Distinct phenotypic characteristics of normal-weight adults at risk of developing cardiovascular and metabolic diseases

Am J Clin Nutr. 2020 Oct 1;112(4):967-978. doi: 10.1093/ajcn/nqaa194.


Background: The normal-weight BMI range (18.5-24.9 kg/m2) includes adults with body shape and cardiometabolic disease risk features of excess adiposity, although a distinct phenotype developed on a large and diverse sample is lacking.

Objective: To identify demographic, behavioral, body composition, and health-risk biomarker characteristics of people in the normal-weight BMI range who are at increased risk of developing cardiovascular and metabolic diseases based on body shape.

Methods: Six nationally representative waist circumference index (WCI, weight/height0.5) prediction formulas, with BMI and age as covariates, were developed using data from 17,359 non-Hispanic (NH) white, NH black, and Mexican-American NHANES 1999-2006 participants. These equations were then used to predict WCI in 5594 NHANES participants whose BMI was within the normal weight range. Men and women in each race/Hispanic-origin group were then separated into high, medium, and low tertiles based on the difference (residual) between measured and predicted WCI. Characteristics were compared across tertiles; P values for significance were adjusted for multiple comparisons.

Results: Men and women in the high WCI residual tertile, relative to their BMI and age-equivalent counterparts in the low tertile, had significantly lower activity levels; higher percent trunk and total body fat (e.g. NH white men, X ± SE, 25.3 ± 0.2% compared with 20.4 ± 0.2%); lower percent appendicular lean mass (skeletal muscle) and bone mineral content; and higher plasma insulin and triglycerides, higher homeostatic model assessment of insulin resistance (e.g. NH white men, 1.45 ± 0.07 compared with 1.08 ± 0.06), and lower plasma HDL cholesterol. Percent leg fat was also significantly higher in men but lower in women. Similar patterns of variable statistical significance were present within sex and race/ethnic groups.

Conclusions: Cardiometabolic disease risk related to body shape in people who are normal weight according to BMI is characterized by a distinct phenotype that includes potentially modifiable behavioral health risk factors.

Keywords: body composition; body shape; chronic disease; obesity; waist circumference.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Body Composition
  • Body Mass Index
  • Body Weight*
  • Cardiovascular Diseases / etiology*
  • Female
  • Humans
  • Male
  • Metabolic Diseases / etiology*
  • Middle Aged
  • Phenotype
  • Waist Circumference