Published online Aug 15, 2024. doi: 10.4239/wjd.v15.i8.1717
Revised: May 28, 2024
Accepted: June 26, 2024
Published online: August 15, 2024
Processing time: 113 Days and 2.6 Hours
Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus (T2DM), that is, patients who have insulin resistance, obesity, and other cardiovascular risk factors, suggesting that the presence of glutamic acid decarboxylase (anti-GAD65), islet antigen 2 (anti-IA2), and zinc transporter 8 (anti-Zn8T) antibodies could have deleterious effects on beta cell function, causing failure and earlier requirement for insulin treatment.
To evaluate anti-GAD65, anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM.
This was a case–control study in patients with clinically diagnosed with T2DM (68 cases and 64 controls with and without early insulin dependence respectively), male and female, aged 12–18 years. Somatometry, blood pressure, glucose, insulin, C-peptide, glycated hemoglobin A1c, and lipid profiles were assessed. ELISA was used to measure anti-GAD65, anti-IA2, and anti-Zn8T antibodies. Descriptive statistics, Pearson's χ2 test, Student's t test, and logistic regression was performed. P < 0.05 was considered statistically significant.
There were 132 patients (53.8% female), with a mean age was 15.9 ± 1.3 years, and there was a disease evolution time of 4.49 ± 0.88 years. The presence of anti-GAD65, anti-IA2, and anti-Zn8T positivity was found in 29.5%, 18.2%, and 15.9%, respectively. Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity: anti-GAD65 odds ratio (OR): 2.42 (1.112–5.303, P = 0.026); anti-IA2: OR: 1.55 (0.859–2.818, P = 0.105); and anti-Zn8T: OR: 7.32 (2.039–26.279, P = 0.002).
Anti-GAD65 positivity was high in our study. Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype, leading to an increased risk of early insulin dependence.
Core tip: We found that adolescent patients with type 2 diabetes mellitus (T2DM) showed a more aggressive phenotype of the disease, with a significant depletion of beta cell function, and where antibodies against pancreatic beta cells were associated with lower levels of insulin and C-peptide conferring a higher risk of early dependence on exogenous insulin. Therefore, in a pediatric patient with T2DM phenotype, the determination of pancreatic antibodies can be a clinical tool to predict early insulin requirements, leading to closer control of the disease to avoid chronic complications.