When it comes to treating type 2 diabetes, losing one gram of fat from the pancreas may hold the key, Donna Chisholm reports.
Ectopic fat, so-called because it’s in an abnormal place, infiltrates muscles and organs including the liver, pancreas, and even the heart, impairing their function and increasing the risk of insulin resistance and type 2 diabetes – a chronic condition that affects how the body metabolises sugar and is often associated with being overweight.
It’s the key target in a five-year, $6 million study, Peak Nutrition for Metabolic Health, involving researchers from the University of Auckland, AgResearch, Plant & Food Research and the University of Otago, with collaborators in the UK and France.
The problem, says principal investigator Sally Poppitt, a professor of human nutrition, is that ectopic fat can be measured only by expensive CT or MRI scans rather than a simple blood test. One of the first tasks for the study team is to find out if higher ectopic fat is associated with measurable biomarkers in the blood.
Among Poppitt’s international collaborators are researchers at Newcastle University in the UK, who in a ground-breaking study in 2016 found that type 2 diabetics may achieve long-term remission from the disease by losing less than one gram of fat from the pancreas.
One gram might not sound much, but those who achieved it in the study had lost about 15kg each in just eight weeks on a very low-energy – about 600 calories a day – diet. Poppitt says Newcastle and Auckland are among very few groups in the world that excel at measuring ectopic fat in the pancreas. “It’s very difficult to do well.”
Ethnicity is an important factor when determining who will develop type 2 diabetes and when. The Auckland team has so far scanned and compared about 200 women in two ethnic groups – Caucasian European and Asian Chinese. “The Chinese cohort, although matched for age and body mass index [BMI], has worse glucose control, worse insulin resistance indicators and worse lipids. They have a higher percentage of visceral fat and more infiltration of fat into the pancreas.”
In the “real world”, says Poppitt, Chinese people have a greater risk of developing type 2 diabetes than Europeans with the same BMI. “If you are Chinese or Indian, the best recommendation is to stay as lean as you can for as long as you can, because for you, things start to go wrong metabolically earlier, and when you are younger and slimmer.”
They’ve measured metabolites in the blood – the chemical compounds produced by the body’s metabolism – and compared the markers between the two groups and found them “completely different”. What causes that difference is still not clear, and the Auckland team plans next year to investigate the contribution of diet.
Poppitt says ectopic fat infiltrating the organs could be more important as a contributor to type 2 diabetes than visceral fat, but it’s not yet clear whether people who had high levels of visceral fat without fat in their organs are still at increased risk. “Some people are a little more dogmatic about the fact that it must be fat in the pancreas, but I don’t think we have enough evidence to say that yet. We don’t have big enough data sets to have enough people with one or the other or both, to be sure yet. We are keeping a very strong watch on the role of ectopic, without losing sight of the visceral.”
Several researchers around New Zealand are operating dual-energy X-ray absorptiometry body scanners to measure visceral fat in clinical trials. One of the researchers is Lindsay Plank, director of Auckland City Hospital’s Body Composition Laboratory. “It seems that when you reach a certain percentage of body fat, you start accelerating the amount of visceral fat that you deposit,” he says.
“The issue is, there are people who have high BMIs and a high body-fat percentage who have low visceral fat, and people with relatively normal BMIs who are fairly lean and have high visceral fat. And people with high visceral fat have high metabolic disease rates.” Those who are slim with high visceral fat are known as “Tofi” – thin on the outside, fat on the inside. Asian Indians, for example, accumulate visceral fat with a much lower BMI than Europeans.
Plank says it’s still a mystery why some people with high BMIs and high visceral fat are resistant to cardiac and metabolic disease and the difference is not simply explained by ethnicity alone.
As we age, we all increase our abdominal fat and there is a sex difference. Premenopausal women with high oestrogen levels tend to deposit fat in the buttocks, thighs and hips and form a pear-shaped body. Post-menopausal women, with the reduction in oestrogen, start to deposit visceral fat in the abdominal region and become more apple shaped as they age.
For men, as their testosterone levels fall off in their thirties and forties and later, the fat tends to deposit in the visceral region as well. “Men tend to form an apple shape a bit earlier than women,” says Plank. “When you have high visceral fat, some of that fat is going to end up as ectopic fat and we don’t fully understand the mechanisms that drive that.”
One explanation, says Poppitt, is the lipid overspill hypothesis, the suggestion that at some point, the adipose tissue, which usually holds the subcutaneous fat – the so-called protective metabolic sink – “puts its hand up and says ‘I’m full, no more is coming here, and I’m diverting it to a different bus depot.’” She says a couple of studies involving people who have been overfed for weeks shows they become susceptible to this overspill, and suggested that once the cell size in the adipose tissue gets to a certain point, it won’t expand any more.
She’s strongly opposed to techniques such as cosmetic liposuction that remove adipose tissue and subcutaneous fat. “The tissue can be very helpful to you. When you remove it, your fat has nowhere to be stored, nowhere safe to go.”
Despite controversy over the value of BMI – on BMI values alone, athletes such as Sonny Bill Williams and Richie McCaw are “overweight” – Poppitt says it’s a useful tool in population health, but differences in ethnicity and fitness need to be taken into account. “If someone stood in front of the mirror would they say their extra weight is all muscle or not? With an All Black it’s clear they’re very muscular, but for most people we’d probably say it’s not.”
The Peak Nutrition for Metabolic Health study is part of the High-Value Nutrition national science challenge, which aims to add $1 billion to the economy by providing evidence to allow health claims to be made on foods or supplements that we sell already or are yet to be developed. The potentially huge Chinese market is one of the reasons Poppitt’s study involves Chinese participants and not people from India who have worse metabolic problems related to visceral and ectopic fat.
‘I was going downhill fast’
Kim Ollivier was able to quit his diabetes medication thanks to a strict fasting diet.
He began the arduous regime after reading the results of a small trial of fasting diets at Newcastle University. The researchers there are collaborating in new research on pancreatic fat and diabetes led by University of Auckland scientists. Although the patients in the British study were largely confined to specially formulated diet shakes and non-starchy vegetables, Ollivier – a keen amateur cook – thought that would be too expensive and too boring.
Breakfast was a grapefruit, cup of tea and pot of low-calorie yogurt or a boiled egg. Lunch was Diet Coke and a Turkish salad – shredded cabbage, lettuce, parsley, slices of onion and lemon juice instead of mayonnaise. Ollivier added crushed chilli to spice up the meal. Dinner was boiled vegetables (excluding carb-laden root vegetables) and tom yum soup, Cajun fish, warm beef salad or cabbage rolls. Alcohol was out and so were carbohydrates.
His weight dropped from 100kg to 83kg on the diet. He’s now back to 92kg after a holiday in France and is working to get it back to his goal of 85kg. He still has to watch carefully what he eats, and his blood-glucose markers go up when his weight does, but his diabetes remains in remission.
In 2013, he joined a University of Auckland trial that included another eight-week fasting diet but hasn’t fasted since.
Doctors warned him the diet could be almost impossible to stick to, but he didn’t find it too difficult. “I was on a slippery slope and I was frightened. I was very depressed about it. There seemed no solution and I was going downhill fast. Then they said an eight-week diet could reverse it. A serious, severe diet, but I thought, how hard could that be? Eight weeks out of my life, that’s nothing.”
This article was first published in the October 19, 2019 issue of the New Zealand Listener.