Obesity and insulin sensitivity effects on cardiovascular risk factors: Comparisons of obese dysglycemic youth and adults

Background: Obesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults. Subjects and Methods: We evaluated 66 pubertal youth (mean ± SD: age 14.2 ± 2.0 years, body mass index [BMI] 36.6 ± 6.0 kg/m2, hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4 years, BMI 35.1 ± 5.1 kg/m2, HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults. Results: Obese pubertal youth were more insulin resistant than comparably obese adults (P \u3c.001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P = NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low-density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high-density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ≤.05 for group differences). Conclusions: Effects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol. Clinical Trial Registration: The RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov

Determinants of Slow-Wave Activity in Overweight and Obese Adults: Roles of Sex, Obstructive Sleep Apnea and Testosterone Levels

Background: Slow-wave activity (SWA) in non-rapid eye movement (NREM) sleep, obtained by spectral analysis of the electroencephalogram, is a marker of the depth or intensity of NREM sleep. Higher levels of SWA are associated with lower arousability during NREM sleep and protect against sleep fragmentation. Multiple studies have documented that SWA levels are higher in lean women, compared to age-matched lean men, but whether these differences persist in obese subjects is unclear. Obstructive sleep apnea (OSA), a condition associated with obesity, is more prevalent in men than in women. Sex differences in SWA could therefore be one of the factors predisposing men to OSA. Furthermore, we hypothesized that higher levels of testosterone may be associated with lower levels of SWA.Objective: The aim of the current study was to identify sex differences in the determinants of SWA in young and middle-aged overweight and obese adults.Methods: We enrolled 101 overweight and obese but otherwise healthy participants from the community (44 men, 57 women) in this cross-sectional study. Participants underwent an overnight in-laboratory polysomnogram. The recordings were submitted to sleep staging and spectral analysis. Sex differences and the potential contribution of testosterone levels were evaluated after adjusting for age, body mass index and race/ethnicity.Results: OSA was present in 66% of men and in 44% of women. After adjustment for differences in age, race/ethnicity and BMI, the odds ratio for OSA in men vs. women was 3.17 (95% CI 1.14–9.43, p = 0.027). There was a graded inverse relationship between the apnea-hypopnea index (AHI) and SWA in men (β = −0.21, p = 0.018) but not in women (β = 0.10, p = 0.207). In a multivariate regression model, higher testosterone levels were independently associated with lower SWA in men after controlling for age, race/ethnicity and apnea-hypopnea index (β = −0.56, p = 0.025).Conclusion: Increasing severity of OSA was associated with significant decrease in sleep intensity in men but not in women. Higher testosterone levels were associated with lower sleep intensity in men. Men with higher testosterone levels may therefore have lower arousal thresholds and higher ventilatory instability in NREM sleep, and be at greater risk of OSA

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome

Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS.Peer reviewe