Weight loss in individuals with obesity (O) and type 2 diabetes (T2D) may improve glycemic control, prevent obesity-related comorbidities and, in some cases, induce remission of T2D. Glucose-lowering ...drugs such as SGLT2i and GLP-1 RAs are able to control simultaneously body weight and glucose levels; their use is recommended in individuals with O and T2D. Recently, we have demonstrated the effectiveness of repetitive Transcranial Magnetic Stimulation (rTMS) in promoting weight loss up to 1 year in individuals with O, with and without T2D. The aim of this retrospective comparative study was to compare the efficacy of SGLT2i, GLP1-RA and rTMS in reducing body weight in the long term in patients with O and T2D. Data obtained from 31 patients with O and T2D were retrospectively analyzed: 11 were treated for O with high frequency rTMS for 5 weeks, 8 subjects were treated for T2D with SGLT2i for 1 year, and 12 individuals were treated for T2D with GLP1-RA for 1 year. Changes in body weight and HbA1c in the 3 groups were analyzed with ANOVA, after 6 months (FU1) and 1 year (FU2) from the beginning of the treatment. The change in body weight between the 3 groups was significant at both FU1 −3.2±1.8% (SGLT2i) vs −3.5%±1.5% (GLP1-RA) vs −6.3±4.0% (rTMS);p=0.026 and FU2 −2.1±2.1% (SGLT2i) vs −2.1±4.2% (GLP1-RA) vs −6.7±4.7% (rTMS); p=0.017. Glycated hemoglobin variation was higher in the SGLT2i and GLP-1 RA groups than in rTMS at FU1 −11.7±25.1% (SGLT2i) vs −11.9%±13.2% (GLP1-RA) vs −8.9±10.4% (rTMS) and at FU2 −15.9±24.2% (SGLT2i) vs −7.8±11.9% (GLP1-RA) vs −5.6±9.0% (rTMS), although not statistically significant. TMS was found to be more effective than SGLT2i and GLP1-RAs in promoting long-term weight loss in a population with O and T2D, likely due to a prevalent effect of rTMS on appetite control at the meso-cortico-limbic system’s level. These findings set the stage for a potential combined use of rTMS with SGLT2i or GLP1-RAs in treatment of O and T2D.
Disclosure
A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. D.Cannavaro: None. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis.
Funding
IRCCS MultiMedica (Ricerca Corrente)
Low Blood Oxygen Saturation (BOS) is associated with increased overall morbidity / mortality and prevalence of diabetes is known to increase with altitude (lower 02 partial pressure). Individuals ...with complicated diabetes commonly have low blood oxygen saturation compared with nondiabetic patients. To unravel the link between low BOS and glucose metabolism, we investigated the correlation between BOS and glucose, BOS and HbA1c levels, BOS and VO2 consumption (Resting Energy Expenditure) in a cohort of adults with diabetes mellitus. The study included 1362 adults with diabetes (616 F, 746 M; 66.4 ± 14.2 years, range 18-85 years; BMI 27.6 ± 5.0 kg/m2, range 18-49.6 kg/m2; SpO2 97.2 ± 1.4%, range 88-100%; glucose 137.7 ± 45.0 mg/dl, range 50.0-323.0 mg/dl). A significant inverse correlation (Pearson) between the glucose (glucometer) and the BOS (pulsoximeter) (p<0.0001*; r = -0.1530). An inverse correlation (Pearson correlation) between the HbA1c levels and the BOS (n=1295; 568 F, 727 M; 67.5 ± 13.1 years, range 18-85 years; BMI 27.8 ± 5.2 kg/m2, range 18-49.8 kg/m2; HbA1c 52.9 ± 13.0, range 25-152 mmol/mol; p<0.0001*; r = -0.1351). In summary, we showed an inverse relationship between oxygen saturation and both glucose and glycosylated hemoglobin levels. Although the exact mechanisms behind lower blood oxygen saturation in diabetes are unknown, we speculate that a reduced pulmonary diffusion capacity as a consequence of pulmonary microvascular damage could play an important role. In conclusion, present preliminary data indicate the routine measurement of BOS along with glucose and glycosylated hemoglobin in the outpatient visit setting of diabetic patients as a biomarker of seriousness of disease.
Disclosure
L. Luzi: Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gelesis. Advisory Panel; Medtronic. Speaker's Bureau; Novo Nordisk, Novartis. C. Macrì: None. A. Ferrulli: None. C.C. Berra: None. C. Romano: None. S. Massarini: None.
Funding
IRCCS MultiMedica (Ricerca Corrente)
Current anti-obesity interventions result in early rapid weight loss, but long-term maintenance of lost weight is much more challenging. Initial weight loss is typically followed by a weight plateau ...and progressive regain. We demonstrated the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in inducing long-term weight loss (up to 1 year) in individuals with obesity by modulating the brain dopaminergic system and the prefrontal cortex. In a post-hoc analysis, we re-evaluated body weight loss up to 3 years after, in 44 individuals treated with a 5-week high frequency rTMS or sham stimulation, for obesity. Out of 44 subjects, 30 individuals (21 F/9 M, BMI 35.3±2.8, age 49.9±9.3) did not undergo any further weight loss treatments (except diet), 9 subjects (5 F/4 M, BMI 40.4±4.7, age 44.7±.6.1) underwent bariatric surgery, and 5 patients were treated for persistent obesity with a GLP-1 receptor agonist (GLP1-RA) (5 F/0 M, BMI 36.8±6.5, age 53.2±13.9). Out of 30 subject who did not undergo any further weight loss intervention, the 16 patients who received real rTMS (10 F/6 M, BMI 34.6±3.2, age 49.2±7.5) reported a significant body weight loss compared to the Sham group (11 F/3M, BMI 36.1±2.0, age 50.7±2.0) at the end of the 5-week intervention (BMI:-4.5±1.7% vs -1.6±1.8%, p=0.0001). Crucially, they continued to lose body weight compared to the Sham even 3 years after the end of intervention (BMI: -9.5±7.6% vs -3.6±8.4%, p=0.056). As expected, during the 3-year follow-up, bariatric surgery was more effective in promoting weight loss compared to the rTMS and the GLP1-RA (p=0.0001), but rTMS has not been shown to be less effective than GLP1-RA in maintaining lost weight (p=0.621). This preliminary evidence of efficacy of rTMS in promoting long-term weight loss (over one year) may be explained via neuronal neuroplasticity. TMS alone or in combination with other anti-obesity approaches may open new ways to sustain the efficacy of weight control interventions.
Disclosure
A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. D.Cannavaro: None. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis.
Funding
IRCCS MultiMedica (Ricerca Corrente)
The association between obesity and psychological distress has been widely demonstrated. Systematic reviews have highlighted the bidirectional nature of this relationship. Strategies aimed at ...improving dopamine function may be beneficial in the treatment of both obesity and the associated psychological symptoms. Deep Transcranial Magnetic Stimulation (dTMS) has been demonstrated capable of inducing satiety and body weight loss in obesity, through modulation of dopaminergic system. Aim of this study was to evaluate possible beneficial effects of a 5-week dTMS treatment on psychological conditions in obesity. A total of 33 obese patients (9 males, 24 females, age 48.1±10.6 years, BMI 36.9±4.7 Kg/m2) were randomized and completed the study: 13 obese subjects underwent a 5-week treatment with high-frequency (HF) dTMS (18 Hz), 10 were treated with low-frequency (LF) dTMS (1 Hz), and 10 were Sham-treated. Depressive symptoms Zung Self-Rating Depression Scale (SDS), Beck Depression Inventory (BDI), state State-Trait Anxiety Inventory (STAI-1) and trait anxiety (STAI-2), impulsiveness Barratt Impulsiveness Scale (BIS) were evaluated at baseline and at the end of 15 dTMS sessions. After 5 weeks, a significant weight loss was found in HF vs. LF and vs. sham (p=0.001). In the same group, a significant decrease in both Zung SDS (37.3±4.2 vs. 26.7±5.4, p=0.049 vs. baseline; p=0.036 vs. Sham) and BDI scores (4.8±4.1 vs. 2.6±2.5, p=0.019 vs. baseline) was found. In HF, state (37.1±7.9 vs. 32.4, p=0.024) and trait anxiety (35.6±10.5 vs. 30.1±7.8, p=0.016), and impulsiveness (55.6±9.3 vs. 51.6±8.4, p=0.021) scores significantly decreased compared to baseline. Weight loss over 5 weeks of dTMS treatment was associated with psychological benefit; the improvement of psychological conditions in obese subjects has been hypothesized to be due to a direct effect of HF dTMS, as well as a weight loss secondary result. The reduction of impulsivity could concur to a greater control of food craving in HF.
Disclosure
A. Ferrulli: None. C. Macrì: None. V. Dangelo: None. L. Luzi: Consultant; Self; McKinsey & Company. Research Support; Self; Allergan, Gelesis, SunStar Inc. Speaker's Bureau; Self; A. Menarini Diagnostics, AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Menarini Group, Novartis AG, Novo Nordisk Inc., Sunstar Foundation.
Funding
Italian Ministry of Health
Consumption of hazelnuts has been associated with reduced cardiovascular risk and improved metabolic outcomes. Furthermore, the Bone Marrow Fat (BMF) might contribute to skeletal as well as systemic ...metabolism, modulating insulin sensitivity and, consequently, cardiovascular risk. Previously, we demonstrated a beneficial effect of hazelnuts and cocoa integration on vascular reactivity and metabolic profile in healthy individuals. Aim of this randomized controlled interventional study with 3 parallel groups was to investigate the effects of a daily supplementation with 30 g of hazelnuts, with or without aerobic physical activity (PA), throughout 8 weeks, on insulin sensitivity and resistance, lipid profile, and on BMF content (evaluated by proton magnetic resonance spectroscopy) in healthy individuals. Twenty-five adults (age 18-50 yrs; BMI 18-28 Kg/m2) were randomized in 3 groups: 9 subjects (5F/4M, age 25.6±8.8 yrs, BMI 23.3±2.5) received 30 g of hazelnuts associated with diet (Group 1); 9 subjects (6F/3M, age 26.3±6.3 yrs, BMI 22.0±2.1) received 30 g of hazelnuts associated with diet and aerobic PA (Group 2); 7 subjects (4 F/3 M, age 29.7±6.4 yrs, BMI 23.3±4.2) received only diet (Group 3). After the 8 weeks-intervention, an improvement in LDL-Cholesterol was found in Groups 1 and 2 -9.3±11.5% (Group 1) vs -5.0±13.6% (Group 2) vs +21.9±35.7% (Group 3); p=0.02. BMF content variation negatively correlated with LDL-Cholesterol change in Group 1 (r=-0.802, p=0.054); variations in BMF content and in HDL-Cholesterol positively correlated in Group 2 (r=+0.8687, p=0.011). This study confirms the beneficial effects of hazelnuts, in association with PA in improving lipid profile. The correlations between HDL- and LDL-cholesterol and BFM changes suggest an impact of bone homeostasis on whole-body lipid metabolism, through a rapid utilization of lipids, drawing them out of the circulation and decreasing their deposition in the organ tissues.
Disclosure
A.Ferrulli: None. S.Massarini: None. C.Macrì: None. P.Senesi: None. I.Terruzzi: None. G.Rosso: Employee; Soremartec Italia Srl, Ferrero Group. M.Charron: Employee; Soremartec Italia Srl, Ferrero Group. R.Menta: Employee; Soremartec Italia Srl, Ferrero Group. L.Luzi: Advisory Panel; Eli Lilly and Company, Medtronic, Research Support; Gelesis, Speaker's Bureau; A. Menarini Diagnostics, Amgen Inc., Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Novo Nordisk, Novartis.
Funding
IRCCS MultiMedica (Ricerca Corrente)
It is known that host cells can produce type I IFNs (IFN-alphabeta) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial ...infections are incompletely understood. We show in this study that IFN-alphabeta signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-alphabetaR or IFN-beta died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-alphabetaR deficiency was marked, with mortality surpassing that seen in IFN-gammaR-deficient mice. Animals lacking both IFN-alphabetaR and IFN-gammaR displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN-alphabeta was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-alphabeta signaling, a marked reduction in macrophage production of IFN-gamma, NO, and TNF-alpha was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-alphabeta in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.
The eradication of bacterial biofilm represents a crucial strategy to prevent a clinical problem associated with microbial persistent infection. In this study we evaluated the ability of the ...exopolysaccharide (EPS) B3-15, produced by the marine
B3-15, to prevent the adhesion and biofilm formation of
ATCC 27853 and
ATCC 29213 on polystyrene and polyvinyl chloride surfaces. The EPS was added at different times (0, 2, 4 and 8 h), corresponding to the initial, reversible and irreversible attachment, and after the biofilm development (24 or 48 h). The EPS (300 µg/mL) impaired the initial phase, preventing bacterial adhesion even when added after 2 h of incubation, but had no effects on mature biofilms. Without exerting any antibiotic activity, the antibiofilm mechanisms of the EPS were related to the modification of the (i) abiotic surface properties, (ii) cell-surface charges and hydrophobicity, and iii) cell-to-cell aggregation. The addition of EPS downregulated the expression of genes (
A and
of
and
A of
) involved in the bacterial adhesion. Moreover, the EPS reduced the adhesion of
(five logs-scale) and
(one log) on human nasal epithelial cells. The EPS could represent a promising tool for the prevention of biofilm-related infections.
Context: The wide family of the phytoestrogens has become an alternative to the classical hormonal therapy in menopause; nevertheless, some findings are still conflicting.
Objective: To examine the ...effect of genistein administration on metabolic parameters and vascular reactivity considering the basal endocrine status of the patients.
Design and Setting: A randomized placebo controlled study was conducted at a university hospital.
Participants: Fifty postmenopausal women participated.
Interventions: Thirty subjects (group A) were randomized to receive 54 mg/d genistein while 20 subjects (group B) were treated with the placebo for 24 wk. In group A, we distinguish two subgroups: 14 normoinsulinemic and 12 hyperinsulinemic patients.
Main Outcome Measures: Anthropometric measures, hormonal and lipid assays, oral glucose tolerance test with glycemic, insulin, and C-peptide evaluation, indexes of insulin sensitivity and endothelial function, and euglycemic-hyperinsulinemic clamps were performed.
Results: The insulin basal values significantly decreased in group A, whereas the homeostasis model index of insulin sensitivity and the fasting glucose levels significantly improved compared with placebo group. The genistein administration decreased fasting glucose and area under the curve glucose levels in the normoinsulinemic patients after treatment. In the hyperinsulinemic patients, a significant reduction in fasting insulin, fasting C-peptide, and area under the curve insulin levels as well as an increase in fractional hepatic insulin extraction was shown. In these patients, high-density lipoprotein cholesterol levels were significantly improved. The endothelium-dependent and -independent dilatation improved in the treated group. Normoinsulinemic patients showed both a significantly enhanced flow-mediated and nitrate-mediated dilatation, whereas no significant changes were found in the hyperinsulinemic group.
Conclusions: The glycoinsulinemic metabolism and the endothelial function were significantly influenced by genistein. In particular, normoinsulinemic patients showed an improvement in glycemic and vascular reactivity indexes. Conversely, an improvement in the insulin sensitivity indexes was noted in hyperinsulinemic patients.
Genistein significantly influences glycoinsulinemic metabolism and endothelial function. Normoinsulinmeic patients show an improvement in glycemic and vascular reactivity indexes, while the insulin sensitivity indexes improve in hyperinsulinemic patients.
The exopolysaccharide (EPS B3-15) and biosurfactant (BS B3-15), produced by the marine Bacillus licheniformis B3-15, were recently reported to possess different antibiofilm activities, with the EPS ...being more active in preventing the adhesion of Pseudomonas aeruginosa and Staphylococcus aureus and the BS in destroying their preformed biofilms on different surfaces. In this study, the synergistic effects of the two exopolymers on the bacterial adhesion and biofilm disruption of P. aeruginosa and S. aureus were evaluated on polystyrene, a medical polyvinyl chloride (PVC) device, and contact lenses (CLs) in order to address their potential use in biomedical applications. To this purpose, EPS B3-15 and BS B3-15 were equally combined (1:1 w/w), and the mixture (BPS B3-15) was added at different concentrations (from 50 to 300 µg mLsup.−1) and at different times of bacterial development. Compared to each polymer, the BPS B3-15 (300 µg mLsup.−1) more efficiently reduced the adhesion of P. aeruginosa and S. aureus on polystyrene (65 and 58%, respectively), PVC devices (62 and 42%, respectively), and CLs (39 and 35%, respectively), also in combination with a CLs care solution (88 and 39%, respectively). Furthermore, BPS B3-15 was able to disrupt mature biofilms, acting more effectively against S. aureus (72%) than P. aeruginosa (6%). The combination of exopolymers at low concentrations exhibited synergistic effects to prevent and eradicate biofilms.
Exopolysaccharide (EPS) production represents an adaptive strategy developed by extremophiles to cope with environmental stresses. The EPS-producing Bacillus licheniformis B3-15, of shallow marine ...vent origin (Vulcano Island, Italy), was previously reported as tolerant to arsenate (AsV). In this study, we evaluated: (i) the increasing production of EPS by Bacillus licheniformis B3-15 in the novel SG17 medium; (ii) the arsenic absorption capacity of the EPS by mass spectroscopy; (iii) the functional groups of EPS interacting with As by ATR-FTIR spectroscopy; and (iv) the ability of EPS to prevent arsenic toxicity by the bioluminescent assay. The EPS yield (240 mg L−1) was 45% higher than previously reported. The EPS was mainly constituted of disaccharide repeating units with a manno-pyranosidic configuration and low protein content, attributed to the poly-gamma glutamic acid component as evidenced by NMR analysis. ATR-FTIR spectra indicated that the functional groups of the EPS (O–H, C=O, C–O and C=C and N–O) were involved in the adsorption of the arsenic cations, with greater interactions between EPS and arsenate (AsV) than arsenite (AsIII). Consequently, the EPS at increasing concentration (100 and 300 µg mL−1) adsorbed AsV more efficiently (20.5% and 34.5%) than AsIII (0.7% and 1.8%). The bioluminescence assay showed that the EPS was not toxic, and its addition reduced the toxicity of both As forms by more than twofold. The crude EPS B3-15 could be used in arsenic bioremediation as a possible eco-friendly alternative to other physical or chemical methods.
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