Paradoxical Preservation of Vascular Function in Severe Obesity

†Initial exclusion criteria were: weight change of 3 kg or more in the last 6 months or any kind of treatment for obesity, known diabetes, chronic lung disease, thyroid dysfunction, myocardial infarction, or angina pectoris assessed on the basis of medical history or history of coronary revascularization procedures or the presence of left bundle branch block, Q or QS waves on the electrocardiogram, renal failure (defined as serum creatinine levels >1.3 mg/dL), or cancer in the previous 5 years. ‡Oral glucose tolerance test excluded individuals with diabetes⁷ (fasting plasma glucose >7.0 mmol/L or 2-hour plasma glucose >11 mmol/L), impaired fasting glucose (fasting plasma glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2-hour plasma glucose: 7.8-11.0 mmol/L), and insulin resistance determined using the Homeostasis Model Assessment of Insulin Resistance with the equation: Homeostasis Model Assessment of Insulin Resistance = (FPI × FPG)/22.5, where FPI is fasting plasma insulin concentration (mU/L) and FPG is fasting plasma glucose (mmol/L); the cutoff value for insulin resistance was 2.5.⁸ BMI = Body mass index; EKG = electrocardiogram; HOMA-IR = Homeostasis Model of Insulin Resistance; OGTT = oral glucose tolerance test.

A, B, Ultrasound studies: assessment of flow-mediated dilation by brachial artery ultrasound and measurement of carotid intima–media thickness by 2-dimensional carotid ultrasound. Subjects were subgrouped according to BMI as normal-weight (n = 13), obese (n = 35), and severely obese (n = 23). A, Maximal diameter during ischemia-induced hyperemia was used to calculate the percentage of flow-mediated dilation: ([maximum diameter-baseline diameter]/baseline diameter × 100%). Flow-mediated dilation was significantly higher in severely obese subjects than in obese and normal-weight subjects (13.02% ± 6.50% vs 7.53% ± 5.47%, P = .019, and 13.02% ± 6.50% vs 7.33% ± 3.68%, P = .011, respectively). No differences were found in flow-mediated dilation between normal-weight and obese subjects (7.33% ± 3.68% vs 7.53% ± 5.47%, respectively, P >.99) (P for trend = .005). B, Three to six measurements at both common carotid arteries were taken, yielding mean intima–media thickness (the average thickness across the 1-cm segment of each carotid arteries) and maximum intima–media thickness (the single highest measurement). Maximum carotid intima–media thickness was significantly lower in severely obese subjects versus obese subjects (0.66 ± 0.14 mm vs 0.89 ± 0.38 mm, P = .04). No differences in maximum intima–media thickness were found between severely obese and normal-weight subjects (0.66 ± 0.14 mm vs 0.70 ± 0.20 mm, P >.99) and between normal-weight and obese subjects (0.70 ± 0.20 mm vs 0.89 ± 0.38 mm, P = .17) (P for trend = .028). No differences were found in mean intima–media thickness among groups (P for trend .08). C-E, Biological parameters: measurement of high-sensitivity C-reactive protein, leptin and endothelial progenitor cells. C, High-sensitivity C-reactive protein was higher in severely obese versus obese subjects (7.42 mg/L [0.95-37.44 mg/L] vs 2.38 mg/L [0.37-35.84 mg/L], P = .05) and in severely obese versus normal-weight subjects (7.42 mg/L [0.95-37.44 mg/L] vs 2.13 mg/L [0.15-5.50 mg/L], P = .018]. No differences were found between normal-weight and obese subjects (P for trend = .012). D, Leptin levels were significantly higher in severely obese versus obese subjects (71.95 ng/L [28.10-100 ng/L] vs 13.10 ng/L [2.00- 55.50 ng/L], P <.001) and in severely obese versus normal-weight subjects (71.95 ng/L [28.10-100 ng/L] vs 9.04 ng/L [1.90-25.70 ng/L], P <.001). No differences were found between normal-weight and obese subjects (P for trend = .0001). E, Endothelial progenitor cells. CD34+KDR+ endothelial progenitor cells were higher in severely obese versus obese subjects (0.29% [0.01%-2.44%] vs 0.16% [0.00%-1.15%], P = .039). No differences were found between normal-weight versus obese subjects (0.14% [0.02%-0.59%] vs 0.16% [0.00%-1.15%] P >.99) or between normal-weight versus severely obese subjects (0.14% [0.02%-0.59%] vs 0.29% [0.01%-2.44%] P = .056) (P for trend = .019). No differences were found in the percentage of CD34+CD133+among groups (P for trend = .28). Dots represent outliers. EPC = Endothelial progenitor cell; IMT = intima–media thickness; N = normal-weight; O = obese; SO = severely obese.