Etiologic Determinants and Characteristics of Diabetes in Haitian Youth (EDDHY Study)

Abstract

Aims: Published information on youth-onset diabetes in Haiti is scarce, with limited data available on diabetes autoimmunity and genetic susceptibility to the disease. We determined the anthropometric, metabolic, and immunological characteristics and human leukocyte antigen (HLA)-associated risks in patients with youth-onset diabetes. Methods: One hundred and ten subjects with type 1 diabetes (T1D) aged <22 years and diagnosed for < 2 years were evaluated. Demographic and clinical information, as well as biochemical parameters, including blood glucose, hemoglobin A1c, fasting C-peptide (FCP), and T1D-associated autoantibodies, were assessed. DNA from 54 subjects and 66 controls was genotyped for classical HLA loci. Results: Of the 110 patients, 54% were male. Onset age was 13.5 ± 4.2 years (range 2-21), and disease duration was 11.7 ± 8.1 months (range 0-24). Idiopathic T1D was found in 62 (56.4%) patients and was diagnosed at an older age than immune-mediated T1D (14.4 ± 3.5 years vs., 12.3 ± 4.8 years, p=0.01), with a higher BMI z-score in patients aged <14 years than in those aged ≥14 years (-0.29 ± 1.52 vs., -1.15 ± 1.18, p=0.01). No correlation was found between immune-mediated T1D and BMI z-score. Diabetic ketoacidosis was present at diagnosis in 18 (16.4%) patients. Zinc transporter 8 autoantibodies (ZnT8A) were marginally more common in younger patients. Low FCP levels were found in 71 (64.5%) patients. Thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin antibodies (TG-Ab) were positive in 1.1% and 2.2% of the patients, respectively. The alleles DRB1⁣ ^∗ 03:01, DRB1⁣ ^∗ 09:01, DQB1⁣ ^∗ 02:01, and DQB1⁣ ^∗ 02:02 showed a significant T1D risk, whereas DRB1⁣ ^∗ 08:04, DRB1⁣ ^∗ 15:03, and DQB1⁣ ^∗ 06:02 were protective. Three DRB1~DQB1 haplotypes were strongly associated with T1D: DRB1⁣ ^∗ 03:01:01~DQB1⁣ ^∗ 02:01:01, DRB1⁣ ^∗ 09:01:02~DQB1⁣ ^∗ 02:02:01, both predisposing, and DRB1⁣ ^∗ 15:03:01~DQB1⁣ ^∗ 06:02:01, protective. Conclusions: Idiopathic T1D is common among youth in Haiti. A significant proportion of all patients had preserved C-peptide secretion. Overall, predisposing and protective HLA patterns were identified. Study results highlight the importance of distinguishing T1D endotypes within and between populations.

Keywords: autoimmunity; genetics; idiopathic type 1 diabetes; youth-onset diabetes.

Figure 1

Age of diabetes onset.

Figure 2

Pairwise matrix of W_n values in Haitian T1D individuals and control Individuals. Pairwise W_n values for T1D individuals are shown in the upper half of the matrix, while W_n values for control individuals are shown in the lower half. As show in the inset scale, the range of values is color coded from red to blue. T1D, type 1 diabetes.