Understanding why some obese people stay sensitive to insulin

 However, it’s not only a question of body weight or fat distribution, because some obese people remain insulin-sensitive, with insulin working as well in their bodies as in someone lean.

It also seems that in addition to having a lower risk of Type 2 diabetes than insulin-resistant people of the same weight, these insulin-sensitive obese individuals appear to have greater protection against death from cardiovascular disease .

While this much is agreed, closer examination shows just how much confusion still reigns in the detail. Even estimates of the proportion of these healthier obese people range from 2% to 30% of the obese population, depending on the definition used and the cohorts of people chosen.

So say the authors of a review of 79 publications on this topic, Drs Dorit Samocha-Bonet and Jerry Greenfield from Sydney’s Garvan Institute of Medical Research. Published in Trends in Endocrinology & Metabolism, the review is now online.

Insulin, a hormone made by the pancreas, helps the body use glucose for energy. ‘Insulin resistance’ arises when muscle cells become less able to use insulin to take in glucose from blood. This causes the pancreas to work harder to produce more insulin. Years of overwork lead to exhaustion of insulin-producing cells, which start to die, and Type 2 diabetes develops.

Dr Jerry Greenfield, Head of the Department of Endocrinology at St. Vincent’s Hospital as well as leader of a clinical research group at Garvan, is keen to delve deeper into the phenomenon of the insulin-sensitive obese, remarking “The key questions are ‘whether it will be meaningful, and, if so, how will we be able to identify these individuals in clinical practice?’”

“A study of these people to examine what protects them from developing diabetes could be very informative in telling us what causes insulin resistance – and in developing targeted therapies.”

“We’re not proposing that insulin-sensitive obese people are completely protected from developing heart disease and diabetes. Rather, they appear to have a lower risk of these diseases compared to someone who is insulin-resistant, yet as obese.”

“Our review made it clear that there is still much work to be done in establishing definitions and ensuring we are all talking about the same thing. In my mind, the only way to be sure that one is actually dealing with a group of insulin-sensitive obese people is to compare them to a group of lean people.”

“We are in the process of recruiting obese people for a clinical study where we’re doing a range of tests to further study these individuals’ protective metabolic features. I think it’s a very valuable area to study because it can inform us a lot about what causes insulin resistance.”

Co-author Dr Dorit Samocha-Bonet agreed that the phenomenon should be used as a tool to investigate insulin resistance – and that future studies should define their terms more rigorously.

“Some of the studies we reviewed were not optimally done – failing to match BMI and gender. Others used different ways of measuring insulin sensitivity, making it difficult to compare apples with apples.”

“It’s clear that there is room for studies with better matching and better markers. Using the hyperinsulinemic euglycemic clamp for example, as we do here, is far more reflective of insulin sensitivity than using surrogate markers, such as fasting blood glucose and insulin. ”

“The studies we reviewed agreed that there was less fat in the liver of the insulin-sensitive obese person, as well as fewer potentially damaging fat metabolites in muscle.”

 “We don’t yet have a profile of all the protective factors – and there have not been enough longitudinal studies done to show how long, or to what degree, the protection continues, although one study suggests up to 30 years.”

The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with over 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Neuroscience and Osteoporosis and Bone Biology. Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.


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