The effect of hypothyroidism on the risk of diabetes and its microvascular complications: a Mendelian randomization study

Ting Fang; Xiaoqing Deng; Jingyi Wang; Fei Han; Xiangyang Liu; Yajin Liu; Bei Sun; Liming Chen

doi:10.3389/fendo.2023.1288284

The effect of hypothyroidism on the risk of diabetes and its microvascular complications: a Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Dec 5:14:1288284. doi: 10.3389/fendo.2023.1288284. eCollection 2023.

Authors

Ting Fang^{1

2}, Xiaoqing Deng^{1

2}, Jingyi Wang^{1

2}, Fei Han^{1

2}, Xiangyang Liu^{1

2}, Yajin Liu^{1

2}, Bei Sun^{1

2}, Liming Chen^{1

2}

Affiliations

¹ NHC Key Laboratory of Hormones and Development, Tianjin Medical University Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
² Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

Abstract

Context: Several observational studies have found that hypothyroidism is associated with diabetes and its microvascular complications. However, the cause and effect have not been clarified.

Objective: The aim of the study was to examine the causality of such associations by a Mendelian randomization study.

Methods: Two-sample Mendelian randomization analysis was conducted to investigate the associations. Summary statistics for hypothyroidism were from the UK Biobank, and diabetes and its microvascular complications were from the largest available genome-wide association studies. MR-Egger, weighted median, inverse variance weighted, simple mode and weighted mode were used to examine the causal associations, and several sensitivity analyses were used to assess pleiotropy.

Results: Inverse variance weighted estimates suggested that hypothyroidism was associated with type 1 diabetes and type 1 diabetes with renal complications (β= 9.059926, se= 1.762903, P = 2.76E-07 and β= 10.18375, se= 2.021879, P = 4.73E-07, respectively) but not type 2 diabetes and type 2 diabetes with renal complications. In addition, hypothyroidism was positively associated with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (β= 8.427943, se= 2.142493, P = 8.36E-05 and β= 3.100939, se= 0.74956, P=3.52E-05, respectively).

Conclusions: The study identified the causal roles of hypothyroidism in diabetes and its microvascular complications. Hypothyroidism can lead to type 1 diabetes, type 1 diabetes with renal complications, severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy.

Keywords: Mendelian randomization; diabetes; diabetic kidney disease; diabetic retinopathy; hypothyroidism; microvascular complications.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 1* / complications
Diabetes Mellitus, Type 1* / genetics
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / genetics
Diabetic Retinopathy* / etiology
Diabetic Retinopathy* / genetics
Genome-Wide Association Study
Humans
Hypothyroidism* / complications
Hypothyroidism* / genetics
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Tianjin Natural Science Foundation (22JCQNJC01230) and the Tianjin Health Science and technology project (TJWJ2021MS020).