Just like some people are overweight but healthy - an obesity paradox - some people are thin but have a three-fold higher risk of mortality and/or cardiovascular events.

Weight is not the best way to understand metabolic health, according to an analysis of lean, overweight and obese people.

A new paper claims that ~20 percent of normal weight adults are still metabolically unhealthy and have a higher risk of mortality and/or cardiovascular events than metabolically healthy obese subjects. Oddly, a reduced accumulation of fat in the lower body puts lean people at risk.

One size does not fit all

Though it's been considered useless by scientists for anything more than broad population studies, the World Health Organisation associates a body-mass index (BMI) in the normal weight range (defined by WHO as a BMI of 18·5-<25·0 kg/m²) with the lowest all-cause mortality. Yet exceptions are plentiful. For some BMI, the risk of cardiometablic disease and death can vary substantially among subjects. Large studies showed that, compared to metabolically healthy people in the normal weight range, obese people who are metabolically healthy only have a moderate (~25 percent) higher risk of all-cause mortality and/or cardiovascular events, while the risk is much higher (~300 percent) in metabolically unhealthy thin people. 

After defining metabolic health as having less than 2 risk parameters of the metabolic syndrome, the scholars analyzed data from 981 subjects and found that 18 percent of thin people were metabolically unhealthy, which matches the numbers detected in larger studies that investigated the relationship of metabolic health with cardiovascular events and mortality.

The team used magnetic resonance imaging and magnetic resonance spectroscopy to precisely determine body fat mass, fat distribution and deposition of fat in the liver. They also determined insulin sensitivity, insulin secretion, thickness of the carotid vessel wall and fitness. They found that among the fat compartments a low percentage leg fat mass was the strongest determinant of metabolic risk in lean subjects, while in obese subjects nonalcoholic fatty liver disease and increased intra-abdominal fat mass strongly determined this risk. Based on these findings, and with support from animal data and genetic data from human studies, they concluded that in lean subjects the problem of storing fat in the leg may be a crucial factor placing lean people at increased risk of cardiometabolic diseases.

They further hypothesize that this phenotype resembles the phenotypes observed in some very rare diseases, called lipodystrophy. However, they highlight that this lipodystrophy-like phenotype has a much less severe form that the ones observed in these diseases.