Search

Abstract Background A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes. Methods The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006–2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%). Results With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min− 1·1.73 m− 2. The median difference was 4.10 ml·min− 1·1.73 m− 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations. Conclusion Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR

Obesity is a heterogeneous condition which results from complex interactions among sex/gender, sociocultural, environmental, and biological factors. Obesity is more prevalent in women in most developed countries, and several clinical and psychological obesity complications show sex-specific patterns. Females differ regarding fat distribution, with males tending to store more visceral fat, which is highly correlated to increased cardiovascular risk. Although women are more likely to be diagnosed with obesity and appear more motivated to lose weight, as confirmed by their greater representation in clinical trials, males show better outcomes in terms of body weight and intra-abdominal fat loss and improvements in the metabolic risk profile. However, only a few relatively recent studies have investigated gender differences in obesity, and sex/gender is rarely considered in the assessment and management of the disease. This review summarizes the evidence of gender differences in obesity prevalence, contributing factors, clinical complications, and psychological challenges. In addition, we explored gender differences in response to obesity treatments in the specific context of new anti-obesity drugs.

BackgroundDietary fat consumption, involved in the pathogenesis of insulin resistance and impaired glucose metabolism, is linked with decline in cognitive functions, dementia, and development of Parkinson’s disease and Alzheimer’s disease. Mature IL-1β, requiring the activation of the P2X7 receptor (P2X7R)-inflammasome complex, is an important mediator of neuroinflammation. The aim of the study was to test whether P2X7R activation might interfere with systemic and cerebral metabolic homeostasis.MethodsWe treated WT and P2X7R KO mice with a high-fat diet (HFD) for 16 weeks, evaluating the effects on the Substantia Nigra and Hippocampus, target areas of damage in several forms of cognitive impairment.ResultsHFD-treated WT and P2X7R KO mice showed a different brain mRNA profile of Insulin and Igf-1, with these genes and relative receptors, more expressed in KO mice. Unlike P2X7R KO mice, WT mice treated with HFD displayed a diameter reduction in dopaminergic neurons in the Substantia Nigra, accompanied by an increased IBA1 expression in this area; they also showed poor performances during Y-Maze and Morris Water Maze, tasks involving Hippocampus activity. Conversely, Parkin, whose reduction might promote neuronal cell death, was increased in the brain of P2X7R KO animals.ConclusionWe report for the first time that HFD induces damage in dopaminergic neurons of the Substantia Nigra and a Hippocampus-related worse cognitive performance, both attenuated in the absence of P2X7R. The involved mechanisms might differ in the two brain areas, with a predominant role of inflammation in the Substantia Nigra and a metabolic derangement in the Hippocampus.

Abstract Background An “obesity paradox” for mortality has been shown in chronic disorders such as diabetes, and attributed to methodological bias, including the use of body mass index (BMI) for obesity definition. This analysis investigated the independent association of BMI versus surrogate measures of central adiposity with all-cause mortality in individuals with type 2 diabetes. Methods The Renal Insufficiency And Cardiovascular Events Italian Multicentre Study is a prospective cohort study that enrolled 15,773 patients in 19 Italian centres in 2006–2008. Exposures were BMI and the surrogate measures of central adiposity waist circumference (WC), waist-to-height ratio (WHtR), and A Body Shape Index (ABSI). Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%), Results Age- and sex-adjusted hazard ratios and 95% confidence intervals were significantly higher in BMI-based underweight (1.729 [1.193–2.505), P = 0.004), moderately obese (1.214 [1.058–1.392), P = 0.006) and severely obese (1.703 [1.402–2.068), P

Abstract Background The prognostic value of common and frequently associated diabetic microvascular complications (MVC), namely chronic kidney disease (CKD), cardiac autonomic neuropathy (CAN), peripheral neuropathy (DPN), and retinopathy (DR), is well established. However, the impact of their different combinations on long-term mortality has not been adequately assessed. Methods We retrospectively analyzed 21-year longitudinal data from 303 patients with long-standing type 1 (T1D) or type 2 diabetes (T2D), who were thoroughly characterized at baseline for the presence of MVC using 99mTc-DTPA dynamic renal scintigraphy, overnight urine collection, cardiovascular autonomic tests, monofilament testing, and dilated fundus oculi examination. Results After a 5,244 person-years follow-up, a total of 133 (43.9%) deaths occurred. The presence of CKD and CAN, regardless of other MVC, increased the adjusted all-cause mortality risk by 117% (HR 2.17 [1.45–3.26]) and 54% (HR 1.54 [1.01–2.36]), respectively. Concomitant CKD&CAN at baseline were associated with the highest mortality risk (HR 5.08 [2.52–10.26]), followed by CKD&DR (HR 2.95 [1.63–5.32]), and CAN&DR (HR 2.07 [1.11–3.85]). Compared with patients free from MVC, the mortality risk was only numerically higher in those with any isolated MVC (HR 1.52 [0.87–2.67]), while increased by 203% (HR 3.03 [1.62–5.68]) and 692% (HR 7.92 [2.93–21.37]) in patients with two and three concomitant MVC, respectively. Conclusions Our study demonstrates the long-term, synergistic, negative effects of single and concomitant diabetic MVC on all-cause mortality, which should encourage comprehensive screenings for MCV in both T1D and T2D to improve risk stratification and treatment.

Abstract Background Phthalates exposure and complete edentulism are related to both low socioeconomic status. No study by far has verified if and to what extent these two conditions are related. We aimed to explore their potential association and interplay in the metabolic control and cardiovascular risk profile. Methods In our small (n = 48) prospective pilot study twenty-four patients with type 2 diabetes (DnE) and twenty-four patients with type 2 diabetes and edentulism (DE) followed for 19 ± 2 months were treated according to best clinical standards. Phthalates’ exposure was evaluated by urinary concentration of di-2-ethylhexylphthalate (DEHP), metabolites, i.e. mono 2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono 2-ethyl-5-hydroxyhexyl phthalate (MEHHP). Results No association between phthalates and edentulism was found, nor did edentulism affect glucose control. Higher phthalates exposure was associated with a glycated haemoglobin worsening. This association was found for all the measured phthalates metabolites, both as a whole (DEHP; r = 0.33, p = 0.0209) and individually: MEHP (r = 0.41, p = 0.0033), MEHHP (r = 0.32, p = 0.028), MEOHP (r = 0.28, p = 0.0386). Conclusions Phthalates are not associated with edentulism but predict the worsening of glucose control in subjects with type 2 diabetes. These findings might prove relevant in identifying novel biomarkers of cardiometabolic risk. Further studies are needed to validate our results and estimate the true potential of phthalates in terms of risk assessment.

Context Lower urinary tract symptoms (LUTS) are common in type 2 diabetes (T2D), affecting quality of life and potentially leading to medication discontinuation. Among various factors contributing to LUTS, recent observations suggest a critical role of the urinary microbiota. Research on urinary dysbiosis in T2D remains underexplored. Objective We conducted a pilot study to investigate differences in the urinary microbiota between patients with T2D and healthy individuals and its potential indirect association with LUTS risk. Methods This case–control study included 50 patients with T2D and no LUTS, and 25 healthy controls. Microbial DNAs were extracted from urinary sediments and bacterial populations quantified by real-time quantitative polymerase chain reaction (PCR) and qualitatively investigated by 16S rRNA gene sequencing. Validation experiments with digital PCR were also performed. Results In patients with T2D a higher total bacterial load and an increased abundance of Bacillota were found. After stratification by gender, these results were observed only in women. However, no significant quantitative differences were observed at the genus level. Alpha diversity analysis showed no significant differences between T2D and control groups, or by gender. At the species level, a substantial qualitative and often gender-dependent shift was present in individuals with T2D. Conclusion The urinary microbiome of subjects with T2D was found to be different from that of healthy controls. Specifically, patients with T2D displayed higher total bacterial load and Bacillota levels, as well as qualitative changes in bacterial species. These changes suggested a dysbiotic condition of the urinary microbiota of subjects with T2D, with some gender-related differences. Although causality cannot be inferred, these findings highlight the impact of T2D on the urinary microbiota and its potential relevance in developing LUTS and, from a broader perspective, metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Francesco Raggi,1 Chiara Rossi,1 Francesco Faita,2 Mariarosaria Distaso,1 Claudia Kusmic,2 Anna Solini1 1Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy; 2Institute of Clinical Physiology, Italian National Research Council, Pisa, ItalyCorrespondence: Anna Solini; Francesco Raggi, Department of Surgical Medical Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, Pisa, I-56126, Italy, Tel +39-50-993482 ; +39-50-992861, Fax +39-50-553235, Email anna.solini@med.unipi.it; francesco.raggi@unipi.itPurpose: Low-grade inflammation contributes to heart failure in obesity or type 2 diabetes mellitus. The P2X7 receptor (P2X7R) is a key regulator of several pro-inflammatory responses in multiple tissues and organs; however, its involvement in the onset of heart dysfunction remains unclear. The study evaluated the role of P2X7R as a cardiac function regulator in C57BL/6J wild-type (WT) and P2X7R knockout (KO) mice by inducing systemic inflammation with high fat diet (HFD).Methods: Specific parameters of systolic and diastolic function and heart morphology were measured in vivo before animal sacrifice by high-frequency ultrasonographic analysis. Gene and protein expression of cardiac biomarkers associated with inflammatory-oxidative pathways were evaluated by real-time PCR and Western Blotting.Results: P2X7R-mediated up-regulation of the NLRP3-caspase-1 complex, increased expression of key oxidative stress (NOS-2, TNFα), and chemotactic (MCP-1) mediators were revealed in WT-HFD animals. In KO-HFD mice, such inflammatory-oxidative pathway was silent. Nevertheless, HFD induced in vivo a clear alteration of diastolic pattern (E/A: p < 0.03 vs WT-HFD) and a cardiac morphologic remodelling (left ventricular mass: p < 0.05 vs WT-HFD) only in P2X7R KO animals. Surprisingly, the transcriptional and protein expression of IL-1β and IL-6, usually regulated through P2X7R activation, were significantly higher in KO-HFD than in WT-HFD mice (both p < 0.05). Furthermore, an up-regulation of miR-214 and a down-regulation of miR-126 in heart of HFD-KO mice were observed, suggesting a link between such epigenetic dysregulation and cytokine overexpression as a potential pathophysiologic mechanism concurring to the progressive cardiac dysfunction.Conclusion: These findings seem to suggest a cardioprotective role of P2X7R toward this tissue-specific inflammatory damage, likely through tissue homeostasis and organ functionality preservation.Keywords: low-grade inflammation, high fat diet, diastolic dysfunction, P2X7 receptor

Sodium glucose cotransporter 2 inhibitors have proven strong efficacy in reducing end-stage renal disease in patients with type 2 diabetes. We are presenting here the case of a 40-year-old woman with acquired partial lipodystrophy, type 2 diabetes and essential hypertension complicated by chronic kidney disease and proteinuria in the nephrotic range. She first came to our attention in 2012; estimated glomerular filtration rate (eGFR) was 41.5 ml/min/1.73 m2 and total proteinuria was 375 mg/24h; she was treated with dual renin angiotensin system blocking. Proteinuria significantly increased during the following years, reaching a nephrotic range (>5 g/day). A kidney biopsy revealed a tubule-interstitial involvement compatible with type 2 diabetes. Leptin replacement therapy, started in 2018, improved glycaemic control and lipid profile, also determining a reduction in insulin total daily dose. In 2019, after the publication of the CREDENCE study, canagliflozin was started on top of losartan and ramipril. After an initial, expected eGFR drop, kidney function stabilized, and albuminuria significantly reduced (from 4120 to 984 mg/24h), while serum potassium showed only minimal increase. At last follow-up (2022) total proteinuria was still reducing (510 mg/24h), while kidney function was substantially unchanged (eGFR 40 ml/min/1.73 m2). This case report suggests that, despite not recommended in international guidelines, the use of SGLT2i in combination with dual renin angiotensin system blockade should be considered in specific conditions and under close clinical monitoring.

In this new study the Authors demonstrated that the IGFBP3/TMEM219 pathway is a physiological regulator of pancreatic beta cell homeostasis and it is dysregulated in diabetes. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.