Determinants of High Parathyroid Hormone Levels in Patients With Severe Obesity and Their Relationship With the Cardiometabolic Risk Factors, Before and After a Laparoscopic Sleeve Gastrectomy Intervention.

BACKGROUND: Obesity is a risk factor for vitamin D deficiency and hyperparathyroidism. Hyperparathyroidism could exert a negative effect on glucose metabolism and vascular function. The aim of this study was to identify the determinants of hyperparathyroidism beyond vitamin D deficiency, whether hyperparathyroidism could have a negative impact on individual health and whether laparoscopic sleeve gastrectomy (LSG) negatively affects the levels of intact parathyroid hormone (iPTH) and 25(OH) vitamin D (25(OH)D). METHODS: We evaluated the levels of iPTH, 25(OH)D, and leptin, together with markers of insulin sensitivity and early cardiovascular disease, in a cohort of 160 patients with severe obesity before and after an LSG intervention. RESULTS: Ninety-seven percent of subjects had vitamin D deficiency, and 72% of them had hyperparathyroidism. After correcting for possible confounders, we found a correlation between iPTH levels and carotid intima-media thickness, as well as with the HOMA index. After the LSG, 25(OH)D levels were significantly increased, while iPTH levels were significantly reduced. The reduction of iPTH was significantly correlated with the reduction of BMI, diastolic blood pressure, and leptin, which was the independent predictor of iPTH reduction. CONCLUSIONS: Our results suggest that vitamin D deficiency is not the sole determinant of hyperparathyroidism in severe obesity because visceral fat deposition and leptin could both play a role. Obesity-related hyperparathyroidism is associated with insulin resistance and atherosclerosis, although the results from previous studies were conflicting. Finally, LSG intervention does not negatively affect vitamin D status and improves hyperparathyroidism.

High serum levels of C-reactive protein (CRP) predict beneficial decrease of visceral fat in obese females after sleeve gastrectomy.

BACKGROUND & AIMS: Gender-related differences represent an emerging investigation field to better understand obesity heterogeneity and paradoxically associated cardiovascular (CV) risk. Here, we investigated if high-sensitivity C-reactive protein (hs-CRP) might differently affect adiposity and predict the clinical response to bariatric surgery in obese males and females. METHODS AND RESULTS: In 110 morbidly obese patients undergoing laparoscopic sleeve gastrectomy, hs-CRP as well as anthropometric assessment of adiposity, completed by electric bioimpedance and ultrasonography quantification of visceral fat area (VFA), were measured before and one year after surgery. As compared to males, obese female showed less severe overweight and prevalent subcutaneous fat deposition, but higher circulating hs-CRP. In obese females, hs-CRP was associated with VFA at baseline, independently of body mass index (BMI) and visceral adiposity index (OR 1.022 [95% CI 1.001-1.044]; p = 0.039). Based on decreases and increases in hs-CRP levels after surgery, two distinct subgroups of females were identified. Post-surgery decreases in hs-CRP was predominantly observed in patients with higher baseline levels of hs-CRP and associated with greater reduction of weight, BMI, fat and lean mass, VFA and visceral to subcutaneous fat ratio. Finally, we observed that high baseline values of hs-CRP were able to predict VFA reduction one-year after surgery, independently of BMI and visceral adiposity index (VAI) loss (OR 1.031 [95% CI 1.009-1.053]; p = 0.005). CONCLUSION: In obese females, hs-CRP levels might be a promising biomarker of visceral fat amount and dysfunction, in addition to predict the effectiveness of bariatric surgery in terms of loss of VFA one-year after surgery.

Laparoscopic sleeve gastrectomy modifies cholesterol synthesis but not cholesterol absorption.

BACKGROUND AND AIMS: Each bariatric surgery procedure impacts differently on cholesterol synthesis and absorption. Although a restrictive procedure, sleeve gastrectomy resolves diabetes mellitus and, like mixed-type procedures, induces early changes in gastrointestinal hormones. To our knowledge the present study is the first to assess the effects of sleeve gastrectomy on cholesterol synthesis and absorption. METHODS AND RESULTS: 42 consecutive subjects with obesity and sleeve gastrectomy candidates were included in the study together with a control group of 20 subjects without obesity. Before sleeve gastrectomy and 10 months afterwards, all subjects underwent a clinical examination, blood tests, ultrasound visceral fat area estimation and determination of plasma lathosterol, campesterol and sitosterol concentrations. After sleeve gastrectomy, significant decreases were observed in BMI, waist circumference, visceral and subcutaneous fat, blood pressure, triglycerides, insulin and glucose levels, lathosterol and HOMA-IR. HDL-C and apolipoprotein AI levels increased significantly. No significant differences emerged in LDL-C, apolipoprotein B levels or cholesterol absorption markers. Lathosterol levels correlated significantly with BMI, visceral fat area and HOMA-IR. Differences in cholesterol intake after surgery were not significantly associated with differences in lathosterol, campesterol and sitosterol concentrations. CONCLUSIONS: Sleeve gastrectomy reduced the markers of cholesterol synthesis but did not modify cholesterol absorption. Changes in cholesterol synthesis and absorption were independent of variations in cholesterol intake, suggesting a specific sleeve gastrectomy-related effect.

Uric acid and bone mineral density in postmenopausal osteoporotic women: the link lies within the fat.

The association between serum uric acid (SUA) levels and bone mineral density (BMD) is controversial. Fat accumulation is linked to SUA and BMD, thus possibly explaining the mixed results. We found that adiposity drives part of the association between SUA and BMD in women with postmenopausal osteoporosis. INTRODUCTION: Both positive and negative associations between SUA and BMD have been reported. SUA levels and BMD increase with higher body weight and other indices of adiposity; hence, the association between SUA and BMD might be a consequence of the confounding effect of adiposity. We investigated in this cross-sectional study whether the association between SUA and BMD is independent of measures of fat accumulation and other potential confounders. METHODS: SUA levels, femur BMD, markers of bone metabolism, body mass index (BMI), fat mass (FM), waist circumference (WC), and abdominal visceral fat area were measured in 180 treatment-naive postmenopausal osteoporotic women (mean age 66.3 ± 8.5 years, age range 48-81 years). RESULTS: Women with higher SUA levels (third tertile) had significantly higher femur BMD and lower cross-linked C-terminal telopeptide of type I collagen (CTX) and bone alkaline phosphatase (bALP) levels. SUA levels were positively associated with all indices of adiposity. In multivariable analysis with femur BMD as dependent variable, the association between logarithmic (LG)-transformed SUA levels and BMD (beta = 0.42, p < 0.001) was lessened progressively by the different indices of adiposity, like LG-BMI (beta = 0.22, p = 0.007), LG-WC (beta = 0.21, p = 0.01), LG-FM (beta = 0.18, p = 0.01), and LG-abdominal visceral fat area (beta = 0.12, p = 0.05). The association between SUA levels and markers of bone metabolism was dependent on the effect of confounders. CONCLUSION: In postmenopausal osteoporotic women, the strong univariable association between SUA levels and femur BMD is partly explained by the confounding effect of indices of adiposity.

Circulating Levels of the Adipokines Monocyte Chemotactic Protein-4 (MCP-4), Macrophage Inflammatory Protein-1ß (MIP-1ß), and Eotaxin-3 in Severe Obesity and Following Bariatric Surgery.

The aim of the study was to investigate the involvement of the adipokines eotaxin-3, MIP-1ß, and MCP-4 in obesity and related comorbidities and the modification of their circulating levels after bariatric surgery. Eighty severely obese subjects and 20 normal-weight controls were included in the study. Circulating levels of MCP-4, MIP-1ß, and eotaxin-3, and the main clinical, biochemical, and instrumental parameters for the evaluation of cardiovascular and metabolic profile were determined in controls and in obese subjects at baseline and 10 months after surgery. Within the obese group at baseline, eotaxin-3 levels were higher in males than females and in smokers than non-smokers and showed a positive correlation with LDL-cholesterol, apolipoprotein B, and leptin. MIP-1ß showed a positive correlation with age and leptin and a negative correlation with adiponectin and was an independent predictor of increased carotid artery intima-media thickness. MCP-4 levels were higher in obese subjects than controls and showed a positive correlation with body mass index, eotaxin-3, and MIP-1ß. Bariatric surgery induced a marked decrease in all the 3 adipokines. MCP-4 is a novel biomarker of severe obesity and could have an indirect role in favoring sub-clinical atherosclerosis in obese patients by influencing the circulating levels of eotaxin-3 and MIP-1ß, which are directly related to the main atherosclerosis markers and risk factors. The reduction of circulating levels of MCP-4, eotaxin-3, and MIP-1ß could be one of the mechanisms by which bariatric surgery contributes to the reduction of cardiovascular risk in these patients.

Pericardial fat, insulin resistance, and left ventricular structure and function in morbid obesity.

BACKGROUND AND AIM: Morbid obesity is often accompanied by insulin resistance and increased ectopic fat surrounding the heart. We evaluated the relation of epicardial and pericardial fat with insulin resistance and left ventricular (LV) structure and function. METHODS AND RESULTS: Epicardial and pericardial fat thicknesses were determined at 2-dimensional echocardiography in 80 morbid obese subjects [age 42 ± 12 years, 31% men, body mass index (BMI) 44.4 ± 7 kg/m(2)]. LV hypertrophy (LV mass ≥51 g/m(2.7)), inappropriately high LV mass for a given cardiac workload (observed vs predicted LV mass >128%), and stress-adjusted LV mid-wall fractional shortening were determined. Pericardial and epicardial fat thicknesses had direct associations with BMI (r = 0.40 and 0.45, both p < 0.01) and waist circumference (r = 0.37 and 0.45, both p < 0.01). Pericardial (partial r = 0.35, p < 0.01), but not epicardial fat thickness (partial r = 0.05, p = n.s.), was correlated with homeostasis model assessment-insulin resistance after adjustment for BMI. Pericardial fat also had a strong negative correlation with mid-wall fractional shortening (p = 0.01) and a positive one with inappropriately high LV mass (p < 0.01), while no such relation was found for epicardial fat (both p = n.s.). Independently of age, male sex, BMI, and anti-hypertensive treatment, pericardial fat thickness had an independent positive association with inappropriately high LV mass (ß = 0.29, p = 0.02), and a negative one with stress-adjusted mid-wall fractional shortening (ß = -0.26, p = 0.04). CONCLUSIONS: Pericardial fat thickness is associated with insulin resistance, inappropriately high LV mass, and LV systolic dysfunction in obese individuals. Findings from this study confirm the existence of a connection between insulin resistance, cardiac ectopic fat deposition and cardiac dysfunction in morbid obesity.

Patterns of cholesterol metabolism: pathophysiological and therapeutic implications for dyslipidemias and the metabolic syndrome.

Investigating cholesterol metabolism, which derives from balancing cholesterol synthesis and absorption, opens new perspectives in the pathogenesis of dyslipidemias and the metabolic syndrome (MS). Cholesterol metabolism is studied by measuring plasma levels of campesterol, sitosterol and cholestanol, that is, plant sterols which are recognised as surrogate cholesterol-absorption markers and lathosterol or squalene, that is, cholesterol precursors, which are considered surrogate cholesterol-synthesis markers. This article presents current knowledge on cholesterol synthesis and absorption, as evaluated by means of cholesterol precursors and plant sterols, and discusses patterns of cholesterol balance in the main forms of primary hyperlipidaemia and MS. Understanding the mechanism(s) underlying these patterns of cholesterol synthesis and absorption will help to predict the response to hypolipidemic treatment, which can then be tailored to ensure the maximum clinical benefit for patients.