Jordi Pujol

Evaluation of Bone Mineral Density Loss in Morbidly Obese Women After Gastric Bypass: 3-Year Follow-Up

Studies that evaluate the influence of gastric bypass (RYGP) on bone mass are limited to short-term follow-up. We analysed changes in bone mineral density (BMD) three years after surgery and evaluated the main determinants of the development of bone disease. Prospective study of 59 morbidly obese white women aged 46 ± 8 years. BMD scanning using DEXA and plasma determinations of calcium, parathyroid hormone, 25-hydroxyvitamin D and insulin-like growth factor-I were made prior, at 12 months and 3 years after surgery. In the first postoperative year BMD decreased at femoral neck (FN) 10.2 % and in the lumbar spine (LS) 3.2 %, in the third year it additionally decreased 2.7 % and 3.1 %, respectively. BMD at both sites remained above the values of women of the same age. In the follow-up, 1.7 % developed osteoporosis at FN and 6.8 % at LS. Patients with bone disease were older, the percentage of women with menopause was greater in this group and had lower initial and final values of lean mass. The percentage of BMD loss at FN remained positively associated with the percentage of lean mass loss [β 0.304, p = 0.045], and menopause [β 0.337, p = 0.025]. Major osteoporotic fracture and hip fracture risk was low even in menopausal patients (3.1 % and 0.40 %, respectively). After RYGP menopausal women and those with greater lean mass loss are at higher risk of BMD loss but progression to osteoporosis is uncommon and the risk of fracture is low.

Long-Term Health-Related Quality of Life Following Gastric Bypass: Influence of Depression

Background: Severe obesity has been associated with impaired quality of life (QoL). We evaluated the long-term health-related quality of life (HRQoL) after gastric bypass. Methods: A cross-sectional study was conducted on 50 morbidly obese patients >5 years after gastric bypass and on a control group of 78 non-operated morbidly obese patients. Both groups were evaluated for the EuroQol 5D measure and the Goldberg General Health Questionnaire. In addition, the Bariatric Analysis of Reporting Outcome System (BAROS) was applied to the surgical group. Depression and severe life events were included in the analysis. Logistic Regresion Model was used, and age was included in the analysis. Results: Groups were similar except for mean age (lower in the surgical group: 40.5±9.0 vs 46.1±8.8 years, P=0.026). 86.5% of patients had >50% Excess Weight Loss. 85.7% showed an improvement in co-morbid conditions. BAROS Global score: 22% excellent, 56% very good, 18% good, 2% fair and 2% failure. After surgery, significant improvements were reported in self-esteem (94%), work conditions (72.6%), physical activity (66.7%), and sexual interest/activity (50.9%). The control group showed poorer results for the EuroQol 5D in mobility (55% vs 21.6%, P=0.005), difficulty with daily activity (55% vs 13.7%, P=0.005) and self-evaluation of well-being (59.2% vs 78.1%, P=0.005). Patients with depression or insufficient weight loss following surgery presented poorer global evaluation in HRQoL. Conclusion: Gastric bypass resulted in significant long-term improvements in co-morbidities, sustained weight loss and increased HRQoL. Depression and insufficient weight loss were associated with poorer HRQoL in surgical patients.

Disruption of GIP/GIPR Axis in Human Adipose Tissue Is Linked to Obesity and Insulin Resistance

CONTEXT Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. OBJECTIVE Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. DESIGN GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. RESULTS GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. CONCLUSIONS GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

Estudio de la relación entre las concentraciones plasmáticas de adiponectina, interleucina 18 y ghrelina y la densidad mineral ósea en mujeres con obesidad mórbida tras bypass gástrico

OBJECTIVE Analysis of the relationship between adiponectin, interleukin-18 (IL-18) and ghrelin and bone mineral density (BMD), in a group of women that had undergone a gastric- bypass for morbid obesity a year before. METHODS Forty-one morbidly obese patients aged 46 +/- 9 years and with an initial body mass index of 49.5 +/- 7.6 were included in the study and a gastric by-pass operation was performed in all of them. Anthropometric variables, body composition measured with dual energy X-ray absorptiometry (DEXA) and plasma concentrations of parathormone (PTH), 25(OH) vitamin D, insulin growth factor (IGF-I), adiponectin, IL-18 and ghrelin were determined before and a year after surgery. BMD was evaluated with DEXA 12 months after bariatric surgery. RESULTS A year after surgery 36.2% of inicial body weight was lost and this was associated with an improvement of the inflammatory profile reflected by a significant reduction of IL-18 and a increase of adiponectin plasma concentrations. In the univariate analysis BMD inversely correlated with age (r = -0.287, p = 0.008) and with lean mass (r = 0.318, p = 0.043) but not with adiponectin, IL-18 and ghrelin concentrations. PTH showed a positive correlation with weight (r = 0.362, p = 0.03), lean mass (r = 0.372, p = 0.039), and a negative association with plasma concentrations of calcium (r = -0.48, p = 0.003) and 25(OH) vitamin D (r = -0.44, p = 0.014). Plasma 25(OH) vitamin D correlated negatively with the sum of fat mass and lean mass measured with DEXA (r = -0.210, p = 0.043). In the multiple regression analysis BMD remained associated only with lean mass (beta = 0.193, p = 0.016). CONCLUSIONS Our study does not support the existance of a direct effect of adipose tissue on bone metabolism through the secretion of adiponectin. The absence of association between inflammatory cytokine IL-18 and ghrelin with BMD also argues against their implication in bone regulation.Objetivo: Analizar la relacion entre adiponectina, interleucina (IL) 18 y ghrelina y la densidad mineral osea (DMO) en un grupo de mujeres intervenidas 1 ano antes de bypass gastrico por obesidad morbida. Metodos: Se incluyo a 41 pacientes intervenidas de bypass gastrico, con una media de edad de 46 ± 9 anos y un indice de masa corporal (IMC) inicial de 49,5 ± 7,6. Se estudiaron variables antropometricas y de composicion corporal por absorciometria mediante rayos X de doble energia (DEXA) y se determinaron, antes y despues de la cirugia, las concentraciones plasmaticas de paratirina (PTH), 25(OH)-vitamina D, factor de crecimiento insulinico I (IGF-I), adiponectina, IL-18 y ghrelina. Se analizo la DMO al ano del bypass gastrico mediante DEXA. Resultados: Al ano de la cirugia se observo una perdida del 36,2% del peso inicial, que se asocio a una mejoria del perfil inflamatorio reflejada por una reduccion significativa de las concentraciones plasmaticas de IL-18 e incremento de adiponectina. En el estudio univariable la DMO se correlaciono negativamente con la edad (r = -0,287; p = 0,008) y con la masa magra (r = 0,318; p = 0,043), pero no con las concentraciones de adiponectina, IL-18 y ghrelina. Las concentraciones de PTH se correlacionaron positivamente con el peso (r = 0,362; p = 0,030), la masa grasa (r = 0,372; p = 0,039) e inversamente con las concentraciones plasmaticas de calcio (r = -0,48; p = 0,003) y de 25(OH)-vitamina D (r = -0,44; p = 0,014). El calcidiol plasmatico se correlaciono negativamente con la suma de masa grasa y masa magra medida por DEXA (r = -0,210; p = 0,043). En el analisis de regresion multiple, la DMO mantuvo relacion unicamente con la masa no grasa (s = 0,193; p = 0,016). Conclusiones: Nuestro estudio no halla efecto directo del tejido adiposo en el metabolismo oseo a traves de la secrecion de adiponectina. Del mismo modo, la falta de relacion entre la citocina inflamatoria IL-18 y la ghrelina con la DMO cuestiona su implicacion en la regulacion osea.

Nutritional deficiencies and bone metabolism after endobarrier in obese type 2 patients with diabetes

Endobarrier® is a minimally invasive, reversible endoscopic treatment for obesity. It provokes malabsorption along 60 cm of the small intestine, which can contribute to the development of vitamin deficiencies and to changes in bone mineral density (BMD). To determine the prevalence of nutrient deficiencies, changes in body composition and BMD during the first year after Endobarrier® placement. Twenty-one patients with type 2 diabetes met inclusion criteria. Levels of vitamins, micro and macronutrients were assessed prior and at 1, 3 and 12 months post-operatively. DEXA was performed before and 12 months after implant. Nineteen patients completed the 12 months follow-up. Vitamin D deficiency was the most prevalent finding before Endobarrier® implant. The percentage of patients with severe deficiency decreased from 19 to 5% at 12 months after supplementation. Microcytic anaemia was initially present in 9.5% of patients and increased to 26.3% at 12 months. Low ferritin and vitamin B12 levels were observed in 14.2 and 4.8% of patients before the implant and worsened to 42 and 10.5%. Low concentrations of magnesium and phosphorus were also common but improved along the study. A significant but not clinically relevant decrease in BMD of 4.14 ± 4.0% at the femoral neck was observed at 12 months without changes in osteocalcin levels. Vitamin deficiencies are common after Endobarrier® implant. It is therefore important to screen patients prior to and at regular intervals after the implant, and to encourage adherence to diet counselling and supplementation.