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ObjectiveCystic fibrosis (CF)-related diabetes (CFRD) resulting from partial-to-complete insulin deficiency occurs in 40-50% of adults with CF. In people with CFRD, poor glycemic control leads to a catabolic state that may aggravate CF-induced nutritional impairment and loss of muscle mass. Sensor augmented pump (SAP) therapy may improve glycemic control as compared to multiple daily injection (MDI) therapy.Research design and methodsThis non-randomized clinical trial was aimed at evaluating the effects of insulin therapy optimization with SAP therapy, combined with a structured educational program, on glycemic control and body composition in individuals with insulin-requiring CFRD. Of 46 participants who were offered to switch from MDI to SAP therapy, 20 accepted and 26 continued the MDI therapy. Baseline demographic and clinical characteristics were balanced between groups using a propensity score-based overlap weighting procedure and weighted mixed-effects regression models were used to estimate changes in study outcomes.ResultsAfter 24 months changes in HbA1c were: -1.1% (-12.1 mmol/mol) (95% CI: -1.5; -0.8) and -0.1% (-1 mmol/mol) (95% CI: -0.5; 0.3) in the SAP and MDI therapy group, respectively, with a between-group difference of -1.0 (-10 mmol/mol) (-1.5; -0.5). SAP therapy was also associated with a decrease in mean glucose (between group difference: -32 mg/dL; 95% CI: -44; -20) and an increase in TIR (between group difference: 19.3%; 95% CI 13.9; 24.7) and in fat-free mass (between group difference: +5.5 Kg, 95% CI: 3.2; 7.8).ConclusionTherapy optimization with SAP led to a significant improvement in glycemic control, which was associated with an increase in fat-free mass.

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 < 30 ml·min - 1 ·1.73 m - 2 , but virtually no impact on mortality prediction., Trial Registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008., (© 2024. The Author(s).)

This study aimed to investigate the prevalence and determinants of glucose metabolism abnormalities and their impact on long-term clinical outcomes in kidney transplant recipients (KTxps). A retrospective analysis of 832 KTxps (2004-2020) was performed. Patients were assessed at 1 (T1), 6 (T6), and 12 (T12) months post-transplantation and clinically followed for an average of 103 ± 60 months. At T6, 484 patients underwent an oral glucose tolerance test for the diagnosis of alterations in glucose metabolism (AMG+) or post-transplant diabetes mellitus (PTDM+). The prevalence of pre-transplant diabetes was 6.2%, with 22.4% of PTDM+ within the 1st year. Patients with AMG were older and exhibited altered lipid profiles, higher body mass index, and increased inflammatory indices. Age at transplantation, lipid profile, and inflammatory status were significant determinants of PTDM. Graft loss was unaffected by glucose metabolism alterations. Survival analysis demonstrated significantly worse long-term survival for KTxps with diabetes (pre- and PTDM+, p = 0.04). In a comparison of the ND and PTDM+ groups, no significant differences in death with a functioning graft were found. The AMG+ group exhibited worse survival ( p < 0.001) than AMG-, even after excluding patients with diabetes mellitus. Future randomized controlled trials are necessary to delve deeper into this subject, specifically examining the effects of new antidiabetic treatments.

The incidence of acute pancreatitis (AP) in liver transplanted people is reported to be 1.5-8%. On the other hand, the evidence for a causal relationship between glucagon-like peptide 1 receptor agonists (GLP1RAs) and pancreatitis in people with type 2 diabetes is still weak. In addition, there are currently no data on a possible increased risk of AP in liver-transplanted individuals with diabetes treated with GLP1RAs. In a population of liver-transplanted individuals with diabetes receiving GLP1RA-based therapy, we reported an incidence of AP of 3.0% (two subjects). No cases were reported in liver-transplanted individuals with diabetes receiving SGLT2 inhibitors, insulin or metformin, neither in kidney or lung-transplanted patients treated with GLP1RAs. In both patients with AP, the only additional risk factor for its development was a history of re-transplantation (liver or combined kidney/liver). For this reason, we suggest particular caution when considering GLP1RAs-based therapies in liver transplanted patients with multiple risk factors for AP, such as a history of repeated and complex abdominal surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Grancini, Cogliati, Gaglio, Resi and Orsi.)

Introduction: One of the most common complications of cirrhosis is diabetes, which prevalence is strictly related to severity of hepatopathy. Actually, there are no data on the persistence of post-transplant glucose abnormalities and on a potential impact of diabetes on development of fibrosis in the transplanted liver. To this aim, we evaluated liver fibrosis in cirrhotic subjects before and after being transplanted., Methods: The study included 111 individuals who had liver transplantation. The assessment was performed before and two years after surgery to investigate a potential impact of the persistence of diabetes on developing de novo fibrosis in the transplanted liver. The degree of fibrosis was assessed using the Fibrosis Index Based on 4 Factors (FIB-4) and the Aspartate to Platelet Ratio Index (APRI)., Results: At pre-transplant evaluation, 63 out of 111 (56.8%) subjects were diabetic. Diabetic subjects had higher FIB-4 (Geometric mean, 95% confidence interval: 9.74, 8.32-11.41 vs 5.93, 4.71-7.46, P <0.001) and APRI (2.04, 1.69-2.47 vs 1.18, 0.90-1.55, P <0.001) compared to non-diabetic subjects. Two years after transplantation, 39 out of 111 (35.1%) subjects remained with diabetes and continued to show significantly higher FIB-4 (3.14, 2.57-3.82 vs 1.87, 1.55-2.27, P <0.001) and APRI (0.52, 0.39-0.69 vs 0.26, 0.21-0.32, P <0.001) compared to subjects without diabetes., Discussion: Thus, persistence of diabetes after surgery is a possible risk factor for an evolution to fibrosis in the transplanted liver, potentially leading to worsened long-term outcomes in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Grancini, Cogliati, Alicandro, Gaglio, Gatti, Donato, Orsi and Resi.)

In recent years, GLP-1 receptor agonists (GLP-1RA), and SGLT-2 inhibitors (SGLT-2i) have become available, which have become valuable additions to therapy for type 2 diabetes as they are associated with low risk for hypoglycemia and cardiovascular benefits. Indeed, SGLT-2i have emerged as a promising class of agents to treat heart failure (HF). By inhibiting SGLT-2, these agents lead to excretion of glucose in urine with subsequent lowering of plasma glucose, although it is becoming clear that the observed benefits in HF cannot be explained by glucose-lowering alone. In fact, multiple mechanisms have been proposed to explain the cardiovascular and renal benefits of SGLT-2i, including hemodynamic, anti-inflammatory, anti-fibrotic, antioxidant, and metabolic effects. Herein, we review the available evidence on the pathophysiology of the cardiological benefits of SGLT-2i. In diabetic heart disease, in both clinical and animal models, the effect of SGLT-2i have been shown to improve diastolic function, which is even more evident in HF with preserved ejection fraction. The probable pathogenic mechanisms likely involve damage from free radicals, apoptosis, and inflammation, and therefore fibrosis, many of which have been shown to be improved by SGLT-2i. While the effects on systolic function in models of diabetic heart disease and HF with preserved ejection fraction is limited and contrasting, it is a key element in patients with HF and reduced ejection fraction both with and without diabetes. The significant improvement in systolic function appears to lead to subsequent structural remodeling of the heart with a reduction in left ventricle volume and a consequent reduction in pulmonary pressure. While the effects on cardiac metabolism and inflammation appear to be consolidated, greater efforts are still warranted to further define the entity to which these mechanisms contribute to the cardiovascular benefits of SGLT-2i., (© 2023. The Author(s).)

We report the case of a 3-year-old girl admitted to her town emergency department for fever (39°C) associated with diarrhea, generalized edema, oliguria, and drowsiness. The blood test revealed metabolic acidosis, leucocytosis, increased inflammatory markers, anemia, thrombocytopenia, and acute kidney failure. Based on the diagnosis of hemolytic-uremic syndrome, the patient was referred to a third-level children hospital. Assisted ventilation, hemodialysis, and parenteral nutrition were instituted. The blood glucose levels increased above 200 mg/dl with peaks at 500 mg/dl. Islet auto-antibodies were negative and C-peptide was undetectable, thus ruling out the diagnosis of type 1 diabetes. Multiple-daily-injection insulin therapy was then instituted with the following regimen: Detemir 2 U once daily and Aspart 0.5 U if blood glucose >200 mg/dl. Despite the very low insulin dosage, the patient experienced frequent and severe hypoglycemic events during the following 24 h and was therefore switched to sensor-augmented pump therapy. Optimal glucose control was achieved without further hypoglycemic episodes. Moreover, thanks to the possibility to customize insulin therapy hour by hour during the day and the use of a pre-low glucose suspend system, glucose control was maintained even despite the continuous modifications in the nutritional scheme due to the multiple complications that arose during hospitalization. This rare case of post-hemolytic-uremic syndrome diabetes, treated with sensor-augmented therapy from its outbreak, suggests for the first time the potential of this therapeutic strategy in achieving glucose control without significant hypoglycemic episodes in children with secondary forms of diabetes associated with very low insulin requirement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grancini, Vianello, Colosimo, Gaglio, Resi, Arosio, Ardissino, Montini and Orsi.)

Objective: The Williams-Beuren syndrome (WS) is associated with impaired glucose metabolism (IGM) early in adulthood. However, the pathophysiology of IGM remains poorly defined, due to the lack of longitudinal studies investigating the contribution of β-cell dysfunction and impaired insulin sensitivity. This study aimed at assessing incidence of IGM and the underlying mechanisms in WS adults., Methods: This observational, longitudinal (5-year), cohort study enrolled thirty-one consecutive WS subjects attending a tertiary referral center. An oral glucose tolerance test (OGTT) was performed yearly and used to classify patients as normal or IGM, including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and diabetes mellitus (DM), and to calculate surrogate measures of insulin secretion and/or sensitivity., Results: IGM patients were 18 (58.1%, three DM) at baseline and 19 (61.3%, five DM) at end-of-follow-up. However, 13 individuals changed category of glucose homeostasis in both directions during follow-up (8 progressors, 5 regressors) and 18 did not (8 non-progressors, 10 non-regressors). New cases of IGM and DM were 11.1 and 2.53 per 100 persons-year, respectively, and were treated non-pharmacologically. In the whole cohort and, to a higher extent, in progressors, indices of early-phase insulin secretion and insulin sensitivity decreased significantly from baseline to end-of-follow-up, with concurrent reduction of the oral disposition index and insulin secretion-sensitivity index-2 (ISSI-2), compensating insulin secretion for the level of insulin resistance. No baseline measure independently predicted progression, which correlated with change from baseline in ISSI-2. Compared with patients with normal glucose homeostasis, IGT subjects had impaired insulin sensitivity, whereas insulin secretion was reduced only in those with IFG+IGT or DM., Conclusions: IGM incidence is high in young adults with WS, suggesting the need of early screening and timed intervention. As in classical type 2 diabetes, impaired insulin sensitivity and β-cell dysfunction contribute, in this sequence, to progression to IGM and DM.

Background: Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib., Methods: The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively., Results: The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatinib- and dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib)., Conclusions: Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.