Type 1 diabetes-related distress: Current implications in care

Type 1 diabetes (T1D) is a complex chronic disease associated with major health and economic consequences, also involving important issues in the psychosocial sphere. In this regard, T1D-related distress, defined as the emotional burden of living with T1D, has emerged as a specific entity related to the disease. Diabetes distress (DD) is an overlooked but prevalent condition in people living with T1D, and has significant implications in both glycemic control and mental health in this population. Although overlapping symptoms may be found between DD and mental health disorders, specific approaches should be performed for the diagnosis of this problem. In recent years, different DD-targeted interventions have been postulated, including behavioral and psychosocial strategies. Moreover, new technologies in this field may be helpful to address DD in people living with T1D. In this article, we summarize the current knowledge on T1D-related distress, and we also discuss the current approaches and future perspectives in its management.Funding for open access charge: Universidad de Málaga / CBUA. J.I.M.M. was supported by a Rio Hortega grant from Instituto de Salud Carlos III, Madrid, Spain (CM22/00217)

Effects of exercise timing on metabolic health

The increasing prevalence of metabolic syndrome is associated with major health and socioeconomic consequences. Currently, physical exercise, together with dietary interventions, is the mainstay of the treatment of obesity and related metabolic complications. Although exercise training includes different modalities, with variable intensity, duration, volume, or frequency, which may have a distinct impact on several characteristics related to metabolic syndrome, the potential effects of exercise timing on metabolic health are yet to be fully elucidated. Remarkably, promising results with regard to this topic have been reported in the last few years. Similar to other time-based interventions, including nutritional therapy or drug administration, time-of-day-based exercise may become a useful approach for the management of metabolic disorders. In this article, we review the role of exercise timing in metabolic health and discuss the potential mechanisms that could drive the metabolic-related benefits of physical exercise performed in a time-dependent manner.Funding for open access charge: Universidad de Málaga/CBUA

Effect of apolipoprotein C3 and apolipoprotein A1 polymorphisms on postprandial response to a fat overload in metabolic syndrome patients

Objectives: Apolipoprotein C-III (APOC3) is a component of triglyceride rich lipoproteins, and SstI polymorphism has been associated with hypertriglyceridemia. Apolipoprotein A-I (APOA1) is the major component of HDL and MspI polymorphism has been associated with APOA1 and HDL-C levels. Thus, we study the influence of these polymorphisms in the postprandial response in metabolic syndrome (MS). Design and methods: 73 MS patients and 21 healthy subjects underwent a fat overload, with measurements of their fasting and postprandial lipid profile. The APOC3 SstI and the APOA1MspI polymorphisms were genotyped. Results: No significant differences were found in the lipid profile with respect to the MspI genotype. Patients with the S2S2 APOC3 genotype had significantly higher fasting and postprandial triglyceride levels and postprandial APOC3 and chylomicron-triglyceride levels compared with the other SstI APOC3 genotypes. Conclusions: Homozygosity for the minor allele of the APOC3 SstI polymorphism was associated to a worse postprandial response in MS patients.The authors wish to thank all the subjects for their collaboration, and IMABIS. We also gratefully acknowledge the help of Ian Johnstone for his expertise in preparing this manuscript and José Rioja for his technical contribution (Centro de Investigaciones Médico-Sanitarias, University of Malaga, Spain). The research group belongs to the “Centros de Investigación en Red” (CIBER, CB06/03/0018) of the “Instituto de Salud Carlos III”. This work was supported in part by a grant from the Instituto de Salud Carlos III CP07/0095, PS09/00997 and PI081655, Madrid, Spain and the Servicio Andaluz de Salud (PI325/2008)

Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome

With aging, the body’s ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in immunoglobulin G (IgG) glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of white men from Europe, aged 29–45 years, under treatment with metformin, testosterone, metformin plus testosterone, and placebo (trial registration number NCT02514629, 2013/07/04), and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.Funding for open access charge: Universidad de Málaga/CBU

Phase angle and COVID-19: a systematic review with meta-analysis

Phase angle (PhA) has been identified as a poor prognostic factor in patients with COVID-19. This study aimed to achieve a systematic review, where we discussed the potential role of PhA value as a prognostic marker of adverse clinical outcomes such as mortality and complication in hospitalized with SARS-CoV2 infection and established the strength of recommendations for use. A systematic literature review with meta-analysis was done in the main electronic databases from 2020 to January 2023. The selected articles had to investigate adverse consequences of the COVID-19 population and raw bioimpedance parameters such as PhA and published in peer-reviewed journals. GRADE tools regarded the quality of the methodology. The review protocol was registered in PROSPERO. Only eight studies, 483 studies, were eligible for the analysis. In general, differences in PhA were seen between the comparative study groups. Patients with a low PhA experienced poor outcomes. A low PhA was associated with a significantly increased mortality risk [RR: 2.44; 95% CI (1.20–4.99), p = 0.01; I2 = 79% (p = 0.0008)] and higher complications risk [OR: 3.47, 95% CI (1.16 – 10.37), p = 0.03; I2 = 82% (p = 0.004)] in COVID-19 patients. Our analysis showed four evidence-based recommendations on the prognostic value of PhA with two strong recommendations, one of moderate and another of low-moderate quality, for predicting mortality and complications, respectively. We recommend using PhA as a prognostic marker for mortality and complications in this population. Although the results are promising, future studies must identify the PhA cut-off to guide therapeutic decisions more precisely.Funding for open access publishing: Universidad Málaga/CBUA. I.C.-P. was the recipient of a postdoctoral grant (Río Hortega CM 17/00169) and is now the recipient of a postdoctoral grant (Juan Rodes JR 19/00054) from the Instituto de Salud Carlos III and co-funded by Fondo Europeo de Desarrollo Regional-FEDER. Funding for open access charge: Universidad de Málaga / CBU

Effect of Moderate Consumption of Different Phenolic-Content Beers on the Human Gut Microbiota Composition: A Randomized Crossover Trial

The moderate consumption of beer has been associated with positive effects on health, and these benefits are driven, in part, by the antioxidant properties of phenolic compounds found in this beverage. However, the potential impact of beer polyphenols on the human gut microbiome and their consequences are yet to be elucidated. In this study, our aim was to evaluate the effect of three different phenolic-content beers on the gut microbiome and the potential role of the induced shifts in the antioxidant capacity of beer polyphenols. In total, 20 subjects (10 healthy volunteers and 10 individuals with metabolic syndrome) were randomly assigned in a crossover design to consume each of the different beers (alcohol-free, lager or dark beer) during a 2-week intervention. Significant changes in the relative abundance of Streptococcaceae and Streptococcus were found after beer consumption. An increased abundance of Streptococcaceae and Streptococcus was observed after the consumption of dark beer, with no detected differences between baseline and alcohol-free/lager beer intervention. Moreover, some of the detected differences appeared to be related to the metabolic status. Finally, a decrease in porphyrin metabolism and heme biosynthesis was found after the intervention, especially after the consumption of dark beer. These results show that the antioxidant capacity of beer polyphenols may induce positive shifts in gut microbiota composition, and some of the observed changes may also boost the antioxidant capacity of these compoundsM.Q.-M. was supported by a Manuel de Oya Research fellowship from Foro para la Investigación de la Cerveza y Estilos de Vida (FICYE). I.M.-I. and C.G.-R. were supported by the Miguel Servet Type I program and P.R.-L. by the Sara Borrell program both of the Carlos III Health Institute (co-founded by the European Regional Development Fund-ERDF-) (CP16/00163, CP20/00066 and CD19/00216, respectively). In addition, this study was supported by the “Network of Centers for Biomedical Research” (CIBER) of the Carlos III Health Institute (ISCIII) (CB06/03/0018), research grants from the ISCIII (PI18/01160, PI21/01677) and co-financed by the Regional Development Fund (ERDF). Partial funding for open access charge: Universidad de Málag

Switching from subcutaneous to oral semaglutidein type 2 diabetes: A prospective study

Funding for open access charge: Universidad de Málaga / CBU

Novel SFRP2 DNA Methylation Profile Following Neoadjuvant Therapy in Colorectal Cancer Patients with Different Grades of BMI

The relationship between body weight and different cancers is now well-recognized and among such cancers, colorectal cancer (CRC) is reported most frequently. Our group recently published findings, through an epigenome-wide association study, suggesting that body mass index (BMI) could act as a relevant risk factor in the CRC. In addition, aberrant SFRP2 methylation is one of the major mechanisms for Wnt signaling activation in CRC. Conversely, neoadjuvant chemo-radiotherapy appears to alter the rectal cancer epigenome. This study was aimed to evaluate the effect of obesity, measured by BMI, on the methylation of SFRP2 in tumor samples of patients with CRC. Non-treated CRC patients and CRC patients treated with pre-operative neoadjuvant therapy from 2011 to 2013 were included and classified by BMI 25.0 kg/m2. SFRP2 DNA methylation in tumor samples was measured by pyrosequencing. Our findings suggest a possible interaction between SFRP2 methylation levels and BMI in CRC tumor samples. The correlation of SFRP2 hypomethylation with an elevated BMI was stronger within the non-treated CRC patient group than within the treated CRC patient group. We have successfully demonstrated that the beneficial association of tumor SFRP2 hypomethylation is dependent on patient BMI in non-treated CRC, suggesting a possible tumor suppressor role for SFRP2 in overweight and obese patients. Additional studies of clinical pathologies would be necessary to strengthen these preliminary resultsThis study was supported by “Centros de Investigación En Red” (CIBER, CB06/03/0018) of the “Instituto de Salud Carlos III” (ISCIII) and a grant from ISCIII (PI8/01399) and it was co-financed by the European Regional Development Fund (FEDER). M.M.G. was the recipient of the Nicolas Monardes Program from the “Servicio Andaluz de Salud, Junta de Andalucía”, Spain (RC-0001-2018 and C-0029-2014). S.M. was the recipient of the Nicolas Monardes Program from the “Servicio Andaluz de Salud, Junta de Andalucía”, Spain (C-0050-2017). A.B.C. was funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII. A.C.-M. was recipient of an FPU grant from Education Ministry, Madrid, SpainS

Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients

The low-grade inflammation observed in obesity has been associated with a high-fat diet, though this relation is not fully understood. Bacterial endotoxin, produced by gut microbiota, may be the linking factor. However, this has not been confirmed in obese patients. To study the relationship between a high-fat diet and bacterial endotoxin, we analyzed postprandial endotoxemia in morbidly obese patients after a fat overload. The endotoxin levels were determined in serum and the chylomicron fraction at baseline and 3 h after a fat overload in 40 morbidly obese patients and their levels related with the degree of insulin resistance and postprandial hypertriglyceridemia. The morbidly obese patients with the highest postprandial hypertriglyceridemia showed a significant increase in lipopolysaccharide (LPS) levels in serum and the chylomicron fraction after the fat overload. Postprandial chylomicron LPS levels correlated positively with the difference between postprandial triglycerides and baseline triglycerides. There were no significant correlations between C-reactive protein (CRP) and LPS levels. The main variables contributing to serum LPS levels after fat overload were baseline and postprandial triglyceride levels but not glucose or insulin resistance. Additionally, superoxide dismutase activity decreased significantly after the fat overload. Postprandial LPS increase after a fat overload is related to postprandial hypertriglyceridemia but not to degree of insulin resistance in morbidly obese patients.This study was funded by the Fondo de Investigación Sanitaria “Centros de Investigación En Red” (CIBER, CB06/03/0018) of the “Instituto de Salud Carlos III”, FIS PS09/00997, FIS 08/1655 and CP07/00095 of the “Instituto de Salud Carlos III”, Madrid, Spain. SAS 08/325 and SAS 10/0696 Consejería de Salud, Junta de Andalucía. M.C.P. was a recipient of a FPU grant from Educa- tion Ministry, Madrid, Spain [AP2009-4537]

Adipogenic Impairment of Adipose Tissue-Derived Mesenchymal Stem Cells in Subjects With Metabolic Syndrome: Possible Protective Role of FGF2

Context: The decreased expansion capacity of adipose tissue plays a crucial role in the onset of disorders associated with metabolic syndrome. Objetive: The aim of this study was to examine the state of adipose tissue-derived mesenchymal stem cells (ASCs) from obese subjects with different metabolic profiles. Design: This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Setting: University Hospital Patients and Intervention: Patients who underwent either bariatric surgery (20 morbidly obese) or cholecystectomy (40 subjects) participated in the study. Main Outcome Measures: ASCs were obtained from both visceral and subcutaneous adipose tissue. Adipogenic, fibrotic genes expression was quantified by qPCR; Smad7 and fibroblast growth factor 2 (FGF2) were quantified by western blotting and ELISA respectively. The susceptibility of ASCs to apoptosis, their population doubling time and clonogenic potential were evaluated Results The worsening metabolic profile of the subjects was accompanied by a decrease in the intrinsic levels of adipogenic genes expression, reduced proliferation rate, clonogenic potential and exportation of FGF2 to the cell surface of the ASCs derived from both tissues. In addition, the ASCs from NonMS subjects showed differences in susceptibility to apoptosis and expression of TGFß signaling inhibitory protein Smad7 with respect to the ASCs from MS subjects. Conclusions/Interpretation Our results suggest that the decrease in adipogenic genes mRNA and clonogenic potential as well as the accumulation of fibrotic proteins with metabolic alterations could be a relevant mechanism controlling the number and size of neogenerated adipocytes and involved in adipose tissue expansion alteration.This work was cofunded by the European Union through the European Regional Development Fund and supported by grants from the Ministry of Economy and Competitiveness, ISCII (Grants PI13/02628, PI12/02355, FIS PI14/00696, and PI12/ 01373), and the Ministry of Economy and Knowledge (Grants PI-CTS-08181/2011, CTS-7895/2011, and CTS-656). R. E.-B. and M. B.-L. are supported by a fellowship from the ISCIII “MiguelServet II” (CP13/00041) and “Miguel Servet I”(CP15/ 00028)