Journal article
Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women
Diabetologia, Vol.58(6), pp.1220-1230
06/2015
DOI: 10.1007/s00125-014-3479-2
PMCID: PMC5947951
PMID: 25567102
Abstract
The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk.
We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were recorded. The total effect of LBW on type 2 diabetes risk was partitioned into effects that were mediated by a specific biomarker and effects that were not mediated by this biomarker, using counterfactual model-based mediation analysis.
LBW was significantly associated with increased risk of type 2 diabetes. Compared with women with birthweight 3.63-4.54 kg, women with LBW (<2.72 kg) had a multivariable-adjusted OR of 2.15 (95% CI, 1.54, 3.00). Insulin resistance (indicated by HOMA-IR) mediated 47% of the total effect. Decreased sex hormone-binding globulin (SHBG) concentration accounted for 24%, elevated E-selectin concentration accounted for 25% and increased systolic blood pressure accounted for 8% of the total effect of LBW on type 2 diabetes risk. (Due to interactions among different mediators, the sum of each individual mediator's contribution could exceed 100%, without an upper limit.)
LBW is directly predictive of higher risk of type 2 diabetes later in life. The effect of LBW on type 2 diabetes risk seems mainly mediated by insulin resistance, which is further explained by circulating levels of SHBG and E-selectin and systolic blood pressure. The study provides potential risk stratification in a population at greater risk of developing type 2 diabetes.
Details
- Title: Subtitle
- Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women
- Creators
- Yan Song - University of California, Los AngelesYen-Tsung HuangYiqing SongAndrea L HevenerKelli K RyckmanLihong QiErin S LeBlancRasa KazlauskaiteKathleen M BrennanSimin Liu
- Resource Type
- Journal article
- Publication Details
- Diabetologia, Vol.58(6), pp.1220-1230
- DOI
- 10.1007/s00125-014-3479-2
- PMID
- 25567102
- PMCID
- PMC5947951
- NLM abbreviation
- Diabetologia
- ISSN
- 1432-0428
- eISSN
- 1432-0428
- Publisher
- Germany
- Grant note
- K01 DK078846 / NIDDK NIH HHS HHSN268201100002I / NHLBI NIH HHS HHSN271201100004C / NIA NIH HHS HHSN268201100046C / PHS HHS HHSN268201100001C / WHI NIH HHS HHSN268201100004I / NHLBI NIH HHS R01 DK109724 / NIDDK NIH HHS R01 DK089109 / NIDDK NIH HHS R21 DK084482 / NIDDK NIH HHS HHSN271201100004C / PHS HHS HHSN268201100003C / PHS HHS HHSN268201100004C / WHI NIH HHS HHSN268201100046C / NHLBI NIH HHS HHSN268201100002C / WHI NIH HHS HHSN268201100001I / NHLBI NIH HHS M01 RR000059 / NCRR NIH HHS R01 DK62290 / NIDDK NIH HHS HHSN268201100004C / PHS HHS R01 DK066401 / NIDDK NIH HHS HHSN268201100002C / PHS HHS HHSN268201100003C / WHI NIH HHS HHSN268201100001C / PHS HHS
- Language
- English
- Date published
- 06/2015
- Academic Unit
- Stead Family Department of Pediatrics; Epidemiology
- Record Identifier
- 9983995115702771
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