Assessment of dyspneic sensation in patients with type 2 diabetes.

Introduction: Individuals with type 2 diabetes (T2D) should be considered a susceptible group for pulmonary dysfunction. So, we aimed to evaluate the sensation of breathlessness in this population by administering two well-validated questionnaires. Methods: This is a crosssectional study with 592 people without known respiratory disease (353 with T2D) who answered the modified Medical Research Council (mMRC) questionnaire. In addition, 47% also responded to the St George Respiratory Questionnaire, a specific instrument designed to be applied to patients with obstructive airway disease. Results: Patients with T2D showed a higher mMRC score in comparison to the control group [1.0 (0.0 - 4.0) vs. 0.0 (0.0 - 4.0), p<0.001]. A higher prevalence of subjects with mMRC ≥2 was observed in T2D that in the control group (20.2% vs. 11.6%, p=0.004). Participants with T2D and mMRC ≥2 showed a higher HbA1c (8.2 ± 1.6% vs. 7.8 ± 1.6%, p=0.048), longer T2D evolution and higher prevalence of nephropathy. In the multivariate analysis, the presence of T2D [OR=1.95 (1.19 to 3.22), p=0.008] in all the population, and HbA1c [OR=1.19 (1.01 to 1.41), p=0.034] and the presence of diabetic nephropathy [OR=2.00 (1.14 to 3.52), p=0.015] in patients with T2D, predicted a mMRC ≥2. Finally, no differences were observed regarding the SGRQ score among groups. Conclusions: Patients with T2D showed a greater sensation of dyspnea than subjects with normal carbohydrate metabolism. Risk factors included poor metabolic control and the presence of renal disease.

Comparative effects of glucagon-like peptide-1 receptors agonists, 4-dipeptidyl peptidase inhibitors, and metformin on metabolic syndrome.

AIMS: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients. METHODS: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires. RESULTS: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: -1.7 mg/dL(± 13.5); ∆ metformin: - 2.5(± 23.9) mg/dL; ∆ DPP-4I: - 4.5(± 42.6); mg/dL ∆ GLP-1RA: - 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: - 0.1(± 0.7) %; ∆ DPP-4I: - 0.1(± 1.0) %; ∆ GLP-1RA: - 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: -0.8(± 1.6) kg/m2; ∆ metformin: - 0.8(± 1.5) kg/m2; ∆ DPP-4I: - 0.6(± 1.3) kg/m2; ∆ GLP-1RA: - 0.5(± 1.2) kg/m2. and their waist circumference (∆ untreated: -2.8(± 5.2) cm; ∆ metformin: - 2.6(± 15.2) cm; ∆ DPP-4I: - 2.1(± 4.8) cm; ∆ GLP-1RA: - 2.4(± 4.1) cm. CONCLUSION: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest.

Prediabetes Is Associated with Increased Prevalence of Sleep-Disordered Breathing.

Type 2 diabetes leads to severe nocturnal hypoxemia, with an increase in apnea events and daytime sleepiness. Hence, we assessed sleep breathing parameters in the prediabetes stage. A cross-sectional study conducted on 966 middle-aged subjects without known pulmonary disease (311 patients with prediabetes and 655 controls with normal glucose metabolism) was conducted. Prediabetes was defined by glycated hemoglobin (HbA1c), and a nonattended overnight home sleep study was performed. Participants with prediabetes (n = 311) displayed a higher apnea−hypopnea index (AHI: 12.7 (6.1;24.3) vs. 9.5 (4.2;19.6) events/h, p < 0.001) and hypopnea index (HI: 8.4 (4.0;14.9) vs. 6.0 (2.7;12.6) events/h, p < 0.001) than controls, without differences in the apnea index. Altogether, the prevalence of obstructive sleep apnea was higher in subjects with prediabetes than in controls (78.1 vs. 69.9%, p = 0.007). Additionally, subjects with prediabetes presented impaired measurements of the median and minimum nocturnal oxygen saturation, the percentage of time spent with oxygen saturations below 90%, and the 4% oxygen desaturation index in comparison with individuals without prediabetes (p < 0.001 for all). After adjusting for age, sex, and the presence of obesity, HbA1c correlated with the HI in the entire population (r = 0.141, p < 0.001), and the presence of prediabetes was independently associated with the AHI (B = 2.20 (0.10 to 4.31), p = 0.040) as well as the HI (B = 1.87 (0.61 to 3.14), p = 0.004) in the multiple linear regression model. We conclude that prediabetes is an independent risk factor for an increased AHI after adjusting for age, sex, and obesity. The enhanced AHI is mainly associated with increments in the hypopnea events.

Dapagliflozin plus exenatide on patients with type 2 diabetes awaiting bariatric surgery in the DEXBASU study.

The glucagon-like peptide-1 receptor agonist family together with the renal sodium/glucose cotransporter-2 inhibitors have garnered interest as potential therapeutic agents for subjects with type 2 diabetes and obesity. In these patients, bariatric surgery is indicated based in a BMI ≥ 35 kg/m2. A 24-week non-blinded, randomized pilot study to assess the efficacy of subcutaneous exenatide 2.0 mg once weekly plus oral dapagliflozin 10 mg once daily (Group A) compared to a control group (Group B) in 56 patients with type 2 diabetes awaiting bariatric surgery was conducted (EudraCTid.: 2017-001,454-33). Both groups received an energy-deficit low-fat diet. The primary endpoint was the proportion of patients running off the criteria for bariatric surgery at the end of the follow-up period (BMI ≤ 35.0 kg/m2 or a BMI ≤ 40.0 kg/m2 plus an HbA1c ≤ 6.0%). Changes in the BMI were also of interest. The proportion of patients who ran off the criteria for bariatric surgery was larger in Group A than in the control group (45.8% vs. 12.0%, p = 0.010). Participants in Group A exhibited an absolute decrease in body weight and BMI of 8.1 kg (95%IC: - 11.0 to - 5.2) and 3.3 kg/m2 (95%IC: - 4.5 to - 2.2), respectively (p < 0.001 for both in comparison with Group B). A higher percentage of participants in Group A reached a BMI < 35 kg/m2 (45.8 vs 12.0%) and lost > 10% of their initial body weight (20.8 vs 0%) compared to Group B. The combination of exenatide plus dapagliflozin appears as a strategic option to reduce the waiting list for bariatric surgery, especially in those patients with type 2 diabetes.

A Clinical-Genetic Score for Predicting Weight Loss after Bariatric Surgery: The OBEGEN Study.

Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805-0.880), p < 0.001; sensitivity 90.1%, specificity 65.5%] was obtained by combining three clinical variables (age, type of surgery, presence diabetes) and nine SNPs located in ADIPOQ, MC4R, IL6, PPARG, INSIG2, CNR1, ELOVL6, PLIN1 and BDNF genes. This predictive model showed a significant higher area under ROC than the clinical score (p = 0.0186). The OBEGEN study shows the key role of combining clinical variables with genetic testing to increase the predictability of the weight loss response after BS. This finding will permit us to implement a personalized medicine which will be associated with a more cost-effective clinical practice.

Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?

Limited reports exist on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes. We examined whether the expression of Hypoxia-Inducible Factor-1α (HIF-1α) and HIF-2α relates to changes in the expression of clock genes (Period homolog proteins (PER)1, PER2, PER3, Retinoid-related orphan receptor alpha (RORA), Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), Circadian locomotor output cycles kaput (CLOCK), and Cryptochrome proteins (CRY) 1 and CRY2) in patients with type 2 diabetes. A total of 129 subjects were evaluated in this cross-sectional study (48% with diabetes). The gene expression was measured by polymerase chain reaction. The lactate and pyruvate levels were used as surrogate of the hypoxia induced anaerobic glycolysis activity. Patients with diabetes showed an increased plasma concentration of both lactate (2102.1 ± 688.2 vs. 1730.4 ± 694.4 uM/L, p = 0.013) and pyruvate (61.9 ± 25.6 vs. 50.3 ± 23.1 uM/L, p = 0.026) in comparison to controls. However, this finding was accompanied by a blunted HIF-1α expression (1.1 (0.2 to 5.0) vs. 1.7 (0.4 to 9.2) arbitrary units (AU), p ≤ 0.001). Patients with diabetes also showed a significant reduction of all assessed clock genes' expression. Univariate analysis showed that HIF-1α and almost all clock genes were significantly and negatively correlated with HbA1c concentration. In addition, positive correlations between HIF-1α and the clock genes were observed. The stepwise multivariate regression analysis showed that HbA1c and clock genes independently predicted the expression of HIF-1α. Type 2 diabetes modifies the expression of HIF-1α and clock genes, which correlates with the degree of metabolic control.

Dynamics of Anthropometric Indices in a Large Paired Cohort With 10 Years of Follow-Up: Paving the Way to Sarcopenic Obesity.

Introduction: Paired cohort investigations assessing the evolution of anthropometric indices are scarce. Here we assessed the 10-year evolution of BMI, total body fat, and lean body mass in 50,019 participants aged 18-90 years at the time of first assessment. Material and Methods: A retrospective cohort study using an electronic database that contains anonymized, longitudinal data from Primary Care medical records covering the 2007-2008 and 2017-2018 periods. Total body fat was estimated using the Clínica Universidad de Navarra-Body Adiposity Estimator formula, and the Hume formula was applied to estimate lean body mass. Results: The mean BMI of participants <60 years old in the 2007-2008 period increased significantly, from 27.5 to 28.3 kg/m2 (p < 0.001). However, the BMI of older subjects decreased during the next decade, from 28.9 to 28.3 kg/m2 (p < 0.001). The estimated total body fat showed a continuous progressive increase over all ages. Finally, lean body mass showed a progressive increase until the 40s, with a plateau between 40-45 years old and an uninterrupted decrease until older ages. Also, subjects who increased their BMI by 2 kg/m2 during the 10-year period were mainly women and younger at baseline, with a lower initial BMI and total body fat in comparison with those who experienced a BMI decrease of ≥2.0 kg/m2. Conclusion: The evolutions of BMI and the estimated body compositions reported here confirm that the adverse decrease in lean body mass begins in middle age. The proportion of older subjects is important when evaluating overweight and obesity prevalence in cross-sectional studies.

Effect of Subcutaneous Insulin on Spirometric Maneuvers in Patients with Type 1 Diabetes: A Case-Control Study.

In order to compare spirometric maneuvers in adults according to the presence of type 1 diabetes, a case-control study including 75 patients with type 1 diabetes and 75 controls matched by sex, age, and body mass index were designed. In addition, 75 patients with type 1 diabetes were added to examine the potential the impact of subcutaneous insulin therapy on pulmonary function. Lung function measurements were assessed according to the global initiative for chronic obstructive lung disease guidelines. Basal insulin included long-acting insulin analogues and the delivered background insulin in patients with pump therapy. Bolus insulin included rapid-acting insulin analogues and the delivered insulin to cover postprandial hyperglycemias. Patients with type 1 diabetes showed lower spirometric values in comparison to the control group, together with a higher prevalence of forced expiratory volume in the first second (FEV1) <80% (10.7% vs. 2.7%, p = 0.044) and restrictive ventilatory pattern (10.7% vs. 0%, p = 0.006) The dose of basal insulin (U/kg/day) showed a negative correlation with forced vital capacity (FVC) (r = -0.205, p = 0.012) and FEV1 (r = -0.182, p = 0.026). The optimal cut-off value for identifying patients with a restrictive spirometric pattern was 0.5 U/kg/day of basal insulin. Additionally, basal insulin (U/kg/day) independently predicted the presence of both a restrictive spirometric pattern (OR = 77.1 (3.2 to 1816.6), p = 0.007) and an abnormal FEV1 (OR = 29.9 (1.5 to 562.8), p = 0.023). In patients with type 1 diabetes, higher basal insulin dosage seems to be related with an impairment of pulmonary function.

Effect of Glucose Improvement on Nocturnal Sleep Breathing Parameters in Patients with Type 2 Diabetes: The Candy Dreams Study.

Type 2 diabetes exerts a negative impact on sleep breathing. It is unknown whether a long-term improvement in glycemic control ameliorates this effect. We conducted an interventional study with 35 patients with type 2 diabetes and obstructive sleep apnea (OSA) to explore this. At home, sleep breathing parameters were assessed at baseline and after a 4-month period in which antidiabetic therapy was intensified. Patients who decreased their body mass index ≥2kg/m2 were excluded. Those with an HbA1c reduction ≥0.5% were considered good responders (n = 24). After the follow-up, good responders exhibited an improvement in the apnea-hypopnea index (AHI: 26-1 (95% IC: 8.6-95.0) vs. 20.0 (4.0-62.4) events/hour, p = 0.002) and in time with oxygen saturation below 90% (CT90: 13.3 (0.4-69.0) vs. 8.1 (0.4-71.2) %, p = 0.002). No changes were observed in the group of non-responders (p = 0.722 and p = 0.138, respectively). The percentage of moderate and severe OSA decreased among good responders (p = 0.040). In the wider population, the change in HbA1c correlated positively to decreases in AHI (r = 0.358, p = 0.035) and negatively to increases in the minimum arterial oxygen saturation (r = -0.386, p = 0.039). Stepwise multivariate regression analysis showed that baseline AHI and the absolute change in HbA1c independently predicted decreased AHI (R2 = 0.496). The improvement of glycemic control exerts beneficial effects on sleep breathing parameters in type 2 diabetes, which cannot be attributed merely to weight loss.

Sympathetic Hyperactivity and Sleep Disorders in Individuals With Type 2 Diabetes.

Introduction: Many studies on the impact of type 2 diabetes mellitus (T2DM) on sleep breathing have shown a higher prevalence and severity of sleep apnea-hypopnea syndrome (SAHS) in those with T2DM. Moreover, an increased activity of the sympathetic nervous system has been described in both pathologies. This cross-sectional study aimed to assess sympathetic activity in patients with T2DM, and to investigate the relationship between sympathetic activity and polysomnographic parameters. Materials and Methods: Thirty-six patients with T2DM without known clinical macrovascular nor pulmonary disease and 11 controls underwent respiratory polygraphy, and their cardiac variability and 24-h urine total metanephrines were measured. Results: SAHS was highly prevalent with a mean apnea-hypopnea index (AHI) in the range of moderate SAHS. In patients with T2DM, the nocturnal concentration of total metanephrines in urine were higher than diurnal levels [247.0 (120.0-1375.0) vs. 210.0 (92.0-670.0), p = 0.039]. The nocturnal total metanephrine concentration was positively and significantly associatedwith the percentage of sleeping time spent with oxygen saturation <90%(CT90). In the entire population and in subjects with T2DM, the multivariate regression analysis showed a direct interaction between the nocturnal concentration of urine metanephrines and the CT90. Conclusion: These findings suggest that the increase in sympathetic activity previously described in patients with T2DM could be mediated through nocturnal breathing disturbances. The diagnosis and treatment of SAHS may influence sympathetic activity disorders and may contribute to an improvement in T2DM and cardiovascular risk.

Dissimilar Impact of a Mediterranean Diet and Physical Activity on Anthropometric Indices: A Cross-Sectional Study from the ILERVAS Project.

There is a close relationship between lifestyle behaviors and excess adiposity. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. However, little is known about the impact of physical activity and adherence to a Mediterranean diet on these indices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects with low to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants' adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet (Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg's formula), central adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher values of total body fat and central adiposity. This result was constant regardless of the indices used to estimate adiposity. However, the association between MedDiet and obesity indices was much less marked and more dependent on sex than that observed for physical activity. Lean body mass was influenced by neither physical activity nor MedDiet adherence. No joint effect between physical activity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion, physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDiet showed a slight impact on estimated anthropometric indices, with no joint effect when considering both lifestyle variables. ClinTrials.gov Identifier: NCT03228459.

Lung function measurements in the prediabetes stage: data from the ILERVAS Project.

AIMS: Patients with type 2 diabetes have been considered a susceptible group for pulmonary dysfunction. Our aim was to assess pulmonary function on the prediabetes stage. METHODS: Pulmonary function was assessed in 4,459 non-diabetic subjects, aged between 45 and 70 years, without cardiovascular disease or chronic pulmonary obstructive disease from the ongoing study ILERVAS. A "restrictive spirometric pattern", an "abnormal FEV1" and an "obstructive ventilatory defect" were assessed. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association criteria. RESULTS: Population was composed of 52.1% women, aged 57 [53;63] years, a BMI of 28.6 [25.8;31.8] kg/m2, and with a prevalence of prediabetes of 29.9% (n = 1392). Subjects with prediabetes had lower forced vital capacity (FVC: 93 [82;105] vs. 96 [84;106], p < 0.001) and lower forced expired volume in the first second (FEV1: 94 [82;107] vs. 96 [84;108], p = 0.011), as well as a higher percentage of the restrictive spirometric pattern (16.5% vs. 13.6%, p = 0.015) and FEV1 < 80% (20.3% vs. 17.2%, p = 0.017) compared to non-prediabetes group. In the prediabetes group, HbA1c was negatively correlated with both pulmonary parameters (FVC: r = - 0.113, p < 0.001; FEV1: r = - 0.079, p = 0.003). The multivariable logistic regression model in the whole population showed that there was a significant and independent association between HbA1c with both restrictive spirometric pattern [OR = 1.42 (1.10-1.83), p = 0.008] and FEV1 < 80% [OR = 1.50 (1.19-1.90), p = 0.001]. CONCLUSIONS: The deleterious effect of type 2 diabetes on pulmonary function appears to be initiated in prediabetes, and it is related to metabolic control. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03228459.

Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project.

A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87⁻109) vs. 94 (82⁻105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89⁻112) vs. 93 (80⁻107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88⁻107) vs. 94 (83⁻105) % of predicted, p = 0.027) and FEV1 (100 (89⁻110) vs. 95 (84⁻108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.

Effect of Glucose Improvement on Spirometric Maneuvers in Patients With Type 2 Diabetes: The Sweet Breath Study.

OBJECTIVE: Type 2 diabetes exerts a deleterious effect on lung function. However, it is unknown whether an improvement in glycemic control ameliorates pulmonary function. RESEARCH DESIGN AND METHODS: Prospective interventional study with 60 patients with type 2 diabetes and forced expiratory volume in 1 s (FEV1) ≤90% of predicted. Spirometric maneuvers were evaluated at baseline and after a 3-month period in which antidiabetic therapy was intensified. Those with an HbA1c reduction of ≥0.5% were considered to be good responders (n = 35). RESULTS: Good responders exhibited a significant improvement in spirometric values between baseline and the end of the study (forced vital capacity [FVC]: 78.5 ± 12.6% vs. 83.3 ± 14.7%, P = 0.029]; FEV1: 75.6 ± 15.3% vs. 80.9 ± 15.4%, P = 0.010; and peak expiratory flow [PEF]: 80.4 ± 21.6% vs. 89.2 ± 21.0%, P = 0.007). However, no changes were observed in the group of nonresponders when the same parameters were evaluated (P = 0.586, P = 0.987, and P = 0.413, respectively). Similarly, the initial percentage of patients with a nonobstructive ventilatory defect and with an abnormal FEV1 decreased significantly only among good responders. In addition, the absolute change in HbA1c inversely correlated to increases in FEV1 (r = -0.370, P = 0.029) and PEF (r = -0.471, P = 0.004) in the responders group. Finally, stepwise multivariate regression analysis showed that the absolute change in HbA1c independently predicted increased FEV1 (R 2 = 0.175) and PEF (R 2 = 0.323). In contrast, the known duration of type 2 diabetes, but not the amelioration of HbA1c, was related to changes in forced expiratory flow between 25% and 75% of the FVC. CONCLUSIONS: In type 2 diabetes, spirometric measurements reflecting central airway obstruction and explosive muscle strength exhibit significant amelioration after a short improvement in glycemic control.

The influence of sleep apnea syndrome and intermittent hypoxia in carotid adventitial vasa vasorum.

Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous disease.

Influence of Morbid Obesity and Bariatric Surgery Impact on the Carotid Adventitial Vasa Vasorum Signal.

INTRODUCTION/PURPOSE: Adventitial vasa vasorum (VV) expansion to the avascular intima precedes an increase in carotid intima-media thickness. However, factors involved in the development of the atherosclerotic process and its reversibility remain unclear. We aimed to evaluate the VV signal in both morbid obesity and after bariatric surgery (BS). MATERIALS/METHODS: We conducted a case-control study to examine the VV signal in the carotid of 40 morbidly obese patients and 40 non-obese controls. The effect of BS was evaluated in 33 patients. Contrast-enhanced carotid ultrasound was used to assess the VV signal. RESULTS: The mean VV density was higher in obese than in non-obese subjects (0.739 ± 0.117 vs. 0.570 ± 0.111, p < 0.001). The VV signal positively correlated with BMI (p < 0.001) and waist circumference (p = 0.001) but was not related to cIMT. The stepwise multivariate regression analysis revealed that waist circumference (beta = 0.507, p < 0.001) together with fasting plasma glucose (beta = 0.229, p = 0.024) were independently associated with the VV signal (R2 = 0.382). Before BS, the median VV signal correlated with soluble intercellular adhesion molecule 1 (p = 0.022). After a 12-month follow-up, a 12.0% decrease in VV (0.731 ± 0.126 vs. 0.643 ± 0.115, p = 0.003) was observed. In the univariate analysis, the decrease in VV was associated with the baseline VV density (p < 0.001), baseline systolic blood pressure (p = 0.019) and a decrease in sICAM (p = 0.005). However, only baseline systolic pressure (beta = 0.417, p = 0.024) independently predicted the absolute change in VV signal (R2 = 0.174). CONCLUSIONS: Morbidly obesity is associated with increased VV density. In addition, BS appears to reduce the earlier expansion of the adventitial vasa vasorum.