Arterial stiffness, lifestyle intervention and a low-calorie diet in morbidly obese patients-a nonrandomized clinical trial.

OBJECTIVE: Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. This study aimed to compare the 7-week effect of a low-calorie diet (LCD) and an intensive lifestyle intervention program (ILI) on arterial stiffness in morbidly obese individuals. DESIGN AND METHODS: Nonrandomized clinical trial. The LCD provided 900 kcal/day, and participants in the LCD group were instructed to maintain their habitual physical activity level. The ILI included two 90-min supervised training sessions 3 days a week at moderate to high intensity (4-8 METs) and a caloric restriction of 1000 kcal/day. RESULTS: A total of 179 individuals completed the study, 88 (56 women) in the ILI group and 91 (57 women) in the LCD group. High-fidelity applanation tonometry (Millar(®) , Sphygmocor(®) ) was used to measure carotid-femoral pulse wave velocity (PWV). After adjustment for relevant confounders, the ILI group had a significantly greater reduction in PWV than the LCD group; -0.4 (-0.6, -0.1) m/s, P = 0.004. When compared to the LCD group, the ILI group showed a larger reduction in systolic and diastolic blood pressure -5 (-9, -1) and -5 (-7, -2) mmHg, P = 0.038 and P ≤ 0.001 respectively, whereas no difference was observed regarding pulse pressure, P = 0.661. No significant differences between groups were found regarding the loss of fat mass, P = 0.259, but the loss of muscle mass was larger in the LCD group, 0.8 (0.5, 1.1) kg, P ≤ 0.001. CONCLUSION: Despite the limitations of a nonrandomized design, our findings indicate that for morbidly obese individuals a moderate caloric restriction combined with aerobic physical exercise is associated with a greater decline in PWV than a LCD alone.

Pulmonary function and blood gases after gastric bypass and lifestyle intervention: a comparative study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Impaired lung function associated with obesity improves with weight loss. WHAT THIS STUDY ADDS: This is the first study to compare the effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases. Arterial oxygenation and pulmonary function improved to a greater extent after gastric bypass than after lifestyle intervention. The superiority of surgical treatment might be mediated by greater weight loss after gastric bypass. Impaired lung function associated with obesity improves with weight loss. The effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases have not previously been subjected to comparative examination. In this 1-year non-randomized controlled clinical trial (ClinicalTrials.gov identifier NCT00273104), 139 morbidly obese subjects (19-66 years, mean [standard deviation] body mass index [BMI] 45.1 kg m(-2) [5.6], 107 women) were treated with either Roux-en-Y gastric bypass surgery (n = 76) or intensive lifestyle intervention (n = 63). Mean weight reduction was 30 (8)% and 8 (9)%, respectively. Dynamic and static lung volumes, gas diffusing capacity and arterial blood gases were measured. Compared with lifestyle intervention, surgery resulted in a significantly greater increase in forced vital capacity (mean [95% confidence interval] between-group difference, 7 [4-10]%), forced expiratory volume in 1 s (7 [5-9]%), total lung capacity (5 [1-8]%), vital capacity (7 [4-9]%), functional residual capacity (18 [12-24]%), expiratory reserve volume (48 [30-66]%) and partial pressure of oxygen in arterial blood (0.5 [0.0-1.0] kPa). These associations either disappeared or diminished after adjusting for weight loss. Reduced central adiposity (waist circumference and waist-to-hip ratio) and systemic inflammation (C-reactive protein and adiponectin) had no effect on pulmonary function beyond the effect of reduced general adiposity (BMI). In morbidly obese subjects, gastric bypass surgery is more effective than lifestyle intervention at improving arterial oxygenation and pulmonary function. The effect might be mediated by greater weight loss after surgical treatment.

Impact of gender on vitamin D deficiency in morbidly obese patients: a cross-sectional study.

BACKGROUND/OBJECTIVE: Obesity is associated with vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) <50 nmol/l). We aimed to examine the effect of gender on vitamin D status in severe obesity. SUBJECTS/METHODS: Cross-sectional study of 2026 morbidly obese patients examined consecutively at a tertiary care centre between November 2005 and June 2010. Serum 25(OH)D concentration and use of vitamin D supplements were registered in all patients. Total vitamin D intake (µg/day) was assessed in a subgroup of 154 patients using a validated food frequency questionnaire. RESULTS: The male (n=690) and female (n=1336) patients had a mean (s.d.) age of 45.0 (12.1) years and 42.2 (12.2) years (P<0.001), body mass index (BMI) of 44.6 (6.0) kg/m(2) and 44.3 (5.9) kg/m(2) (P=0.30) and waist circumference (WC) of 140 (13) cm and 127 (13) cm (P<0.001), respectively. Male patients had significantly lower mean 25(OH)D concentrations than female patients 50.0 (22.0) nmol/l versus 53.6 (22.4) nmol/l (P=0.001) and a higher rate of vitamin D deficiency (56% versus 47%; P<0.001). Obese men had significantly higher odds of vitamin D deficiency than women (odds ratio=1.41; 95% confidence interval: 1.17-1.70, P<0.001), also after adjustment for season, age, current smoking, intake of vitamin D supplements, BMI and WC (odds ratio=1.39; 95% confidence interval: 1.10-1.76). CONCLUSIONS: Morbidly obese Norwegian men seeking weight loss treatment have significantly higher odds of vitamin D deficiency than women. Monitoring of 25(OH)D concentrations in obese patients should therefore take gender into account.

The relationship between various measures of obesity and arterial stiffness in morbidly obese patients.

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. Arterial stiffness assessed by carotid femoral pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. We aimed to investigate how various measures of body composition affect arterial stiffness. METHODS: This is an analysis of cross-sectional baseline data from a controlled clinical trial addressing changes in arterial stiffness after either surgery or lifestyle intervention in a population of morbidly obese patients. High-fidelity applanation tonometry (Millar, Sphygmocor) was used to measure pulse wave velocity (PWV). Carotid femoral PWV is a direct measure of arterial stiffness and is considered to be the gold standard method. The Inbody 720 Body Composition Analyzer was used for bioelectrical impedance analysis (BIA). Spearman's correlation, independent samples t-test, chi-square tests, Fisher's exact test and multiple linear regression analyses were used as statistical methods. RESULTS: A total of 133 patients (79 women), with a mean (SD) age of 43 (11) years were included in the study. Men had a significantly higher prevalence of obesity related comorbidities and significantly higher PWV, 9.1 (2.0) m/s vs. 8.1 (1.8) m/s, p = 0.003, than women. In the female group, PWV was positively correlated with WC, WHtR, BMI and visceral fat area. In the male group, PWV was negatively correlated with BMI. Multiple linear regression analysis showed that increasing BMI, WC, WHtR, visceral fat area and fat mass were independently associated with higher PWV in women, but not in men, after adjustment for age, hypertension and type 2 diabetes. CONCLUSION: Most measures of general and abdominal obesity were predictors of arterial stiffness in female morbidly obese patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00626964.

Beta cell function after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention.

OBJECTIVE: The effects of various weight loss strategies on pancreatic beta cell function remain unclear. We aimed to compare the effect of intensive lifestyle intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell function. DESIGN: One year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). METHODS: One hundred and nineteen morbidly obese participants without known diabetes from the MOBIL study (mean (s.d.) age 43.6 (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m², 84 women) were allocated to RYGB (n = 64) or ILI (n = 55). The patients underwent repeated oral glucose tolerance tests (OGTTs) and were categorised as having either normal (NGT) or abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m², 19 women) served as controls. OGTT-based indices of beta cell function were calculated. RESULTS: One year weight reduction was 30% (8) after RYGB and 9% (10) after ILI (P < 0.001). Disposition index (DI) increased in all treatment groups (all P<0.05), although more in the surgery groups (both P < 0.001). Stimulated proinsulin-to-insulin (PI/I) ratio decreased in both surgery groups (both P < 0.001), but to a greater extent in the surgery group with AGT at baseline (P < 0.001). Post surgery, patients with NGT at baseline had higher DI and lower stimulated PI/I ratio than controls (both P < 0.027). CONCLUSIONS: Gastric bypass surgery improved beta cell function to a significantly greater extent than ILI. Supra-physiological insulin secretion and proinsulin processing may indicate excessive beta cell function after gastric bypass surgery.

Obesity-related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention.

OBJECTIVE: Weight reduction improves several obesity-related health conditions. We aimed to compare the effect of bariatric surgery and comprehensive lifestyle intervention on type 2 diabetes and obesity-related cardiovascular risk factors. DESIGN: One-year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). METHODS: Morbidly obese subjects (19-66 years, mean (s.d.) body mass index 45.1 kg/m(2) (5.6), 103 women) were treated with either Roux-en-Y gastric bypass surgery (n=80) or intensive lifestyle intervention at a rehabilitation centre (n=66). The dropout rate within both groups was 5%. RESULTS: Among the 76 completers in the surgery group and the 63 completers in the lifestyle group, mean (s.d.) 1-year weight loss was 30% (8) and 8% (9) respectively. Beneficial effects on glucose metabolism, blood pressure, lipids and low-grade inflammation were observed in both groups. Remission rates of type 2 diabetes and hypertension were significantly higher in the surgery group than the lifestyle intervention group; 70 vs 33%, P=0.027, and 49 vs 23%, P=0.016. The improvements in glycaemic control and blood pressure were mediated by weight reduction. The surgery group experienced a significantly greater reduction in the prevalence of metabolic syndrome, albuminuria and electrocardiographic left ventricular hypertrophy than the lifestyle group. Gastrointestinal symptoms and symptomatic postprandial hypoglycaemia developed more frequently after gastric bypass surgery than after lifestyle intervention. There were no deaths. CONCLUSIONS: Type 2 diabetes and obesity-related cardiovascular risk factors were improved after both treatment strategies. However, the improvements were greatest in those patients treated with gastric bypass surgery.

Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers.

OBJECTIVES: The majority of solid human malignancies demonstrate DNA aneuploidy as a consequence of chromosomal instability. We wanted to investigate whether Aurora A, Aurora B, BUB1B and Mad2 were associated with the development of aneuploidy in colorectal adenocarcinomas as suggested by several in vitro studies, and if their protein levels were related to alterations at the corresponding chromosomal loci. MATERIALS AND METHODS: Expression levels of these spindle proteins were investigated by immunohistochemistry using tissue micro-arrays in a series of DNA aneuploid and diploid colorectal adenocarcinomas previously examined for genomic aberrations by comparative genomic hybridization. RESULTS: All proteins were overexpressed in malignant tissues compared to controls (P < 0.001 for all). BUB1B level was significantly reduced in aneuploid compared to diploid cancers (P = 0.001), whereas expression of the other proteins was not associated with DNA ploidy status. High levels of Aurora A (P = 0.049) and low levels of Aurora B (P = 0.031) were associated with poor prognosis, but no associations were revealed between protein expression and genomic aberration. CONCLUSIONS: A significant reduction of BUB1B level was detected in aneuploid compared to diploid colorectal cancers, consistent with earlier studies showing that loss of spindle checkpoint function may be involved in development of DNA aneuploidy. Our data also show that spindle proteins are overexpressed in colorectal cancers, and that expression of the Aurora kinases is associated with prognosis in colorectal cancer.

Treatment-related differences in cardiovascular risk factors in long-term survivors of testicular cancer.

OBJECTIVE: Treatment in testicular cancer survivors (TCSs) may be followed by cardiovascular disorders. We have examined whether today's three treatment modalities are associated with a biochemical cardiovascular risk profile. MATERIALS AND METHODS: In this cross sectional study serum inflammatory markers, atherogenic lipoproteins and gonadal hormones were measured in 589 orchiectomized TCSs who have been treated 5-20 years previously. There were 140 patients treated by surgery alone (SURG), 231 who had had infradiaphragmatic radiotherapy alone (RAD), and 218 who had chemotherapy with or without additional surgery (CHEM). RESULTS: (1) The RAD group had higher levels of high-sensitivity C-reactive protein and soluble CD40 ligand compared to the SURG group. (2) The CHEM group had lower levels of high density lipoprotein cholesterol and an increased apolipoprotein B/apolipoprotein A-1 ratio than the SURG group. The prevalence of metabolic syndrome was higher in the CHEM group than in the SURG group. (3) Hypogonadism was significantly more prevalent in the CHEM than in the SURG group. CONCLUSION: Treatment for TC was related to long-term biochemical cardiovascular risk factors by different pathways: Radiation treatment is followed by elevated serum markers of chronic inflammation and endothelial dysfunction, whereas chemotherapy is followed by the development of atherogenic lipid changes and of the metabolic syndrome. This study provides justification for a prospective study of the impact of these treatment modalities on cardiovascular risk in testicular cancer survivors. In the interim testicular cancer survivors should monitor cardiovascular risk over time.