Genetic evidence strongly supports managing weight and blood pressure in addition to glycemic control in preventing vascular complications in people with type 2 diabetes
Open accessAbstract
OBJECTIVE: To investigate the causal association of type 2 diabetes and its components with risk of vascular complications independent of shared risk factors obesity and hypertension and to identify the main driver of this risk. RESEARCH DESIGN AND METHODS: We conducted Mendelian randomization (MR) using independent genetic variants previously associated with type 2 diabetes, fasting glucose, HbA1c, fasting insulin, BMI, and systolic blood pressure as instrumental variables. We obtained summary-level data for 18 vascular diseases (15 for type 2 diabetes) from FinnGen and publicly available genome-wide association studies as our outcomes. We conducted univariable and multivariable MR, in addition to sensitivity tests to detect and minimize pleiotropic effects. RESULTS: Univariable MR analysis showed that type 2 diabetes was associated with 9 of 15 outcomes; BMI and systolic blood pressure were associated with 13 and 15 of 18 vascular outcomes, respectively; and fasting insulin was associated with 4 and fasting glucose with 2. No robust association was found for HbA1c instruments. With adjustment for correlated traits in the multivariable test, BMI and systolic blood pressure, consistent causal effects were maintained, while five associations with type 2 diabetes (chronic kidney disease, ischemic heart disease, heart failure, subarachnoid hemorrhage, and intracerebral hemorrhage) were attenuated to null. CONCLUSIONS: Our findings add strong evidence to support the importance of BMI and systolic blood pressure in the development of vascular complications in people with type 2 diabetes. Such findings strongly support the need for better weight and blood pressure management in type 2 diabetes, independent of glucose lowering, to limit important complications.
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Additional evidence confirms that obesity is a contributing factor for type 2 diabetes, hypertension, and thrombotic episodes, as well as conditions linked to inflammation such as heart failure with preserved ejection fraction.
“Additional evi dence confirms that obesity is a contributing factor for type 2 diabetes, hypertension, and thrombotic ep isodes, as well as conditions linked to inflammation such as heart failure with preserved ejection frac tion. 2-7”
From Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide (2026) · cites this paper as [3]
The Introduction (page unavailable) identifies excess adiposity as an upstream factor in type 2 diabetes, and the vascular-complications results link higher BMI to several outcomes. The paper also discusses heart failure and pulmonary embolism, but the passages do not establish obesity as a cause of hypertension or thrombotic episodes generally, and they do not address inflammation or heart failure with preserved ejection fraction specifically. (LLM, conf=0.85)
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Comprehensive Long-Term Changes in Cardiovascular Risk Biomarkers With Tirzepatide
Sattar, N., Linetzky, B., Ruotolo, G., Verma, S., Sourij, H., Wang, H., Vanderman, K., Wilson, J. M., Griffin, R. M., Stefanski, A., et al. (2026) · JACC · doi:10.1016/j.jacc.2026.04.044 · Cited by 5 · see citing works
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- Authors
- Ahmed, A., Amin, H., Drenos, F., Sattar, N., & Yaghootkar, H.
- Affiliations
- Brunel University of London (GB)
- University of Glasgow (GB)
- University of Lincoln (GB)
- Corresponding author
- Yaghootkar, Hanieh
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2023-08-09
- Volume
- 46
- Issue
- 10
- Pages
- 1783-1791
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W4385690655
- Cited by
- 10
- References
- 41
- Citations by year
- 2026: 2 · 2024: 8
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- green
- bura.brunel.ac.uk
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- Brunel University Research Archive (BURA) (Brunel University London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- British Heart Foundation (RE/18/6/34217)
- Diabetes UK (17/0005594)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- type 2 diabetes, vascular complications, body mass index, systolic blood pressure, weight management, blood pressure control, glycemic control, fasting insulin, fasting blood glucose, HbA1c, chronic kidney disease, ischemic heart disease, heart failure, subarachnoid hemorrhage, intracerebral hemorrhage, causal relationship, pleiotropy
- MeSH terms
- Glycemic Control, Blood Glucose, Blood Pressure, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Insulin, Risk Factors, Body Mass Index, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis
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