Explore the vast range of titles available.

Background/Objectives: Food-induced thermogenesis is generally reported to be higher in the morning, although contrasting results exist because of differences in experimental settings related to the preceding fasting, exercise, sleeping and dieting. To definitively answer to this issue, we compared the calorimetric and metabolic responses to identical meals consumed at 0800 hours and at 2000 hours by healthy volunteers, after standardized diet, physical activity, duration of fast and resting. Subjects/Methods: Twenty subjects (age range 20–35 years, body mass index=19–26 kg m − 2 ) were enrolled to a randomized cross-over trial. They randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal calorimetry was performed; a further 60-min calorimetry was done 120-min after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the ‘morning effect’, that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables. Results: Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI)=1792, 2041 vs 1756; 1648, 1863 kcal; P <0.001). RMR was significantly increased after the morning meal (90.5; 95% CI=40.4, 140.6 kcal; P <0.001), whereas differences in areas-under-the-curve for glucose (−1800; −2564,−1036 mg dl −1 × h, P <0.001), log-insulin (−0.19; −0.30,−0.07  μ U ml −1 × h; P =0.001) and fatty free acid concentrations (−16.1;−30.0,−2.09 mmol l −1 × h; P =0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals. Conclusions: The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. The timing of meals should probably be considered when nutritional recommendations are given.

Aim Oral semaglutide, an innovative orally administered GLP-1 receptor agonist for type 2 diabetes (T2D) management was herein evaluated for its effectiveness in a multi-center retrospective real-world study. Methods We included new-users of oral semaglutide from 18 specialist care centres and collected retrospective data on baseline clinical characteristics. Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. Results The study included 166 individuals with T2D, predominantly men (64.5%), with a mean age of 64.4 years and a mean diabetes duration of 10.1 years. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. At baseline, mean BMI was 28.9 kg/m 2 and HbA1c was 7.5%. During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of − 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. Additionally, there was a substantial reduction in body weight, with an estimated change of − 3.4 kg at 18 months, and 30.3% of patients experienced a 5% or greater reduction in baseline body weight. Only 24.2% of patients reached the 14 mg dose. Subgroup analysis revealed that baseline HbA1c > 7%, persistence on drug, not being on a prior therapy with DPP-4 inhibitors, and loosing 5% or more the initial body weight were associated with greater HbA1c reductions. Conclusion This study supports oral semaglutide as an effective option for T2D treatment, offering improved glucose control and weight management in a real-world setting.

Rheumatoid Arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality and osteometabolic alterations risk, associated with chronic inflammation, the use of glucocorticoids (GC) and the reduced physical exercise.[1] The objective of the study is to cross-sectionally estimate cardiovascular risk and osteometabolic status in patients (pts) with RA and to evaluate the association with some disease parameters such as positivity of autoantibodies, disease activity and steroid therapy. At the current time, 61 consecutive pts with diagnosis of RA, admitted to the Rheumatology Unit of the University Hospital of Turin, were prospectively recruited and assessed for cardiometabolic risk by the Endocrinology Unit, by undergoing laboratory and instrumental tests. The following prevalences were observed: arterial hypertension (52%), type 2 diabetes mellitus (7%), dyslipidemia (56%), osteoporosis (42%), and vertebral fracture (30%). At the univariate analysis, the enrolled pts were divided according to serodiagnosis, GC therapy and disease remission. No statistically significant results were highlighted stratifying population by serodiagnosis. Pts with high disease activity showed lower bone mineral density (BMD) values [BMD femoral trochanter: 0.53± 0.08 vs 0.60 ± 0.08 (g/m2), p=0.031] and T-score value on bone densitometry [T-score Femoral total: -1.88 ± 0.53 vs -1.07 ± 0.83, p=0.005], higher percentage of osteoporosis [67% vs 27%, p=0.047] and vertebral fractures [60% vs 12%, p=0.001], and higher sarcopenia score [SARC-F: 5 (3-7) vs 2 (2-4), p=0.020], in comparison with pts with remission disease. These differences were not confirmed when the population was divided according to the use of GC therapy. For CV risk factors, disease activity group showed a trend of higher prevalence compared to remission group, but without reaching statistical significance. At the multivariate analysis, advanced age (p=0.001), GC therapy (p=0.021) and copeptin (p=0.002) showed an inverse association and lumbar T-score (p=0.002) a direct one with lumbar trabecular bone score (TBS). Moreover, male gender (p=0.001) revealed a direct and significant association, while copeptin (p=0.086) an inverse and not significant one with percentage of lean mass on total densitometry, correcting for advanced age, duration of disease, GC therapy, and disease activity. In the last model, advanced age (p<0.001) and copeptin (p<0.001) showed a direct and significant association with HeartSCORE, correcting for parameters of disease while serodiagnosis, duration of disease, GC therapy, and disease activity. At univariate analysis osteometabolic alterations were associated with disease activity, but not with GC therapy and serodiagnosis. At the multivariate analysis, the association of disease activity and TBS values, did not reach the statistical significance, probably for the loss of statistical power. However, GC therapy, as well as advanced age, low lumbar T-score and high value of copeptin, remained independently associated with lower TBS value. Disease parameters were not associated with lower percentage of lean mass at total body densitometry and higher HeartSCORE values, while advanced age and copeptin were associated with bone health and cardiovascular risk. [1] Mackey RH et al. Rheum Dis Clin North Am 2018. NIL. None Declared. Table 1Multivariate linear regression analysisCovariates associated with lumbar TBSB-coefficientCI 95%p-valueAge-0.005(-0.007- -0.002)0.001GC-0.068(-0.125- -0.011)0.021T-Score0.049(0.020-0.079)0.002Copeptin-0.014(-0.023- -0.006)0.002Covariates associated with HeartSCORE cardiovascular risk scoreB-coefficientCI 95%p-valueAge0.242(0.180-0.304)<0.001Duration of disease-0.045(-0.099-0.008)0.096RF and/or ACPA +-0.224(-1.855-1.407)0.782GC0.840(-0.454-2.135)0.195Copeptin0.345(0.172-0.518)<0.001Remission0.502(-0.848-1.853)0.454

Aim To compare effectiveness of dapagliflozin versus DPP-4 inhibitors on individualized HbA1c targets and extra-glycaemic endpoints among elderly patients with type 2 diabetes (T2D). Methods This was a multicentre retrospective study on patients aged 70–80 years with HbA1c above individualized target and starting dapagliflozin or DPP-4 inhibitors in 2015–2017. The primary outcome was the proportion reaching individualized HbA1c targets. Confounding by indication was addressed by inverse probability of treatment weighting (IPTW), multivariable adjustment (MVA), or propensity score matching (PSM). Results Patients initiating dapagliflozin ( n  = 445) differed from those initiating DPP-4i ( n  = 977) and balance between groups was achieved with IPTW or PSM. The median follow-up was 7.5 months and baseline HbA1c was 8.3%. A smaller proportion of patients initiating dapagliflozin attained individualized HbA1c target as compared to those initiating DPP-4 inhibitors (RR 0.73, p  < 0.0001). IPTW, MVA, and PSM yielded similar results. Between-group difference in the primary outcome was observed among patients with lower eGFR or longer disease duration. Dapagliflozin allowed greater reductions in body weight and blood pressure than DPP-4 inhibitors. Conclusions Elderly patients with T2D initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors but displayed better improvements in extra-glycaemic endpoints.

Sleep disturbances may be associated with impaired glucose metabolism . The aim of this study was to evaluate sleep duration and quality in relation to glycemic control in patients with type 2 diabetes. In a cross-sectional study, sleep duration and quality were assessed in 47 middle-aged patients with type 2 diabetes treated with oral agents and without sleep disturbing complications and 23 healthy control subjects similar by age, sex, body mass index, occupation and schooling. Sleep was recorded by wrist-actigraphy for three consecutive days under free-living conditions. Univariate analysis showed lower sleep maintenance ( P  = 0.002) and sleep efficiency ( P  = 0.005), and higher fragmentation index ( P  < 0.0001), total activity score ( P  = 0.05) and moving time ( P  < 0.0001) in patients with type 2 diabetes. After adjusting for age, gender and schooling, fragmentation index and moving time remained significantly higher in the patients with diabetes ( P  < 0.05, both). HbA1c correlated inversely with sleep efficiency ( r  = −0.29; P  = 0.047) and positively with moving time ( r  = 0.31; P  = 0.031). These findings suggest that type 2 diabetes is associated with sleep disruptions even in the absence of complications or obesity. The relevance of sleep abnormalities to metabolic control and possible strategies to improve sleep quality in type 2 diabetes deserve further investigation.

The aim of this study is to describe a potential modulatory effect of acute acylated ghrelin (AG) administration on the glucose, insulin, and free fatty acids (FFA) responses to salbutamol (SALBU). Six healthy young male volunteers underwent the following four testing sessions in random order at least 7 days apart: (a) acute AG administration (1.0 μg/kg i.v. as bolus at 0′); (b) SALBU infusion (0.06 μg/kg/min i.v. from −15′ to +45′); (c) SALBU infusion + AG; and (d) isotonic saline infusion. Blood samples for glucose, insulin, and FFA levels were collected every 15 min. As expected, with respect to saline, SALBU infusion induced a remarkable increase in glucose (10.8 ± 5.6 mmol/l × min; P < 0.05), insulin (2436.8 ± 556.9 pmol/l × min; P < 0.05), and FFA (18.9 ± 4.5 mmol/l × min; P < 0.01) levels. A significant increase in glucose (7.4 ± 3.9 mmol/l × min; P < 0.05) and FFA levels (10.0 ± 2.8 mmol/l × min; P < 0.01) without significant variations in insulin levels were recorded after AG administration. Interestingly, the hyperglycemic effect of AG appeared to be significantly potentiated during SALBU infusion (26.7 ± 4.8 mmol/l × min; P < 0.05). On the other hand, the stimulatory effect of SALBU on insulin and FFA was not significantly modified by AG administration. The results of this study show that acute AG administration has a synergic effect with β2-adrenergic receptor activation by SALBU on blood glucose increase, suggesting that their pharmacological hyperglycemic action takes place via different mechanisms. On the other hand, AG has a negligible influence on the other pharmacological metabolic effects of SALBU infusion.

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl molecules with strong, dose-dependent, and reproducible growth hormone (GH)-releasing activity even after oral administration. GHSs release GH via actions on specific receptors (GHS-R) at the pituitary and, mainly, at the hypothalamic levels. GHSs likely act as functional somatostatin antagonists and meantime enhance the activity of GH-releasing hormone (GHRH)-secreting neurons. The GH-releasing effect of GHSs is independent of gender but undergoes marked age-related variations. Estrogens play a major role in enhancing the GH response to GHSs at puberty, which GHRH hypoactivity, somatostatinergic hyperactivity and impaired activity of the putative GHS-like ligand and receptors probably explain the reduced GH-releasing effect of GHSs in aging. The activity of GHSs is not fully specific for GH. Their slight prolactin-releasing activity probably comes from direct pituitary action. In physiological conditions, the ACTH-releasing activity of GHSs is dependent on central actions; a direct action on GHS-R in pituitary ACTH-secreting tumors likely explains the peculiar ACTH and cortisol hyperresponsiveness to GHSs in Cushing disease. GHSs have specific receptor subtypes in other central and peripheral endocrine and nonendocrine tissues mediating GH-independent biologic activities. GHSs influence sleep pattern, stimulated food intake, and have cardiovascular activities. GHs have specific binding in normal and neoplastic follicular derived human thyroid tissue and inhibit the proliferation of follicular-derived neoplastic cell lines. The discovery of ghrelin, a 28 amino acid peptide synthesized in the stomach but also in other tissues, has opened new fascinating perspectives of research in this field.

Background: Lipodystrophy is one of the most frequent complications in people with diabetes following subcutaneous insulin therapy, and poor management can lead to several problems, such as impaired glycemic control and adherence to therapy, anxiety, and depression. Poor injection technique represents the main risk factor for lipodystrophies. In order to enhance the patient’s insulin injection technique to heal lipodystrophy, improve psychological indices, and promote involvement in their health and care, the efficacy of emerging person-centered care called the IARA model was tested. Methods: A total of 49 patients were randomly allocated to the IARA group (Experimental; n = 25) or standard education (Control; n = 24). The following questionnaires were used in a mixed-method design: (i) State Anxiety Scale; (ii) Beck Depression Inventory; (iii) Italian Summary of Diabetes Self-Care Activities. An ad hoc open-ended questionnaire was structured for the qualitative analysis. Finally, photos were taken in order to verify if injection sites were changed until the follow-up at 12 months. The number of patients who participated until the completion of the study was 17 in the IARA and 11 in the Control group. Results: State anxiety was significantly reduced in people who followed IARA to follow-up at 3 and 6 months (p < 0.05). The IARA group also demonstrated better compliance in blood glucose monitoring and foot-care compared to Control at follow-up at 12 months. The management of insulin injections dramatically improved in participants who received IARA intervention. Conclusions: IARA could be considered an effective strategy to improve well-being and compliance in people affected with diabetes mellitus and lipodystrophy complications.

Background Timing of food intake impacts on metabolic diseases. Few data are available about post-meal changes in epinephrine (E), norepinephrine (NE), and acylated ghrelin (AG) at different times of the day. Subjects and methods This randomized cross-over trial investigated E/NE/AG concentrations after identical meals consumed at 0800 or 2000 hours in 20 healthy volunteers, by standardizing diet, exercise, duration of fast, and resting. Participants randomly received the test meal at 0800 or 2000 hours, and vice versa after 1 week. Blood samples were collected before and up to 180-min post-meal, every 30 min, with participants supine, motionless, but awake. Results Median E levels increased at 30–60 min, then declined and rose again at 150 min; values at 60 min (19.0 vs. 15.0 ng/l, p  = 0.03) and 180 min (25.0 vs. 11.0 ng/l, p  < 0.001) were higher after the morning meals. NE rose at 30–60 min and then progressively declined; median values at 60 min (235.3 vs. 206.3 ng/l, p  = 0.02) and 120 min (208.8 vs. 142.0 ng/l, p  = 0.04) increased more after morning meals. AG progressively declined to increase again at 90 min after meal; median AG area-under-the-curve (AUC) values were lower at morning (7206.8 vs. 8828.3 pg/mL×h). AG-AUC was inversely associated with diet-induced thermogenesis ( β  = −121.6; 95% CI −201.0 to 42.2; p  = 0.009 for each unit increase), while log NE-AUC was inversely associated with log-triglyceride AUC ( β  = −0.57; 95% CI −0.98 to 0.16; p  = 0.015) in a multiple regression model, after multiple adjustments. Conclusions In conclusion, E/NE concentrations were higher after the morning meal, while AG showed an opposite behavior. These data, although requiring confirmation in larger samples, suggest an adjunctive possible mechanism explaining the unfavorable effects of evening eating on metabolic risk

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl molecules that possess strong growth hormone-releasing activity acting on specific pituitary and hypothalamic receptor subtypes. Differently from nonpeptidyl GHSs, peptidyl molecules such as hexarelin, a hexapeptide, possess specific high-affinity binding sites in animal and human heart and, after prolonged treatment, protect rats in vivo from ischemiainduced myocardial damage. To verify the hypothesis that peptidyl GHSs protect heart cells from cell death, we have investigated the cellular effects of hexarelin on H9c2 cardiomyocytes, a fetal car diomyocyte-derived cell line, and on Hend, an endothelial cell line derived from transformed murine heart endothelium. We show that (i)H9c2 cardiomyocytes show specific binding for 125I-Tyr-Ala-hexarelin, which is inhibited by peptidyl GHSs such as Tyr-Ala-hexarelin and hexarelin but not by the nonpeptidyl GHS MK-0677, (ii) hexarelin promotes survival of H9c2 cardiomyocytes induced to die by doxorubicin, and (iii) that hexarelin inhibits apoptosis, as measured by DNA fragmentation, induced in both H9c2 myocytes and endothelial cells. In conclusion, our findings show that peptidyl GHSs such as hexarelin act as survival factors for cardiomyocytes and endothelium-derived cells in culture. These findings suggest that the inhibitory activity of hexarelin on cardiomyocytes and endothelial cell death could explain, at least partially, its cardioprotective effect against ischemia recorded in rats in vivo.