Origins of diabetes may be different in men and women

Over the past four decades, global cases of Type 2 diabetes mellitus have skyrocketed. According to the World Health Organization, the number of people estimated to have the disease jumped from 108 million in 1980 to 422 million in 2014, with the fastest growth observed in low- and middle-income countries.

Although the disease is common, there is still much research left to be done to fully understand it. For instance, while diabetes is linked to obesity, researchers still do not know the exact reasons why obesity causes diabetes.

In a new paper published in the journal Obesity Reviews, Concordia researchers Kerri Delaney and Sylvia Santosa look at how fat tissue from different parts of the body may lead to diabetes onset in men and women. They reviewed almost 200 hundred scientific papers looking for a deeper understanding of how fat operates at the surface and tissue level, and the mechanisms by which that tissue contributes to diabetes onset.

"There are many different theories about how diabetes develops, and the one that we explore posits that different regions of fat tissue contributes to disease risk differently," says Kerri Delaney, a PhD candidate at Concordia's PERFORM Centre and the paper's lead author. "So the big question is, how do the different depots uniquely contribute to its development, and is this contribution different in men and women?"

From surface to cell level

Men and women store fat in different places. Diabetes, like many other diseases, is closely associated with abdominal fat. Women tend to store that fat just under the skin. This is known as subcutaneous fat. In men, abdominal fat is stored around the organs. This is visceral fat.

Fat appears to exhibit different features in men and women. They grow differently, are dispersed differently and interact with the inflammatory and immune system differently. For example, in men fat tissue expands because the fat cells grow in size; in women, fat cells multiply and increase in number. This changes with the loss of the protective hormone estrogen that disappears with menopause and may explain why men are more susceptible to diabetes earlier in life than women.

Working from the hypothesis that diabetes risk is driven by expansions of visceral fat in men and of subcutaneous fat in women, the researchers then looked through the papers to see what was happening in the cell-level microenvironments.

Though more research is needed, there were overall differences observed in the immune cell, hormone, and cell signalling level in men and women that seem to support different origins in diabetes between the sexes.

Delaney and Santosa hope that by identifying how diabetes risks are different in men and women, clinical approaches to treatment of the disease can be better defined between the sexes.

Read more at Science Daily

‘Battle of the sexes’ begins in womb as father and mother’s genes tussle over nutrition

Cambridge scientists have identified a key signal that the fetus uses to control its supply of nutrients from the placenta, revealing a tug-of-war between genes inherited from the father and from the mother. The study, carried out in mice, could help explain why some babies grow poorly in the womb.

As the fetus grows, it needs to communicate its increasing needs for food to the mother. It receives its nourishment via blood vessels in the placenta, a specialised organ that contains cells from both baby and mother.

Between 10% and 15% of babies grow poorly in the womb, often showing reduced growth of blood vessels in the placenta. In humans, these blood vessels expand dramatically between mid and late gestation, reaching a total length of approximately 320 kilometres at term.

In a study published today in Developmental Cell, a team led by scientists at the University of Cambridge used genetically engineered mice to show how the fetus produces a signal to encourage growth of blood vessels within the placenta. This signal also causes modifications to other cells of the placenta to allow for more nutrients from the mother to go through to the fetus.

Dr Ionel Sandovici, the paper's first author, said: "As it grows in the womb, the fetus needs food from its mum, and healthy blood vessels in the placenta are essential to help it get the correct amount of nutrients it needs.

"We've identified one way that the fetus uses to communicate with the placenta to prompt the correct expansion of these blood vessels. When this communication breaks down, the blood vessels don't develop properly and the baby will struggle to get all the food it needs."

The team found that the fetus sends a signal known as IGF2 that reaches the placenta through the umbilical cord. In humans, levels of IGF2 in the umbilical cord progressively increase between 29 weeks of gestation and term: too much IGF2 is associated with too much growth, while not enough IGF2 is associated with too little growth. Babies that are too large or too small are more likely to suffer or even die at birth, and have a higher risk to develop diabetes and heart problems as adults.

Dr Sandovici added: "We've known for some time that IGF2 promotes the growth of the organs where it is produced. In this study, we've shown that IGF2 also acts like a classical hormone -- it's produced by the fetus, goes into the fetal blood, through the umbilical cord and to the placenta, where it acts."

Particularly interesting is what their findings reveal about the tussle taking place in the womb.

In mice, the response to IGF2 in the blood vessels of the placenta is mediated by another protein, called IGF2R. The two genes that produce IGF2 and IGF2R are 'imprinted' -- a process by which molecular switches on the genes identify their parental origin and can turn the genes on or off. In this case, only the copy of the igf2 gene inherited from the father is active, while only the copy of igf2r inherited from the mother is active.

Lead author Dr Miguel Constância, said: "One theory about imprinted genes is that paternally-expressed genes are greedy and selfish. They want to extract the most resources as possible from the mother. But maternally-expressed genes act as countermeasures to balance these demands."

"In our study, the father's gene drives the fetus's demands for larger blood vessels and more nutrients, while the mother's gene in the placenta tries to control how much nourishment she provides. There's a tug-of-war taking place, a battle of the sexes at the level of the genome."

The team say their findings will allow a better understanding of how the fetus, placenta and mother communicate with each other during pregnancy. This in turn could lead to ways of measuring levels of IGF2 in the fetus and finding ways to use medication to normalise these levels or promote normal development of placental vasculature.

The researchers used mice, as it is possible to manipulate their genes to mimic different developmental conditions. This enables them to study in detail the different mechanisms taking place. The physiology and biology of mice have many similarities with those of humans, allowing researchers to model human pregnancy, in order to understand it better.

Read more at Science Daily