José I. Botella-Carretero

Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women

Aims/HypothesisIncreased serum inflammatory markers have been found in obesity and insulin-resistant states, and could play a causative role in insulin resistance, atherosclerosis and cardiovascular disease. The polycystic ovary syndrome represents a human model of insulin resistance because both lean and obese polycystic ovary syndrome patients are insulin-resistant compared with non-hyperandrogenic women. We evaluated whether obesity, insulin resistance, or both, are related to the increased concentrations of inflammatory markers in pre-menopausal women.MethodsWe compared 35 patients with polycystic ovary syndrome and 28 healthy women, paired for BMI, prevalence of obesity and smoking. Measurements included serum inflammatory markers, BMI, waist-to-hip ratio, blood pressure, serum glucose, insulin, lipid and hormone concentrations, and insulin sensitivity index.ResultsThe insulin sensitivity index was reduced in polycystic ovary syndrome patients compared with controls. However, no differences were observed between both groups in C-reactive protein, interleukin 6, tumour necrosis factor-α, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. When considering patients and controls as a whole, C-reactive protein and interleukin 6, were increased in obese subjects compared with lean women. Inverse correlations existed between insulin sensitivity index and C-reactive protein, interleukin 6, tumour necrosis factor-α, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. Only the weak correlation with C-reactive protein persisted after controlling for BMI.Conclusion/interpretationObesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women.

Perioperative oral nutritional supplements in normally or mildly undernourished geriatric patients submitted to surgery for hip fracture: A randomized clinical trial

BACKGROUND Oral nutritional supplements have been recommended after orthopedic surgery in geriatric patients. This has been shown to be effective even in normally nourished or mildly undernourished geriatric patients. Whether perioperative administration of these products is also effective and suitable is not known. METHODS Randomized, controlled, open, paralleled two-arms clinical trial, comparing energy-protein supplements (40 g of protein and 400 kcal per day), with no intervention in normally nourished or mildly undernourished patients. Outcomes were serum proteins, body mass index, postoperative complications among others. RESULTS 60 Elderly patients were included. Patients in the intervention group (n = 30) ingested 52.2 ± 12.1% of the prescribed supplements per day for 5.8 ± 1.8 days before surgery and until hospital discharge. There was a significant change in serum albumin at follow-up (F = 22.536, P < 0.001), and between the two groups (F = 5.763, P = 0.002), favouring the intervention. The same was observed for serum prealbumin (F = 6.654, P = 0.001 within subjects, F = 2.865, P = 0.045 for interaction). Logistic regression showed that only supplemented proteins per day (OR[95%CI] = 0.925[0.869-0.985]) were associated with less postoperative complications (R(2) = 0.323, χ(2) = 11.541, P = 0.003). CONCLUSION Perioperative supplements in geriatric patients with hip fracture submitted to surgery showed better recovery of plasma proteins. Higher daily protein intakes were associated with less postoperative complications.

Effects of Oral Nutritional Supplements in Normally Nourished or Mildly Undernourished Geriatric Patients After Surgery for Hip Fracture: A Randomized Clinical Trial

BACKGROUND Oral nutritional supplements have been recommended after orthopedic surgery in geriatric patients to reduce postoperative complications. However, tolerability of supplements could be a limitation, and their universal use is not supported by the heterogeneity of previous studies, especially in patients without malnutrition. METHODS This study is a randomized, controlled, open, parallel, 3-arm clinical trial comparing supplementation with protein powder dissolved in liquids to aim at 36 g of protein per day, energy and protein supplements to aim at 37.6 g of protein and 500 kcal per day, or no intervention in normally nourished or mildly undernourished patients. Outcomes were serum albumin, prealbumin, retinol-binding globulin, and body mass index, among others. Postoperative complications were also recorded. RESULTS Ninety patients aged 83.8 +/- 6.6 years were included. The mean ingested amount of supplements was 41.1% +/- 20.6% in the protein powder supplement group and 51.4% +/- 13.2% in the energy protein supplement group (t = 2.278, P = .027). Postoperative supplements had no effect on the nutrition status during in-hospital follow-up, as assessed by serum albumin (P = .251), prealbumin (P = .530), retinol-binding globulin (P = .552), or body mass index (P = .582). Multivariate analysis showed that length of hospital stay with an established complication until its resolution (beta = .230, P = .031), total hospital stay (beta = .450, P < .001), baseline body mass index (beta = .204, P = .045), and total daily ingested proteins per body weight (beta = .252, P = .018) were predictive variables on the change in serum albumin (R2 = 0.409, F = 11.246, P < .001). CONCLUSIONS Oral nutritional supplements in normally nourished or only mildly undernourished geriatric patients with hip fracture submitted to surgery may be of interest for patients with postoperative complications and long hospital stays.

Chronic Increase of Bone Turnover Markers After Biliopancreatic Diversion is Related to Secondary Hyperparathyroidism and Weight Loss. Relation with Bone Mineral Density

BackgroundBiliopancreatic diversion (BPD) is the most effective bariatric procedure. Around 70% of these patients have secondary hyperparathyroidism (SH) in the long term as a consequence of calcium and vitamin D malabsorption. This work was aimed to study the influence of SH on bone turnover and its relationship with bone mineral density (BMD).MethodsBone turnover markers were determined in 63 BPD patients and 34 morbidly obese controls. In the BPD group, we also studied the influence of age, loss of weight, common channel length, PTH, vitamin D, and serum calcium on bone turnover as well as its relation with BMD.ResultsBPD patients showed significantly higher PTH, osteocalcin, and β-CTx levels than controls. In the multivariate regression analysis, only PTH (β = 0.42; P = 0.0002), menopausal status (β = 0.31; P = 0.007) and the percentage of lost BMI (β = −0.24; P = 0.03) significantly predicted the osteocalcin level (R2 = 0.33; F = 9.56; P < 0.0001). Similarly, only PTH (β = 0.39; P = 0.0005), menopausal status (β = 0.37; P = 0.001) and the percentage of lost BMI (β = −0.23; P = 0.04) significantly predicted the β-CTx level (R2 = 0.33; F = 9.82; P < 0.0001). Osteocalcin and β-CTx levels correlated negatively with BMD at lumbar spine (r = −0.38, P = 0.002 and r = −0.30, P = 0.02, respectively).ConclusionsChronic SH and the loss of weight determine a high rate of bone turnover that is associated with decreasing BMD in BPD patients.

Retinol and α-Tocopherol in Morbid Obesity and Nonalcoholic Fatty Liver Disease

BackgroundWe aimed to study serum retinol and α-tocopherol in a cohort of obese patients and their possible association with several obesity-related conditions, given that the former may be implicated in a diminished capacity of anti-inflammatory and antioxidant potential in obese patients.MethodsEighty patients with morbid obesity participated in the study. Many clinical and biochemical variables were measured including serum retinol, α-tocopherol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Fatty liver was detected by ultrasonography.ResultsBoth serum retinol and α-tocopherol inversely correlated with body mass index (r = −0.334, P = 0.002 and r = −0.299, P = 0.007, respectively). Serum retinol inversely correlated with AST (r = −0.236, P = 0.036) and ALT (r = −0.241, P = 0.032). Multivariate regression analyses confirmed these results after correcting for the effects of other variables. Eighty-five percent of patients had fatty liver. When restricting the analysis to them, multivariate regression identified male sex (β = 0.451, P = 0.003), age (β = −0.275, P = 0.039), and serum retinol concentrations (β = −0.414, P = 0.005) as predictive variables on serum AST (R2 = 0.230, F = 3.408, P = 0.009) and male sex (β = 0.448, P = 0.003), age (β = −0.236, P = 0.046), insulin resistance determined by homeostasis model assessment (β = 0.243, P = 0.050), and serum retinol concentrations (β = −0.305, P = 0.022) as predictive variables on serum ALT (R2 = 0.296, F = 5.817, P = 0.001).ConclusionSerum retinol and α-tocopherol concentrations are inversely associated with body mass index in morbid obesity, and serum retinol is also inversely associated with serum concentrations of transaminases in those patients with nonalcoholic fatty liver disease.

The striking similarities in the metabolic associations of female androgen excess and male androgen deficiency

Androgen excess in women and androgen deficiency in men facilitate abdominal adiposity and related metabolic disorders. Moreover, obesity-associated gonadal dysfunction consists of hyperandrogenism in women but hypogonadism in men. We have reviewed the existing evidence on the interplay between sex steroids, adipose tissue and lean mass distribution, and developed a novel hypothesis to explain these apparent paradoxes. We hypothesize that the most beneficial adipose tissue distribution and function is that of normal women, who have low androgen and high estrogen concentrations. Any imbalance favoring an increase in androgen levels in women, and the very high androgen levels characteristic of healthy men, influence adipose tissue distribution and function. Sex steroids determine a favorable (female) or unfavorable (male) body fat distribution and function. However, sex hormones also provide defensive mechanisms against visceral fat accumulation: androgens increase lean and muscle mass in men, decreasing the amount of visceral fat relative to total body mass and its negative consequences, whereas estrogens determine the metabolically safer deposition of body fat into the subcutaneous gluteal-femoral depot in women. This delicate equilibrium may be altered by the presence of gonadal dysfunction, a sedentary life-style or the normal ageing process leading to sarcopenia, and by the development of obesity leading to abdominal adiposity and metabolic disorders in both sexes. In conclusion, sex hormones and gonadal dysfunction play important roles in the pathogenesis of diabesity and its metabolic associations.

Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight

To study the prevalence of male obesity‐secondary hypogonadism (MOSH) in patients with moderate to severe obesity, we performed a prospective prevalence study including 100 male patients with moderate to severe obesity at a university tertiary hospital. Total testosterone (TT) and sex hormone‐binding globulin (SHBG) concentrations among others were assayed in all patients. Serum‐free testosterone (FT) concentration was calculated from TT and SHBG levels. Semen analysis was conducted in 31 patients. We found a prevalence of 45% (95% CI: 35–55%) when considering decreased TT and/or FT concentrations. Serum concentrations of TT were correlated negatively with glucose (r = −0.328, p < 0.001) and insulin resistance (r = −0.261, p = 0.011). The same occurred with FT and glucose (r = −0.340, p < 0.001) and insulin resistance (r = −0.246, p = 0.016). Sixty‐two percent (95% CI: 39–85%) of the patients with seminogram also presented abnormal results in semen analysis. The frequencies of low TT or low FT values were similar in patients with abnormal or normal semen analysis (p = 0.646 and p = 0.346, respectively). Ejaculate volume inversely correlated with BMI (ρ = −0.400, p = 0.029) and with excess body weight (ρ = −0.464, p = 0.010). Our data show the prevalence of MOSH in patients with moderate to severe obesity is high. Low circulating testosterone is associated with insulin resistance and low ejaculate volume with higher BMI and excess body weight. Semen analysis must be performed in these patients when considering fertility whether or not presenting low circulating testosterone.

Serum osteoprotegerin concentrations are decreased in women with the polycystic ovary syndrome

OBJECTIVE Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, has a variety of functions including anti-inflammatory effects and a possible cardiovascular protective role. Both low-grade chronic inflammation and cardiovascular risk are increased in women with the polycystic ovary syndrome (PCOS). We aimed to study serum OPG concentrations in PCOS patients. DESIGN Case-control study including 40 PCOS patients matched with 40 non-hyperandrogenic women for age and body mass index. METHODS Basal serum sampling and standard oral glucose tolerance test, and measurement of serum OPG concentrations by commercial ELISA. RESULTS Serum OPG concentrations were lower in women with PCOS compared with those of controls (304+/-120 vs 363+/-105 pg/ml respectively; F=7.641, P=0.007) independently of obesity. No differences were observed in serum receptor activator of nuclear factor-kappaB ligand (RANKL) levels and in the RANKL/OPG molar ratio. A multivariate linear regression model (R(2)=0.208, F=6.579, P=0.001) showed that PCOS (beta=-0.281, P=0.008), obesity (beta=-0.245, P=0.022) and age (beta=0.296, P=0.006) were predictive of serum OPG concentrations. CONCLUSIONS Serum OPG concentrations are reduced in PCOS patients independently of obesity. Considering the anti-inflammatory effects of OPG, its reduced serum concentrations might contribute to the proinflammatory state and cardiovascular risk of PCOS patients.

Thyroid hormone deficiency and postmenopausal status independently increase serum osteoprotegerin concentrations in women

OBJECTIVE To study the impact of thyroxine (T4) withdrawal on serum osteoprotegerin concentrations in women, using a healthy euthyroid control group matched for age and postmenopausal status as reference. SUBJECTS AND DESIGN Nineteen women with differentiated thyroid carcinoma were studied the last day on T4 suppressive treatment, 4-7 days after withdrawal and the day before whole body scanning. Eighteen women matched for age and postmenopausal status served as controls. Serum thyroid hormones, urinary bone markers and serum osteoprotegerin concentrations were measured. Statistical methods included repeated measures analysis of variance and one-way analysis of variance. RESULTS Patients progressed from subclinical or mild hyperthyroidism at baseline to normal free T4 and triiodothyronine levels 4-7 days later, ending in overt hypothyroidism before scanning. Serum osteoprotegerin increased, and urinary deoxypyridolines/creatinine and pyridolines/creatinine ratios decreased, with acute hypothyroidism (P = 0.026, P = 0.003, and P < 0.001 respectively). Urinary deoxypyridolines/creatinine ratio, pyridolines/creatinine ratio, and serum osteocalcin during hypothyroidism were lower compared with those of healthy controls (P = 0.023, P = 0.019, and P = 0.011 respectively). Serum osteoprotegerin concentrations were higher in postmenopausal patients when compared with premenopausal ones, irrespective of the changes in thyroid function (P = 0.001). CONCLUSION Serum osteoprotegerin concentrations increase following acute hypothyroidism after T4 withdrawal in women with differentiated thyroid carcinoma, and also with postmenopausal status.

Role of parenteral nutrition in oncologic patients with intestinal occlusion and peritoneal carcinomatosis

INTRODUCTION AND AIMS the precise role of parenteral nutrition in the management of oncologic patients with intestinal occlusion is not well defined yet. We aimed to identify the effects of parenteral nutrition in these patients regarding prognosis. MATERIAL AND METHODS 55 patients with intestinal occlusion and peritoneal carcinomatosis were included. Parenteral nutrition aimed at 20-35 kcal/Kg/day, and 1.0 g/kg/day of amino-acids. Weight, body mass index, type of tumor, type of chemotherapy, and ECOG among others were recorded and analyzed. RESULTS 69.1% of the patients had gastrointestinal tumors, 18.2% gynecologic and 12.7% others. Age was 60 ± 13y, baseline ECOG 1.5 ± 0.5 and body mass index 21.6 ± 4.3. Malnutrition was present in 85%. Survival from the start of parenteral nutrition was not significant when considering baseline ECOG (log rank = 0.593, p = 0.743), previous lines of chemotherapy (log rank = 2.117, p = 0.548), baseline BMI (log rank = 2.686, p = 0.261), or type of tumor (log rank = 2.066, p = 0.356). Survival in patients who received home parenteral nutrition after hospital discharge was higher than those who stayed in-hospital (log rank = 7.090, p = 0.008). Survival in patients who started chemotherapy during or after parenteral nutrition was higher than those who did not so (log rank = 17.316, p < 0.001). A total of 3.6% of patients presented catheter related infection without affecting survival (log rank = 0.061, p = 0.804). CONCLUSIONS Parenteral nutrition in patients with advanced cancer and intestinal occlusion is safe, and in tho se who respond to chemotherapy, further administration of home parenteral nutrition together with chemotherapy may enhance prolonged survival.