Hypoglycaemia increases aldosterone in a dose-dependent fashion
Open accessAbstract
Diabet. Med. 27, 1250–1255 (2010) Aims Intensive glycaemic control increases the incidence of hypoglycaemia. We sought to define the effects of hypoglycaemia on aldosterone, a hormone involved in cardiovascular injury and baroreflex impairment. Methods To contrast the effects of hypoglycaemia and euglycaemia on aldosterone and plasma renin activity, in Study 1, we assessed hormone levels in 13 subjects who participated in euglycaemic (5.0 mmol/l) and hypoglycaemic (2.8 mmol/l) hyperinsulinaemic clamp protocols in random order. To determine the relationship between aldosterone and the depth of hypoglycaemia, in Study 2, we assessed hormone levels in an additional 13 subjects who participated in a 3‐h stepped hypoglycaemic hyperinsulinaemic clamp protocol; blood glucose was reduced in 0.55 mmol/l steps from 5.0 to 2.2 mmol/l. Subjects were healthy and consumed controlled sodium diets. Results In Study 1, aldosterone increased approximately 2.5‐fold during hypoglycaemic hyperinsulinaemia, P < 0.001, but did not rise with euglycaemic hyperinsulinaemia. Plasma renin activity increased during both hyperinsulinaemic clamps; however, the increase was greater during hypoglycaemia (Δ = 1.5 ± 0.2 ng ml−1 h−1) vs. euglycaemia (Δ = 0.5 ± 0.1 ng ml−1 h−1), P < 0.005. In Study 2, aldosterone increased significantly at glucose levels of 2.8 mmol/l; this increase was amplified with glucose of 2.2 mmol/l. Aldosterone increases paralleled those of ACTH. Conclusions Hypoglycaemia increases aldosterone in a dose‐dependent fashion. This increase is likely attributable to activation of the renin‐angiotensin‐aldosterone system and increases in ACTH. Because aldosterone activation of the mineralocorticoid receptor is implicated in the pathophysiology of cardiovascular injury, including vascular dysfunction, inflammation, baroreflex impairment and cardiac arrhythmias, these findings may be of relevance in individuals who experience hypoglycaemia.
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Hypoglycemia activates the renin-angiotensin-aldosterone system, increasing aldosterone levels in a dose-dependent manner.
“Hypoglycemia activates the renin-angiotensin-aldosterone system, increasing aldosterone levels in a dose-dependent manner (17).”
From Effect of Hypoglycemia on QT Interval in Individuals With and Without Type 2 Diabetes: A Randomized Crossover Trial (2025) · cites this paper as [17]
The Discussion reports that hypoglycaemia increased plasma renin activity and that the aldosterone rise depended on the depth of hypoglycaemia. Its Conclusions describe activation of the renin–angiotensin–aldosterone system as a likely explanation, alongside increased ACTH; the claim presents that mechanism as established. (LLM, conf=0.84)
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Cites
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
Pitt, B., Zannad, F., Remme, W. J., Cody, R., Castaigne, A., Perez, A., Palensky, J., & Wittes, J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909023411001 · Cited by 9,214 · see citing works
Effects of Intensive Glucose Lowering in Type 2 Diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802743 · Cited by 7,888 · see citing works
Intensive versus Conventional Glucose Control in Critically Ill Patients
(2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810625 · Cited by 5,119 · see citing works
Pitt, B., Remme, W., Zannad, F., Neaton, J., Martinez, F., Roniker, B., Bittman, R., Hurley, S., Kleiman, J., & Gatlin, M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030207 · Cited by 4,941 · see citing works
Rovere, M. T. L., Bigger, J. T., Marcus, F. I., Mortara, A., & Schwartz, P. J. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11144-8 · Cited by 3,120 · see citing works
Scherrer, U., & Sartori, C. (1997) · Circulation · doi:10.1161/01.cir.96.11.4104 · Cited by 371 · see citing works
Guo, C., Ricchiuti, V., Lian, B. Q., Yao, T. M., Coutinho, P., Romero, J. R., Li, J., Williams, G. H., & Adler, G. K. (2008) · Circulation · doi:10.1161/circulationaha.107.748640 · Cited by 342 · see citing works
Self-citationGüder, G., Bauersachs, J. K., Frantz, S., Weismann, D., Allolio, B., Ertl, G., Angermann, C. E., & Störk, S. (2007) · Circulation · doi:10.1161/circulationaha.106.653964 · Cited by 294 · see citing works
Neural control of the kidney: past, present, and future.
DiBona, G. (2003) · HYPERTENSION · doi:10.1161/01.hyp.0000047205.52509.8a · Cited by 261 · see citing works
Aldosterone and Vascular Inflammation
Brown, N. J. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.095489 · Cited by 253 · see citing works
Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function
Adler, G. K., Bonyhay, I., Failing, H., Waring, E., Dotson, S., & Freeman, R. (2009) · Diabetes · doi:10.2337/db08-1153 · Cited by 216 · see citing works
Self-citationProinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects
Razavi Nematollahi, L., Kitabchi, A. E., Stentz, F. B., Wan, J. Y., Larijani, B. A., Tehrani, M. M., Gozashti, M. H., Omidfar, K., & Taheri, E. (2009) · Metabolism · doi:10.1016/j.metabol.2008.10.018 · Cited by 210 · see citing works
Adler, G. K., Kinsley, B. T., Hurwitz, S., Mossey, C. J., & Goldenberg, D. L. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00074-1 · Cited by 200 · see citing works
Self-citationBeygui, F., Collet, J., Benoliel, J. J., Vignolles, N., Dumaine, R. L., Barthélémy, O., & Montalescot, G. (2006) · Circulation · doi:10.1161/circulationaha.106.634626 · Cited by 188 · see citing works
Luther, J. M., Gainer, J. V., Murphey, L. J., Yu, C., Vaughan, D. E., Morrow, J. D., & Brown, N. J. (2006) · Hypertension · doi:10.1161/01.hyp.0000248135.97380.76 · Cited by 170 · see citing works
Ferrari, G. M. D., Sanzo, A., Bertoletti, A., Specchia, G., Vanoli, E., & Schwartz, P. J. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.08.043 · Cited by 168 · see citing works
Gomez, A. M., Rueda, A., Sainte–Marie, Y., Pereira, L., Zissimopoulos, S., Zhu, X., Schaub, R., Perrier‐Groult, E., Perrier, R., Latouche, C., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.805804 · Cited by 103 · see citing works
Aldosterone blunts the baroreflex response in man
YEE, K. M., & Struthers, A. D. (1998) · Clinical Science · doi:10.1042/cs0950687 · Cited by 93 · see citing works
Hypoglycemia Increases Serum Interleukin-6 Levels in Healthy Men and Women
Dotson, S., Freeman, R. L., Failing, H. J., & Adler, G. K. (2008) · Diabetes Care · doi:10.2337/dc07-2243 · Cited by 79 · see citing works
Self-citationAldosterone impairs baroreflex sensitivity in healthy adults
Monahan, K. D., Leuenberger, U. A., & Ray, C. A. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00622.2006 · Cited by 65 · see citing works
Insulin influences the renin-angiotensin-aldosterone system in humans
Trovati, M., Massucco, P., Anfossi, G., Cavalot, F. L., Mularoni, E., Mattiello, L., Rocca, G., & Emanuelli, G. (1989) · Metabolism · doi:10.1016/0026-0495(89)90207-2 · Cited by 61 · see citing works
Rooney, D. P., Edgar, D., Sheridan, B., Atkinson, A. B., & Bell, P. M. (1991) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1991.tb01391.x · Cited by 44 · see citing works
Perlstein, T. S., Gerhard-Herman, M., Hollenberg, N. K., Williams, G. H., & Thomas, A. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006091026 · Cited by 39 · cited 2× · see citing works
“Specifically, plasma renin activity is increased by an insulin infusion under euglycaemic conditions (8,9), but it is not known if it is further increased by an insulin infusion in the presence of hypoglycaemia.”
Yee, & Struthers, A. D. (1998) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1998.00832.x · Cited by 28 · see citing works
Acute aldosterone antagonism improves cardiac vagal control in humans
Fletcher, J., Buch, A. N., Routledge, H., Chowdhary, S., Coote, J. H., & Townend, J. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.10.058 · Cited by 23 · see citing works
Aldosterone Blunts Human Baroreflex Sensitivity by a Nongenomic Mechanism
Schmidt, B., Horisberger, K., Feuring, M., Schultz, A., & Wehling, M. (2005) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2005-837650 · Cited by 18 · see citing works
AT1 receptor blockade and the sympathoadrenal response to insulin-induced hypoglycemia in humans
Worck, R. H., Ibsen, H., Frandsen, E., & Dige‐Petersen, H. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.272.3.e415 · Cited by 18 · see citing works
Ramírez, G., Ganguly, A., Brueggemeyer, C. D., & SMITH, L. S. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-1-46 · Cited by 16 · see citing works
Trovati, M., Massucco, P., Mularoni, E., Cavalot, F. L., Anfossi, G., Mattiello, L., & Emanuelli, G. (1988) · Diabetologia · doi:10.1007/bf00277483 · Cited by 12 · see citing works
Aldosterone Response to Hypoglycemia: Evidence of ACTH Mediation
HATA, S., KUNITA, H., & Okamoto, M. (1976) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-43-1-173 · Cited by 9 · see citing works
Autonomic Neural Control Mechanisms and the Release of Adrenal Steroids after Hypoglycaemia in Man
Frier, B. M., Al‐Dujaili, E. A. S., Corrall, R. J. M., Pritchard, J., & Edwards, C. R. W. (2008) · Hormone and Metabolic Research · doi:10.1055/s-2007-1014918 · Cited by 5 · see citing works
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Cited by
Sorted by citations
Amiel, S. A., Aschner, P., Childs, B., Cryer, P. E., de Galan, B. E., Frier, B. M., Gonder-Frederick, L., Heller, S. R., Jones, T., Khunti, K., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30315-2 · Cited by 526 · see citing works
Cardiac implications of hypoglycaemia in patients with diabetes – a systematic review
Hanefeld, M., Dütting, E. D., & Bramlage, P. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-135 · Cited by 93 · see citing works
Effects of Hypoglycemia on Cardiovascular Function in Patients with Diabetes
Christou, M., Christou, P. A., Kyriakopoulos, C., Christou, G. A., & Tigas, S. K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119357 · Cited by 61 · see citing works
Treatment induced neuropathy of diabetes—Long term implications in type 1 diabetes
Gibbons, C. H. (2017) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2017.01.010 · Cited by 40 · see citing works
Heller, S. R., Geybels, M. S., Iqbal, A., Liu, L., Wagner, L., & Chow, E. (2021) · Diabetologia · doi:10.1007/s00125-021-05556-7 · Cited by 34 · see citing works
Stress, hypoglycemia, and the autonomic nervous system
Haas, A. V., Borsook, D., Adler, G. K., & Freeman, R. L. (2022) · Autonomic Neuroscience · doi:10.1016/j.autneu.2022.102983 · Cited by 26 · see citing works
Self-citationBaroreflex sensitivity impairment during hypoglycemia: implications for cardiovascular control
Rao, A. D., Bonyhay, I., Dankwa, J., Baimas-George, M., Kneen, L., Ballatori, S., Freeman, R., & Adler, G. K. (2016) · Diabetes · doi:10.2337/db15-0871 · Cited by 25 · see citing works
Self-citationInpatient dysglycemia and clinical outcomes: Association or causation?
Umpierrez, G. E., & Kosiborod, M. (2014) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2014.03.008 · Cited by 20 · see citing works
He, A., Guo, Y., Xu, Z., Yan, J., Xie, L., Li, Y., Lv, D., & Luo, M. (2022) · Microvascular Research · doi:10.1016/j.mvr.2022.104468 · Cited by 18 · see citing works
How to Escape from Primary Aldosteronism? News and Views on an Adrenal Disorder of Salt Retention
Willenberg, H. S. (2017) · Hormone and Metabolic Research · doi:10.1055/s-0043-100767 · Cited by 13 · see citing works
Non-glycemic Adverse Effects of Insulin
Hoffman, R. P., & Guarneri, A. (2021) · Current Diabetes Reviews · doi:10.2174/1573399817666210129104420 · Cited by 6 · see citing works
Hypoglycaemia in diabetic patients: highly undesirable by cardiologists
Ponikowski, P. P., & Jankowska, E. A. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht374 · Cited by 3 · see citing works
The effect of 30 min of supine rest on plasma renin concentrations in paediatric patients
Alzoubaidi, D., Johannsen, T. H., Jørgensen, N. R., & Main, K. M. (2024) · Acta Paediatrica · doi:10.1111/apa.17360 · Cited by 1 · see citing works
Haas, A. V., Koefoed, A. W., Celli, J., Bonyhay, I., White, J., Meyer, K. M., Easly-Merski, R. M., Heydarpour, M., Adler, G. K., & Freeman, R. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae919
Self-citationImpacto cardiovascular de la hipoglicemia
Espitia, M. D. L. (2017) · Revista Colombiana de Cardiología · doi:10.1016/j.rccar.2016.12.002
Li, N., Yang, M., Ren, J., Wang, M., Zhu, Q. C., Hong, J., Guo, B., Wu, T., & Lin, Y. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5345114
Yang, M., Wang, M., Zhu, Q., & Li, N. (2026) · Scientific Reports · doi:10.1038/s41598-026-48499-y
Li, N., Yang, M., Ren, J., Wang, M., Zhu, Q., Guo, B., Wu, T., & Lin, Y. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1836569
- Authors
- Adler, G. K., Bonyhay, I., Curren, V., Waring, E., & Freeman, R.
- Affiliations
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Freeman, R.
- ORCID
- Adler, G. K.
- Venue
- Diabetic Medicine
- Publisher
- Wiley
- Published
- 2010-07-14
- Volume
- 27
- Issue
- 11
- Pages
- 1250-1255
- ISSN
- 0742-3071 (ISSN-L)
- 1464-5491
- PMC
- PMC3957466
- OpenAlex
- W1512647157
- Cited by
- 18
- References
- 31
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2019: 1 · 2017: 3 · 2015: 1 · 2014: 1 · 2013: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetic Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL109634)
- National Institute on Drug Abuse (R01DA043130)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK063296)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR43130, R01AR043130)
- National Center for Research Resources (M01RR002635)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- hypoglycemia, aldosterone, plasma renin activity, ACTH, renin-angiotensin-aldosterone system, hyperinsulinemic-euglycemic clamp, tight glycemic control, mineralocorticoid receptor, cardiovascular damage, dose-response relationship
- MeSH terms
- Adult, Aldosterone, Blood Glucose, Dose-Response Relationship, Drug, Female, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Middle Aged, Renin-Angiotensin System, Glucose Clamp Technique
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