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The Paradox of Healthy Obesity

Researchers have defined key characteristics that enable some obese individuals to remain free from type 2 diabetes and other metabolic disorders.

“It has been known for some time that some obese individuals seem to stay metabolically healthy,” said A/Prof Jerry Greenfield of Sydney’s St Vincent’s Hospital and the Garvan Institute of Medical Research. “However, there has been no consensus about how to define ‘metabolically healthy’ obesity – so it has not been easy to understand what underpins these individuals’ apparent protection from disease.”

Greenfield’s research, published in the Journal of Clinical Endocrinology and Metabolism (, examined “whether or not obese individuals also have… a resistance to the hormone insulin, which regulates the level of sugar in the blood after a meal. We consider that obese individuals who are not insulin-resistant, but instead remain sensitive to insulin, can be thought of as being metabolically healthy.”

In people with insulin resistance, the body’s tissues become progressively less responsive to insulin. Muscle cells become sluggish at removing glucose from the bloodstream, and liver cells are less able to halt their release of glucose into the blood. As a result, the insulin-production machinery is overworked and ultimately becomes exhausted, leading to type 2 diabetes.

Greenfield’s team measured the response of insulin to blood glucose levels in 64 individuals. “We were intrigued to find that some participants were sensitive to insulin at muscle but were resistant at liver – whilst others had the opposite profile,” said study co-author Dr Dorit Samocha-Bonet. “So, we now know it’s not enough to label an individual as ‘insulin-resistant’ or ‘insulin-sensitive’. Instead, they can be insulin-resistant at liver, at muscle, at both sites, or at neither.”

The researchers next tested how each participant’s insulin response profile related to other key readouts of metabolic health. “What we found,” said Samocha-Bonet, “is that obese individuals who are sensitive to insulin in muscle only or liver only are metabolically healthier in many respects than the group that is insulin-resistant at both sites.

“Not only do they have lower blood pressure, but they also have less deep abdominal fat and less fat within the liver. In fact, judging by these criteria, the metabolic health of these people is similar to that of individuals who are insulin-sensitive at both muscle and liver.”

Greenfield added that “being insulin-sensitive at either muscle or liver conferred as much metabolic protection as being insulin-sensitive at both sites… The findings suggest that there are different drivers of insulin action at liver and muscle that may be determined by specific genetic pathways.

“The demonstration that insulin sensitivity in the liver and muscle may occur independently in humans potentially paves the way for earlier detection and individualised treatment of people at risk of developing metabolic disease.”