Liver indicators affecting the relationship between BMI and hypertension in type 2 diabetes: a mediation analysis

Abstract

Background: Body mass index (BMI) is an important risk factor for hypertension in diabetic patients. However, the underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored them in the association between BMI and hypertension in diabetes.

Objective: To investigate the role of liver enzymes in mediating the relationship between BIM exposure and hypertension in type 2 diabetes mellitus (T2DM).

Methods: We included a total of 1765 participants from the China National Diabetic Chronic Complications Study Cohort. Associations between liver enzymes and hypertension were estimated using multivariable regression models. The function of liver indicators in the relationship between BMI and hypertension was assessed using mediation analysis. Mediation analysis was conducted, taking into account age, diabetes duration, current smoking, fasting plasma glucose level, glycated hemoglobin, anti-diabetic therapy, and family history of diseases, including diabetes, hypertension, obesity, and hyperlipidemia.

Results: For men, the association of BMI with hypertension was partially mediated by alanine aminotransferase (ALT), with a proportion of mediation was 68.67%, by aspartate aminotransferase (AST) was 27.02%, and by γ-glutamyltransferase (GGT) was 38.58%, by AST/ALT was 63.35%; for women, the proportion mediated by ALT was 36.93%, and by AST was 37.47%, and GGT was 44.60%, and AST/ALT was 43.73% for BMI (all P < 0.05).

Conclusion: The effect of BMI on hypertension is partly mediated by liver indicators (ALT, AST, GGT, and AST/ALT) in diabetic patients. Our results may provide opportunities to identify new targets for hypertension interventions.

Keywords: BMI; Hypertension; Liver indicators; Mediation effect; Type 2 diabetes mellitus.

Fig. 1

Flow charts for participants’ enrollment

Fig. 2

The mediating effect of liver indicators on the BMI associated-hypertension among T2DM adults. The upper (blue) box indicated male patients with T2DM, while the lower (red) box indicated female. A–D illustrated how liver indicators, specifically ALT, AST, GGT, and AST/ALT, mediate the link between BMI and hypertension. E–H showed the mediating effect of the relationship between BMI and hypertension mediated by liver indicators, including ALT, AST, GGT, AST/ALT, respectively