Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis.
OBJECTIVE
To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D).


METHODS
Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal-stimulated C-peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally.


RESULTS
Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta-cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C-peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C-peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C-peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non-white Caucasian ethnicity (p = 0.002).


CONCLUSIONS
Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta-cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month.
Mortensen
Henrik B
HB
Department of Pediatrics, Glostrup University Hospital, Glostrup, Denmark. hbmo@glo.regionh.dk
Swift
Peter G F
PG
Holl
Reinhard W
RW
Hougaard
P
P
Hansen
Lars
L
Bjoerndalen
Hilde
H
de Beaufort
Carine E
CE
Knip
Michael
M
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D016883:Diabetic Ketoacidosis / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000627:therapeutic use; D007223:Infant; D007328:Insulin / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D007330:Insulin Antibodies / Q000097:blood; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D008297:Male; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D016896:Treatment Outcome
D001323:Autoantibodies; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D006680:HLA Antigens; D007004:Hypoglycemic Agents; D007328:Insulin; D007330:Insulin Antibodies; C096322:ICA512 autoantibody; C517652:hemoglobin A1c protein, human; C024211:islet cell antibody