Analysis Reveals Causal Association Between Hypothyroidism and Type 1 Diabetes

Credit: Teslariu Mihai/Unsplash

A Mendelian randomization analysis provided new insight into the effect of hypothyroidism on the risk of diabetes and its related microvascular complications.¹

According to the analysis, an increase in hypothyroidism was associated with an increased risk of developing type 1 diabetes (T1D), T1D with renal complications, severe nonproliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). No association between type 2 diabetes (T2D) and T2D with renal complications was observed in the analysis.

“This study provides new insights into the prevention and treatment of diabetes and its microvascular complications, suggesting that hypothyroidism is a risk factor for new-onset diabetes and antithyroid drugs can worsen diabetes mellitus and its microvascular complications,” wrote the investigative team, led by Liming Chen from the NHC Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital.

Diabetic microvascular complications are the most common complication of diabetes, including diabetic kidney disease and diabetic retinopathy. Hypothyroidism is a systemic hypometabolic syndrome, with the main causes ranging from an autoimmune impairment, thyroid destruction, iodine overdose, and the use of antithyroid medications.² Several studies have identified an increased prevalence of diabetes and complications in patients with hypothyroidism, as well as the reverse.

Chen and colleagues noted the causal relationship between hypothyroidism and diabetes and its complications has not been established and requires further investigation. In their analysis, two-sample Mendelian randomization using genome-wide association study (GWAS) summary statistics from the UK Biobank and FinnGen consortium was performed to assess this potential causal association.

Investigators collected hypothyroidism genetic variants from the UK Biobank. The FinnGen consortium was used to gather variants for T1D, T2D, and T1D with renal complications, severe NPDR, and PDR. Multiple methods of Mendelian randomization analysis, including MR–Egger regression, weighted median, inverse variance weighted, simple mode, and weighted model, were used to examine the causal association between hypothyroidism and diabetes and its microvascular complications.

Investigators identified 10,894,596 single nucleotide polymorphisms (SNPs) associated with hypothyroidism in the UK Biobank. After applying inclusion criteria, 83 SNPs were used for Mendelian randomization analysis. According to inverse variance weighted estimate analysis, hypothyroidism was associated with T1D (β = 9.059926; SE = 1.762903; P = 2.76E-07) and T1D with renal complications (β = 10.18375; SE = 2.021879; P = 4.73E-07).

However, hypothyroidism showed no causal relationship with T2D (β = 0.05664379; SE = 0.3902611; P = .8845977) or T2D with renal complications (β = -1.842231; SE = 2.440639; P = 0.45269264). Meanwhile, hypothyroidism was positively associated with severe NPDR (β = 8.427943; SE = 2.142493; P = 8.36E-05), as well as PDR (β = 3.100939; SE = 0.74956; P = 3.52E-05).

Chen and colleagues indicated the study is limited by the greater frequency of subclinical hypothyroidism over overt disease and is often asymptomatic. As a result, undiagnosed and the genetic variants associated with hypothyroidism are poorly defined. The analysis only included cases with diagnosed hypothyroidism, meaning GWAS including subclinical disease should be included in future research.

“This will guide the clinical use of medications in patients with hyperthyroidism and suggest the importance of diabetes screening in patients with hypothyroidism,” investigators wrote.

References

1. _{Fang T, Deng X, Wang J, et al. The effect of hypothyroidism on the risk of diabetes and its microvascular complications: a Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1288284. Published 2023 Dec 5. doi:10.3389/fendo.2023.1288284}
2. _{Chaker L, Razvi S, Bensenor IM, Azizi F, Pearce EN, Peeters RP. Hypothyroidism. Nat Rev Dis Primers. (2022) 8(1):30. doi: 10.1038/s41572-022-00357-7}