The classic description of diabetic kidney disease (DKD) involves progressive stages of glomerular hyperfiltration, microalbuminuria, proteinuria, and a decline in the estimated glomerular filtration rate (eGFR), leading to dialysis. In recent years, this concept has been increasingly challenged as evidence suggests that DKD presents more heterogeneously. Large studies have revealed that eGFR decline may also occur independently from the development of albuminuria. This concept led to the identification of a new DKD phenotype: non-albuminuric DKD (eGFR < 60 mL/min/1.73 m², absence of albuminuria), whose pathogenesis is still unknown. However, various hypotheses have been formulated, the most likely of which is the acute kidney injury-to-chronic kidney disease (CKD) transition, with prevalent tubular, rather than glomerular, damage (typically described in albuminuric DKD). Moreover, it is still debated which phenotype is associated with a higher cardiovascular risk, due to contrasting results available in the literature. Finally, much evidence has accumulated on the various classes of drugs with beneficial effects on DKD; however, there is a lack of studies analyzing the different effects of drugs on the various phenotypes of DKD. For this reason, there are still no specific guidelines for therapy in one phenotype rather than the other, generically referring to diabetic patients with CKD.

The controlling nutritional status (CONUT) score represents poor nutritional status and has been identified as an indicator of adverse outcomes. Our aim was to evaluate the prognostic role of the CONUT score on in-hospital outcomes in an Internal Medicine Department. This is a retrospective study analyzing data from 369 patients, divided into four groups based on the CONUT score: normal (0–1), mild–high (2–4), moderate–high (5–8), and marked high (9–12). In-hospital all-cause mortality increased from normal to marked high CONUT score group (2.2% vs. 3.6% vs. 13.4% vs. 15.3%, p < 0.009). Furthermore, a higher CONUT score was linked to a longer length of hospital stay (LOS) (9.48 ± 6.22 vs. 11.09 ± 7.11 vs. 12.45 ± 7.88 vs. 13.10 ± 8.12, p < 0.013) and an increased prevalence of sepsis. The excess risk of a high CONUT score relative to a low CONUT score remained significant after adjusting for confounders (all-cause mortality: OR: 3.3, 95% CI: 1.1–9.7, p < 0.02; sepsis: OR: 2.7, 95% CI: 1.5–4.9, p < 0.01; LOS: OR: 2.1, 95% CI: 1.2–3.9, p < 0.007). The present study demonstrated that an increased CONUT score is related to a higher risk of short-term in-hospital death and complications.

The increasing utilization of Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) in managing type 2 diabetes mellitus has raised interest regarding their impact on thyroid function. In fact, while these agents are well known for their efficacy in glycemic control and weight management, their association with thyroid disorders requires clarification due to the complex interplay between thyroid hormones and metabolic pathways. Thyroid dysfunction commonly co-occurs with metabolic conditions such as diabetes and obesity, suggesting a profound interconnection between these systems. This review aims to contribute to a deeper understanding of the interaction between GLP-1 RAs and thyroid dysfunction and to clarify the safety of GLP-1 RAs in diabetic patients with thyroid disorders. By synthesizing existing evidence, this review highlights that, despite various studies exploring this topic, current evidence is inconclusive, with conflicting results. It is important to note that these drugs are relatively recent, and longer-term studies with larger sample sizes are likely needed to draw clearer conclusions. Currently, no existing guidelines provide definitive directions on this clinical issue; however, it is advisable to include thyroid function tests in the routine screening of diabetic patients, particularly those treated with GLP-1 Ras, with the goal of optimizing patient care and management.

Familial hypercholesterolemia (FH) is a genetic condition characterized by high low-density lipoprotein cholesterol (LDL-C). The presence of risk modifiers could promote the atherosclerotic injury beyond LDL-C. Our aim was to evaluate metabolic and innate immunity profiles in FH subjects with or without subclinical atherosclerosis. In this cross-sectional observational study, we evaluated 211 genetically confirmed FH subjects on LDL-C target and without cardiovascular diseases. Biochemical analyses, LDL-C burden (LCB) calculation and vascular profile evaluation were obtained from all subjects. Study population was divided into two groups according to subclinical atherosclerosis: the subclinical atherosclerosis (SA) group and non-subclinical atherosclerosis (NSA) group. SA group had higher LDL-C at diagnosis (288.35 ± 24.52 vs 267.92 ± 23.86, p < 0.05) and LCB (13,465.84 ± 3617.46 vs 10,872.63 ± 3594.7, p < 0.001) than NSA group. SA group had higher white blood cell count (WBCC, 6.9 ± 1.66 vs 6.1 ± 1.16), neutrophil count (NC, 4.2 ± 1.3 vs 3.6 ± 1.11), monocyte count (MC, 0.8 ± 0.2 vs 0.4 ± 0.1), triglyceride to high-density lipoprotein ratio (TG/HDL, 1.73 ± 0.72 vs 1.45 ± 0.69), triglyceride-glucose index (TyG, 8.29 ± 0.35 vs 8.01 ± 0.33) than NSA group (p value for all < 0.01). Multivariate logistic regression analysis showed that LCB (p < 0.01), WBCC (p < 0.01), NC (p < 0.05), MC (p < 0.05) were associated with subclinical atherosclerosis. Simple linear regression analyses showed that LCB was associated with WBCC, NC, MC (p value for all < 0.01). An increased LCB and an impaired innate immunity profile were found in FH subjects with subclinical atherosclerosis and they were independently associated with atherosclerotic injury. LCB could modulate the innate immunity profile.

Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein-cholesterol (LDL-C) and increased cardiovascular risk. While the role of LDL-C in atherogenesis is well established, the contribution of inflammatory activation in FH, particularly in relation to genotype, remains poorly defined. We aimed to evaluate the impact of genotype on neutrophil-to-lymphocyte ratio (NLR) and on subclinical atherosclerosis in a cohort of FH subjects. Methods: We conducted a cross-sectional study on 423 FH subjects not on lipid-lowering therapy and free from atherosclerotic cardiovascular disease. Biochemical, genetic, and vascular assessments were performed in all participants. The population was divided into 2 groups based on genotype: low-density lipoprotein receptor (LDLR; n = 273) and non-LDLR (NLDLR, n = 150). Vascular profile was assessed by coronary artery calcium score and carotid/femoral plaque presence. NLR was calculated from peripheral blood counts. Results: The LDLR group exhibited an higher NLR (2.27 ± 0.86 vs 2.05 ± 0.68, P < .05) than the NLDLR group. LDL-C levels and LDLR genotype were significantly associated with NLR (both P < .05). Multiterritorial plaque involvement was more frequent in the LDLR group than the NLDLR group (P for trend <.05). Age (P < .001), LDL-C (P < .001), smoking status (P < .05), and NLR (P < .05) were independently associated with subclinical atherosclerosis. Conclusion: FH subjects with LDLR mutations had a higher NLR and a more severe atherosclerosis distribution. Our findings support the role of NLR as a noninvasive biomarker of early immune activation and highlights the importance of lipoinflammatory status evaluation in FH subjects.

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.