Effects of testosterone (T) on the cardiovascular system of men remain controversial. The impact of T-replacement therapy (TRT) in men with functional hypogonadism and type 2 diabetes mellitus (T2DM) has to be elucidated. This study included 80 men (mean age 51.5 ± 6.3 years) with newly diagnosed T2DM (according to ADA criteria) and functional hypogonadism (according to EAU criteria). Randomization: Group1 (n = 40): TRT using 1%-transdermal T-gel (50 mg/day), Group2 (n = 40) no TRT (controls). Dietary treatment applied to both. Parameters at baseline/after 9 months: anthropometric parameters, lipids and indicators of carbohydrate metabolism (fasting glucose, insulin, HbA1c, HOMA-IR), markers of adipose tissue and EnD (leptin, resistin, p- and e-selectin, ICAM- 1, VCAM- 1 and CRP). ANCOVA for repeated measurements revealed TRT to cause a significant decrease in waist circumference (WC), HOMA-IR and HbA1c vs controls (p < .001, p = .002, p = .004, respectively). Leptin declined in subjects receiving TRT vs controls (p = .04). Concentrations of resistin, ICAM-1, p-selectin and CRP decreased significantly vs controls (all p < .001); no effects for e-selectin and VCAM-1. Advanced age attenuated effects, higher delta testosterone levels augmented effects. Decrement of WC was related to decreasing markers of adipose tissue secretion/EnD. TRT in men with functional hypogonadism and T2DM improved carbohydrate metabolism and markers of endothelial dysfunction.

Type 2 diabetes mellitus (T2DM) is an endocrine and metabolic disorder that requires ongoing medical management. If T2DM is not adequately assessed and managed, a wide spectrum of clinical manifestations and complications may occur. This article provides clinical guidance to NPs on the management of T2DM in primary care settings.

Canagliflozin is a novel drug for diabetes mellitus with the mechanisms of inducing glucosuria through inhibition of the sodium-glucose cotransporter 2 in the kidney independent of insulin activity. We are reporting euglycemic ketoacidosis with severe life-threatening metabolic acidosis. The 2 patients described had type 2 diabetes mellitus and were in a state of relative starvation after abdominal surgery. The first patient had been given an oral diet but was restricted with regard to calorie and sugar intake. The second patient had been nil per os since the operation.

Cardiometabolic diseases are one of the leading causes for disability and mortality in the Western world. The prevalence of these chronic diseases is expected to rise even further in the next decades. Insulin resistance (IR) and related metabolic disturbances are linked to ectopic fat deposition, which is the storage of excess lipids in metabolic organs such as liver and muscle. Notably, a vicious circle exists between IR and ectopic fat, together increasing the risk for the development of cardiometabolic diseases. Nutrition is a key-determining factor for both IR and ectopic fat deposition. The macronutrient composition of the diet may impact metabolic processes related to ectopic fat accumulation and IR. Interestingly, however, the metabolic phenotype of an individual may determine the response to a certain diet. Therefore, population-based nutritional interventions may not always lead to the most optimal (cardiometabolic) outcomes at the individual level, and differences in the metabolic phenotype may underlie conflicting findings related to IR and ectopic fat in dietary intervention studies. Detailed metabolic phenotyping will help to better understand the complex relationship between diet and metabolic regulation, and to optimize intervention outcomes. A subgroup-based approach that integrates, among others, tissue-specific IR, cardiometabolic parameters, anthropometrics, gut microbiota, age, sex, ethnicity, and psychological factors may thereby increase the efficacy of dietary interventions. Nevertheless, the implementation of more personalized nutrition may be complex, costly, and time consuming. Future studies are urgently warranted to obtain insight into a more personalized approach to nutritional interventions, taking into account the metabolic phenotype to ultimately improve insulin sensitivity and reduce the risk for cardiometabolic diseases.

The aim of the present study was to investigate the function and mechanism of action of microRNA (miRNA or miR)-199a-3p in vascular endothelial cell injury induced by type 2 diabetes mellitus (T2DM). A total of 36 patients with T2DM (26 males and 10 females; mean age, 52.5±7.0 years) and 20 healthy subjects (10 males and 10 females; mean age, 55.6±4.5 years) were included in the present study. Peripheral blood samples were obtained from all participants and total RNA was extracted Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of miR-199a-3p. Following the transfection of human umbilical vein endothelial cells (HUVECs) with a negative control (NC) miRNA or miR-199a-3p mimics, cell proliferation was assessed using a Cell Counting kit-8 assay. Cell migration was investigated using Transwell assays and flow cytometry was performed to detect the apoptosis of HUVECs. HUVECs were infected with Ad-GFP-LC3B and laser-scanning confocal microscopy was performed to observe autophagosomes in HUVECs. Western blotting was used to measure the expression of proteins associated with autophagy and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-κB signaling pathway. MiR-199a-3p was downregulated in peripheral blood from patients with T2DM compared with healthy subjects. Transfection with miR-199a-3p mimics promoted the proliferation and migration of HUVECs. However, miR-199a-3p overexpression inhibited the apoptosis of HUVECs. MiR-199a-3p facilitated HUVEC autophagy by affecting autophagy-associated signaling pathways. Furthermore, miR-199a-3p regulated the biological functions of HUVECs via the PI3K/AKT/NF-κB signaling pathway. The results of the present study suggest that miR-199a-3p expression was reduced in patients with T2DM compared with healthy subjects and may be associated with vascular endothelial cell injury. In addition, miR-199a-3p promoted the proliferation, migration and autophagy of HUVECs, potentially by regulating the PI3K/AKT/NF-κB signaling pathway. Therefore, miR-199a-3p may function as protector of vascular endothelia.

It is established that a decrease in β-cell number and deficiency in the function of existing β-cells contribute to type 1 and type 2 diabetes mellitus. Therefore, a major focus of current research is to identify novel methods of improving the number and function of β-cells, so as to prevent and/or postpone the development of diabetes mellitus and potentially reverse diabetes mellitus. Based on prior knowledge of the above-mentioned causes, promising therapeutic approaches may include direct transplantation of islets, implantation and subsequent induced differentiation of progenitors/stem cells to β-cells, replication of pre-existing β-cells, or activation of endogenous β-cell progenitors. More recently, with regards to cell replacement and regenerative treatment for diabetes patients, the identification of cellular signaling pathways with related genes or corresponding proteins involved in diabetes has become a topic of interest. However, the majority of pathways and molecules associated with β-cells remain unresolved, and the specialized functions of known pathways remain unclear, particularly in humans. The current article has evaluated the progress of research on pivotal cellular signaling pathways involved with β-cell proliferation and survival, and their validity for therapeutic adult β-cell regeneration in diabetes. More efforts are required to elucidate the cellular events involved in human β-cell proliferation in terms of the underlying mechanisms and functions.

Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) in atherosclerosis animal model of type 2 diabetes mellitus treated with simvastatin was investigated. Clean grade mature Sprague Dawley (SD) rats were divided into three groups: Normal control (n=10), model (n=13) and treatment group (n=13); low-dose simvastatin was administered. The changes of VEGF and TGF-β1 levels were analyzed by tail vein blood sampling. The relationship between levels of VEGF, TGF-β1 and treatment time was analyzed. The expression level of VEGF in the treatment group after 4 and 8 weeks of intervention was lower compared with the model group (P<0.05). The expression level of TGF-β1 in the treatment group after 8 weeks of intervention was higher than that in the model group (P<0.05). The expression level of VEGF in the treatment group after 8 weeks of intervention was lower than that after 1 week of intervention (P<0.05). The expression level of TGF-β1 was increased in the model group after 8 weeks of intervention compared with 1 week before and after the intervention (P<0.05). The expression level of TGF-β1 in the treatment group at 2, 4 and 8 weeks after intervention were significantly higher than that before intervention (P<0.05). The expression of TGF-β1 increased after 4 and 8 weeks after intervention compared with 1 week after intervention (P<0.05). The expression of VEGF was negatively correlated with TGF-β1 expression in the treatment group; negative correlation was found between VEGF and treatment time. There was a positive correlation between TGF-β1 and treatment time. VEGF and TGF-β1 may be involved in the development of type 2 diabetes (T2MD) atherosclerosis (AS). Simvastatin may play a therapeutic role in T2MD AS by downregulating VEGF and upregulating the expression of TGF-β1.

In this study, we examined the relationship between the fractal dimension (FD), the morphology of the foveal avascular zone (FAZ) and the macular circulation in healthy controls and patients with type 2 diabetes mellitus (T2DM) with and with no diabetic retinopathy (DR). Cross-sectional data of 47 subjects were analyzed from a 5-year longitudinal study using a multimodal optical imaging approach. Healthy eyes from nondiabetic volunteers (n = 12) were selected as controls. Eyes from patients with T2DM were selected and divided into two groups: diabetic subjects with mild DR (MDR group, n = 15) and subjects with DM but without DR (DM group, n = 20). Our results demonstrated a higher FD in the healthy group (mean, 1.42 ± 0.03) than in the DM and MDR groups (1.39 ± 0.02 and 1.35 ± 0.03, respectively). Also, a bigger perimeter, area, and roundness of the FAZ were found in MDR eyes. A significant difference in area and perimeter (p ≤ 0.005) was observed for the MDR group supporting the enlargement of the FAZ due to diabetic complications in the eye. A moderate positive correlation (p = 0.014, R2 = 43.8%) between the FD and blood flow rate (BFR) was only found in the healthy control group. The BFR calculations revealed the lowest values in the MDR group (0.98 ± 0.27 μl/s vs. 1.36 ± 0.86 μl/s and 1.36 ± 0.57 μl/sec in the MDR, DM, and healthy groups, respectively, p = 0.2). Our study suggests that the FD of the foveal vessel arborization could provide useful information to identify early morphological changes in the retina of patients with T2DM. Our results also indicate that the enlargement and asymmetry of the FAZ might be related to a lower BFR because of the DR onset and progression. Interestingly, due to the lack of FAZ symmetry observed in the DM and MDR eyes, it appears that the distribution of flow within the retinal vessels loses complexity as the vascular structures distributing the flow are not well described by fractal branching. Further research could determine how our approach may be used to aid the diagnosis of retinal neurodegeneration and vascular impairment at the early stage of DR.