Fetal exposure to the Ukraine famine of 1932-1933 and adult Type 2 Diabetes Mellitus (Public data and analytical code)

Abstract

The short-term impact of famines on death and disease is well documented but it is difficult to estimate their potential long-term impact. We used the setting of the man-made Ukrainian Holodomor famine of 1932-1933 to examine the relationship between prenatal famine and adult Type 2 diabetes mellitus (T2DM). This ecological study included 128,225 T2DM cases diagnosed between 2000-2008 among 10,186,016 male and female Ukrainians born between 1930 and 1938. Individuals who were born in the first half-year of 1934, and hence exposed in early gestation to the mid-1933 peak famine period, had a larger than two-fold likelihood of T2DM (OR 2.21; 95% CI 2.00-2.45) compared to unexposed controls. There was a dose-response relationship between severity of famine exposure and adult T2DM risk comparing individuals born in regions with severe, very severe, and extreme famine to births in the no-famine region.

Description of the data and analytical code

In exploratory analyses we first examined whether the odds for T2DM were elevated for any month of birth in the period January 1930 to December 1938 in any of the four regions of varying famine intensity. This was achieved by comparing, within each region, the T2DM odds for births in any month and year of birth relative to the T2DM odds for births in the same month combining all other years of birth. The analysis served to identify potential relations of famine with specific months and years of birth, controlling for month of birth effects. We observed increased T2DM odds ratios for births between January and June 1934 in famine-exposed oblasts, with smaller increases for births in 1935 and 1936 in these months. Our findings suggested that in multivariate modelling statistical control for month of birth effects could be accomplished by adjusting for the January-June period. Our findings are presented in the data file '01 Odds Ratio for T2DM Over Time' and show the odds ratios (ORs) for Type 2 Diabetes Mellitus (T2DM) comparing the region-specific T2DM odds for each birth year and month relative to births in the same months but combining all other years of birth. The R syntax file '01 Odds of T2DM Over Time Figure' provides the code necessary to reproduce the figure.

For confirmatory analyses we employed a Difference-in-Differences approach to quantify associations between prenatal exposure to famine and T2DM, taking into account year of birth, half-year of birth (Jan-Jun vs Jul-Dec), region, and their interactions. This analysis was conducted initially for each gender separately and then for both genders combined, adjusting for We carried out sensitivity analyses to assess potential changes in T2DM odds arising from the use of pre-famine births vs post-famine births as controls.  Our findings are presented in the data file '02 Ukraine Famine 1932-33 Main Data'. Information on the number of T2DM cases by gender, region of residence, and year and month of birth 1930-1938 in Ukraine was collected by the national Ukraine Diabetes Register (Komisarenko Institute of Endocrinology and Metabolism, Kyiv) between 2000-2008. The number of births in the same subgroups, representing the populations at risk for T2DM, was estimated by demographic population reconstruction methods as reported in the publication. We classified the birth counts by year of birth, the semi-annual birth period (January-June vs. July-December), region of birth, and gender. The SPSS syntax file titled '02 Ukraine Famine 1932-33 Main Analysis' provides the code to replicate our main findings as presented in the publication.

In a separate analysis we visualized by a meta-regression approach the relation between famine intensity at the oblast level in 1933 and the odds for adult T2DM.  The data required for the replication of our findings are included in the file '03 Odds Ratio for T2DM and Famine Intensity at Oblast Level'. The R syntax file titled '03 Ukraine Famine 1932-33 Meta-regression' provides details on conducting the meta-regression using the R package ‘metafor’.

Funding

Ukraine State complex program Diabetes Mellitus, project number 0106U000844 (M.K.). Holodomor Research and Education Consortium in Canada (L.H.L., O.W.). NIDI-NIAS Fellowship of the Royal Netherlands Academy of Sciences (L.H.L.). National Institute of Aging R01 AG028593 (L.H.L.). National Institute of Aging R01 AG06687 (L.H.L.).

Sharing/Access information

Data sharing and use are unrestricted with acknowledgement of the original publication and listing of the funding sources as per the above. Researchers are encouraged to contact the Principal Investigators (PIs) for consultations on data structure and use as needed (L.H. Lumey, [e-mail]; Oleh Wolowyna, [e-mail]).