Age at menarche and the future risk of gestational diabetes: a systematic review and dose response meta-analysis

Acta Diabetologica, Aug 2018

Published studies show an inconsistent association between age at menarche and the subsequent risk of developing gestational diabetes mellitus when pregnant. This systematic review and meta-analysis was performed to clarify any trends in this association in published observational population studies. We searched online databases for relevant studies, entered into them up until June 21st 2017. Five eligible studies were found and a pooled random effects dose response meta-analysis of results from these was conducted. This included coverage of 58,133 pregnancies, from which 3,035 women developed gestational diabetes. There was evidence of a non-linear association between age at menarche and gestational diabetes (overall p = 1.4 × 10−8; p for non-linearity = 2.4 × 10−4), along with evidence of relatively low heterogeneity (I2 = 25.5%). The largest predicted risk of gestational diabetes was associated with having a low age at menarche; the mean (95% confidence interval) risk relative to that associated with menarche at age 13 years being: 9 years 2.0 (1.6, 2.4), 10 years 1.6 (1.4, 1.9), 11 years 1.3 (1.2, 1.4), 12 years 1.1 (1.1, 1.1), 13 years was the reference, 14 years 1.0 (1.0, 1.0), 15 years 1.1 (0.9, 1.2), 16 years 1.1 (0.9, 1.4). There was evidence of potential publication bias, such that the maximal true relative risk of gestational diabetes, associated with an age at menarche of 9 years, may be closer to 1.6 than 2. Nevertheless, the curvilinear relationship between age at menarche and the future risk of gestational diabetes in pregnancy appears robust.

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Age at menarche and the future risk of gestational diabetes: a systematic review and dose response meta-analysis

Acta Diabetologica pp 1–11 | Cite as Age at menarche and the future risk of gestational diabetes: a systematic review and dose response meta-analysis AuthorsAuthors and affiliations Clive J. PetryKen K. OngDavid B. Dunger Open Access Review Article First Online: 29 August 2018 Received: 28 June 2018 Accepted: 12 August 2018 8 Shares 165 Downloads Part of the following topical collections:Pregnancy and diabetes Abstract Published studies show an inconsistent association between age at menarche and the subsequent risk of developing gestational diabetes mellitus when pregnant. This systematic review and meta-analysis was performed to clarify any trends in this association in published observational population studies. We searched online databases for relevant studies, entered into them up until June 21st 2017. Five eligible studies were found and a pooled random effects dose response meta-analysis of results from these was conducted. This included coverage of 58,133 pregnancies, from which 3,035 women developed gestational diabetes. There was evidence of a non-linear association between age at menarche and gestational diabetes (overall p = 1.4 × 10−8; p for non-linearity = 2.4 × 10−4), along with evidence of relatively low heterogeneity (I2 = 25.5%). The largest predicted risk of gestational diabetes was associated with having a low age at menarche; the mean (95% confidence interval) risk relative to that associated with menarche at age 13 years being: 9 years 2.0 (1.6, 2.4), 10 years 1.6 (1.4, 1.9), 11 years 1.3 (1.2, 1.4), 12 years 1.1 (1.1, 1.1), 13 years was the reference, 14 years 1.0 (1.0, 1.0), 15 years 1.1 (0.9, 1.2), 16 years 1.1 (0.9, 1.4). There was evidence of potential publication bias, such that the maximal true relative risk of gestational diabetes, associated with an age at menarche of 9 years, may be closer to 1.6 than 2. Nevertheless, the curvilinear relationship between age at menarche and the future risk of gestational diabetes in pregnancy appears robust. KeywordsMenstruation Puberty Pregnancy Random effects  Managed by Massimo Porta. Electronic supplementary material The online version of this article ( https://doi.org/10.1007/s00592-018-1214-z) contains supplementary material, which is available to authorized users. Introduction The relationship between age at menarche (AAM) and the subsequent risk of developing gestational diabetes (GDM) in pregnancy is a potentially important one for preventive medicine as there has been a generalised global lowering of AAM in the last century [1] combined with an increasing prevalence of GDM [2]. This increasing prevalence of GDM is thought to be one of the factors fuelling the current and future predicted worldwide diabetes epidemic [3]. The strong links between GDM development in pregnancy and the future development of type 2 diabetes (women who experienced GDM having a greater than seven times higher risk of developing type 2 diabetes than those with normoglycaemic pregnancies [4]), and the fact that in utero exposure to GDM increases the number of GDM risk factors female babies have when they get pregnant as adults [5, 6], means that being able to predict those women most at risk of GDM when they become pregnant may be important in targeting lifestyle interventions. Treating susceptible women earlier may become possible [7], which could help reduce the incidence of associated complications. Partially due to shared genetic risk factors [8], it has been suggested that GDM represents an early manifestation of type 2 diabetes [9], with the physiological insulin resistance of pregnancy causing the premature expression of the disease. Risk of type 2 diabetes has already been shown to be associated with AAM [10], including by use of a Mendelian randomisation approach [11]. As long ago as 1975 it was suggested that AAM may be linked to the development of GDM [12], although it was not formally tested. More recently, various studies have investigated links between AAM and the risk of developing GDM in pregnancy and whilst some significant associations have been found [13, 14, 15, 16, 17] (with maximal relative risks for GDM, associated with the earliest AAMs relative to those at the median, ranging from 1.3 to 3.7), this is not true of all studies [18]. Even where a relationship has been observed, sometimes the significantly higher relative risk of GDM is just associated with earliest AAM [13] whereas in other studies a more curvilinear relationship between AAM and GDM is evident (even if it were not always formally tested for or statistical significance reached [14, 15, 16, 17, 18]), albeit smaller in magnitude than that associated with the earliest AAMs. This systematic review and meta-analysis was therefore designed to clarify the relationship between AAM and the risk of developing GDM in pregnancy, both in terms of its association and the shape of that association. Materials and methods The present systemati (...truncated)


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Clive J. Petry, Ken K. Ong, David B. Dunger. Age at menarche and the future risk of gestational diabetes: a systematic review and dose response meta-analysis, Acta Diabetologica, 2018, pp. 1-11, DOI: 10.1007/s00592-018-1214-z