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Lehn-Stefan, A. ; Peter, A. ; Machann, J. ; Schick, F. ; Randrianarisoa, E. ; Heni, M. ; Wagner, R. ; Birkenfeld, A.L. ; Fritsche, A. ; Schulze, M.B.* ; Stefan, N. ; Kantartzis, K.

Impaired metabolic health and low cardiorespiratory fitness independently associate with subclinical atherosclerosis in obesity.

J. Clin. Endocrinol. Metab. 107, e2417-e2424 (2022)

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BACKGROUND: For a given body-mass index (BMI), both, impaired metabolic health (MH) and reduced cardiorespiratory fitness (CRF), associate with an increased risk of cardiovascular disease (CVD). It is still unknown whether both risk phenotypes relate to CVD independently of each other, and whether these relationships differ in normal weight, overweight and obese subjects. METHODS: Data from 421 participants from the Tübingen Diabetes Family Study, who had measurements of anthropometrics, metabolic parameters, CRF (maximal aerobic capacity [VO2max]) and carotid intima-media thickness (cIMT), an early marker of atherosclerosis, were analysed. Subjects were divided by BMI and MH status into 6 phenotypes. RESULTS: In univariate analyses higher age, increased BMI and a metabolic risk profile correlated positively, while insulin sensitivity and VO2max negatively with cIMT. In multivariable analyses in obese subjects, higher age, male sex, lower VO2max (std. ß -0.21, p=0.002) and impaired MH (std. ß 0.13, p=0.02) were independent determinants of increased cIMT. After adjustment for age and sex, subjects with metabolically healthy obesity (MHO) had higher cIMT than subjects with metabolically healthy normal weight (MHNW; 0.59±0.009 mm vs 0.52±0.01 mm, p<0.05). When VO2max was additionally included in this model, the difference in cIMT between the MHO and MHNW groups became statistically non-significant (0.58 ±0.009 mm vs 0.56 ±0.02 mm, p>0.05). CONCLUSIONS: These data suggest that impaired MH and low CRF independently determine increased cIMT in obese subjects and that a low CRF may explain part of the increased CVD risk observed in subjects with MHO, when compared to subjects with MHNW.

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