Association between thyroid function and type 2 diabetes mellitus based on the NHANES and Mendelian randomization...

Area of Science:

• Endocrinology
• Metabolic Diseases
• Genetic Epidemiology

Background:

• Observational studies suggest a link between thyroid function and type 2 diabetes mellitus (T2DM).
• The causal relationship between thyroid dysfunction and T2DM remains unclear.
• Investigating this link is crucial for understanding T2DM pathogenesis.

Purpose of the Study:

• To examine the association between thyroid function and T2DM.
• To determine the causal relationship using Mendelian randomization (MR) analysis.
• To leverage NHANES database (2007-2012) and GWAS data.

Main Methods:

• Cross-sectional analysis of NHANES data with logistic regression.
• Mendelian randomization (MR) analysis using GWAS data for thyroid function and T2DM.
• Instrumental variables (SNPs) for free thyroxine (FT4), TSH, hyperthyroidism, and hypothyroidism.
• Inverse-variance weighting (IVW), MR-Egger, and weighted median methods for causal inference.
• Cochran's Q test and MR-Egger intercept for heterogeneity and pleiotropy assessment.

Main Results:

• NHANES analysis showed no association between thyroid function and T2DM in adjusted models.
• MR analysis indicated a potential causal effect of TSH on T2DM (ORs ranging from 0.86 to 0.94).
• MR analysis revealed a significant causal effect of hypothyroidism on T2DM (ORs ranging from 2.60 to 5.71).
• Heterogeneity was observed for hypothyroidism-related SNPs, necessitating the IVW random effects model.

Conclusions:

• Findings suggest a potential causal relationship between TSH, hypothyroidism, and T2DM.
• Thyroid dysfunction, particularly hypothyroidism, may play a causal role in T2DM development.
• Further research is warranted to elucidate the complex interplay between thyroid function and T2DM.