Efficacy and Safety of Insulin Lispro in Obese Patients with Type 2 Diabetes: A Retrospective Meta-Analysis of 7 Randomized Controlled Trials

ObjectiveTo evaluate the efficacy and safety of insulin lispro in the treatment of patients with type 2 diabetes (T2DM) who had a body mass index (BMI) ≥ 30 kg/m² (obese) compared with patients with BMIs < 30 kg/m² (nonobese).MethodsA retrospective analysis of predefined endpoints from 7 randomized clinical trials of T2DM patients treated with insulin lispro was performed. The primary efficacy measure was to assess the noninferiority of insulin lispro in obese patients versus nonobese patients as measured by the change in hemoglobin A1C (HbA_1c) from baseline to Month 3 (n = 1,518), using a noninferiority margin of 0.4%. The secondary measures included overall hypoglycemia incidence and event rates and relative change in body weight.ResultsMean changes in HbA_1c from baseline (9.06% for obese and 8.92% for nonobese) to Month 3 were similar for obese patients (–1.03%) and nonobese (–1.02%), with a least squares (LS) mean difference (95% confidence interval [CI]) of –0.05% (–0.17%, 0.07%; P = .384). The overall incidence of hypoglycemia (53% vs. 63%; P < .001) and rate of hypoglycemia (0.93 vs. 1.76 events per 30 days; P < .001) was significantly lower in obese patients compared with nonobese patients. The 2 BMI cohorts did not demonstrate a significant difference in mean percent changes in body weights (LS mean difference = 0.4% [–0.2%, 0.9%]; P = .202).ConclusionObese patients with T2DM treated with insulin lispro were able to achieve the same level of glycemic control as their nonobese counterparts, with some evidence supporting a reduced risk of hypoglycemia. (Endocr Pract. 2014;20:389-398)     

Levothyroxine Replacement In Obese Hypothyroid Females After Total Thyroidectomy

Objective: Levothyroxine (LT4) replacement in hypothyroid obese patients is poorly understood. We assessed whether the LT4 regimen required to achieve euthyroidism differs between nonobese and obese hypothyroid females.Methods: We retrospectively identified nonobese and obese females who received LT4 starting with a standard dose of 1.6 μg/kg after total thyroidectomy for preoperative diagnosis of benign goiter. We examined the association between LT4 dosage required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4–2.5 mIU/L) and patient characteristics using linear regression models with and without adjustment for age, ethnicity, medication use, and postoperative hypoparathyroidism.Results: We identified 32 females (15 nonobese/17 obese) who achieved euthyroid state. Obese patients weighed more (104.1 ± 22.5 vs. 64.9 ± 10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 ± 38 vs. 102 ± 12 μg, P = .0002) but LT4 requirements per kg total body weight (TBW) were similar (1.60 ± 0.29 vs. 1.42 ± 0.38 μg/kg, P = .15). LT4 dose per kg ideal body weight (IBW) was higher in obese than in nonobese females (2.62 ± 0.67 vs. 1.88 ± 0.28 μg/kg, P = .0004) and this difference persisted after adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese patients had subnormal TSH episodes, respectively (P = .11). After taking LT4 compliance, malabsorption, and competing medication use into consideration, we found marked LT4 dose variability in obese patients. Patients who needed a mean daily LT4 dose ≤150 mg (124 ± 16 μg/day) compared with >150 μg (198 ± 4 μg/day) demonstrated lower LT4 per TBW (1.25 ± 0.18 vs. 1.84 ± 0.43 μg/kg, P = .03) and IBW (2.28 ± 0.47 vs. 3.44 ± 0.18 μg/kg, P<.0001), respectively.Conclusion: The standard approach to LT4 replacement in obese and nonobese females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and nonobese patients were similar if expressed per kg TBW, though there was variability in the final LT4 among obese patients. We suggest initiating LT4 at a dose lower than that routinely recommended in obese females.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationBMI = body mass indexIBW = ideal body weightLT4 = levothyroxineTBW = total body weightTSH = thyroid-stimulating hormone     

Association between selenium nutritional status and metabolic risk factors in men with visceral obesity

Background and aimPrevious evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity.MethodsPlasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n = 78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group.ResultsIn the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r = 0.390, P < 0.05) and with fatty acid binding protein-4 (FABP4) (r = 0.474, P < 0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r = ?467, P < 0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r = 0.413, P < 0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r = ?0.429, P < 0.05).ConclusionsThese results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.     

Association between nesfatin-1 levels and metabolic improvements in severely obese patients who underwent biliopancreatic derivation with duodenal switch

ContextNesfatin-1 is a neuroendocrine peptide with potent anorexigenic activity in rodents. The potential role of nesfatin-1 on the regulation of energy balance, metabolic functions and inflammation is currently debated in obese humans. In the present study, nesfatin-1 fluctuations and their associations with metabolic factors were investigated in severely obese patients who underwent biliopancreatic diversion with duodenal switch (BPD/DS) and severely obese controls (SOC).Basic proceduresSixty severely obese patients who underwent BPD/DS and 15 SOC (matched for BMI and age) were included in the study. Associations between nesfatin-1 levels and body composition, glucose metabolism, lipid profile as well as inflammatory markers were evaluated at baseline and over a post-surgery12-month (12 M) period.Main findingsBody weight was reduced at 6 M and at 12 M in BPD/DS patients (P < 0.001). Nesfatin-1 levels were reduced at 6 M (women: P < 0.05) and at 12 M (men and women; P < 0.001) in BPD/DS patients. At baseline, nesfatin-1 levels negatively correlated with weight, fat (FM) and fat-free mass (FFM) in the whole population (combined BPD/DS and SOC patients). At 12 M, nesfatin-1 concentrations positively correlated with weight, FM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, triglyceride and apoB values. At 12 M, % changes in nesfatin-1 were positively associated with% changes in weight, FM, FFM, fasting insulin, insulin resistance, total cholesterol, LDL-cholesterol, apoB and C-reactive protein.ConclusionNesfatin-1 levels decrease following BPD/DS-induced weight loss and are significantly associated with parameters of metabolic health.     

Effect of hENT1 polymorphism G-706C on clinical outcomes of gemcitabine-containing chemotherapy for Chinese non-small-cell lung cancer patients

AimTo identify the single-nucleotide polymorphism (SNP) of hENT1 G-706C that is associated with response to gemcitabine-containing chemotherapy, and to determine the prognosis in patients with non-small-cell lung cancer (NSCLC).MethodsPatients with stage III (A + B) or IV NSCLC were recruited for this study (n = 225). Each subject received gemcitabine-containing chemotherapy. The association between human equilibrative nucleoside transporter 1 (hENT1) polymorphism G-706C (rs61758845) and therapeutic effect was evaluated. The SNP hENT1 G-706C was genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays.ResultsThe polymorphic genotype and the allele frequency of hENT1 G-706C was significantly different between chemotherapy responders and non-responders; to be specific, the response rate of patients carrying an hENT1-706 GG allele was higher than that of patients with a GC or CC genotype. Logistic regression analysis showed that having the GC or CC genotypes was associated with a higher risk of being a non-responder compared with having the GG genotype (OR = 2.34, 95% CI: 1.14–4.80; P = 0.02). The overall survival in patients with the GG genotype was significantly longer than in those with GC or CC genotype (19.0 versus 15.1 months, P < 0.001). The hazard ratio for the (GC + CC) genotype was 1.89 (95% CI: 1.23–2.90) compared with GG carriers (P = 0.004).ConclusionsThe hENT1 genetic polymorphism of hENT1 G-706C was associated with response to the gemcitabine-containing chemotherapy and prognosis of NSCLC. Moreover, assaying this SNP in blood cells may represent a valuable biomarker for individualized treatment for NSCLC patients.     

Body mass index,iron absorption and iron status in childbearing age women

BackgroundThe prevalence of obesity has increased at an alarming rate worldwide. Some studies have observed an association between iron (Fe) deficiency (ID) and obesity, however more research is needed.ObjectiveTo assess whether body mass index (BMI) is associated with both Fe absorption and Fe status.MethodsA cross sectional sample of 318 Chilean childbearing age women was studied. The women received either a single dose of 0.5 mg of Fe (n = 137, group 1) or 3 mg of Fe plus ascorbic acid (1:2 molar ratio) (n = 181, group 2), both as FeSO₄ with labeled radioisotopes. Fe absorption was assessed through radio Fe erythrocyte incorporation. Fe status was determined by hemoglobin (Hb), mean corpuscular volume, serum Fe, total iron binding capacity, transferrin saturation, erythrocyte Zn protoporphyrin and serum ferritin (SF).Results29%, 47% and 24% of the women were classified as normal, overweight or obese, respectively. Fe absorption was significantly lower in obese women (p < 0.05). In group 1, the geometric mean and range ±1 SD of the percentage of Fe absorption for normal-weight women was 32.9% vs. 19.7% in obese. For group 2, this percentage was 36% vs. 30%, respectively (2-way ANOVA: BMI classification and Fe dose p < 0.05; interaction p = 0.34). Although Fe absorption was lower in obese women, they had higher SF (p < 0.01) and Hb (p < 0.05) concentrations.ConclusionAlthough we did not observe a relationship between BMI and Fe status, obese women displayed lower Fe absorption compared with overweight and normal weight women, possibly due to subclinical inflammation associated with obesity.     

The Quételet index revisited in children and adults

BackgroundThe body mass index (BMI) is based on the original concept that body weight increases as a function of height squared. As an indicator of obesity the modern BMI assumption postulates that adiposity also increases as a function of height in states of positive energy balance.ObjectiveTo evaluate the BMI concept across different adiposity magnitudes, in both children and adults.MethodsWe studied 975 individuals who underwent anthropometric evaluation: 474 children and 501 adults. Tetrapolar bioimpedance analysis was used to assess body fat and lean mass.ResultsBMI significantly correlated with percentage of body fat (%BF; children: r = 0.893; adults: r = 0.878) and with total fat mass (children: r = 0.967; adults: r = 0.953). In children, body weight, fat mass, %BF and waist circumference progressively increased as a function of height squared. In adults body weight increased as a function of height squared, but %BF actually decreased with increasing height both in men (r = −0.406; p < 0.001) and women (r = −0.413; p < 0.001). Most of the BMI variance in adults was explained by a positive correlation of total lean mass with height squared (r² = 0.709), and by a negative correlation of BMI with total fat mass (r = −0.193).ConclusionsBody weight increases as a function of height squared. However, adiposity progressively increases as a function of height only in children. BMI is not an ideal indicator of obesity in adults since it is significantly influenced by the lean mass, even in obese individuals.     

Interferon gamma gene +874A/T polymorphism and intracellular interferon gamma expression in pulmonary tuberculosis

We investigated whether IFN-γ gene +874(A/T) polymorphism influences intracellular interferon gamma expression in T-cell subsets of normal healthy subjects (NHS) and pulmonary tuberculosis patients (PTB). Peripheral blood mononuclear cells were stimulated with live Mycobacterium tuberculosis (MTB) and the intracellular IFN-γ expression was studied using flow cytometry. Genotyping of IFN-γ gene +874(A/T) was done using allele specific polymerase chain reaction. Significantly increased IFN-γ expressing CD3+CD4+ and CD3+CD8+ T cells were observed in NHS with AA genotype compared to TT genotype in unstimulated (p = 0.0308 and p = 0.0157) and MTB stimulated (p = 0.0494 and p = 0.0287) cultures and this difference was not observed in PTB patients. The present study suggests that the variant genotypes of IFN-γ (+874) may be associated with altered expression of IFN-γ at the intracellular level and play an immunoregulatory role at the site of M. tuberculosis infection.     

Macrophage Migration Inhibitory Factor Deficiency Ameliorates High-Fat Diet Induced Insulin Resistance in Mice with Reduced Adipose Inflammation and Hepatic Steatosis

Macrophage infiltration is a critical determinant of high-fat diet induced adipose tissue inflammation and insulin resistance. The precise mechanisms underpinning the initiation of macrophage recruitment and activation are unclear. Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, displays chemokine-like properties. Circulating MIF levels are elevated during obesity however its role in high-fat diet induced adipose inflammation and insulin resistance remains elusive. Wildtype and MIF^−/− C57Bl\6J mice were fed chow or high-fat diet. Body weight and food intake was assessed. Glucose homeostasis was monitored by glucose and insulin tolerance tests. Adipose tissue macrophage recruitment and adipose tissue insulin sensitivity was evaluated. Cytokine secretion from stromal vascular fraction, adipose explants and bone marrow macrophages was measured. Inflammatory signature and insulin sensitivity of 3T3-L1-adipocytes co-cultured with wildtype and MIF^−/− macrophage was quantified. Hepatic triacylglyceride levels were assessed. MIF^−/− exhibited reduced weight gain. Age and weight-matched obese MIF^−/− mice exhibited improved glucose homeostasis coincident with reduced adipose tissue M1 macrophage infiltration. Obese MIF^−/− stromal vascular fraction secreted less TNFα and greater IL-10 compared to wildtype. Activation of JNK was impaired in obese MIF^−/−adipose, concomitant with pAKT expression. 3T3-L1-adipocytes cultured with MIF^−/− macrophages had reduced pro-inflammatory cytokine secretion and improved insulin sensitivity, effects which were also attained with MIF inhibitor ISO-1. MIF^−/− liver exhibited reduced hepatic triacyglyceride accumulation, enhanced pAKT expression and reduced NFκB activation. MIF deficiency partially protects from high-fat diet induced insulin resistance by attenuating macrophage infiltration, ameliorating adipose inflammation, which improved adipocyte insulin resistance ex vivo. MIF represents a potential therapeutic target for treatment of high-fat diet induced insulin resistance.     

Methylenetetrahydrofolate reductase gene polymorphisms contribute to acute myeloid leukemia and chronic myeloid leukemia susceptibilities: Evidence from meta-analyses

PurposeThe expression of methylenetetrahydrofolate reductase (MTHFR) is associated with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Most studies have linked the common functional C677T and A1298C polymorphisms of the MTHFR gene and susceptibility to AML and CML, but the results were not consistent. The aim of the present study was to derive a more precise estimation of the relationship.MethodsMeta-analyses assessing the association of MTHFR C677T and A1298C variations with AML and CML were conducted. Eligible articles were identified from the PubMed and EMBASE databases. All statistical analyses were conducted using Review Manager Software.Results10 and 10 studies were included in the meta-analysis about the role of C677T polymorphism on the AML and CML risks, respectively; 6 and 4 studies were included about the role of A1298C polymorphism on the AML and CML risks, respectively. Overall, both the C677T and A1298C polymorphisms were significantly associated with CML risk under the recessive model (P = 0.04, OR = 1.35, 95% CI = 1.02–1.79 for C677T and P = 0.003, OR = 2.17, 95% CI = 1.29–3.63 for A1298C). In addition, the risk of CML was higher in 1298CC genotype carriers than in 1298AA genotype carriers (P = 0.004, OR = 2.17, 95% = 1.28–3.69). Conversely, the overall data failed to indicate a significant association of C677T or A1298C polymorphisms with AML risk under any model.ConclusionsThe findings provide evidence that C677T and A1298C polymorphisms are risk factors for CML risk.     

Paget’s disease of bone is not associated with common polymorphisms in interleukin-6, interleukin-8 and tumor necrosis factor alpha genes

BackgroundCytokines, specially interleukin (IL)-6, play an important role in the differentiation and activation of osteoclasts and might be involved in osteoblast stimulation in Paget’s disease of bone (PDB).ObjectivesThe aim of this study was to investigate the association of polymorphisms in IL-6, IL-8 and tumor necrosis factors-alpha (TNFA) genes among Spanish patients with PDB.MethodsWe studied four single nucleotide polymorphisms (−174 G > C IL-6, −251 T > A IL-8, −238 G > A TNFA and −308 G > A TNFA) in 172 PDB patients and 150 healthy controls. Distribution of alleles and pro-inflammatory genotypes were studied for association with the presence of the disease and with clinical and laboratory data, as well as the response to bisphosphonate treatment in PDB patients.ResultsWe found no statistically significant association between genotype and allele distribution of any of the cytokines polymorphism studied and PDB. No association between the clinical and therapeutic characteristics of PDB and the investigated polymorphism were found.ConclusionsThis study does not support the hypothesis that the analyzed IL6, IL8 and TNFA polymorphism are associated with PDB.     

Nonobese Young Females with Polycystic Ovary Syndrome Have Nutritive Microvascular Dysfunction: A Pilot Study

ObjectiveTo investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables.MethodsFourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/ m²) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCV_max), and time taken to reach RBCV_max (TRBCV_max).ResultsSubjects with PCOS had lower RBCV and higher TRBCV_max compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, F < .01) and (5 [5-6] vs. 4 [3-5] s, P < .05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCV_max (ρ = -0.49, P < .05) and to TRBCV_max (ρ = 0.41, P < .05). SHBG correlated with RBCV_max (ρ = 0.52, P < .01) while estradiol (E₂) levels correlated with RBCV (ρ = 0.80, P < .001) and RBCV_max (ρ = 0.46, P < .05).ConclusionMicrovascular dysfunction characterized by reduced RBCV_maxand prolonged TRBCV_maxwas present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction. (Endocr Pract. 2014;20:1281-1289)     

A Fraxinus excelsior L. seeds/fruits extract benefits glucose homeostasis and adiposity related markers in elderly overweight/obese subjects: A longitudinal,randomized, crossover,double-blind,placebo-controlled nutritional intervention study

PurposeThe aim of this study was to investigate the potential benefits of an extract obtained from seeds/fruits of an Oleaceae (Fraxinus excelsior L.) on glucose homeostasis and associated metabolic markers in non-diabetic overweight/obese subjects.Materials and methodsThis study was performed in 22 participants (50–80 years-old; BMI 31.0 kg/m²). The design was a longitudinal, randomized, crossover, double-blind, placebo-controlled 7-week nutritional intervention. The participants received daily 3 capsules each containing either 333 mg of an extract from Fraxinus excelsior L. seeds (Glucevia^®) or placebo capsules (control) in a random order for 3 weeks with 1 week of washout between treatments. Moreover, they followed a balanced covert energy-restricted diet (−15% energy). All variables were measured at the beginning and at the end of each period.ResultsCompared to baseline, the administration of 1 g of Glucevia^® for 3 weeks resulted in significantly lower incremental glucose area under the curve (−28.2%; p < 0.01), and significantly lower 2 h blood glucose values (−14%; p < 0.01) following an oral glucose tolerance test. No significant changes were found in the control group (−7.9% AUC, −1.6% 2 h blood glucose). Furthermore, significant differences were found between responses in the control and Glucevia^® groups with respect to serum fructosamine and plasma glucagon levels (p < 0.01 and p < 0.05, respectively). Interestingly, administration of Glucevia^® significantly increased the adiponectin:leptin ratio (p < 0.05) and decreased fat mass (p < 0.01) compared to control (p < 0.05).ConclusionThe administration of an extract from Fraxinus excelsior L. seeds/fruits in combination with a moderate hypocaloric diet may be beneficial in metabolic disturbances linked to impaired glucose tolerance, obesity, insulin resistance and inflammatory status, specifically in older adults.     

Macrophage migration inhibitory factor (MIF) -173 polymorphism is associated with clinical erythema nodosum in Löfgren’s syndrome

Introduction: Macrophage migration inhibitory factor (MIF) has been shown to be a key regulator in innate and adaptive immune responses. A single nucleotide polymorphism in the 5′ region of the MIF gene, MIF -1731G/C, is associated with increased MIF protein production, in vivo and in vitro. Associations have been shown between the minor MIF -173C allele and sarcoidosis patients with erythema nodosum (EN). Löfgren’s syndrome is an acute and usually self-remitting phenotype of sarcoidosis. It is defined as having an acute onset with bilateral hilar lymphadenopathy (BHL), fever, erythema nodosum (EN) and/or arthritis.The aim of this study was to investigate whether MIF -173G/C associates with the susceptibility to and the clinical manifestations, i.e. arthritis or EN, of Löfgren’s syndrome.A total of 171 patients with Löfgren’s syndrome and 313 controls were genotyped for a single nucleotide polymorphism at position -173 of the MIF gene (SNP rs755622), using a PCR and a restriction enzyme technique.Results: There were no significant differences found in the MIF -173C allele frequencies between patients with Löfgren’s syndrome and controls. In patients with Löfgren’s syndrome with only EN, a significantly increased frequency of the C minor allele was observed compared to patients with arthritis only (p = 0.0095; OR 3.08, CI: 1.28–7.39).Patients with only EN compared to patients with EN and arthritis showed a significantly increased frequency of the minor C allele (p = 0.044; OR 1.97, CI: 1.01–3.85). But patients with only arthritis compared to patients with EN and arthritis did not show a significant difference in C allele frequency (p = 0.270; OR 0.64, CI: 0.29–1.42).Conclusions: The MIF -173C allele is associated with erythema nodosum in Löfgren’s syndrome, but not with susceptibility to sarcoidosis. This indicates a role for MIF after antigen presenting to the T cell has taken place and the sarcoid inflammatory response has begun.     

Increased Arterial PET/CT 18F-Fluorodeoxyglucose Uptake in Obese and Overweight Patients

ObjectivesWe aimed to investigate the association between BMI and early atherosclerotic activity in cancer patients. We also compared the inflammatory and macroscopic calcification processes of atherosclerosis in the aortic segments and large arteries by ¹⁸F-FDG PET/CT of between normal and high BMI patients.MethodsWe conducted a retrospective review of cancer patients presented to our institution within the period between February and May 2018. Patients were classified according to their BMI into two groups: normal BMI group and high BMI group. Data of average SUVmax and SUVmean for four segments of the aorta, common iliac arteries, and femoral arteries were estimated and compared between both groups. Moreover, the macroscopic calcification on CT images for each vascular section was also reported.ResultsNinety-eight patients were classified into two groups: normal BMI group (n = 52; 53.1%), and high BMI group (n = 46; 46.9%). Average SUVmax was significantly higher in obese participants in all arterial segments (P < 0.05). However, the SUVmean was significantly higher in obese patients in only three arterial segments aortic arch, left femoral artery and descending thoracic aorta (P < 0.05).Moreover, the differences between the two study groups in terms of the frequency of macroscopic calcifications were not statistically significant for all vascular segments. BMI positively correlated with SUVmax and SUVmean of the vascular segments (r value from 0,219 to 0,575/p value between 0,023 and 0,0001).ConclusionsFluorine-18-FDG PET/CT imaging revealed that patients with high BMI have more accelerated atherosclerotic inflammatory process in their major vessels compared to their age-matched controls with normal BMI. Future studies should assess the associated between these findings and the cardiovascular events in the long term.     

Association of physical activity and polymorphisms in FGFR2 and DNA methylation related genes with breast cancer risk

PurposePhysical activity, a protective factor for breast cancer, increases the level of DNA methylation. Fibroblast growth factor receptor 2 (FGFR2), a confirmed breast cancer susceptibility gene, is predisposed to be methylated. Therefore, DNA methylation related genes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and DNA methyltransferase (DNMT), together with physical activity and FGFR2, may interact with each other to effect breast cancer risk.MethodsA total of 839 incident breast cancer cases and 863 age-matched controls from Guangzhou, China were included in this study. We used questionnaires to assess physical activity in metabolic equivalent (MET)-h/week/year and a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform to ascertain genotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models.ResultsExercise activity and FGFR2 rs2981582 were confirmed to be associated with breast cancer risk, and were found to significantly interact (P for multiplicative and additive interactions = 0.045 and 0.021, respectively). Women who had CT/TT genotypes of FGFR2 rs2981582 and experienced exercise activity <3 MET-h/week/year had significantly increased risk (OR = 3.15, 95% CI = 2.28–4.35) compared to women with CC genotype and ≥3 MET-h/week/year. There was also a significant interaction between FGFR2 rs2981582 and MTHFR rs1801133 on breast cancer risk (P for multiplicative and additive interactions = 0.039 and 0.023, respectively).ConclusionWe found both a gene–environment (FGFR2-exercise activity) and a gene–gene (FGFR2–MTHFR) interaction on breast cancer risk. Our results suggest that environmental factors, such as physical activity, may be able to counteract genetic susceptibility to breast cancer.     

Efficiency of energy use for maintenance and gain by growing crossbred Boer and Spanish Goats consuming diets differing in forage level

Eight Boer (75%) × Spanish (BS) and eight Spanish (S) wether goats (155 ± 8 days of age and 19.2 ± 2.3 kg BW, initial) were used in a replicated crossover design experiment with a 2 × 2 factorial arrangement of treatments to determine the effects of genotype and diet quality on heat production with ad libitum, near maintenance and fasting levels of feed intake. Diets were 65% concentrate (CON 15% CP, DM basis) and coarsely ground alfalfa hay (FOR 23% CP). There were no significant interactions between genotype and diet. ME intake was similar between genotypes and greater (P < 0.05) for CON versus FOR both when intake was ad libitum (7.60 versus 5.43 MJ/day) and near maintenance (4.31 versus 4.09 MJ/day). DE concentration was greater (P < 0.05) for CON than for FOR with ad libitum (74.4 versus 55.5%) and restricted intake (77.0 versus 59.6%). Energy expenditure (EE), determined by respiration calorimetry, at all levels of intake was similar between genotypes. EE was greater (P < 0.05) for CON than for FOR at each of the three levels of intake, ad libitum (573 and 521 kJ/kg BW^0.75 while fasting), near maintenance (426 and 400 kJ/kg BW^0.75) and fasting (280 and 255 kJ/kg BW^0.75). Efficiencies of ME utilization for maintenance (k_m) and gain (k_g) and the ME requirement for maintenance (ME_m) were similar between genotypes. k_m was similar between diets (0.705 and 0.690 for CON and FOR, respectively), although k_g was greater (P < 0.05) for CON than for FOR (0.603 versus 0.387). ME_m was numerically greater (P < 0.17) for CON than for FOR (407 versus 379 kJ/kg BW^0.75), which may have involved higher ME intake with CON. In conclusion, under the conditions of this experiment energy requirements and efficiency of utilization were not different between growing Boer crossbred and Spanish goats regardless of diet quality.     

Functional polymorphisms in the IL6 gene promoter and the risk of urinary bladder cancer in India

BackgroundInterleukin-6 is a multifunctional cytokine, which plays a key role in tumor proliferation and differentiation. Variations in its gene (IL6) sequence may affect the risk of developing various cancers, including urinary bladder cancer. The present study was done to find the association of functional polymorphisms in the IL6 promoter with urinary bladder cancer.Materials and methodsSingle nucleotide polymorphisms were genotyped in histologically confirmed 232 cases of urinary bladder cancer and 250 healthy controls. The controls subjects were matched to the cases by age, sex, and ethnicity. Genotyping of the polymorphisms (−174G>C; −572G>C, −596A>G) was undertaken by direct DNA sequencing. The level of association between the genotypes and urinary bladder cancer risk was estimated by odds ratios and 95% confidence intervals generated by applying the chi-square test. Linkage disequilibrium (LD) between SNPs and haplotype analysis were performed using Haploview software.ResultSignificantly higher number of smokers (p = 0.047), tobacco chewers (p = <0.001) and those with non-vegetarian food habits (p = 0.016) were seen in the case group. The distribution of genotypes at −174G>C locus differed significantly between cases and controls and the variant genotypes GC + CC were significantly rarer in the cases (p = 0.00073; OR = 0.52 95% CI 0.35–0.75). Variant genotypes (GC + CC) were more common in grade I than grade III tumors (p = 0.032), further suggesting a protective effect. No LD was found between the SNPs; however, the frequency of haplotype AGC was significantly lesser in the cases than controls (p = 0.0103), suggesting a protective effect. Genotype distribution at the other two loci (−572G>C and −596A>G) did not show association with bladder cancer.ConclusionsIL6 (−174G>C) substitution confers significant protection against the risk of urinary bladder cancer in the study population, while other substitutions in this gene (−572G>C and −596A>G) do not affect the risk. In general, there is a lack of studies on the cytokine gene polymorphisms in urinary bladder cancer.     

The ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) is present in human plasma and expressed dependent on body mass index

Ghrelin is the only known peripherally produced and centrally acting peptide hormone stimulating food intake. The acylation of ghrelin is essential for binding to its receptor. Recently, the ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) was identified in mice, rats and humans. In addition to gastric mucosal expression, GOAT was also detected in the circulation of rodents and its expression was dependent on metabolic status. We investigated whether GOAT is also present in human plasma and whether expression levels are affected under different conditions of body weight. Normal weight, anorexic and obese subjects with body mass index (BMI) 30–40, 40–50 and >50 were recruited (n = 9/group). In overnight fasted subjects GOAT protein expression was assessed by Western blot and ghrelin measured by ELISA. GOAT protein was detectable in human plasma. Anorexic patients showed reduced GOAT protein levels (−42%, p < 0.01) whereas obese patients with BMI > 50 had increased concentrations (+34%) compared to normal weight controls. Ghrelin levels were higher in anorexic patients compared to all other groups (+62–78%, p < 0.001). Plasma GOAT protein expression showed a positive correlation with BMI (r = 0.71, p < 0.001) and a negative correlation with ghrelin (r = −0.60, p < 0.001). Summarized, GOAT is also present in human plasma and GOAT protein levels depend on the metabolic environment with decreased levels in anorexic and increased levels in morbidly obese patients. These data may indicate that GOAT counteracts the adaptive changes of ghrelin observed under these conditions and ultimately contributes to the development or maintenance of anorexia and obesity as it is the only enzyme acylating ghrelin.