Type 2 diabetes and renal damage are strictly linked. The progressive increase in T2D incidence has stimulated the interest in novel biomarkers to improve the diagnostic performance of the commonly utilized markers such as albuminuria and eGFR. Through microarray method, we analyzed the entire transcriptome expressed in 12 serum samples of diabetic patients, six without DKD and six with DKD; the downregulation of the most dysregulated transcripts was validated in a wider cohort of 69 patients by qPCRs. We identified a total of 33 downregulated transcripts. The downregulation of four mitochondrial messenger RNAs (MT-ATP6, MT-ATP8, MT-COX3, MT-ND1) and other two transcripts (seysnoy, skerdo) was validated in patients with eGFR stage G3 versus G2 and G1. The four messenger RNAs correlated with creatinine and eGFR stages, while seysnoy and skerdo were associated with white blood cell values. All transcripts correlated also with Blood Urea Nitrogen. The four mitochondrial messenger RNAs had a high diagnostic performance in G3 versus G2 discrimination, with AUC values above 0.8. The most performant transcript was MT-ATP6, with an AUC of 0.846; sensitivity = 90%, specificity = 76%, p-value = 7.8 × 10−5. This study led to the identification of a specific molecular signature of DKD, proposing the dosage of RNAs, especially mitochondrial RNAs, as noninvasive biomarkers of diabetes complication.
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.
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.
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