Type 1 diabetes mellitus (T1DM) is highly prevalent in Kuwait with incidence of around 40.1/100,000 individuals. Evidence indicate that vitamin D plays an important role in modulating the immune system and could thus impact the onset and high prevalence of T1DM. We report serum vitamin D levels in Kuwaiti children with T1DM and non-diabetic controls to explore its relationship with prevalence and onset of the disease. This study included 216 Kuwaiti Arab children with T1DM. The diagnosis of T1DM was based on the ISPAD criteria. The control subjects (204 Kuwaitis) were age and gender matched, healthy, non-diabetic, and had no close relative with T1DM. Vitamin D levels were determined in serum using an enzyme immunoassay (EIA) method. The age of onset of T1DM was 6y in 52 % patients. In T1DM patient group, 84 % subjects were found to be deficient in serum vitamin D level compared to 77 % of the controls (p = 0.046). Collectively, the deficient and insufficient vitamin D status was detected in 99 % of the T1DM patients compared to 92 % of the controls (p = 0.027). The mean serum vitamin D levels were found to be significantly different in early onset cases (age <4y) compared to the late onset sub-group (p = 0.001). A significant correlation was found between some elements of socioeconomic status, SES (i.e. parent’s profession and family’s income) and lower vitamin D levels in Kuwaiti T1DM children. There was no significant difference between mean serum vitamin D levels during winter and summer months in the T1DM patients. The proportion of cases with a deficient vitamin D status was significantly high in Kuwaiti T1DM children compared to the controls. The serum vitamin D levels were found to be significantly different in early onset and late onset T1DM patients. Therefore, serum vitamin D status can be considered an important contributor in high prevalence of T1DM in Kuwaiti children.
The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility. The genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays. Statistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C > T, rs10735810 and TaqI, C > T, rs731236) between T1DM patients and controls (P < 0.0001). In both, the frequency of variant alleles was considerably high in T1DM than in the controls. In contrast, the VDR gene ApaI (G > T, rs7975232) and BsmI (A > G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and > 6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes. Our results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.