Lean or Obese, Low Inflammation Predicts Metabolic Health

Marlene Busko

September 17, 2013

Adults with normal blood levels of inflammatory markers were likely to have favorable "metabolic health" whether they were lean or obese, a new study shows.

The concept of "metabolically healthy obesity" — that is, individuals with a body mass index (BMI) above 30 who do not have metabolic-syndrome factors that put them at risk for cardiovascular disease events — is not new, but is only now being more widely recognized by clinicians, say experts. Up to 35% of obese individuals may be metabolically healthy despite their size, the researchers write, but the true prevalence of this phenomenon is difficult to assess due to large disparities in defining metabolic health.

"From a public-health standpoint, we need better methods for identifying which obese people face the greatest risk of diabetes and heart disease," says lead author Catherine M. Phillips, PhD, from University College Cork, Ireland, in a statement.

"Inflammatory markers offer a potential strategy for pinpointing people who could benefit most from medical interventions," she observes.

The study was published online August 27 in the Journal of Clinical Endocrinology & Metabolism.

Inflammation, Metabolic Health, and Obesity

Dr. Phillips and colleagues aimed to determine whether differences in metabolic health could be explained by differences in inflammation among obese and nonobese adults.

They examined data from 2040 adults, an equal number of men and women, aged 50 to 69, who were participating in the phase 2 Cork and Kerry Diabetes and Heart Disease Study. Included were 668 obese individuals with a BMI >30 and 1572 nonobese individuals with a BMI <30.

The participants were further classed as being metabolically healthy or unhealthy, based on 5 definitions of metabolic health, which included measures such as blood pressure, triglycerides, LDL-cholesterol, HDL-cholesterol, total cholesterol, fasting plasma glucose, and homeostasis model of assessment (HOMA, a measure of insulin resistance).

Serum acute-phase reactants, adipocytokines, proinflammatory cytokines, and white blood cell counts were also determined.

The associations between inflammatory markers and metabolic health phenotypes were somewhat dependent on which definition was used to identify metabolic health status, the researchers note. They urge the development of a unique definition of "metabolic health," something other experts in the field have also called for.

But in general, obese and nonobese individuals who, according to most of the 5 definitions, were metabolically healthy had lower (below-the-median) levels of complement component 3 (C3), C-reactive protein, IL-6, TNF-alpha, plasminogen activator inhibitor-1, and white blood cell counts and higher levels of adiponectin — compared with their non–metabolically healthy counterparts.

And obese individuals were up to 3.5 times more likely to be metabolically healthy if they had normal levels of certain biomarkers of inflammation than if they had abnormal levels.

Odds of Metabolically Healthy Obesity Associated With Favorable Inflammatory Marker Levels Among Obese Individuals

Marker of Inflammationa Odds Ratio Rangeb
C3 2–3.5
IL-6 1.7–2.9
Plasminogen activator inhibitor-1 1.7–2.9
White blood cells 2.1–2.5
Adiponectin 2.6–4.0

a. C3, IL-6, PAI-1, and WBCs below the median; adiponectin above the median

b. Odds of being metabolically healthy based on 5 definitions of metabolic health

"The results of our study suggest that reduced inflammatory status increases the likelihood of metabolic health, particularly among obese subjects," the researchers state.

"These findings are of public-health and clinical significance in terms of screening and stratification based on metabolic-health phenotype to identify those at greatest cardiometabolic risk for whom appropriate therapeutic or intervention strategies should be developed," they conclude.

The authors have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online August 26, 2013. Abstract

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