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Cambridge University researchers battle scourge of diabetes

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Close-up Of Person Hands Holding Glucometer At Desk
Close-up Of Person Hands Holding Glucometer At Desk

Diabetes is, according to the charity Diabetes UK, “the fastest growing epidemic of our time”.

University of Cambridge researcher Luca Lotta
University of Cambridge researcher Luca Lotta

The condition, which is now estimated to affect an estimated four million adults in the UK, can lead to amputations and difficulties with sight; it can also cause severe heart disease and other problems.

An international team led by researchers at the University of Cambridge has been involved in a mammoth study aimed at unlocking some of the secrets of this severe condition.

A key finding made by the study team, which could mark a significant step forward in diabetes research, is that the ability to store fat properly in what are described as the peripheral areas of the body such as the legs and arms is an important factor in determining whether or not a person will develop diabetes and cardiovascular disease.

Between 85 and 90 per cent of people with diabetes have the ‘type 2’ variety. A key risk factor in developing the condition is the progressive resistance of the body to the hormone insulin.

Insulin controls levels of blood sugar: when the body becomes resistant to insulin, levels of blood sugars and triglycerides rise, increasing the chances of developing diabetes and other conditions, including heart disease.

Too much time slouched in front of the TV gorging on fried food and a lack of physical activity are known to be significant factors behind the diabetes epidemic, which has seen cases among the adult population in the UK rise by more than 50 per cent over the past 10 years.

But for years researchers have puzzled over why some overweight people with sedentary habits are prone to developing insulin resistance while others with equally unhealthy lifestyles do not.

The Cambridge-led team, mainly funded by the Medical Research Council (MRC) with support from the Wellcome Trust, found that how and where we store ‘unspent’ calories – derived from overeating and a sedentary lifestyle – plays a significant role in determining whether or not a person builds up insulin resistance and, as a consequence, becomes more likely to develop type 2 diabetes and heart attacks.

Researchers, examining nearly two million genetic variants in 200,000 people across Europe and elsewhere, found 53 inherited DNA sequence variants in the genome – the combined human genetic material – which are associated with insulin resistance and a higher risk of diabetes and heart disease. Previously, only 10 DNA variants in the genome had been linked to insulin resistance.

Dr Luca Lotta, working at the MRC’s Epidemiology Unit, is one of the many researchers involved in the research.

“Our study suggests that individuals who carry a greater number of these genetic variants are generally unable to store excess calories as fat in their bodies and this puts them at higher risk of cardiovascular and metabolic disease,” he says.

But Dr Lotta points out that while a person’s genetic make-up is an important part of the diabetes jigsaw puzzle, other, more easily understood factors are crucial to controlling the condition. It seems that going for a regular walk or swim, getting on a bike – and eating fish or fruit and vegetables instead of biscuits or bacon sandwiches – are key.

“While genetic make-up contributes to the risk of diabetes in the general population, the current global epidemic of type 2 diabetes is without doubt due to overeating and a low level of physical activity,” says Dr Lotta. “Individuals with a poor genetic make-up can overcome their higher genetic risk by having a healthy diet and a good level of physical activity, regardless of what their body weight is.”

The statistics and degree of co-operation involved in such a study are mind-boggling. Dozens of researchers – led by the MRC Epidemiology Unit and MRC Metabolic Diseases Unit at Cambridge but comprising scientists and academics from around the world – gathered data from various sources and combined it using a method termed ‘meta-analysis’.

The genetic make-up of men and women of differing ages and from various socio-economic groups was analysed. A follow-up study was then embarked on which involved taking body scans of more than 12,000 volunteers in areas of the Fenlands and Norfolk.

The scans looked at fat deposits in various regions of the body: the results indicated that those with a greater number of the 53 genetic risk variants for insulin resistance stored lower amounts of fat under the skin, particularly in the lower halves of their bodies.

This inability to develop fat tissue adequately to store excess calories may lead to storage of fat elsewhere in the body, such as in the liver, pancreas and other organs, making the body insulin resistant.

“We are undertaking several studies aimed at extending the findings of this research and to fully understand its implications,” says Dr Lotta. “In particular, we are working with other academics as well as drug researchers to try and develop new drugs to target the genes and pathways that we’ve identified and perhaps take another step forward in combatting this burdensome condition.”

Luca Lotta

The 33-year-old was born in Milan and is a graduate in medicine at the University of Milan where he did the first of two PhDs he now holds. He has also studied in Leiden in the Netherlands, Houston in the US and at Oxford. Luca, along with his wife, moved to Cambridge three years ago.

“It’s a good place to live,” he says. “A small dynamic city, open to the world and multicultural but at the same time it has strong roots in its traditions and past.”

When he’s not battling to understand genetic codes and learning more about the causes of diabetes, Luca spends time with his wife and friends, playing football or basketball, going to the central market, lapping up the ethnic cuisine on Mill Road or cycling to Wolfson College.

“I’m a junior research fellow there: a great way to relax is to spend time in the lovely college garden,” he says.

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