TY - JOUR
T1 - Anti-Mullerian hormone levels and risk of type 2 diabetes in women
AU - Verdiesen, Renée M.G.
AU - Onland-Moret, N. Charlotte
AU - van Gils, Carla H.
AU - Stellato, Rebecca K.
AU - Spijkerman, Annemieke M.W.
AU - Picavet, H. Susan J.
AU - Broekmans, Frank J.M.
AU - Verschuren, W. M.Monique
AU - van der Schouw, Yvonne T.
N1 - Funding Information:
The authors wish to thank all participants of the Doetinchem Cohort Study and P. Vissink and A. Blokstra (Centre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment, the Netherlands) for their contribution to the study. FJMB has received fees and grant support from Merck Serono, Gedeon Richter, Ferring BV and Roche. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
Funding Information:
The Doetinchem Cohort Study is financially supported by the Ministry of Health, Welfare and Sports of the Netherlands. The funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. Ansh Labs performed the AMH measurements free of charge and was involved in data collection only. RMGV is funded by the Honours Track of MSc Epidemiology, University Medical Center Utrecht with a grant from the Netherlands Organization for Scientific Research (NWO) (grant no. 022.005.021). NWO was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. Acknowledgements Authors’ relationships and activities
Funding Information:
FJMB has received fees and grant support from Merck Serono, Gedeon Richter, Ferring BV and Roche. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/2
Y1 - 2021/2
N2 - AIMS/HYPOTHESIS: Given its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is considered to be a marker of reproductive ageing. Although accelerated reproductive ageing has been associated with a higher risk of type 2 diabetes, research on the relationship between AMH and type 2 diabetes risk is scarce. Therefore, we aimed to investigate whether age-specific AMH levels and age-related AMH trajectories are associated with type 2 diabetes risk in women.METHODS: We measured AMH in repeated plasma samples from 3293 female participants (12,460 samples in total), aged 20-59 years at recruitment, from the Doetinchem Cohort Study, a longitudinal study with follow-up visits every 5 years. We calculated age-specific AMH tertiles at baseline to account for the strong AMH-age correlation. Cox proportional hazards models adjusted for confounders were used to assess the association between baseline age-specific AMH tertiles and incident type 2 diabetes. We applied linear mixed models to compare age-related AMH trajectories for women who developed type 2 diabetes with trajectories for women who did not develop diabetes.RESULTS: During a median follow-up of 20 years, 163 women developed type 2 diabetes. Lower baseline age-specific AMH levels were associated with a higher type 2 diabetes risk (HR
T2vsT3 1.24 [95% CI 0.81, 1.92]; HR
T1vsT3 1.62 [95% CI 1.06, 2.48]; p
trend = 0.02). These findings seem to be supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages in women who developed type 2 diabetes compared with women who did not. The trajectories also suggested that AMH levels declined at a slower rate in women who developed type 2 diabetes, although differences in trajectories were not statistically significant.
CONCLUSIONS/INTERPRETATION: We observed that lower age-specific AMH levels were associated with a higher risk of type 2 diabetes in women. Longitudinal analyses did not show clear evidence of differing AMH trajectories between women who developed type 2 diabetes compared with women who did not, possibly because these analyses were underpowered. Further research is needed to investigate whether AMH is part of the biological mechanism explaining the association between reproductive ageing and type 2 diabetes. Graphical abstract.
AB - AIMS/HYPOTHESIS: Given its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is considered to be a marker of reproductive ageing. Although accelerated reproductive ageing has been associated with a higher risk of type 2 diabetes, research on the relationship between AMH and type 2 diabetes risk is scarce. Therefore, we aimed to investigate whether age-specific AMH levels and age-related AMH trajectories are associated with type 2 diabetes risk in women.METHODS: We measured AMH in repeated plasma samples from 3293 female participants (12,460 samples in total), aged 20-59 years at recruitment, from the Doetinchem Cohort Study, a longitudinal study with follow-up visits every 5 years. We calculated age-specific AMH tertiles at baseline to account for the strong AMH-age correlation. Cox proportional hazards models adjusted for confounders were used to assess the association between baseline age-specific AMH tertiles and incident type 2 diabetes. We applied linear mixed models to compare age-related AMH trajectories for women who developed type 2 diabetes with trajectories for women who did not develop diabetes.RESULTS: During a median follow-up of 20 years, 163 women developed type 2 diabetes. Lower baseline age-specific AMH levels were associated with a higher type 2 diabetes risk (HR
T2vsT3 1.24 [95% CI 0.81, 1.92]; HR
T1vsT3 1.62 [95% CI 1.06, 2.48]; p
trend = 0.02). These findings seem to be supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages in women who developed type 2 diabetes compared with women who did not. The trajectories also suggested that AMH levels declined at a slower rate in women who developed type 2 diabetes, although differences in trajectories were not statistically significant.
CONCLUSIONS/INTERPRETATION: We observed that lower age-specific AMH levels were associated with a higher risk of type 2 diabetes in women. Longitudinal analyses did not show clear evidence of differing AMH trajectories between women who developed type 2 diabetes compared with women who did not, possibly because these analyses were underpowered. Further research is needed to investigate whether AMH is part of the biological mechanism explaining the association between reproductive ageing and type 2 diabetes. Graphical abstract.
KW - AMH
KW - Anti-Müllerian hormone
KW - Longitudinal
KW - Reproductive ageing
KW - Trajectories
KW - Type 2 diabetes
KW - Women
KW - Anti-Mullerian hormone
UR - http://www.scopus.com/inward/record.url?scp=85092442284&partnerID=8YFLogxK
U2 - 10.1007/s00125-020-05302-5
DO - 10.1007/s00125-020-05302-5
M3 - Article
C2 - 33048171
AN - SCOPUS:85092442284
SN - 0012-186X
VL - 64
SP - 375
EP - 384
JO - Diabetologia
JF - Diabetologia
IS - 2
ER -