Eight weeks of mineralocorticoid blockade does not improve insulin sensitivity in type 2 diabetes

Stine H Finsen, Mie R Hansen, Joachim Hoffmann-Petersen, Henrik F Højgaard, Stefan P Mortensen, Stine H Finsen, Mie R Hansen, Joachim Hoffmann-Petersen, Henrik F Højgaard, Stefan P Mortensen

Abstract

Individuals with type 2 diabetes have an increased risk of cardiovascular disease. A correlation between plasma aldosterone and hyperinsulinemia has been demonstrated in vivo, and hyperinsulinemia and insulin resistance are independently associated with the development of cardiovascular complications. We investigated if mineralocorticoid blockade (Eplerenone) improves insulin sensitivity in individuals with type 2 diabetes compared to healthy controls. We included 13 participants with type 2 diabetes (<5 years; male/female, Caucasians) and 10 healthy control participants (male/female, Caucasians). On 2 experimental days, before and at the end of the 8 weeks of treatment with mineralocorticoid blockade, a two-stage hyperinsulinemic-isoglycemic clamp (20 and 50 mU∙m-2 min-1 ) was performed for the determination of insulin sensitivity. No change in insulin sensitivity was detected at the end of the mineralocorticoid blockade in the individuals with type 2 diabetes or the healthy controls. Both before and at the end of the treatment with mineralocorticoid blockade, the individuals with type 2 diabetes had a lower insulin sensitivity compared to healthy controls. In conclusion, mineralocorticoid receptor blockade does not appear to improve insulin sensitivity in individuals with type 2 diabetes. CLINICAL TRIAL REGISTRATION: NCT03017703. https://ichgcp.net/clinical-trials-registry/NCT03017703.

Keywords: aldosterone; insulin sensitivity; mineralocorticoid blockade; type 2 diabetes.

Conflict of interest statement

The authors declare no conflict of interest.

© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Figures

FIGURE 1
FIGURE 1
Experimental protocol. A two‐stage hyperinsulinemic‐isoglycemic clamp was performed. At −30, −20 and −10 min before initiating the first stage and during periods of steady state in both clamp stage one and two, blood samples were measured for every 10 min. Red arrows indicate blood samples drawn at steady state periods during baseline, clamp stage one and clamp stage two
FIGURE 2
FIGURE 2
Glucose infusion rate (GIR; mL h‐1) before and following mineralocorticoid blockade (MR). T2D: individuals with type 2 diabetes. CON: control participants. *p = 0.04 in the individuals with type 2 diabetes
FIGURE 3
FIGURE 3
Difference in calculated baseline sensitivity (panel A) and insulin resistance (panel B) by HOMA2 between the individuals with type 2 diabetes and healthy controls before and following mineralocorticoid blockade (MR). CON: healthy controls, T2D: individuals with type 2 diabetes. Pre: prior to MR blockade. Post: following MR blockade. Panel A: pre MR: *p = 0.03, post MR: *p = 0.02. Panel B: pre MR: *p = 0.03

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