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Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs. non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D. [ABSTRACT FROM AUTHOR]

The increased mortality reported with intensive glycaemic control has been attributed to an increased risk of treatment-related hypoglycaemia. This study investigated the relationships of haemoglobin (Hb) A1c, anti-hyperglycaemic treatment, and potential risks of adverse effects with all-cause mortality in patients with type 2 diabetes. Patients (n = 15,773) were stratified into four categories according to baseline HbA1c and then assigned to three target categories, based on whether HbA1c was ≤0.5% below or above (on-target), >0.5% below (below-target) or >0.5% above (above-target) their HbA1c goal, personalized according to the number of potential risks among age > 70 years, diabetes duration > 10 years, advanced complication(s), and severe comorbidity (ies). The vital status was retrieved for 15,656 patients (99.26%). Over a 7.4-year follow-up, mortality risk was increased among patients in the highest HbA1c category (≥8.5%) (adjusted hazard ratio, 1.34 (95% confidence interval, 1.22–1.47), p < 0.001) and those above-target (1.42 (1.29–1.57), p < 0.001). Risk was increased among individuals in the lowest HbA1c category (<6.5%) and those below-target only if treated with agents causing hypoglycaemia (1.16 (1.03–1.29), p = 0.01 and 1.10 (1.01–1.22), p = 0.04, respectively). These data suggest the importance of setting both upper and lower personalized HbA1c goals to avoid overtreatment in high-risk individuals with type 2 diabetes treated with agents causing hypoglycaemia. [ABSTRACT FROM AUTHOR]