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

Pediatr Diabetes. 2010 Jun;11(4):218-26. doi: 10.1111/j.1399-5448.2009.00566.x. Epub 2008 Aug 25.

Abstract

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).

Subjects and 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.

MeSH terms

  • Adolescent
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • C-Peptide / blood
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetic Ketoacidosis / blood
  • Diabetic Ketoacidosis / diagnosis*
  • Diabetic Ketoacidosis / metabolism*
  • Female
  • Glutamate Decarboxylase / blood
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin A / analysis
  • HLA Antigens / blood
  • HLA Antigens / immunology*
  • Humans
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / therapeutic use
  • Infant
  • Insulin / blood
  • Insulin / immunology
  • Insulin / therapeutic use
  • Insulin Antibodies / blood
  • Insulin-Secreting Cells / immunology*
  • Insulin-Secreting Cells / metabolism
  • Male
  • Multicenter Studies as Topic
  • Prospective Studies
  • Treatment Outcome

Substances

  • Autoantibodies
  • C-Peptide
  • Glycated Hemoglobin A
  • HLA Antigens
  • Hypoglycemic Agents
  • ICA512 autoantibody
  • Insulin
  • Insulin Antibodies
  • hemoglobin A1c protein, human
  • islet cell antibody
  • Glutamate Decarboxylase