Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study

Kwun Kiu Wong; Feifei Cheng; Cadmon K.P. Lim; Claudia H.T. Tam; Greg Tutino; Lai Yuk Yuen; Chi Chiu Wang; Yong Hou; Michael H.M. Chan; Chung Shun Ho; Mugdha V. Joglekar; Anandwardhan A. Hardikar; Alicia J. Jenkins; Boyd E. Metzger; William L. Lowe; Wing Hung Tam; Ronald C.W. Ma

doi:10.1186/s12916-022-02687-5

Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study

Kwun Kiu Wong, Feifei Cheng, Cadmon K.P. Lim, Claudia H.T. Tam, Greg Tutino, Lai Yuk Yuen, Chi Chiu Wang, Yong Hou, Michael H.M. Chan, Chung Shun Ho, Mugdha V. Joglekar, Anandwardhan A. Hardikar, Alicia J. Jenkins, Boyd E. Metzger, William L. Lowe, Wing Hung Tam, Ronald C.W. Ma^*

^*Corresponding author for this work

Medicine, Endocrinology Division

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children’s LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life. Methods: This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children’s glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction. Results: Sex- and age-adjusted children’s LTL was found to be associated with children’s HOMA-IR (β=−0.046 ± 0.016, p=0.005). Interestingly, both children’s and maternal post-load glucose levels were positively associated with children’s LTL. However, negative associations were observed between children’s LTL and children’s OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels. Conclusions: Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.

Original language	English (US)
Article number	490
Journal	BMC Medicine
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12916-022-02687-5
State	Published - Dec 2022

Funding

This study was supported by the Research Grants Council General Research Fund (ref. 14118718), Research Impact Fund (R4012-18) and the Croucher Foundation Senior Medical Research Fellowship. The HAPO study was funded by the National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive Diseases (grant nos. R01-HD34243 and R01-HD34242). The HAPO follow-up study at the Hong Kong centre was supported by funding from the Research Grants Council of the Hong Kong SAR, China (grants CUHK 473408, and in part, 471713, 14118316 and 14102719). R.C.W.M. has received research grants for clinical trials from AstraZeneca, Bayer, MSD, Novo Nordisk, Sanofi and Tricida Inc. and honoraria for consultancy or lectures from AstraZeneca, Bayer, Boehringer Ingelheim and Roche Diagnostics, all used to support diabetes research at the Chinese University of Hong Kong. R.C.W.M. is a co-founder of GemVCare, a technology start-up initiated with support from the Hong Kong Government Innovation and Technology Commission and its Technology Start-up Support Scheme for Universities (TSSSU). A.J.J. has received research grants for clinical trials from Abbott and Sanofi-Aventis and honoraria for consultancy for Abbott, Amgen, Medtronic and Sanofi-Aventis. No other potential conflicts of interest relevant to this article were reported.

Keywords

Early programming
Glucose
Longitudinal study
Sexual dimorphism
Telomere

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12916-022-02687-5

Cite this

Wong, K. K., Cheng, F., Lim, C. K. P., Tam, C. H. T., Tutino, G., Yuen, L. Y., Wang, C. C., Hou, Y., Chan, M. H. M., Ho, C. S., Joglekar, M. V., Hardikar, A. A., Jenkins, A. J., Metzger, B. E., Lowe, W. L., Tam, W. H., & Ma, R. C. W. (2022). Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study. BMC Medicine, 20(1), Article 490. https://doi.org/10.1186/s12916-022-02687-5

@article{69de3d4401ca4463ab2220c636b37be0,

title = "Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children{\textquoteright}s glucose metabolism—a longitudinal study",

abstract = "Background: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children{\textquoteright}s LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life. Methods: This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children{\textquoteright}s glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction. Results: Sex- and age-adjusted children{\textquoteright}s LTL was found to be associated with children{\textquoteright}s HOMA-IR (β=−0.046 ± 0.016, p=0.005). Interestingly, both children{\textquoteright}s and maternal post-load glucose levels were positively associated with children{\textquoteright}s LTL. However, negative associations were observed between children{\textquoteright}s LTL and children{\textquoteright}s OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels. Conclusions: Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.",

keywords = "Early programming, Glucose, Longitudinal study, Sexual dimorphism, Telomere",

author = "Wong, {Kwun Kiu} and Feifei Cheng and Lim, {Cadmon K.P.} and Tam, {Claudia H.T.} and Greg Tutino and Yuen, {Lai Yuk} and Wang, {Chi Chiu} and Yong Hou and Chan, {Michael H.M.} and Ho, {Chung Shun} and Joglekar, {Mugdha V.} and Hardikar, {Anandwardhan A.} and Jenkins, {Alicia J.} and Metzger, {Boyd E.} and Lowe, {William L.} and Tam, {Wing Hung} and Ma, {Ronald C.W.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s12916-022-02687-5",

language = "English (US)",

volume = "20",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central",

number = "1",

}

Wong, KK, Cheng, F, Lim, CKP, Tam, CHT, Tutino, G, Yuen, LY, Wang, CC, Hou, Y, Chan, MHM, Ho, CS, Joglekar, MV, Hardikar, AA, Jenkins, AJ, Metzger, BE , Lowe, WL, Tam, WH & Ma, RCW 2022, 'Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study', BMC Medicine, vol. 20, no. 1, 490. https://doi.org/10.1186/s12916-022-02687-5

TY - JOUR

T1 - Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study

AU - Wong, Kwun Kiu

AU - Cheng, Feifei

AU - Lim, Cadmon K.P.

AU - Tam, Claudia H.T.

AU - Tutino, Greg

AU - Yuen, Lai Yuk

AU - Wang, Chi Chiu

AU - Hou, Yong

AU - Chan, Michael H.M.

AU - Ho, Chung Shun

AU - Joglekar, Mugdha V.

AU - Hardikar, Anandwardhan A.

AU - Jenkins, Alicia J.

AU - Metzger, Boyd E.

AU - Lowe, William L.

AU - Tam, Wing Hung

AU - Ma, Ronald C.W.

PY - 2022/12

Y1 - 2022/12

N2 - Background: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children’s LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life. Methods: This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children’s glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction. Results: Sex- and age-adjusted children’s LTL was found to be associated with children’s HOMA-IR (β=−0.046 ± 0.016, p=0.005). Interestingly, both children’s and maternal post-load glucose levels were positively associated with children’s LTL. However, negative associations were observed between children’s LTL and children’s OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels. Conclusions: Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.

AB - Background: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children’s LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life. Methods: This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children’s glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction. Results: Sex- and age-adjusted children’s LTL was found to be associated with children’s HOMA-IR (β=−0.046 ± 0.016, p=0.005). Interestingly, both children’s and maternal post-load glucose levels were positively associated with children’s LTL. However, negative associations were observed between children’s LTL and children’s OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels. Conclusions: Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.

KW - Early programming

KW - Glucose

KW - Longitudinal study

KW - Sexual dimorphism

KW - Telomere

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U2 - 10.1186/s12916-022-02687-5

DO - 10.1186/s12916-022-02687-5

M3 - Article

C2 - 36536359

AN - SCOPUS:85144316659

SN - 1741-7015

VL - 20

JO - BMC Medicine

JF - BMC Medicine

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ER -

Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children’s glucose metabolism—a longitudinal study

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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