factors; D055502:Secondary Prevention
D001323:Autoantibodies; D015415:Biomarkers; D005947:Glucose; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; C402565:glutamate decarboxylase 1