The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes

Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

Low bone mineral density in Type 1 diabetic patients: influence of reduced IGF1, IGF1R, and TGFB1 expression

BACKGROUND:The negative effect of Type 1 diabetes (T1D) on growth factors of bone metabolism leads to a reduction in bone mineral density (BMD). Therefore, this study aimed to evaluate the association between BMD and IGF1, IGF1R and TGFB1 expression in children and adolescents with T1D. Moreover, the influences of age at diagnosis, time since diagnosis, glycemic control, and albuminuria on BMD were investigated.METHODS:Eighty-six T1D children/adolescents (T1D group) and ninety normoglycemic controls (NG group) were included. T1D patients were analyzed altogether, and divided into two groups according to their glycemic profile (T1D with good glycemic control [T1DG group] and T1D with poor glycemic control [T1DP group]). BMD was assessed by dual energy X-ray absorptiometry. Glycemic control, renal function, and bone markers were also assessed. IGF1, IGF1R, and TGFB1 expressions were measured by real-time PCR.RESULTS:Patients with T1D showed low BMD and poor glycemic control. Serum total calcium and albumin-to-creatinine ratio were higher in the T1DP group compared to the T1DG group (p = 0.003 and p = 0.035, respectively). There was a reduction of IGF1, IGF1R, and TGFB1 expression in the T1D and T1DP groups compared to the NG group (p < 0.05).CONCLUSIONS:The decreased IGF1, IGF1R, and TGFB1 expression in the T1D and T1DP group of patients, who presented with T1D at an early age, had been diagnosed with T1D for a longer time, had poor glycemic control and albuminuria, may contribute to low BMD. This article is protected by copyright. All rights reserved.