Mendelian randomization showed BMI and systolic blood pressure were associated with 13 and 15 of 18 vascular outcomes, respectively, while 5 associations with type 2 diabetes were attenuated to null.
Observational
Do genetic variants associated with BMI and systolic blood pressure causally increase the risk of vascular complications in people with type 2 diabetes independent of glycemic control?
Mendelian randomization provides strong evidence that BMI and systolic blood pressure, rather than glycemic control alone, are the main drivers of vascular complications in type 2 diabetes.
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.
Ahmed et al. (Wed,) conducted a observational in Type 2 diabetes and vascular complications. Genetic variants for type 2 diabetes, BMI, and systolic blood pressure was evaluated on 18 vascular diseases. Mendelian randomization showed BMI and systolic blood pressure were associated with 13 and 15 of 18 vascular outcomes, respectively, while 5 associations with type 2 diabetes were attenuated to null.
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