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Famine may alter metabolism of next generation

A horrific famine in China between 1959 and 1961 lingers in the form of increased hyperglycemia risk—not only among people who were born then, but also the children they had a generation later.

Hyperglycemia is a high blood glucose level and a common sign of diabetes. The new study in the American Journal of Clinical Nutrition reports that hundreds of people whose mothers were pregnant with them during the famine had significantly elevated odds of both hyperglycemia and type 2 diabetes.

Even more striking, however, was that their children also had significantly higher odds of hyperglycemia, even though the famine had long since passed when they were born.

Public health researchers at Brown University and Harbin Medical University in China studied more than 3,000 local residents and their children. Some of the subjects were gestated during famine and some were gestated just afterward. Some of the offspring in the study were born to two, one, or no parents who had been famine-exposed.

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This study population allowed the scientists, who interviewed and took blood samples from the participants in 2012, to make well-controlled, multigenerational comparisons of the effects of in utero famine exposure that would never be ethical to intentionally create.

“These were unique ‘experiments,’ so to speak, that were unfortunately done to those populations at a time when the society was under revolutionary, social, and political upheavals,” says Simin Liu, the study’s co-corresponding author and a professor of epidemiology and of medicine at Brown. “By studying these families we could determine multiple-generational exposure to nutritional factors and genetic interactions that occur due to famine.”

The second generation

Among 983 people gestated during the famine years, 31.2 percent had hyperglycemia and 11.2 percent had type 2 diabetes. By comparison, among 1,085 people gestated just after the famine ended, the prevalence of hyperglycemia was 16.9 percent, and the prevalence of type 2 diabetes as 5.6 percent. Controlling for factors such as gender, smoking, physical activity, calorie consumption, and body-mass index, the researchers calculated that in utero famine exposure was associated with 1.93-times higher odds of hyperglycemia and a 1.75 times greater chance of type 2 diabetes.

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The next generation sustained the significant risk of hyperglycemia when both parents had been famine-exposed. Overall in the second generation, hyperglycemia prevalence were 5.7 percent for 332 people with no famine-exposed parents, 10.0 percent for 251 people with famine-exposed fathers, 10.6 percent for 263 people with famine-exposed mothers, and 11.3 percent for the 337 people for whom both parents had famine exposure. Adjusting for all the same lifestyle factors, the offspring of two famine-exposed parents had 2.02 times the odds of hyperglycemia of people with no famine-exposed parents. The odds of hyperglycemia from one-parent exposure were also substantially elevated but not quite statistically significant.

The odds of type 2 diabetes were not statistically significant after adjustment for multiple comparisons among the second generation, but co-corresponding author Sun Changhao, professor of nutrition and dean of the School of Public Health at Harbin, notes that these people were only in their 20s and 30s and could still be at increased risk as they age and that the research team will continue to follow up on these participants.

Genes, epigenetics, or something else?

Because the study only shows an association between metabolic changes and in utero famine exposure, it can’t prove causality or the biological mechanism underlying a cause. But prior research on the effects of famine in humans and in laboratory animals suggest that famine does indeed cause such health risks, the study authors say.

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“It is indeed a remarkable finding that is consistent what with what one would have expected from prior findings from animal experiments,” says lead author Jie Li, a postdoctoral fellow at Brown.

A prior team’s study in mice showed a multigenerational effect on metabolism, and other studies of famine exposure in people have produced evidence of changes in the endocrine systems and in prenatal gene expression in reproductive systems.

Liu says he hopes to continue working with colleagues and participants in China to further investigate how gene and environmental interaction may affect health outcomes across generations. Findings of such work would have implications not only for improving biological understanding of mechanisms but also for clinical and public health interventions.

“Genetic, epigenetic reprogramming, and subsequent gene-diet interaction are all possible explanations,” he says. “By establishing this Chinese famine cohort of families, we hope to conduct a much more comprehensive and in-depth assessment of the whole genome and epigenome along with metabolic biomarkers of these participants moving forward.”

Several government and academic sources in China provided funding for the study.

Source: Brown University

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