Tuesday March 8 2011
The physiology of rats differs from that of humans
“A poor diet during pregnancy may increase the risk of a woman’s children and grandchildren developing type 2 diabetes in later life”, reported the Daily Mail. It said a study has suggested that mothers who eat unhealthily could “programme” susceptibility into the cells of their unborn baby. This genetic vulnerability could then be passed down to future generations.
This is good quality research, but it was in rats and the results are preliminary. Further research is needed before it can be established that the process suggested happens in humans. In addition, this study did not assess glucose metabolism or regulation as an outcome, even in rats, and the implication of its findings for the development of diabetes is unclear.
This study should not cause undue concern for pregnant women. There are, however, well established reasons for a healthy diet during pregnancy. Being overweight is a risk factor for glucose intolerance and gestational diabetes for mothers. The claim by the Daily Mail that the study found a mother's diet increases risk for her grandchildren is unsubstantiated, even in rats. The study gave no indication that the effects of maternal diet on offspring are passed on to subsequent generations.
Where did the story come from?
The study was carried out by researchers from the University of Cambridge, Malmö University in Sweden, the National Cancer Institute at Frederick in the USA, the Medicines Research Centre in Stevenage and the University of Birmingham Medical School. The study was published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences.
Several news sources covered this study. The Express, Guardian and Daily Mail headlines may give the mistaken impression that this association between diabetes and maternal diet directly applies to humans, when the study was actually carried out in rats.
Animal research is important, but it is preliminary and the physiology of rats and humans differs. While these researchers have established that the DNA region they were studying in rats was also present in human pancreatic cells, they have yet to prove that maternal diet has a similar effect on these regions in human offspring.
What kind of research was this?
This was laboratory research in rats that investigated how environmental pressures, in this case the mother’s diet while pregnant, can affect the expression of genes in their offspring.
The researchers note that their previous studies have shown that maternal diet affects the physical health of the offspring. They say that when pregnant rats are fed a low-protein diet, their offspring are smaller, but have normal glucose metabolism until they are young adults, when they develop an age-related loss of glucose tolerance (failure to metabolise glucose correctly). However, the studies showed that as the offspring aged, they developed a type 2 diabetes-like disease. The researchers draw a similarity between this rat model and human babies born with low birth weight. They set up this study to investigate further the molecular mechanisms that link poor early growth to type 2 diabetes in rats.
They focused specifically on the effects of a chemical called hepatocyte nuclear factor 4-alpha (HNF 4-alpha). This chemical is known to be critical in glucose metabolism and in the normal functioning of pancreatic cells. They say that previous studies have linked failures in chemical pathways involving HNF 4-alpha with the development of type 2 diabetes. Meanwhile, other research has linked HNF 4-alpha to a genetic region called the P2 promoter. The aim of this study, therefore, was to assess whether maternal diet was linked to the functioning of the P2 promoter in the pancreas.
What did the research involve?
The researchers collected pancreatic cells from rats aged three months and 15 months whose mother had been exposed to a normal or a low-protein diet during pregnancy. The structure and function of parts of the DNA were then compared between the two groups. To verify whether the P2 promoter was present in humans, they also looked at human pancreatic cells in the lab. They concluded it was, and conducted further studies in rats. These studies examined in more detail what chemical and DNA pathways were responsible for the differences between the offspring of well fed and poorly fed mother rats. Researchers looked at the specific changes in DNA activity that might be linked to different levels of HNF 4-alpha between the two sets of offspring and between three-month-old and 15-month-old rats.
At each step, the researchers compared the findings in the offspring from poorly fed mothers with those from well fed mothers using appropriate statistical tests.
What were the basic results?
The study found that the offspring of poorly fed mothers showed evidence of malfunctions in particular parts of their DNA and this was slightly worse in older rats. However, they say that diet and ageing did not fully account for the differences and that other unknown factors were also playing a role.
The study also found that the offspring of rats fed a normal diet had greater levels of HNF 4-alpha than those born to malnourished mothers.
How did the researchers interpret the results?
The researchers conclude that their study has identified a fundamental mechanism by which diet interacts with the genes during critical periods of development. Specifically, they say they have found that suboptimal nutrition during early life modifies certain interactions in a particular gene called HNF 4-alpha. They believe that these mechanisms may be one cause of malfunctioning pancreatic cells and the subsequent development of type 2 diabetes.
Previous studies have shown that malnutrition in the mother is known to affect the way genes are expressed in her offspring without actually changing their underlying genetic code.
By finding that diet can also have this effect, this study is a step towards understanding how maternal diet can affect the health of a foetus. Importantly, this study was in rats and it is unclear whether the precise changes seen here would occur in humans. The researchers have gone some way to establishing whether this is the case by looking at human pancreatic cells, and finding that some of the key genetic components they were studying are also present in these cells. However, they did not conduct experiments to determine whether malnutrition has a similar effect in humans.
This study did not assess glucose metabolism or regulation as an outcome, even in rats, and the implication of its findings for the development of diabetes is unclear. The researchers themselves use cautious language when discussing the link with diabetes. For example, they say that their study provides evidence of an age-related effect on certain processes in pancreatic cells that “may lead to an increased risk of type 2 diabetes with age”.
This study should not cause undue concern for pregnant women. There are, however, well established reasons for a healthy diet during pregnancy. Being overweight is a risk factor for glucose intolerance and gestational diabetes in mothers. The claim made by the Daily Mail that the study found a mother’s diet increases risk for her grandchildren is unsubstantiated. These findings gave no indication that the effects of maternal diet on offspring are passed on to subsequent generations.