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Introduction Advanced glycation end products (AGEs) are frequently increased in the skin of subjects with type 2 diabetes mellitus (T2DM). This study aimed to examine the correlation of AGEs with cardiac autonomic neuropathy (CAN) in T2DM. Methods To this aim, 132 participants (88 men) with a mean age of 64.57 years and a median T2DM duration of 14.5 years were included. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm (both single and automated triplicate measurements). Diagnosis of CAN, sympathetic and parasympathetic nervous system impairment was based on the four standardised cardiovascular reflex tests (CARTs). Results On a single measurement, AGEs were increased in subjects with vs. those without CAN (3.20±0.74 vs. 2.66±0.66, p<0.001). As compared with normal results, AGEs were increased for each one of the 4 abnormal CARTs: Valsalva Ratio (3.36±0.67 vs. 2.66±0.72, p=0.004), E/I ratio (3.01±0.72 vs. 2.53±0.68, p=0.001), 30:15 ratio (3.08±0.76 vs. 2.75±0.69, p=0.011), postural hypotension (3.30±0.72 vs. 2.75±0.66, p<0.001). Similar results were obtained for triplicate measurements. Discussion Among T2DM subjects, skin AGEs appear to increase in the presence of CAN. This holds true both for sympathetic and parasympathetic nervous system impairment. [ABSTRACT FROM AUTHOR]

Aim of the Study. To examine the correlation between skin AGEs and parameters of distal sensorimotor polyneuropathy (DSPN) in type 2 diabetes mellitus (T2DM). Materials and Methods. We included 132 subjects (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm. The device enables single and automated triplicate measurements: both of these were performed. DSPN was diagnosed through the neuropathy disability score (NDS). Small nerve fibre function was assessed by temperature and pinprick sensation on the foot. Bilateral measurement of the vibration perception threshold (VPT) on the hallux was carried out by using a neurothesiometer (Horwell Scientific Laboratory Supplies). Results. Single and triplicate AGE measurements were positively correlated with each other (Pearson's correlation coefficient r = 0.991 , 95 % CI = 0.987 -0.994, p < 0.001). AGEs were higher among subjects with vs. those without DSPN (p < 0.001). Furthermore, they were higher among subjects with reduced vs. normal temperature sensation (p < 0.001), among subjects with reduced vs. normal pinprick sensation (p = 0.002), among those with abnormal vs. normal monofilament examination (p < 0.001), and among those with abnormal vs. normal VPT (p < 0.001). AGEs were correlated with NDS, VPT, and monofilament score. Conclusions. In T2DM, skin AGEs are increased in the presence of DSPN. This holds true both for large and for small nerve function impairment. Moreover, AGEs are correlated with DSPN severity. [ABSTRACT FROM AUTHOR]

Introduction: Assessment for cardiovascular autonomic neuropathy (CAN) remains difficult in everyday clinical practice. We sought to examine the diagnostic utility of various simple tools for diabetic peripheral neuropathy (DPN) in the detection of CAN in type 2 diabetes mellitus. Methods: We examined 153 type 2 diabetes mellitus subjects by various DPN tools (vibration perception threshold, 10 g Semmes-Weinstein monofilament, Ipswich touch test, NC-stat®/DPNCheck, neuropathy disability score) for the detection of CAN. CAN was diagnosed by the standardised cardiovascular autonomic reflex function tests. Results: For the diagnosis of CAN, assessment of small nerve fibre function (pinprick sensation, temperature perception) yielded a very high negative predictive value (97%), with high sensitivity (89%) and moderate specificity (73%). The vibration perception threshold was second in diagnostic utility (91% negative predictive value, 62% sensitivity and 75% specificity). Conclusions: Based on their high negative predictive value, simple tools for DPN may prove useful to exclude CAN in type 2 diabetes mellitus. These encouraging results merit further evaluation to enable wider screening for CAN. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the performance of VibraTip, a device used to test a person's vibration perception during routine checks for peripheral neuropathy, against two thresholds of the Neuropathy Disability Score (NDS) for diagnosing distal symmetrical polyneuropathy (DSPN) in patients with type 2 diabetes mellitus (T2DM). Methods: One hundred consecutive subjects with T2DM were enrolled in the study, of whom 54 were men. The mean age was 62.3 years, and the mean T2DM duration was 12.6 years. VibraTip was used at one foot site (on the pulp of the hallux; protocol A) and at three foot sites (pulp of the hallux and first and third metatarsal head; protocol B). NDS thresholds of ≥ 3 and ≥ 6 were used to establish the diagnosis of DSPN. Results: Against the NDS ≥ 3 threshold, VibraTip showed a very high sensitivity (91.3%) and negative predictive value (NPV) (92%) and a high specificity (85.2%) with protocol A, and a very high sensitivity (95.6%) and NPV (96.1%) and a very high specificity (90.7%) with protocol B. Against the NDS ≥ 6 threshold, VibraTip showed a very high sensitivity (100%) and NPV (100%) and a very high specificity (95.2%) with protocol A, and very high sensitivity (100%) and NPV (100%) and very high specificity (96.8%) with protocol B. Conclusions: The diagnostic performance of VibraTip is very high in patients with T2DM, rendering it a very useful device as a screening tool, particularly for the exclusion of DSPN. VibraTip performs very well at both NDS thresholds, but particularly well at the NDS ≥ 6 threshold. There appears to be no need to examine sites other than the hallux site with Vibratip. [ABSTRACT FROM AUTHOR]

Aim Of the Study: To examine the diagnostic utility of skin advanced glycation end products (AGEs) as screening tool of neuropathy in type 2 diabetes mellitus (T2DM).Patients and Methods: We included 132 participants (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm and were interpreted as normal vs. elevated. Distal sensorimotor polyneuropathy (DSPN) was diagnosed by the Neuropathy Disability Score. Cardiovascular autonomic neuropathy (CAN), sympathetic and parasympathetic nervous system impairment were diagnosed by cardiovascular autonomic reflex tests.Results: For DSPN, AGEs yielded high sensitivity (82.8%) and NPV (80.4 %) with moderate specificity (55.4 %). For CAN, they yielded relatively high sensitivity (75.0 %) and NPV (74.5 %) with low specificity (48.7 %). For sympathetic nervous system impairment, AGEs yielded relatively high sensitivity (75.0 %) and high NPV (84.3 %) with low specificity (43.9 %). For parasympathetic nervous system impairment, they yielded high PPV (81.0 %) with moderately high sensitivity (66.7 %) and moderate specificity (55.9 %).Conclusions: In a simplified approach, skin AGEs may be used as a screening tool of DSPN and CAN (including sympathetic and parasympathetic nervous system impairment) in T2DM. [ABSTRACT FROM AUTHOR]

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) comprises fatty liver (steatosis), non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis and may lead to end-stage liver failure or hepatocellular carcinoma. NAFLD is tightly associated with the most frequent metabolic disorders, such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Both multisystem diseases share several common mechanisms. Alterations of tissue communications include excessive lipid and later cytokine release by dysfunctional adipose tissue, intestinal dysbiosis and ectopic fat deposition in skeletal muscle. On the hepatocellular level, this leads to insulin resistance due to abnormal lipid handling and mitochondrial function. Over time, cellular oxidative stress and activation of inflammatory pathways, again supported by multiorgan crosstalk, determine NAFLD progression. Recent studies show that particularly the severe insulin resistant diabetes (SIRD) subgroup (cluster) associates with NAFLD and its accelerated progression and increases the risk of diabetes-related cardiovascular and kidney diseases, underpinning the critical role of insulin resistance. Consequently, lifestyle modification and certain drug classes used to treat T2DM have demonstrated effectiveness for treating NAFLD, but also some novel therapeutic concepts may be beneficial for both NAFLD and T2DM. This review addresses the bidirectional relationship between mechanisms underlying T2DM and NAFLD, the relevance of novel biomarkers for improving the diagnostic modalities and the identification of subgroups at specific risk of disease progression. Also, the role of metabolism-related drugs in NAFLD is discussed in light of the recent clinical trials. Finally, this review highlights some challenges to be addressed by future studies on NAFLD in the context of T2DM. • T2DM and NAFLD are heterogeneous tightly associated diseases. • Insulin resistance is a common player in both NAFLD and T2DM. • Tissue cross-talk and multicellular network drives NAFLD initiation and progression. • The performance of NAFLD biomarkers is suboptimal in T2DM. • Antihyperglycemics, GLP-1ra and SGLT2i, have beneficial effects on NAFLD and CVD. [ABSTRACT FROM AUTHOR]

Diabetes represents the leading risk factor for the development of cardiovascular disease (CVD). Chronic hyperglycemia and/or acute post-prandial changes in blood glucose determine an increase in reactive oxygen species (ROS), which play a fundamental role in endothelial dysfunction and in the nuclear transport of pro-atherogenic transcription factors that activate the "inflammasome". In addition, the glycemic alteration favors the formation and stabilization of atherosclerotic plaque through the mechanism of non-enzymatic glycation of different molecules, with the establishment of the so-called "advanced glycosylation end products" (AGE). Laboratory information provided by the level of biomarkers could make a quantitative and qualitative contribution to the clinical process of screening, prediction, prevention, diagnosis, prognosis and monitoring of cardiovascular (CV) risk linked to diabetes. This review describes the importance of specific biomarkers, with particular focus on novel ones, for stratifying and management of diabetes CV risk. [ABSTRACT FROM AUTHOR]