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The relationship between normal thyroid function and type 2 diabetes mellitus (T2DM) has been a particular focus for concern. The present study determined the relationship between thyroid hormone levels and the prevalence of diabetic retinopathy (DR) in T2DM patients. A cross-sectional study (n = 633) was performed in Xi'an, Shaanxi Province, China. Subjects were evaluated for anthropometric measurements, thyroid function, and diabetic retinopathy. Logistic regression models were used to assess the relationships between thyroid hormones and DR. Of 633 patients, 243 (38.4%) patients suffered from DR. The prevalence of DR showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) (FT3 quartile 1 group [FT3-Q1] <4.35 pmol/L, FT3 quartile 2 group [FT3-Q2] 4.35–4.70 pmol/L, FT3 quartile 3 group [FT3-Q3] 4.70–5.08 pmol/L, and FT3 quartile 4 group [FT3-Q4] ≥5.08 pmol/L) (56.7%, 42.5%, 33.1%, 23.8%, P < 0.001). In comparison with all participants categorized in FT3-Q1, the multivariable adjusted odds ratios (95% confidence interval) of DR in FT3-Q2, FT3-Q3, and FT3-Q4 were 0.587 (0.340–1.012), 0.458 (0.258–0.813), and 0.368 (0.201–0.673), (P = 0.055 , P = 0.008 , P = 0.001), respectively. FT3 levels within the normal range are negatively associated with DR in euthyroid patients with type 2 diabetes. Further studies should be aimed at clarifying the relationship between thyroid hormones and T2DM. [ABSTRACT FROM AUTHOR]

Background: Folate deficiency is an independent risk factor for congenital heart disease (CHD); however, the maternal plasma folate level is paradoxically not a good diagnostic marker. Genome-wide surveys have identified variants of nonfolate metabolic genes associated with the plasma folate level, suggesting that these genetic polymorphisms are potential risk factors for CHD.Methods: To examine the effects of folate concentration-related variations on CHD risk in the Han Chinese population, we performed 3 independent case-control studies including a total of 1489 patients with CHD and 1745 control subjects. The expression of the Fidgetin (FIGN) was detected in human cardiovascular and decidua tissue specimens with quantitative real-time polymerase chain reaction and Western blotting. The molecular mechanisms were investigated by luciferase reporter assays, surface plasmon resonance, and chromatin immunoprecipitation. FIGN-interacting proteins were confirmed by tandem affinity purification and coimmunoprecipitation. Proteasome activity and metabolite concentrations in the folate pathway were quantified with a commercial proteasome activity assay and immunoassays, respectively.Results: The +94762G>C (rs2119289) variant in intron 4 of the FIGN gene was associated with significant reduction in CHD susceptibility (P=5.1×10-14 for the allele, P=8.5×10--13 for the genotype). Analysis of combined samples indicated that CHD risks in individuals carrying heterozygous (GC) or homozygous (CC) genotypes were reduced by 44% (odds ratio [OR]=0.56; 95% confidence interval [CI]=0.47-0.67) and 66% (OR=0.34; 95% CI=0.23-0.50), respectively, compared with those with the major GG genotype. Minor C allele carriers who had decreased plasma folate levels exhibited significantly increased FIGN expression because the transcription suppressor CREB1 did not bind the alternative promoter of FIGN isoform X3. Mechanistically, increased FIGN expression led to the accumulation of both reduced folate carrier 1 and dihydrofolate reductase via inhibition of their proteasomal degradation, which promoted folate absorption and metabolism.Conclusions: We report a previously undocumented finding that decreased circulating folate levels induced by increased folate transmembrane transport and utilization, as determined by the FIGN intronic variant, serves as a protective mechanism against CHD. Our results may explain why circulating folate levels do not have a good diagnostic value. [ABSTRACT FROM AUTHOR]