Endocrine Abstracts

Background

Graves’ Disease (GD) is characterized by production of stimulating autoantibodies to thyrotropin receptor resulting in hyperthyroidism. Hyperthyroidism is associated with insulin resistance, hyperglycemia and ketosis. Our aim was to evaluate if single nucleotide polymorphism (SNP) in pro-inflammatory cytokines contributes to dysglycemia in GD.

Methods

We evaluated 98 patients with Graves’ disease. Genetic variants in IL6-174 G/C, TNFA-308 G/A, IL1B-511 C/T, and IFNGR1-56 T/C were analyzed by real-time PCR. Patients were evaluated with oral glucose tolerance test with determination of glucose, insulin, C peptide and indexes of insulin resistance: HOMA-IR (homeostatic assessment insulin resistance index), HOMA-β (HOMA of β-cell function) and WBISI (whole-body insulin sensitivity index). Diabetes was defined according to ADA criteria. The associations of genetic variants with glycemic profile were evaluated with analysis unadjusted and adjusted for age and sex.

Results

The allele T in IL1B-511 C/T was significantly associated with a higher prevalence of diabetes (P = 0.029). The A allele in TNFA-308 G/A was associated with higher levels of fasting insulin in the adjusted analysis (P = 0.042) and higher levels of HOMA-β in both analyses (P = 0.027; P = 0.020). The T allele in IFNGR1-56 T/C polymorphism was associated with significantly higher mean values of fasting glucose (P = 0.047), as well as higher levels of C peptide (P = 0.026) in the unadjusted analysis.

Conclusions

SNP in pro-inflammatory cytokines may affect glycemic profile in patients with GD. These polymorphisms are associated with higher levels of fasting insulin and HOMA-β, increased fasting glucose and C peptide, and higher prevalence of diabetes.