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Relationship between type 2 diabetes mellitus and hypothalamic-pituitary-adrenal axis

Zusammenhang zwischen Typ 2 Diabetes mellitus und der Hypothalamus-Hypophysen-Nebennieren Achse

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Zusammenfassung

EINLEITUNG: Hyperkortizismus führt häufig zu einer Störung der Glukosetoleranz beziehungsweise zu Typ 2 Diabetes mellitus. Andererseits werden bei Patienten mit Typ 2 Diabetes mellitus in letzter Zeit Änderungen in der Regulation der Hypothalamus-Hypophysen-Nebennieren Achse diskutiert. PATIENTEN, MATERIAL UND METHODEN: Bei 50 Patienten mit Typ 2 Diabetes mellitus, sowie bei 25 Alters-, Geschlechts- und BMI- gematchten Kontrollpersonen ohne Diabetes mellitus wurde von den Autoren die Aktivität der Hypothalamus-Hypophysen-Nebennieren Achse, sowie auf das Vorkommen eines subklinischen Cushing Syndroms geprüft. Es wurde der 1mg Dexamethason Test mit dem vom NIH empfohlenen Cut-off Wert für ein Inzidentalom der Nebenniere (Serum Kortisol nach Suppression >138 nmol/l) verwendet, um die Diagnose eines subklinischen Hyperkortizismus zu stellen. ERGEBNISSE: Die Serumkonzentrationen von ACTH, DHEA-S, Cortisol (sowohl basal als auch nach Suppression mit 1mg Dexamethason), sowie die Prävalenz eines subklinischen Cushing Syndroms (18% versus 24%, p = 0.54) waren in beiden Gruppen ähnlich und ohne signifikanten Unterschied. Es bestand auch keine Beziehung zur Art der Therapie des Diabetes mellitus (orale Antidiabetika oder Insulin). Eine Trennung nach Alter ergab, dass Diabetiker über 60 Jahre signifikant schlechter als ihre altersgematchen Kontrollen ihr Cortisol supprimierten (99,3 vs. 85,5 nmol/l, p = 0,0001). Außerdem konnte der altersabhängige Abfall von DHEA-S bei Diabetikern im Gegensatz zu den Ergebnissen bei Kontrollen nicht beobachtet werden (r = –0,302, p = 0,033; r = –0,596, p = 0,0017). Innerhalb der Gruppe der diabetischen Patienten wurde eine positive Korrelation zwischen C-Peptid Konzentrationen und basalem Cortisol, beziehungsweise DHEA-S festgestellt (r = 0,445, p = 0,001 und r = 0,339, p = 0,017). SCHLUSSFOLGERUNGEN: Unsere Ergebnisse zeigen eine relativ hohe – aber bei beiden Gruppen vergleichbare - Rate von verminderter Suppression des Cortisols. Wir glauben, dass diese hohe Prävalenz von subklinischem Cushing Syndrom auf das angewandte, sehr strenge, Diagnosekriterium zurückzuführen ist. Es besteht kein Einfluss der Therapieart des Diabetes mellitus (Insulin oder orale Antidiabetika) auf die Aktivität der Hypothalamus-Hypophysen-Nebennieren Achse. Unsere Ergebnisse könnten auf eine mögliche Rolle des Cortisols bei der Pathogenese des Typ 2 Diabetes mellitus bei Patienten mit metabolischem Syndrom hindeuten. Außerdem könnten sie auch als Hinweis auf die protektive Rolle des DHEA-S im Rahmen der sekundären gegenregulatorischen Mechanismen zur Verbesserung der Insulinsensitivität und Reduktion der Hyperinsulinämie gedeutet werden.

Summary

INTRODUCTION: Hypercortisolism often leads to impaired glucose tolerance or type 2 diabetes mellitus. On the other hand, changes in the regulation of hypothalamic-pituitary-adrenal axis become a matter of debate in patients with type 2 diabetes mellitus/metabolic syndrome. PATIENTS, MATERIALS, AND METHODS: Authors assessed the hypothalamic-pituitary-adrenal axis activity and subclinical Cushing's syndrome occurrence in 50 patients with type 2 diabetes mellitus in comparison to 25 sex-, age-, and BMI-matched control nondiabetic subjects. 1 mg dexamethasone suppression test with NIH recommended cut-off level for adrenal incidentaloma (serum cortisol after suppression > 138 nmol/l) was used to postulate the diagnosis of subclinical hypercortisolism. RESULTS: There were no significant differences in serum ACTH, DHEA-S, baseline serum cortisol as well as serum cortisol after suppression of 1 mg dexamethasone/subclinical Cushing's syndrome prevalence in both diabetic and control groups (18 vs. 24% respectively, p = 0.54) and there was no relation to the type of treatment (OAD vs. insulin) in group of diabetics. When divided according to age, diabetics older than 60 years suppressed their serum cortisol significantly worse than their age-related controls (99.3 vs. 85.5 nmol/l, p = 0.0001). Furthermore, diabetics did not show an age-related decrease in DHEA-S levels, whereas controls did (r = –0.302, p = 0.033; r = –0.596, p = 0.0017 respectively). Within the group of diabetics, a positive correlation between C-peptid levels and baseline serum cortisol/DHEA-S levels was detected as well (r = 0.445, p = 0.001 and r = 0.339, p = 0.017 respectively). CONCLUSION: Our data show relatively high but comparable lack of cortisol suppression in both diabetic and control groups; however, we consider the subclinical Cushing's syndrome diagnose to be criteria dependent. There is no dependence of type of diabetes treatment (OAD vs. insulin) on HPA axis activity. Our results might indicate the possible role of cortisol in pathogenesis of type 2 diabetes mellitus in patients with metabolic syndrome as well as possible protective role of DHEA-S within the frame of secondary contraregulatory mechanisms aimed to improve insulin sensitivity and reduce the hyperinsulinemia.

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Authors and Affiliations

  1. 1st Department of Internal Medicine, L. Pasteur University Hospital and Medical Faculty of P. J. Šafárik University, Košice, Slovakia

    Marek Felšöci & Ivica Lazúrová

  2. 4th Department of Internal Medicine, L. Pasteur University Hospital and Medical Faculty of P. J. Šafárik University, Košice, Slovakia

    Zbyněk Schroner

  3. Institute of Biostatistics, P. J. Šafárik University, Košice, Slovakia

    Jozefína Petrovičová

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  1. Marek Felšöci
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  2. Zbyněk Schroner
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  3. Jozefína Petrovičová
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  4. Ivica Lazúrová
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Correspondence to Marek Felšöci.

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Felšöci, M., Schroner, Z., Petrovičová, J. et al. Relationship between type 2 diabetes mellitus and hypothalamic-pituitary-adrenal axis. Wien Klin Wochenschr 123, 28–33 (2011). https://doi.org/10.1007/s00508-010-1497-8

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