Use of continuous glucose monitoring trend arrows in the younger population with type 1 diabetes

Early control of glycaemia is key to reduce vascular complications in individuals with Type 1 diabetes. Therefore, encouraging children and adolescents with T1DM to take responsibility for controlling glucose levels is an important yet a challenging task. The rapid expansion of continuous glucose monitoring (CGM) systems has allowed for more comprehensive analysis of glycaemia in T1D. Moreover, CGM devices have the ability to calculate rate of change in glucose levels and display the information as trend arrows. In turn, this can help to take evasive actions to return glucose levels to near physiological glycaemia, which can be highly motivating for young people with T1DM. In the absence of standardised, evidence-based guidance, this consensus document, generated by experts from the Arab Society of Paediatric Endocrinology and Diabetes and international advisors, summarises recent literature on the use of trend arrows in young people with T1DM. The use of trend arrows in different CGM systems is reviewed and their clinical significance is highlighted. Adjusting insulin doses according to trend arrows is discussed while also addressing special situations, such as exercise, fasting, nocturnal hypoglycaemia and menstruation. Adequate understanding of trend arrows should facilitate optimisation of glycaemic control in the T1D population.

Silencing of FOS-like antigen 1 represses restenosis via the ERK/AP-1 pathway in type 2 diabetic mice

Restenosis is a major limiting factor for a successful outcome in type 2 diabetes (T2D) patients undergoing percutaneous coronary intervention (PCI). The aim of this study is to explore the role and regulatory mechanism of FOS-like antigen 1 (FOSL1) in restenosis in T2D. A T2D with restenosis mouse model was established by the combination of high-fat diet and streptozotocin injection and by wire-injury. High glucose (HG)-treated vascular smooth muscle cells (VSMCs) were used to mimic T2D in vitro. The results of quantitative real time PCR and western blotting demonstrated that the expression of FOSL1 was increased not only in T2D mice or HG-induced VSMCs, but also in T2D mice that underwent wire-injury. HE staining revealed that FOSL1 knockdown significantly reduced the intimal/media ratio of T2D mice after wire-injury. Silencing of FOSL1 reversed the promoting effects of HG treatment on viability, migration and inflammation reactions, and the inhibiting effect on the apoptosis of VSMCs. Inhibition of ERK/AP-1 pathway obtained similar patterns in HG-induced VSMCs. The activation of ERK/AP-1 pathway reversed the influence of FOSL1 knockdown on HG-induced VSMCs. Our findings indicate that silencing of FOSL1 may suppress restenosis via regulation of the ERK/AP-1 pathway in T2D mice, pointing out a potential therapeutic target to prevent restenosis in T2D.

Peripheral oscillometric arterial performance does not depict coronary status in patients with type 2 diabetes mellitus

Background Arterial stiffness is associated with cardiovascular events. Matrix metalloproteases (MMPs), their tissue inhibitors (TIMPs) and galectin-3 are involved in the pathogenesis of end organ damage. This study aimed to evaluate the contribution of arterial stiffness, MMPs, TIMPs and galectin-3 with the current vascular status in type 2 diabetes mellitus (T2DM). Methods 74 patients with T2DM, 36 with coronary heart disease (CHD) (T2DM + CHD) and 38 without CHD (T2DM − CHD) were included. Aortic pulse wave velocity (PWVao), aortic and brachial augmentation indices (AIx aortic and AIx brachial) and central-aortic blood pressure values were determined by non-invasive arteriography. MMPs, TIMPs and galectin-3 plasma concentrations were analysed by ELISA. Results Patients with T2DM and CHD presented with significantly increased arterial stiffness determined as AIx and significantly elevated values for TIMP-4 and galectin-3. Heterogeneous peripheral vascular status regardless of the CHD status was observed, and increasing severity of CHD was associated with an increased arterial stiffness. TIMP-4 correlated significantly with an elevated PWVao in the whole cohort independently from CHD status. Conclusion Determination of arterial stiffness is an effective and, compared to laboratory markers, more reliable method for determining the peripheral vascular situation in patients with T2DM, but it does not clearly depict coronary situation.

Impaired subendocardial perfusion in patients with metabolic syndrome

Background Metabolic Syndrome (MS) is associated to vascular damage, increased arterial stiffness, and impaired myocardial perfusion. Subendocardial viability ratio (SEVR) is a noninvasive estimation of myocardial workload, oxygen supply, and perfusion. The aim of the study was to describe the relation between arterial stiffness, SEVR, and cardio-metabolic risk factors. Methods A cohort of 55 patients, aged 59.9 ± 10.8 years, was studied; 28 subjects (50.9%) had metabolic syndrome. All patients underwent a clinical evaluation and blood venous sampling, to assess glico-lipid profile. Applanation tonometry was performed, to obtain pulse wave analysis and SEVR values. Results In the overall study population, SEVR showed negative associations with mean (r = −0.301; p = 0.026) and systolic (borderline relation, r = −0.257; p = 0.058) arterial pressure. Metabolic syndrome patients presented lower level of SEVR ( p = 0.012), even after adjusting for age, sex, and mean arterial pressure ( p = 0.040). Subdividing the study population by the number of metabolic syndrome components, SEVR significantly decreased as the number of Metabolic Syndrome components increased ( p for trend 0.005). In a logistic backward regression analysis, both metabolic syndrome and mean arterial pressure resulted significant predictors of SEVR, accounting for 18% of variance. Conclusion The reduced SEVR in metabolic syndrome patients could be an important pathophysiological determinant of the increased cardiovascular risk.

IGF-1 is not related to long-term outcome in hyperglycemic acute coronary syndrome patients

Purpose Insulin-like growth factor-1 (IGF-1) has been associated with both protective and detrimental effects on the development of ischemic heart disease. The relationship between IGF-1 levels and major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients remains unclear. This study aimed to investigate the relationship between IGF-1 admission levels in hyperglycemic ACS patients and: (1) MACE over a 5 years follow-up, (2) type 2 diabetes at discharge, and (3) post-ACS myocardial infarct size and dysfunction. Methods This was a post hoc analysis of the BIOMArCS-2 randomized controlled trial. From July 2008 to February 2012, 276 ACS patients with admission plasma glucose level between 140 and 288 mg/dL were included. Records of the composite of all-cause mortality and recurrent non-fatal myocardial infarction were obtained during 5 years follow-up. Venous blood samples were collected on admission. IGF-1 was measured batchwise after study completion. Oral glucose tolerance test was performed to diagnose type 2 diabetes, whereas infarct size and left ventricular function were assessed by myocardial perfusion scintigraphy (MPS) imaging, 6 weeks post-ACS. Results Cumulative incidence of MACE was 24% at 5 years follow-up. IGF-1 was not independently associated with MACE (HR:1.00 (95%CI:0.99–1.00), p = 0.29). Seventy-eight patients (28%) had type 2 diabetes at discharge, and the highest quartile of IGF-1 levels was associated with the lowest incidence of diabetes (HR:0.40 (95%CI:0.17–0.95), p = 0.037). IGF-1 levels were not associated with post-ACS myocardial infarct size and dysfunction. Conclusions IGF-1 carries potential for predicting type 2 diabetes, rather than long-term cardiovascular outcomes and post-ACS myocardial infarct size and dysfunction, in hyperglycemic ACS patients.

Alteration of autophagy-related protein 5 (ATG5) levels and Atg5 gene expression in diabetes mellitus with and without complications

Background Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary intracellular components and responsible for normal cellular homeostasis. Autophagy pathway and its key participant ATG5/LC3 are associated with several pathologies such as diabetes mellitus and its complications. Methods Levels and expression of autophagy key components ATG5 and LC3B were analyzed in both human model and murine tissues. One hundred and twenty human subjects were divided into four groups: Healthy (control), diabetes mellitus without complications, diabetic nephropathy, and diabetic retinopathy. Additionally, we used kidneys from WT healthy and diabetic nephropathy mice. Lysate derived from human peripheral blood mononuclear cells and murine renal cortex lysates were subjected to western blot and immunohistochemical analysis. Results Western blot and immunohistochemical analysis demonstrate that ATG5 protein levels were significantly decreased in diabetes mellitus, diabetic nephropathy (DN), and diabetic retinopathy patients versus healthy controls and in DN mice compared to healthy mice (0.65 ± 0.04; 1.15 ± 0.13 A.U. units, respectively). Quantification of staining area (%) of ATG5 mice tissue expression also decreased in DN versus healthy mice (4.42 ± 1.08%; 10.87 ± 1.01%, respectively). LC3B levels and expression Significant reduction in peripheral blood mononuclear cells in diabetic patients (with or without complications) vs. healthy controls. Renal LC3B levels were lower in DN versus healthy mice (0.36 ± 0.03; 0.68 ± 0.07 A.U. units). Renal LC3B staining quantification revealed significant reduction in DN versus healthy mice (1.7 ± 0.23%; 8.56 ± 1.7%). Conclusion We conclude that ATG5, as well as LC3B, are down regulated in diabetic patients with or without complications. This diminution contributes to deficiencies in the autophagy process.

Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature

Type 2 diabetes mellitus is a pathology of heterogeneous etiology characterized by hyperglycemia resulting from lack of insulin action, insulin secretion, or both, and the population with diabetes mellitus is predicted to be about 439 million worldwide by 2030. Prolong diabetes has been related with microvascular complications especially diabetic nephropathy. DN is the most common complication of type 2 diabetes mellitus, and it is the leading cause of end-stage renal disease worldwide. It is crucial to diagnose patients who are more sensible to develop DN for better control of the process of disease. Several factors and mechanisms contribute to the development and outcome of diabetic nephropathy. Microalbuminuria is an early marker of DN and use it as a routine for screening, but the renal damages may be happening even without microalbuminuria. There are several significant kidney damage and disease biomarkers which helps in early detection of DN. An early biomarker may allow earlier diagnosis, treatment reduces DN prevalence and slows DN progression. Therefore, this review focuses on laboratory biomarkers that are earlier, more validation of an early and specific biomarker could potentially make it possible for early diagnosis, treatment, and retardation of progression of diabetic nephropathy.

Circulating microRNAs are associated with variability in fasting blood glucose over 12-months and target pathways related to type 2 diabetes: A pilot study

Introduction MicroRNAs (miRs) may be important regulators of risk for type 2 diabetes (T2D). Circulating miRs may provide information about which individuals are at risk for T2D. The purpose of this study was to assess longitudinal associations between circulating miR expression and variability in fasting blood glucose (FBG) and to identify miR-targeted genes and biological pathways. Methods Variability in FBG was estimated using standard deviation from participants ( n = 20) in a previously completed yoga trial. Expression of 402 miRs was measured using hydrogel particle lithography. MirTarBase was used to identify mRNAs, and miRPathDB was used to identify pathways targeted by differentially expressed miRs. Results Six circulating miRs (miR-192, miR-197, miR-206, miR-424, miR-486, and miR-93) were associated with variability in FBG and targeted 143 genes and 23 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Six mRNAs ( AKT1, CCND1, ESR1, FASN, SMAD7, and VEGFA) were targeted by at least two miRs and four of those were located in miR-targeted KEGG pathways. Conclusions Circulating miRs are associated with variability in FBG in individuals at risk for T2D. Further studies are needed to determine whether miRs may be prodromal biomarkers that can identify which individuals are at greatest risk to progress to T2D and which biological pathways underlie this risk.

Polymorphism in the HaeIII single nucleotide polymorphism of the SLC2A1 gene and cardiovascular disease in the early type 2 diabetes mellitus

Introduction: SLC2A1 polymorphism may play a role in the smooth muscle cell proliferation and extracellular matrix synthesis in vessels. However, the role of SLC2A1 polymorphism on diabetic cardiovascular disease (CVD) have not yet been identified. In this study, we aimed to investigate the association between SLC2A1 HaeIII polymorphism and CVD in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. Methods: A total of 846 patients with T2DM who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of SLC2A1 gene was determined by real time polymerase chain reaction method. Genotyping results were presented GG, AG, or AA. Subgroup analysis was performed according to duration of T2DM (⩽10, 11–20, >20 years). Results: The AA genotype was significantly associated with higher prevalence of CVD in patients with DM duration less than 10 years (26.3% vs 9.2%, p = 0.014). There was no significant association between SLC2A1 HaeIII polymorphism and other diabetic complications including, retinopathy, nephropathy, neuropathy, cerebrovascular disease, and peripheral artery disease. Conclusions: The SLC2A1 HaeIII polymorphism was associated with CVD in Korean patients with T2DM with short disease duration.

Deteriorated regional calf microcirculation measured by contrast-free MRI in patients with diabetes mellitus and relation with physical activity

Objective: To evaluate regional calf muscle microcirculation in people with diabetes mellitus (DM) with and without foot ulcers, compared to healthy control people without DM, using contrast-free magnetic resonance imaging methods. Methods: Three groups of subjects were recruited: non-DM controls, DM, and DM with foot ulcers (DM + ulcer), all with ankle brachial index (ABI) > 0.9. Skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in calf muscle were measured at rest and during a 5-min isometric ankle plantarflexion exercise. Subjects completed the Yale physical activity survey. Results: The exercise SMBF (ml/min/100 g) of the medial gastrocnemius muscle were progressively impaired: 63.7 ± 18.9 for controls, 42.9 ± 6.7 for DM, and 36.2 ± 6.2 for DM + ulcer, p < 0.001. Corresponding exercise SMOEF was the lowest in DM + ulcers (0.48 ± 0.09). Exercise SMBF in the soleus muscle was correlated moderately with the Yale physical activity survey ( r = 0.39, p < 0.01). Conclusions: Contrast-free MR imaging identified progressively impaired regional microcirculation in medial gastrocnemius muscles of people with DM with and without foot ulcers. Exercise SMBF in the medial gastrocnemius muscle was the most sensitive index and was associated with HbA1c. Lower exercise SMBF in the soleus muscle was associated with lower Yale score.