The Normal-Weight Obese Syndrome

Summarized by Robert W. Griffith, MD
February 5, 2007

Summary

Normal-weight-but-obese women (diagnosed by a fat mass above 30% with a BMI below 25) have increased inflammatory agents in their plasma that put them at risk for the metabolic syndrome and other cardiovascular disorders.

Introduction

Obese people have an increased amount of fat tissue, which can act like an endocrine gland, i.e. it can produce hormone-like substances without actually having a duct or any storage of the product. In the case of fat, these "messenger" substances, which are called adipokines, include inflammatory agents, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 (IL-1). These have been shown to take part in the onset of cardiovascular disease, atherosclerosis, and insulin resistance - suggesting a prominent role for them in the causation of the metabolic syndrome.¹ Levels of the inflammatory agents are increased in the plasma of obese individuals.

Italian researchers have identified a new syndrome, which they call "Normal-Weight Obese syndrome". Candidates have a normal weight and body mass index (BMI), but a high fat mass (i.e. over 30%). They have measured the levels of inflammatory agents in women with this condition, comparing them with healthy non-obese women and with overweight/obese women (BMI above 25 and fat mass above 30%). Their findings are reported in the American Journal of Clinical Nutrition, and are summarized here.

What was done

Sixty women aged 20-35 were selected from a Roman population of 3000 potential volunteers. Based on their body measurements they were allocated to one of three groups:

There were 20 women in each group. Blood was collected for determination of the adipokines TNF-alpha, interleukins IL-1, -2, -6, -8, -10, and -12, C-reactive protein (CRP), lipid levels, glucose, insulin, and insulin resistance.

What as found

The average values for each group for body measurements and for two of the adipokines (TNF-alpha and IL-6) are given in the table.

The values for the Normal-Weight Obese group lie, for all measures listed, roughly midway between the Non-Obese (control) and Overweight/Obese groups. The differences between the Normal-Weight Obese and the Non-Obese were statistically significant (i.e. could not have occurred by chance) in the case of fat mass and TNF-alpha (in the table above) and for IL-1 and IL-8 (not shown in table). Individual TFN-alpha levels were correlated with the individual fat mass numbers in the Normal-Weight Obese subjects.

There were no significant differences between the non-obese group and the normal-weight obese group with respect to blood pressure, lipid levels, fasting glucose, insulin, and insulin resistance.

What the findings suggest

In struggling to define borderline cases between 'normal weight' and the frankly overweight, different classes have been suggested by earlier researchers. The 'metabolically healthy but obese' and the 'metabolically obese but normal weight' are two of these. Some years ago the Italian authors of this study proposed the existence of a 'normal-weight obese' class, and they have tried to characterize this class further. From the results obtained it would seem that the normal-weight obese subjects are half-way towards overweight, with the exception that fat mass and IL-6 levels are more advanced than might be expected. The other inflammation markers - TNF-alpha and CRP - are also increased over the controls, although not significantly. This all supports the researchers' contention that normal-weight obese women (diagnosed by a fat mass above 30%) have increased inflammatory agents in their plasma that puts them at risk for the metabolic syndrome, itself a risk factor for diabetes, atherosclerosis, and increased mortality.

The practical implications of this study are probably limited to the more widespread use of fat mass measurements, especially in those who are approaching overweight, though still in normal bounds. The study results should, however, reinforce the realization that overweight is itself a serious risk factor for cardiovascular disease and type 2 diabetes.

Source

• Normal-weight obese syndrome: early inflammation. A. De Lorenzo, V. Del Gobbo, MG. Premrov,  et al., Am J Clin Nutr, 2007, vol. 85, pp. 40--45

Footnotes
1. The metabolic syndrome requires 3 of the following risk factors to be present: (a) Waist size over 40 inches (102 cm) in men, or 35 inches (88 cm) in women. (b) Serum triglyceride level over 150 mg/dL (1.7 mmol/L). (c) Serum HDL ('good') cholesterol below 40 mg/dL (1.0 mmol/L) in men, or 50 mg/dL (1.29 mmol/L) in women. (d) Blood pressure over 130/85 mm Hg (either number), or being on blood pressure medication. (e) Fasting blood sugar over 110 mg/dL (6.1 mmol/L). Take the self-test, at the link below.

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