Elevated Concentrations of Liver Enzymes and Ferritin Identify a New Phenotype of Insulin Resistance: Effect of Weight Loss After Gastric Banding

BACKGROUND: Several studies have associated elevated liver enzymes (LFTs), obesity, and type 2 diabetes (T2DM), and a link has been established between insulin resistance (IR) and elevated ferritin concentrations. We examined the relationship between LFTs, ferritin, and IR in morbid obese subjects and the effect of weight loss after bariatric surgery. METHODS: We measured liver enzymes, ferritin, insulin resistance, and glucose tolerance (by OGTT) in 159 morbid obese subjects (BMI = 44.4 +/- 0.4 kg/m(2)) at baseline, 6 months and 1 year after laparoscopic-adjustable-gastric banding (LAGB). Subjects were divided in two groups: increased LFTs (ALT > 30; AST/ALT < 1) vs. normal LFTs. RESULTS: A large proportion of morbid obese subjects had increased LFTs (44%) which were associated with increased IR and ferritin, suggesting potential liver disease. A majority of the morbidly obese with increased LFTs, IGT, and T2DM, were male and had almost double ferritin concentrations, strongly correlated with ALT (r = 0.43, p < 0.0001). Both ferritin and ALT correlated with waist circumference and IR. One year after, LAGB glucose tolerance improved, LFTs and IR were reduced; ferritin did not change significantly, but was still correlated with IR. CONCLUSIONS: Ferritin may be an additional useful marker for more severe hepatic IR

Zn-doped titania nanoparticles as building blocks for solid foam filters of water and air via photocatalytic oxidation

Photocatalytic oxidation (PCO) could provide energy-efficient purification of water and air. Its efficacy is constrained mainly by limited photocatalytic activity and active surface. To address both, solid foams with hierarchic porous structures spanning multiple length-scales, stabilized by photocatalytic Zn-doped titania nanoparticles (NP) were synthesized and tested. The NP were characterized by SEM, EDS, DLS, XRD, Raman and UV–Vis spectroscopies. Solid foams were stabilized by NP complexes with cationic surfactants. The foam morphology was characterized and photocatalytic activity was demonstrated in water. The present work paves the way for the development of efficient systems for air and water purification in demanding technological sectors, such as aerospace

Erythrocytosis in a patient with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) can be accompanied by compensatory secondary erythrocytosis. However, the exact prevalence of secondary erythrocytosis in COPD is unknown. Although diagnostic criteria for polycythemia vera versus secondary erythrocytosis are mutually exclusive, we describe here the coexistence of polycythemia vera and COPD in the same patient

Snoring, hypertension and Type 2 diabetes in obesity. Protection by physical activity

Sleep-related breathing disorders are recognized as major health problems in obesity. They are involved in both hypertension and Type 2 diabetes, through mechanisms possibly related to increased sympathetic tone. We studied the association of habitual snoring with diabetes, hypertension, weight cycling and physical activity in a large Italian database of treatment-seeking obese subjects. Clinical and behavioral data were assessed by standardized questionnaires. Consecutive data of 1890 obese patients were analyzed [average body mass index (BMI), 38.2 kg/m(2), median age: 46 yr, 78% females], from 25 obesity Italian centers, with low prevalence of clinical manifestations of cardiovascular disease. Habitual snoring was reported in 56% of the cases, and was associated with day-time sleepiness. The prevalence increased with obesity class and waist circumference, and was positively associated with weight cycling and weight gain since the age of 20, and smoking. Regular physical activity had a protective effect. Snoring was associated with diabetes and hypertension at univariate analysis, but in multivariate analysis an independent effect was only observed for hypertension. After adjustment for age, gender and BMI, physical activity maintained an independent, protective effect on both snoring (odds ratio 0.65, 95% confidence interval 0.49-0.84; p = 0.001), diabetes (0.50, 0.30-0.86; p = 0.011) and hypertension (0.71, 0.53-0.95; p = 0.023). We conclude that in treatment-seeking, obese subjects with low prevalence of cardiovascular disease, snoring independently increases the risk of hypertension, whereas physical activity exerts a protection on both snoring and complications. These data underline the importance of lifestyle interventions to limit the burden of obesity and associated diseases.ABSTRACT. Sleep-related breathing disorders are recognized as major health problems in obesity. They are involved in both hypertension and Type 2 diabetes, through mechanisms possibly related to increased sympathetic tone. We studied the association of habitual snoring with diabetes, hypertension, weight cycling and physical activity in a large Italian database of treatmentseeking obese subjects. Clinical and behavioral data were assessed by standardized questionnaires. Consecutive data of 1890 obese patients were analyzed [average body mass index (BMI), 38.2 kg/m2, median age: 46 yr, 78% females], from 25 obesity Italian centers, with low prevalence of clinical manifestations of cardiovascular disease. Habitual snoring was reported in 56% of the cases, and was associated with day-time sleepiness. The prevalence increased with obesity class and waist circumference, and was positively associated with weight cycling and weight gain since the age of 20, and smoking. Regular physical activity had a protective effect. Snoring was associated with diabetes and hypertension at univariate analysis, but in multivariate analysis an independent effect was only observed for hypertension. After adjustment for age, gender and BMI, physical activity maintained an independent, protective effect on both snoring (odds ratio 0.65, 95% confidence interval 0.49–0.84; p=0.001), diabetes (0.50, 0.30–0.86; p=0.011) and hypertension (0.71, 0.53–0.95; p=0.023). We conclude that in treatment-seeking, obese subjects with low prevalence of cardiovascular disease, snoring independently increases the risk of hypertension, whereas physical activity exerts a protection on both snoring and complications. These data underline the importance of lifestyle interventions to limit the burden of obesity and associated diseases

Insulin-secreting pituitary GH3 cells : a potential beta-cell surrogate for diabetes cell therapy

In a companion article, we describe the engineering and characterization of pituitary GH3 cell clones stably transfected with a furin-cleavable human insulin cDNA (InsGH3 cells). This article describes the performance of InsGH3 (clones 1 and 7) cell grafts into streptozotocin (STZ)-induced diabetic nude mice. Subcutaneous implantation of 2 7 106 InsGH3 cells resulted in the progressive reversal of hyperglycemia and diabetic symptoms, even though the progressive growth of the transplanted cells (clone 7) eventually led to glycemic levels below the normal mouse range. Proinsulin transgene expression was maintained in harvested InsGH3 grafts that, conversely, lose the expression of the prolactin (PRL) gene. Elevated concentrations of circulating mature human insulin were detected in graft recipients, demonstrating that proinsulin processing by InsGH3 cells did occur in vivo. Histologic analysis showed that transplanted InsGH3 grew in forms of encapsulated tumors composed of cells with small cytoplasms weakly stained for the presence of insulin. Conversely, intense insulin immunoreactivity was detected in graft-draining venules. Compared to pancreatic \u3b2TC3 cells, InsGH3 cells showed in vitro a higher rate of replication, an elevate resistance to apoptosis induced by serum deprivation and proinflammatory cytokines and significantly higher antiapoptotic Bcl-2 protein levels. Moreover, InsGH3 cells were resistant to the streptozotocin toxicity that, in contrast, reduced \u3b2TC3 cell viability to 50-60% of controls. In conclusion, proinsulin gene expression and mature insulin secretion persisted in transplanted InsGH3 cells that reversed hyperglycemia in vivo. InsGH3 cells might represent a potential \u3b2-cell surrogate because they are more resistant than pancreatic \u3b2 cells to different apoptotic insults and might therefore be particularly suitable for encapsulation

A 23-year study of mortality and development of co-morbidities in patients with obesity undergoing bariatric surgery (laparoscopic gastric banding) in comparison with medical treatment of obesity

Background and aimSeveral studies have shown that bariatric surgery reduces long term mortality compared to medical weight loss therapy. In a previous study we have demonstrated that gastric banding (LAGB) is associated with reduced mortality in patients with and without diabetes, and with reduced incidence of obesity co-morbidities (cardiovascular disease, diabetes, and cancer) at a 17year follow-up. The aim of this study was to verify at a longer time interval (23years) mortality and incidence of co-morbidities in patients undergoing LAGB or medical weight loss therapy.Patients and methodsAs reported in the previous shorter-time study, medical records of obese patients [body mass index (BMI)>35kg/m(2) undergoing LAGB (n=385; 52 with diabetes) or medical treatment (controls, n=681; 127 with diabetes), during the period 1995-2001 (visit 1)] were collected. Patients were matched for age, sex, BMI, and blood pressure. Identification codes of patients were entered in the Italian National Health System Lumbardy database, that contains life status, causes of death, as well as exemptions, prescriptions, and hospital admissions (proxies of diseases) from visit 1 to June 2018. Survival was compared across LAGB patients and matched controls using Kaplan-Meier plots adjusted Cox regression analyses.ResultsFinal observation period was 19.51.87years (13.4-23.5). Compared to controls, LAGB was associated with reduced mortality [HR=0.52, 95% CI 0.33-0.80, p=0.003], significant in patients with diabetes [HR=0.46, 95% CI 0.22-0.94, p=0.034], borderline significant in patients without diabetes [HR=0.61, 95% CI=0.35-1.05, p=0.076]. LAGB was associated with lower incidence of diabetes (15 vs 75 cases, p=0.001), of CV diseases (61 vs 226 cases, p=0.009), of cancer (10 vs 35, p=0.01), and of renal diseases (0 vs 35, p=0.001), and of hospital admissions (92 vs 377, p=0.001).Conclusion p id=Par4 The preventive effect of LAGB on mortality is maintained up to 23years, even with a decreased efficacy compared with the shorter-time study, while the preventive effect of LAGB on co-morbidities and on hospital admissions increases with time

Duodenal adipose tissue is associated with obesity in baboons (Papio sp) : a novel site of ectopic fat deposition in non-human primates

AimsEctopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity.MethodsDuodenal tissues were collected from aged (21.21.3years, 19.53.1kg, n=39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated.Results Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 +/- 6.93%) and was correlated with AC (r=0.60, p&lt;0.001), weight (r=0.38, p=0.02), leptin (r=0.63, p&lt;0.001), adiponectin (r=-0.32, p&lt;0.05), and triglyceride (r=0.41, p=0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 mu m(2), p=0.02).Conclusions Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition

Cholesterol metabolism after bariatric surgery in grade 3 obesity : differences between malabsorptive and restrictive procedures

OBJECTIVEdMalabsorptive bariatric surgery (biliopancreatic diversion and biliointestinal bypass [BIBP]) reduces serum cholesterol levels more than restrictive surgery (adjustable gastric banding [AGB]), and this is thought to be due to greater weight loss. Our aim was to evaluate the changes of cholesterol metabolism induced by malabsorptive and restrictive surgery independent of weight loss. RESEARCH DESIGNANDMETHODSdIn a nonrandomized, self-selected, unblinded, active-comparator, bicenter, 6-month study, glucose metabolism (blood glucose and serum insulin levels and homeostasis model assessment of insulin resistance [HOMA-IR] index) and cholesterol metabolism (absorption: serum campesterol and sitosterol levels; synthesis: serum lathosterol levels; catabolism: rate of appearance and serum concentrations of serum 7-a- and serum 27-OH-cholesterol after infusions of deuterated 7-a- and 27-OH-cholesterol in sequence) were assessed in grade 3 obesity subjects undergoing BIBP (n = 10) and AGB (n = 10). Evaluations were performed before and 6 months after surgery. RESULTSdSubjects had similar values at baseline.Weight loss was similar in the two groups of subjects, and blood glucose, insulin levels, HOMA-IR, and triglycerides decreased in a similar way. In contrast, serumcholesterol, LDL cholesterol, non-HDL cholesterol, serum sitosterol, and campesterol levels decreased and lathosterol levels increased only in BIBP subjects, not in AGB subjects. A significant increase in 7-a-OH-cholesterol occurred only with BIBP; serum 27-OHcholesterol decreased in both groups. CONCLUSIONSdMalabsorptive surgery specifically affects cholesterol levels, independent of weight loss and independent of glucose metabolism and insulin resistance. Decreased sterol absorption leads to decreased cholesterol and LDL cholesterol levels, accompanied by enhanced cholesterol synthesis and enhanced cholesterol catabolism. Compared with AGB, BIBP provides greater cholesterol lowering