Una nuova sfida per linagliptin: diabete, trapianto d'organo e insufficienza renale cronica nel medesimo paziente

The association between liver cirrhosis and type 2 diabetes mellitus (DMT2) has been known for many years. It is estimated that changes in glucose metabolism are present in at least two thirds of cirrhosis patients. Diabetes can be both a consequence of liver disease and a pre-existing condition. In the first case, liver transplantation would be the solution but post-transplant diabetes remains a common condition. For patients with liver cirrhosis the therapeutic approach for the treatment of DMT2 is extremely limited and the studies available on this type of population are very few. The pharmacokinetic characteristics of linagliptin are well suited for patients with DMT2 and chronic liver disease; in fact, no dose adjustment is required in patients regardless of the degree of hepatic impairment. With regard to the treatment of diabetes in post-transplantation, data on the efficacy and safety of oral hypoglycemic drugs are scarce; however, the available studies suggest that dipeptidyl peptidase 4 (DPP4i) inhibitors are safe and effective in these patients. In describing this clinical case, we discuss how the use of a DPP4i, and in particular of linagliptin, may represent a valid therapeutic strategy in the management of diabetic, cirrhotic patients who undergo liver transplantation (Diabetology)

SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes and may also improve glucose control in type 1 diabetes. In 2015, regulatory agencies warned that SGLT2i may favour diabetic ketoacidosis (DKA). We provide a detailed analysis of DKA reports in which an SGLT2i was listed among suspect or concomitant drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS)

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9-related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

Subclinical Hypothyroidism and Metabolic Syndrome: A Common Association by Chance or a Cardiovascular Risk Driver?

The metabolic syndrome (MS) and subclinical hypothyroidism (SCH) are highly prevalent in the general population. Cross-sectional epidemiological data suggest that a mutual association exists between the two, although the cause-effect relationship remains poorly elucidated. As SCH raises cholesterol, blood pressure, and visceral fat, it is easy to understand why it associates with MS. Rather, the reasons whereby MS patients are at higher risk for SCH are less apparent. Some studies have reported that SCH is itself characterized by high cardiovascular risk. Therefore, the coexistence of SCH and MS may identify subjects at a particularly high risk for future cardiovascular events. Recent data published in Metabolic Syndrome and Related Disorders indicate that carotid intima-media thickness, a marker of initial atherosclerosis and a possible predictor of future events, is higher in patients with both SCH and MS than in the presence of each condition alone. In this Editorial, we discuss the clinical implications of SCH and MS association and the interpretation of such recent findings

Effects of exenatide long-acting release on cardiovascular events and mortality in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Patients with type 2 diabetes (T2D) have an increased risk of cardiovascular disease. Recent cardiovascular outcome trials (CVOTs) with liraglutide, semaglutide, and albiglutide have shown significant reduction in major adverse cardiovascular events. Conversely, the CVOT with exenatide long-acting release (ELAR) confirmed cardiovascular safety of the drug, but did not reached superiority versus placebo. Herein, we systematically evaluated the effect of ELAR versus placebo or active comparators on cardiovascular events and mortality in patients with T2D

Euglycemic Ketoacidosis

Purpose of Review Diabetic ketoacidosis is a life-threatening complication of diabetes characterized by hyperglycemia, acidosis, and ketosis. Ketoacidosis may occur with blood glucose level < 200 mg/dl (improperly defined as euglycemic ketoacidosis, euKA) and also in people without diabetes. The absence of marked hyperglycemia can delay diagnosis and treatment, resulting in potential serious adverse outcomes. Recent Findings Recently, with the wide clinical use of sodium glucose co-transporter 2 inhibitors (SGLT2i), euKA has come back into the spotlight. Use of SGLT2i use can predispose to the development of ketoacidosis with relatively low or normal levels of blood glucose. This condition, however, can occur, in the absence of diabetes, in settings such as pregnancy, restriction on caloric intake, glycogen storage diseases or defective gluconeogenesis (alcohol abuse or chronic liver disease), and cocaine abuse. euKA is a challenging diagnosis for most physicians who may be misled by the presence of normal glycemia or mild hyperglycemia. In this article, we review pathophysiology, etiologies, clinical presentation and the management of euKA

Angiogenic Abnormalities in Diabetes Mellitus: Mechanistic and Clinical Aspects

Diabetes causes severe pathological changes to the microvasculature in many organs and tissues and is at the same time associated with an increased risk of coronary and peripheral macrovascular events. We herein review alterations in angiogenesis observed in human and experimental diabetes and how they contribute to diabetes onset and development of vascular complications

Synergistic Interactions Among Metabolic Syndrome Components and Homeostasis Model Assessment of Insulin Resistance in a Middle-Aged General Population over Time.

Background: Insulin resistance is considered a hallmark feature of the metabolic syndrome, but how metabolic syndrome components and insulin resistance measures interact over time is unclear. The homeostasis model assessment of insulin resistance (HOMA-IR) is a static index of insulin resistance typically used in epidemiological studies. We explored how HOMA-IR is affected by clustering metabolic syndrome components over time in a population of middle-aged, healthy subjects. Methods: A total of 1757 subjects aged 41.3 +/- 7.5 years (39% males) free from diabetes at baseline were followed-up for a median of 5.7 years. At baseline and at the end of observation, we determined metabolic syndrome components and HOMA-IR. Results: Cross-sectionally, HOMA-IR was synergistically increased by clustering of at least two to three metabolic syndrome components as determined at baseline and at study end by departure from additivity. Some combinations of metabolic syndrome components were associated with a significant synergic increase in HOMA-IR, and some combinations of two components entailed a synergistic risk of developing metabolic syndrome. Over time, the average change in HOMA-IR was more than additively affected by change in the number of metabolic syndrome components. Baseline HOMA-IR values were predictive of incident metabolic syndrome independent from age, sex, and each metabolic syndrome component. Conclusions: We show synergistic interaction between clustering metabolic syndrome components and insulin resistance, estimated by HOMA-IR, cross-sectionally and over time. This more than additive effect explains the incremental value of HOMA-IR in predicting metabolic risk