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Birth Weight and Risk of Type 2 Diabetes:  A Systematic Review

Peter H. Whincup, PhD; Samantha J. Kaye, MSc; Christopher G. Owen, PhD; Rachel Huxley, PhD; Derek G. Cook, PhD; Sonoko Anazawa, MD; Elizabeth Barrett-Connor, MD; Santosh K. Bhargava, MD; Bryndís E. Birgisdottir, PhD; Sofia Carlsson, PhD; Susanne R. de Rooij, PhD; Roland F. Dyck, MD; Johan G. Eriksson, MD; Bonita Falkner, MD; Caroline Fall, DM; Tom Forsén, MD; Valdemar Grill, MD; Vilmundur Gudnason, MD; Sonia Hulman, MD; Elina Hyppönen, PhD; Mona Jeffreys, PhD; Debbie A. Lawlor, PhD; David A. Leon, PhD; Junichi Minami, MD; Gita Mishra, PhD; Clive Osmond, PhD; Chris Power, PhD; Janet W. Rich-Edwards, ScD; Tessa J. Roseboom, PhD; Harshpal Singh Sachdev, MD; Holly Syddall, MSc; Inga Thorsdottir, PhD; Mauno Vanhala, MD; Michael Wadsworth, PhD; Donald E. Yarbrough, MD
JAMA. 2008;300(24):2886-2897. doi:10.1001/jama.2008.886.
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Context Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined.

Objective To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults.

Data Sources and Study Selection Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included.

Data Extraction Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations.

Data Synthesis Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight–type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I2 = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight–type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias.

Conclusion In most populations studied, birth weight was inversely related to type 2 diabetes risk.

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Figure 1. Summary of Article Selection Process
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Figure 2. Odds Ratios of Type 2 Diabetes per 1-kg Increase in Birth Weight
Graphic Jump Location

CI indicates confidence interval. Values less than 1 indicate an inverse association of birth weight to type 2 diabetes. Markers are proportional in size to study weight (denoted by the inverse of the variance). The mean age (in years) of each study's participants is shown in descending order of age at which type 2 diabetes was ascertained.
aNative North American population.
bGeneral population (predominantly white origin).

Figure 3. Odds Ratios of Type 2 Diabetes at Different Birth Weights
Graphic Jump Location

Results are based on individual participant data from 16 studies8,9,18,2025,27,29,30,32,33,35,37 and data from the Nurses' Health Study31 (NHS) and the Health Professionals Follow-up Study (HPFS).13 Data from the NHS and the HPFS are presented separately because birth weight data were available only in grouped form. Mean birth weights for each group were calculated directly from data for the 16 studies, based on estimates provided in the published report (NHS),31 and estimated using published data on birth weight distribution (HPFS).13

Figure 4. Odds Ratios of Type 2 Diabetes in 3 Populations Showing Positive Birth Weight–Type 2 Diabetes Associations
Graphic Jump Location

Results are based on data from Pima Indians,28 native North Americans,15 and the Canadian general population.15 Mean birth weights for each group were calculated directly from data for the native North Americans15 and the Canadian general population15 and estimated using published data on birth weight distribution (Pima Indians).28

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