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Aim: Evaluate the expression of exomiRs-126, -146, and -155 in urinary exosomes of patients with T2DM and diabetic kidney disease to establish a predictive classification model with exomiRs and clinical variables in order to determine their contribution to DKD., Methods: The study group included 92 subjects: 64 patients diagnosed with T2DM subclassified into two groups with albuminuria (T2DM with albuminuria, n = 30) and without albuminuria (TD2M, n = 34) as well as 28 healthy, non-diabetic participants. Exosomes were isolated from urine and identified by TEM and flow cytometry. Profile expression of exomiRs-126, -146 and -155 was evaluated by RT-qPCR. Data were analysed by permutational multivariate analysis of variance (PERMANOVA), similarity percentage (SIMPER), principal coordinate analysis (PCO), and canonical analysis of principal coordinates (CAP)., Results: T2DM patients with and without albuminuria showed higher levels of miR-155 and miR-146 compared with controls. In addition, T2DM patients with albuminuria presented a significant increase in miR-126 contrasted to controls and patients without albuminuria. PCO analysis explained 34.6% of the total variability of the data (PERMANOVA; p < .0001). Subsequently, SIMPER analysis showed that miR-146, miR-155, and miR-126 together, with some clinical parameters, contributed to 50% of the between-group significance. Finally, the CAP analysis developed showed a correct classification of 89.01% with the analysed parameters., Conclusion: A platform using a combination of clinical variables and exomiRs could be used to classify individuals with T2D as risk for developing DKD., (© 2022 Asian Pacific Society of Nephrology.)

Metabolomics is a potential tool for the discovery of new biomarkers in the early diagnosis of diseases. An ultra-fast gas chromatography system equipped to an electronic nose detector (FGC eNose) was used to identify the metabolomic profile of Volatile Organic Compounds (VOCs) in type 2 diabetes (T2D) urine from Mexican population. A cross-sectional, comparative, and clinical study with translational approach was performed. We recruited twenty T2D patients and twenty-one healthy subjects. Urine samples were taken and analyzed by FGC eNose. Eighty-eight compounds were identified through Kovats's indexes. A natural variation of 30% between the metabolites, expressed by study groups, was observed in Principal Component 1 and 2 with a significant difference (p < 0.001). The model, performed through a Canonical Analysis of Principal coordinated (CAP), allowed a correct classification of 84.6% between healthy and T2D patients, with a 15.4% error. The metabolites 2-propenal, 2-propanol, butane- 2,3-dione and 2-methylpropanal, were increased in patients with T2D, and they were strongly correlated with discrimination between clinically healthy people and T2D patients. This study identified metabolites in urine through FGC eNose that can be used as biomarkers in the identification of T2D patients. However, more studies are needed for its implementation in clinical practice., (© 2020 John Wiley & Sons, Ltd.)

Background: Individuals with type 2 diabetes (T2D) are at greater risk of bone fractures than those without diabetes. Certain oral diabetic medications may further increase the risk of fracture. Dipeptidyl peptidase-IV (DPP-IV) inhibitors are incretin-based therapies that are being increasingly used for the management of T2D. It has been hypothesized that these agents may reduce fracture risk in those with T2D. In this study, we used a mouse model of T2D to examine the effects of the DPP-IV inhibitor, MK-0626, on bone., Methods: Male wild type (WT) and diabetic muscle-lysine-arginine (MKR) mice were treated with MK-0626, pioglitazone, alendronate or vehicle. The effects of treatment with MK-0626 on bone microarchitecture and turnover were compared with treatment with pioglitazone, alendronate and vehicle. Osteoblast differentiation was determined by alkaline phosphatase staining of bone marrow cells from WT and MKR mice after treatment with pioglitazone, MK-0626 or phosphate buffered saline., Results: We found that MK-0626 had neutral effects on cortical and trabecular bone in diabetic mice. Pioglitazone had detrimental effects on the trabecular bone of WT but not of diabetic mice. Alendronate caused improvements in cortical and trabecular bone architecture in diabetic and WT mice. MK-0626 did not alter osteoblast differentiation, but pioglitazone impaired osteoblast differentiation in vitro., Conclusions: Overall, the DPP-IV inhibitor, MK-0626, had no adverse effects on bone in an animal model of T2D or directly on osteoblasts in culture. These findings are reassuring as DPP-IV inhibitors are being widely used to treat patients with T2D who are already at an increased risk of fractures., (Copyright © 2013 John Wiley & Sons, Ltd.)

Aims: Antioxidant selenium (Se) properties and, its protective role against oxidative damage play an important role in diabetic complications. Our objective was to gain further insight on a link between selenium status and diabetic nephropathy., Methods: We assessed glutathione peroxidase (GPx) and Se in type 2 diabetes mellitus patients with microalbuminuria (MA) (group 1), without microalbuminuria (group 2), and in control subjects (group 3). Glucose, urea, creatinine and glycated hemoglobin tests were tested in sera. A complete clinical record was elaborated., Results: For diabetic patients both, the time from diagnosis and plasma glucose concentration were higher in group 1 as compared to group 2. Control group showed higher serum Se concentrations as compared to the diabetic groups. The two groups of diabetic patients showed similar serum Se levels. Serum concentration of GPx was significantly lower in group 1 as compared to groups 2 and 3. Microalbuminuria (MA) test showed a positive correlation with glucose, and a negative relationship with serum Se and GPx. Multiple regression revealed an inverse relationship between selenium or GPx in serum and the results of the MA test., Conclusions: Our results suggest that lower Se and GPx levels in diabetic patients may be implicated in the diabetic nephropathy.

Background/aims: During the first 10 years, two thirds of the patients with type 2 diabetes mellitus (DM) have microalbuminuria (MA). Functional renal reserve (FRR) and its relationship with proteinuria and metabolic control are unknown at the early phases of disease. We investigated the frequency of MA in recently diagnosed type 2 DM patients, and its association with FRR., Methods: We studied 181 type 2 DM patients with less than 6 months since diagnosis. Renal volume, MA, glomerular filtration rate (GFR) and renal plasma flow (ERPF) were evaluated before and after an acute oral protein load in 28 type 2 DM patients (14 with, and 14 without MA), and in 7 healthy subjects., Results: A total of 10.6% of the patients had MA. MA patients had higher cholesterol and triglyceride levels than those normoalbuminuric. Twenty recently diagnosed type 2 diabetic patients showed high basal GFR. Twelve of them had MA and insulin resistance. After the acute oral protein load, the control subjects and the patients without MA increased their GFR and their ERPF. The group with MA did not., Conclusions: Seventy-five percent of the patients were hyperfiltering. Normoalbuminuric patients had larger increase in GFR and ERRPF than MB patients. We conclude that FRR measurement can be an important tool for the diagnosis of latent diabetic nephropathy., (Copyright 2001 S. Karger AG, Basel)