High Plasma 18β-Glycyrrhetinic Acid Levels Are Associated With More Intensive Antihypertensive Treatment, Resistant Hypertension and Apparent Mineralocorticoid Excess in Patients With Type 2 Diabetes

Background

Excessive consumption of glycyrrhizin (GL), a licorice-derived substance, can cause blood pressure (BP) elevation and apparent mineralocorticoid excess (AME). However, self-reported intake can be unreliable due to unrecognized sources of GL. Plasma levels of 18β-glycyrrhetinic acid (GA), a major metabolite of GL, may serve as a biochemical marker of exposure. Identifying individuals with high plasma levels of GA could be relevant in BP management in at-risk patients.

Objectives

To examine whether plasma levels of GA are associated with BP, antihypertensive treatment intensity, resistant hypertension, and biochemical markers of AME in patients with type 2 diabetes (T2D).

Methods

In this cross-sectional study, we measured GA in plasma from 1160 patients with T2D. Participants were divided into high GA (top quartile) and low GA (bottom 3 quartiles). Linear and logistic regression models assessed associations of GA levels with BP, antihypertensive treatment intensity (defined daily dose; DDD), resistant hypertension and markers of AME. Models were adjusted for confounders such as age, sex, sociodemographic, lifestyle, diabetes duration, estimated glomerular filtration rate, glycated hemoglobin, homoeostasis model assessment 2 for insulin sensitivity, and where appropriate systolic BP and treatment.

Results

High GA was not significantly associated with higher BP but with more intensive antihypertensive treatment (+0.28 DDD [0.03–0.52], P = 0.03) compared with low GA. High GA was also associated with higher risk of resistant hypertension (adjusted odds ratio: 1.91 [1.12–3.24], P = 0.02). Additionally, high GA was associated with markers of AME (lower aldosterone (−41.5 pmol/L [−63.1 to −20.0]; P < 0.001), lower potassium (−0.06 mmol/L [−0.10 to −0.01]; P = 0.01), lower cortisone (−6.08 nmol/L [−7.78 to −4.38]; P < 0.001), and higher cortisol/cortisone ratio (+1.26 [1.00–1.52]; P < 0.001)).

Conclusion

High GA levels, a possible marker of excessive licorice consumption, were associated with greater antihypertensive treatment intensity, resistant hypertension and biochemical markers consistent with AME in patients with T2D. These findings suggest that licorice-related exposure may be relevant to BP management in this population.