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Type 2 diabetes mellitus (T2DM) is a major cause of cardiovascular (CV) disease. Several large clinical trials have shown that the risk for patients with diabetes of developing CV complications is only partially reduced by early, intensive glycaemic control and lifestyle interventions, and that such complications result from changes in complex, not fully explored networks that contribute to the maintenance of endothelial function. The accumulation of senescent cells and the low-grade, systemic, inflammatory status that accompanies aging (inflammaging) are involved in the development of endothelial dysfunction. Such phenomena are modulated by epigenetic mechanisms, including microRNAs (miRNAs). MiRNAs can modulate virtually all gene transcripts. They can be secreted by living cells and taken up in active form by recipient cells, providing a new communication tool between tissues and organs. MiRNA deregulation has been associated with the development and progression of a number of age-related diseases, including the enduring gene expression changes seen in patients with diabetes. We review recent evidence on miRNA changes in T2DM, focusing on the ability of diabetes-associated miRNAs to modulate endothelial function, inflammaging and cellular senescence. We also discuss the hypothesis that miRNA-containing extracellular vesicles (i.e. exosomes and microvesicles) could be harnessed to restore a 'physiological' signature capable of preventing or delaying the harmful systemic effects of T2DM. [ABSTRACT FROM AUTHOR]

Aims To investigate the validity and reliability of the Audit of Diabetes-Dependent Quality of Life instrument in older Italians with diabetes and to test the association of diabetes-related quality of life with glycaemic control over time. Methods A total of 558 outpatients with Type 2 diabetes from the Diabetic Unit of the Italian National Research Centre on Aging Hospital in Ancona were enrolled to complete questionnaires (Audit of Diabetes-Dependent Quality of Life-19 and the Short-Form-12), and to undergo clinical and biochemical testing at baseline and at 12 months of follow-up. The overall impact of diabetes using the average weighted impact score from the Audit of Diabetes-Dependent Quality of Life questionnaire was calculated. Participants were categorized according to this score as having either less or more negative diabetes-related quality of life. Results Participants had a mean ± sd age of 67.7 ± 9.2 years and 51.8% were male. Factor analysis and Cronbach's coefficient of internal consistency (Cronbach's α = 0.931) confirmed that the 19 domain-specific Audit of Diabetes-Dependent Quality of Life items could be combined into a single scale in this Italian population. The impact score correlated with the physical ( r = 0.275; P < 0.001) and mental components ( r = 0.291; P < 0.001) of the Short-Form-12 questionnaire. Significant differences were found according to diabetic complications in specific Audit of Diabetes-Dependent Quality of Life items and impact scores. Insulin use had a greater association with a more negative quality of life compared with other antidiabetic agents. A multivariate linear regression model with restricted linear spline application showed that the relationship between HbA1c and impact score was not linear and that the change in the impact score was associated with improved glycaemic control in those with a less negative diabetes-related quality of life at 12 months. Conclusions The Audit of Diabetes-Dependent Quality of Life-19 is a valid tool for measuring the impact of diabetes on quality of life in older Italians. Perception of diabetes-related quality of life is associated with glycaemic control over time. [ABSTRACT FROM AUTHOR]

Background: Contradictory results have been reported in the literature concerning the correlation between glycosylated haemoglobin (HbA1c) and peroxidation level in serum of diabetic patients. Objective: To evaluate this correlation in type 2 diabetic patients by comparing the level of HbA1c with the oxygen radical absorbance capacity (ORAC[sub OH] ) of serum. Methods: One hundred and five type 2 diabetic patients were enroled for the study. After having obtained informed consent, venous blood samples were drawn after overnight fast at the time of routine diabetic check-ups. The blood was collected in plain and EDTA (1 mg/ml) tubes. Glycosylated haemoglobin (HbA1c) was determined by cation-exchange chromatography (HPLC), and spectrophotometric detection (Diamat Analyzer, BioRad). Serum was used for biochemical determinations performed by standard laboratory procedures and for ORAC[sub OH] analysis. This last parameter was determined measuring the loss of β-phycoerytrin fluorescence due to oxidation by hydroxyl radicals generated by Cu[sup 2+] and H[sub 2] O[sub 2] , in the presence and absence of serum. Seventy-eight control age-matched subjects were obtained from the personnel staff of our Research Department and old healthy subjects, selected on the basis of Senieur Protocol, were relatives of the above mentioned personnel. Results: When the population of diabetic patients was taken as a whole, a decrease of ORAC[sub OH] has been observed compared to the controls. Moreover, negative correlations were found comparing ORAC[sub OH] either with HbA1c (r = –0.213; p = 0.029) and with the age of patients (r = –0.27; p = 0.005). To better understand the effect of age, the data were re-examined dividing the diabetics into two populations, i.e. under and over 65 years of age. An age-dependent decrease of ORAC[sub OH] and an increase in HbA1c levels has been observed comparing these two populations; however, the correlation between the two parameters remained statistically significant only in the oldest group (r = –0.31; p = 0.026). Conclusions: Present data point to an involvement of oxidative stress in the glycation of haemoglobin especially in old diabetic patients, and provide support for the potential use of an antioxidant therapy in these patients, irrespective of their glycaemic control.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: C-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. “In vitro” studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications. Methods and results: Two hundred and ninety-five type 2 diabetic patients (age 60.9±10.5years) and 290 healthy controls (age 59.2±11.5years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r =0.45, p <0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r =0.31, p <0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r =0.64 p <0.001) and 4G/5G (partial r =0.47, p <0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r =0.45, p <0.001) and in 4G/5G (partial r =0.34, p =0.007) diabetic patients. Conclusions: These findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers. [Copyright &y& Elsevier]

Abstract: Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position −174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6–174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 –174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p <0.01). Control subjects, both C+ (CG+CC genotypes) and C− (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C− carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6–174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance “IL-6-sensitive”, while C− carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance. [Copyright &y& Elsevier]

Aims To analyse the association of smoking with paraoxonase (PON1) in Type 2 diabetic patients. Methods Type 2 diabetic patients were recruited independently in two centres (Ancona, Italy and Geneva, Switzerland) and serum PON1 mass and activities were assayed. Current smoking status was established and its association with serum PON1 analysed. Results Type 2 diabetic patients who smoked had significantly lower serum PON1 mass and activity. This was evident in both groups of patients, even though Swiss patients were composed of coronary patients. Multivariate analyses established that smoking was an independent determinant of serum PON1 status. Conclusions Smoking is associated with reduced serum levels of the antioxidant enzyme, PON1, even against an already unfavourable background of diabetes and coronary disease. It suggests that a combination of smoking and diabetes may be particularly deleterious for PON1 and consequently for the anti-oxidant capacity of high-density lipoproteins. [ABSTRACT FROM AUTHOR]

Abstract Aims To determine if apolipoprotein E polymorphism is associated with cardiovascular or all-cause mortality in Italian Type 2 diabetic patients. Methods A prospective study of mortality in Type 2 diabetic patients (n = 433) as a function of apolipoprotein E phenotype, which was assessed at entry into the study. During follow up (10 years), 110 (25·4%) patients died of which 66 (15·2%) were the result of cardiovascular causes. Cause of death was established from death certificates and clinical records. The clinical status of the survivors was determined at the end of the study. Results Apolipoprotein E polymorphisms were not associated with excess cardiovascular or all-cause mortality in the Italian Type 2 diabetic patients either in univariate or multivariate analyses. Age, duration of diabetes and glycated haemoglobin levels at entry were the primary determinants of premature mortality in the diabetic population. Conclusions Apolipoprotein E polymorphisms are not markers for premature mortality in Italian Type 2 diabetic patients. The impact of apolipoprotein E mutations may be attenuated by environmental factors, notably a healthier diet, in Italian patients. [ABSTRACT FROM AUTHOR]

Introduction and purpose Diabetes is a set of metabolic disorders whose common, characteristic feature is the occurrence of hyperglycemia. Elevated glycemia levels result from impaired insulin secretion and/or defects in its action. In type 2 diabetes, we have modified risk factors such as improper diet, reduced physical activity, and obesity. In the context of these reversible factors, intervention in patients' lifestyle, with particular emphasis on physical activity, seems advisable. To investigate the implementation of recommendations for the treatment of type 2 diabetes, relating to physical activity as a component of behavioral treatment of diabetes. Materials and methods. Author's survey covering patients' knowledge about their disease, needs and expectations regarding education. The questionnaire examines the physical activity of patients newly diagnosed and already treated for type 2 diabetes. Results. The most frequently undertaken exercise was of medium intensity in the form of walking or "Nordic walking". This was also more likely to be intensified. Patients choosing this type of activity practiced it much more often and more regularly than other types of activity. Running and cycling were other activities undertaken by the patients, although in the younger group of patients. Patients who enjoyed physical exercise were more likely and willing to do it and it was more regular. Conclusions. Patients were reluctant to undertake physical exercise and usually did not treat it as an integral part of treatment. Usually, it was not a very intense effort. They also rarely intensified it when the diagnosis was made. Most of the respondents did not understand the role of exercise in the treatment process and its impact on sugar levels. [ABSTRACT FROM AUTHOR]

Introduction and purpose Diabetes comprises a group of metabolic disorders characterized by persistent hyperglycemia. This elevated blood glucose level arises from impaired insulin secretion and/or action. In type 2 diabetes, modifiable risk factors include an unhealthy diet, sedentary lifestyle, and obesity. Given the reversibility of these factors, lifestyle interventions, particularly those promoting physical activity, are deemed beneficial. To evaluate the adherence to type 2 diabetes management guidelines, focusing on the incorporation of physical activity as a critical aspect of behavioral treatment for diabetes. . Materials and methods. Author's survey covering patients' knowledge about their disease, needs and expectations regarding education. The questionnaire examines the physical activity of patients newly diagnosed and already treated for type 2 diabetes. Results The most performed exercise among patients was moderate-intensity activities such as walking or Nordic walking. These activities were more frequently intensified compared to others. Patients engaging in these forms of exercise did so more frequently and consistently than those participating in other types of physical activity. Additional activities included running and cycling, predominantly among the younger patient cohort. Patients who derived enjoyment from physical exercise demonstrated a higher likelihood of regular and willing participation. Conclusions. Patients exhibited reluctance to engage in physical exercise and typically did not regard it as a crucial component of their treatment regimen. The exercise they performed was generally of low intensity, and few patients increased their physical activity following their diagnosis. A significant number of respondents lacked understanding of the role of exercise in the management of their condition and its effect on blood glucose levels. [ABSTRACT FROM AUTHOR]

Introduction: There exists a gap in the health status of immigrants in comparison to the overall population, and health literacy has been shown to be a mediator for health outcomes and may predict their quality of life (QoL). We aimed to systematically map and synthesize research findings on adult immigrants' health literacy in terms of their health beliefs, understanding, and self-management of Type 2 Diabetes Mellitus. Methods: A scoping review guided by Arksey and O'Malley's framework was conducted, based on systematic searches in the Embase, Ovid MEDLINE, and APA PsycInfo databases in June 2023. The retrieved articles were screened and assessed by the two authors independently. Results: Of 568 identified studies, 16 (9 qualitative, 4 cross-sectional, 1 mixed-methods, and 2 experimental) were included in this review. Low/moderate health literacy levels with no sex-related differences were reported. Immigrants' access to health information was limited by language barriers and a lack of culturally adapted information, especially from their physicians. Among women, access to health information was limited by patriarchal norms. Knowledge gaps were primarily related to understanding the necessity of medication and the importance of a healthy lifestyle. Healthcare professionals played an important role in motivating immigrants to adhere to treatment. Conclusion: Few studies were found on this topic, and additional research is needed to enhance health literacy among immigrants. Limited health information, language barriers, and a shortage of culturally sensitive knowledge appear to hinder immigrants' ability to access, understand, and apply health information. Cultural norms and personal factors further suppress these abilities, ultimately impacting their health outcomes. The findings of this study suggest that health literacy is a crucial component of healthcare professionals' curricula, equipping them with the skills to identify and assist patients with low health literacy. [ABSTRACT FROM AUTHOR]

Background: Glycemic variability is a novel predictor for diabetic complications. Different studies have demonstrated contradictory results for the association between HbA1c variability and diabetic retinopathy. We aimed to assess the relationship between visit-to-visit variability in glycemic profile (HbA1c, 2hPP, and FBS) and diabetic retinopathy. Methods: Patients with type 2 diabetes were monitored for the development of retinopathy for 10 years. The association between the incidence of retinopathy and glycemic variability was assessed via Cox regression analysis, and coefficient of variation for glycemic indices was compared using independent sample t -test. Results: Patients with diabetic retinopathy had significantly higher glycemic profile variability. The incidence of retinopathy was positively correlated with cv-FBS10% (10% of coefficient of variance), cv-FBS20%, cv-2hpp10%, and cv-HbA1c5%. Our analysis revealed that the higher variability of FBS increased the incidence and progression of retinopathy (HR: 12.29, p -value = 0.003). Conclusion: Our findings demonstrated glycemic profile variability as an independent risk factor for diabetic retinopathy in patients with type 2 diabetes and support glycemic profile variability measurement in addition to common glycemic parameters to improve risk stratification in patients with type 2 diabetes. Further investigation is required to demonstrate the long-term effects of alleviating glycemic variability on the prognosis of patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To explore factors that may contribute to a possible reduced compliance in patients with type 2 diabetes mellitus (T2DM) with a migrant (i.e. North African) background living in a western society. Methods: Semi-structured interviews with people with T2DM both of Moroccan and Belgian origin, recruited within the diabetes clinic of the University Hospital Brussel, Belgium. Data was analysed thematically using NVivo. Results: Participants indicated they were adequately informed about T2DM, however results show a demand for culturally tailored preventive education for Moroccan participants. Both groups generally had good knowledge of a healthy lifestyle and what is expected after diagnosis, but considered maintaining healthy lifestyle and correct medication adherence, intensive. Participants mentioned a wide range of themes that affected their compliance, both positively and negatively. Perceived barriers were social issues, lack of motivation, insufficient support from the environment, stress, forgetfulness, winter conditions and COVID. Culturally shaped views on eating habits, illness, medication use and health were clear barriers in the Moroccan group. Conclusion: Findings highlight the need for future in depth research into diabetes related knowledge within the Moroccan community living in Belgium (and similar other Western countries) whilst considering differences between generations of migrants, gender and level of education. [ABSTRACT FROM AUTHOR]

Introduction: Contradictory claims about the efficacy of several medicinal plants to promote glycemic control in patients with type 2 diabetes mellitus (T2DM) have been explained by divergences in the administration form and by extrapolation of data obtained from healthy individuals. It is not known whether the antidiabetic effects of traditional herbal medicines are influenced by gelatin capsules. This randomized crossover trial aimed to evaluate the acute effect of a single dose of raw cinnamon consumed orally either dissolved in water as a beverage or as ordinary hard gelatin capsules on postprandial hyperglycemia (>140 mg/dL; >7.8 mmol/L) in T2DM patients elicited by a nutritionally-balanced meal providing 50 g of complex carbohydrates. Methods: Fasting T2DM patients (n = 19) randomly ingested a standardized meal in five experimental sessions, one alone (Control) and the other after prior intake of 3 or 6 g of crude cinnamon in the form of hard gelatin capsules or powder dissolved in water. Blood glucose was measured at fasting and at 0.25, 0.5, 0.75, 1, 1.5 and 2 hours postprandially. After each breakfast, its palatability scores for visual appeal, smell and pleasantness of taste were assessed, as well as the taste intensity sweetness, saltiness, bitterness, sourness and creaminess. Results: The intake of raw cinnamon dissolved in water, independently of the dose, decreased the meal-induced large glucose spike (peak-rise of +87 mg/dL and Δ1-hour glycemia of +79 mg/dL) and the hyperglycemic blood glucose peak. When cinnamon was taken as capsules, these anti-hyperglycemic effects were lost or significantly diminished. Raw cinnamon intake did not change time-to-peak or the 2-h post-meal glycaemia, but flattened the glycemic curve (lower iAUC) without changing the shape that is typical of T2DM patients. Conclusions: This cinnamon's antihyperglycemic action confirms its acarbose-like property to inhibit the activities of the carbohydrate-digesting enzymes α-amylases/α-glucosidases, which is in accordance with its exceptionally high content of raw insoluble fiber. The efficacy of using raw cinnamon as a diabetes treatment strategy seems to require its intake at a specific time before/concomitantly the main hyperglycemic daily meals. Trial registration: Registro Brasileiro de Ensaios Clínicos (ReBEC), number RBR-98tx28b. [ABSTRACT FROM AUTHOR]

Background: No study has investigated the association between ultra-processed food (UPF) and pre-diabetes development. Furthermore, prior investigations on the association between UPF and the risk of type 2 diabetes (T2D) were primarily conducted in Europe and America, and studies in other regions are lacking. We investigated the association between ultra-processed foods and the risk of pre-diabetes and T2D in a cohort of Iranians. Methods: This prospective study, with a sample size of 1954 for pre-diabetes and 2457 for T2D, was conducted among adults' participants (aged ≥ 18 years) from the Tehran Lipid and Glucose Study (TLGS). We defined UPF intake using NOVA calcification as a proportion of total energy, and calculated its average intake during the follow-ups. The hazard ratios (HR) and 95% confidence intervals (95% CI) for pre-diabetes/T2D across tertiles of total UPF and per 10% of its increment were examined using Cox proportional hazards models. We also investigated the possibility of non-linear association using a restricted cubic spline regression. Results: We identified 766 and 256 cases of pre-diabetes and T2D, respectively, during a median follow-up of 7 years for pre-diabetes and 8.6 years for T2D. In the multivariable adjusted model, a 10% increase in total UPF intake was associated with a 12% higher risk of pre-diabetes (HR = 1.12; 95% 1.02, 1.23). The incidence of pre-diabetes was also higher in those in tertile 3 than those in tertile 1 (HR = 1.28; 95% CI = 1.07, 1.52). Following additional adjustment for diet quality, the results remained unchanged. Spline regression demonstrated a J-shaped association between UPF and the risk of pre-diabetes; the risk of pre-diabetes did not increase until UPF consumption exceeded about 24% of total energy intake. Of the individual UPF, hydrogenated fat/mayonnaise/ margarine group was related to an increased risk of pre-diabetes. The total UPF and its individual items were not associated with T2D. Conclusions: This study found a positive, non-linear relationship between total UPF and the risk of pre-diabetes in Iranian adults. Our data could not show any significant association between UPF and T2D risk. [ABSTRACT FROM AUTHOR]

Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP > 2 mg/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to explore the prognostic value of the aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio in non-surgical patients with type 2 diabetes hospitalized for heart failure. Material and methods: Using a large electronic medical record-based cohort of diabetes in China (WECODe), we gathered data on non-surgical hospitalized patients with type 2 diabetes and heart failure from 2011 to 2019. Baseline AST/ALT ratio was calculated. The primary outcomes were all-cause death within 30 days after discharge, composite cardiac events, major acute kidney injury, and major systemic infection. A multivariable Cox proportional regression model was utilized to evaluate the association between the AST/ ALT ratio and outcomes. Results: This retrospective cohort included 8,073 patients (39.4% women) with type 2 diabetes hospitalized for heart failure. The median age was 71 years. Higher AST/ALT ratio was associated with higher risks of poor endpoints (with per standard deviation increment in AST/ALT ratio, for death within 30 days after discharge: adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI], 1.21 to 1.50; for composite cardiac events: HR = 1.18, 95% CI: 1.06 to 1.31). Compared to patients in the lowest quartile for the AST/ALT ratio, those in the highest quartile have elevated risk of death within 30 days after discharge and major systemic infection (HRs [95% CIs] 1.61 [1.18 to 2.19] and 1.28 [1.06 to 1.56], respectively). Subgroup analyses and sensitivity analyses confirmed the robustness of the findings. Conclusions: Type 2 diabetes patients hospitalized for heart failure with the AST/ALT ratio in the highest quartile face a poor short-term prognosis. [ABSTRACT FROM AUTHOR]

Telomeres, the protective chromosomal ends, progressively shorten and potentially are implicated in the pathogenesis of age-related diseases. In type 2 diabetes (T2DM), telomere shortening may play an important role, but the whole 'picture' remains limited. From a therapeutic perspective, the phytonutrient quercetin appears to be clinically effective and safe for patients with T2DM. Considering the above, we aimed to examine whether quercetin could interfere with telomere length (TL) dynamics. One hundred patients with T2DM on non-insulin medications registered within a primary healthcare facility were stratified by age and sex and randomly assigned to either standard care or standard care plus quercetin (500 mg/day) for 12 weeks, succeeded by an 8-week washout period and another 12 weeks of supplementation. Of the 88 patients completing the trial, 82 consented to blood sampling for TL measurements. Health assessments and whole blood absolute TL measurements using quantitative polymerase chain reaction (qPCR) were conducted at baseline and study end, and the findings of this subcohort are presented. Quercetin supplementation was associated with a significant increase in mean TL (odds ratio ≥ 2.44; p < 0.05) with a strengthened association after full adjustment for potential confounders through multiple logistic regression analysis (odds ratio = 3.48; p = 0.026), suggesting it as a potentially promising supplementation option. Further studies are needed to confirm this finding, elucidating the underlying molecular mechanisms of quercetin. [ABSTRACT FROM AUTHOR]

The coexistence of SAH with T2DM is a common comorbidity. In this study, we investigated the link between altered plasma antioxidant trace elements (ATE: manganese, selenium, zinc, and copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile, which is modified during SAH-T2DM association compared to the healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of total SFA, palmitic acid, arachidonic acid, and PUFA ω6/PUFA ω3; drop in tandem of PUFA/SFA and EPA + DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA rise, concurrent drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitant enhancement of Cu, Mn, and Fe); endothelial dysfunction (endotheline−1 increase); athero-thrombogenesis risk (concomitant rise of ApoB100/ApoA1, Ox-LDL, tHcy, and Lp(a)), and inflammation (higher of Hs-CRP, fibrinogen and ferritin). Our study opens to new therapeutic targets and to better dietary management, such as to establishing dietary ATE and PUFA ω6/PUFA ω3 or PUFA/SFA reference values for atherosclerotic risk prevention in hypertensive/diabetic patients. [ABSTRACT FROM AUTHOR]

Background: The association between baseline triglyceride glucose index (TyG index) and incident non-communicable diseases, mainly in Asian populations, has been reported. In the current study, we aimed to evaluate the association between index-year, average, and visit-to-visit variability (VVV) of the TyG index with incident type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), and all-cause mortality among the Iranian population. Methods: The study population included 5220 participants (2195 men) aged ≥ 30 years. TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). Average values of the TyG index and also VVV (assessed by the standard deviation (SD) and variability independent of mean) were derived during the exposure period from 2002 to 2011 (index-year). Multivariable Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the TyG index for incident different health outcomes. Results: During more than 6 years of follow-up after the index year, 290, 560, 361, and 280 events of T2DM, hypertension, CVD, and all-cause mortality occurred. 1-SD increase in the TyG index values at the index-year was independently associated with the incident T2DM [HR (95% CI) 2.50 (2.13–2.93)]; the corresponding values for the average of TyG index were 2.37 (2.03–2.76), 1.12 (0.99–1.26, pvalue = 0.05), 1.18 (1.01–1.36), and 1.29 (1.08–1.53) for incident T2DM, hypertension, CVD, and all-cause mortality, respectively. Compared to the first tertile, tertile 3 of VVV of the TyG index was independently associated with incident hypertension [1.33 (1.07–1.64), Ptrend <0.01]. Likewise, a 1-SD increase in VVV of the TyG index was associated with an 11% excess risk of incident hypertension [1.11 (1.02–1.21)]. However, no association was found between the VVV of the TyG index and other outcomes. Moreover, the impact of index-year and average values of the TyG index was more prominent among women regarding incident CVD (P for interactions < 0.05). Conclusion: Although the higher TyG index at index-year and its VVV were only associated with the incident T2DM and hypertension, respectively, its average value was capable of capturing the risk for all of the health outcomes. [ABSTRACT FROM AUTHOR]

Background: Endothelial cellular senescence is emerging as a key mechanism of age-related vascular dysfunction. Disruption of the endothelium glycocalyx and shedding of the syndecan (SDC) ectodomains have been associated with several age-related diseases. Although SDC4 is highly expressed in endothelial cells, its levels and shedding in senescent endothelial cells and vascular endothelial dysfunction associated with aging are still unknown. Methods: To assess whether SDC4 expression was affected by inflammatory conditions, we evaluated its levels in young human umbilical vein endothelial cells (HUVECs) treated with TNF-α at a concentration of 50 ng/mL for 24 h and in cells undergoing replicative senescence. Plasma levels of SDC4 were evaluated in two previously recruited cohorts of (i) subjects with type 2 diabetes (T2D, n = 110) followed for a median of 16.8 years and age- and gender-matched healthy subjects (n = 100), and (ii) middle-aged subjects with mild-to-moderate dyslipidemia. Binomial logistic regression was used to assess whether SDC4 levels could be prognostic for major adverse cardiovascular events (MACE). Results: In the in vitro study, we showed that HUVECs, when exposed to TNF-α or undergoing replicative senescence, exhibited elevated expression levels of SDC4 and matrix metallopeptidase 9 (MMP-9), as well as increased shedding of SDC4 into the extracellular microenvironment, in comparison to actively proliferating young HUVECs. Analysis of human samples revealed that patients with T2D without complications exhibited higher SDC4 levels compared to healthy controls and those with T2D vascular complications. In particular, patients with a history of major adverse cardiovascular events (MACE) had lower SDC4 levels. The longitudinal evaluation revealed that higher SDC4 levels predict the onset of new MACE during a 16.8-year follow-up. In the second cohort, no significant association was observed between SDC4 and endothelial dysfunction, assessed by flow-mediated dilation (FMD) or nitric oxide metabolites. SDC4 levels correlated positively with C-reactive protein (CRP) in both cohorts and with PAI-1 in the cohort of patients with T2D. Conclusion: Overall, we conclude that the shedding of SDC4 from endothelial cells increases under acute (TNF-α treatment) and chronic (senescence) inflammatory conditions and that increased circulating SDC4 levels are associated with systemic inflammation in pathological aging. [ABSTRACT FROM AUTHOR]

Background/Objectives: Elevated glycemic variability (GV) has been associated with postoperative morbidity. Traditional preoperative fasting guidelines may contribute to high GV by driving the body into catabolism. Enhanced recovery after surgery (ERAS) protocols that include a preoperative carbohydrate load (PCL) reduce hospital length of stay and healthcare costs; however, it remains unclear whether PCL improves GV in surgical patients. The aim of this retrospective study was to determine the effect of a PCL on postoperative GV in diabetic and non-diabetic patients having gynecological surgery. Methods: Retrospective data were collected on patients who had gynecological surgery before and after the rollout of an institutional ERAS protocol that included PCL ingestion. The intervention group included patients who underwent surgery in 2019 and were enrolled in the ERAS protocol and, therefore, received a PCL. The control group included patients who underwent surgery in 2016 and, thus, were not enrolled in the protocol. The primary endpoint was GV, calculated by the coefficient of variance (CV) and glycemic lability index (GLI). Results: A total of 63 patients in the intervention group and 45 in the control were analyzed. GV was not statistically significant between the groups for CV (19.3% vs. 18.6%, p = 0.65) or GLI (0.58 vs. 0.54, p = 0.86). Postoperative pain scores (4.5 vs. 5.2 p = 0.23) and incentive spirometry measurements (1262 vs. 1245 p = 0.87) were not significantly different. A subgroup analysis of patients with and without type 2 diabetes mellitus revealed no significant differences in GV for any of the subgroups. Conclusions: This retrospective review highlights the need for additional GV research, including consensus agreement on a gold standard GV measurement. Large-scale prospective studies are needed to test the effectiveness of the PCL in reducing GV. [ABSTRACT FROM AUTHOR]

Background: Within-day glycemic variability (GV), characterized by frequent and significant fluctuations in blood glucose levels, is a growing concern in hospitalized patients with type 2 diabetes mellitus (T2DM). It is associated with an increased risk of hypoglycemia and potentially higher long-term mortality rates. Robust clinical evidence is needed to determine whether traditional Chinese medicine (TCM) decoctions can be a beneficial addition to the management of within-day GV in this patient population. Methods: This retrospective cohort study utilized data from adult inpatients diagnosed with T2DM admitted to the Traditional Chinese Medicine Hospital of Kaifeng. The primary outcome investigated was the association between the use of TCM decoctions and improved stability of within-day GV. Blood glucose variability was assessed using the standard deviation of blood glucose values (SDBG). For each patient, the total number of hospitalization days with SDBG below 2 mmol/L was calculated to represent within-day GV stability. Hospitalization duration served as the secondary outcome, compared between patients receiving TCM decoctions and those who did not. The primary analysis employed a multivariable logistic regression model, with propensity score matching to account for potential confounding variables. Results: A total of 1,360 patients were included in the final analysis. The use of TCM decoctions was significantly associated with enhanced stability of withinday GV (OR = 1.77, 95% CI: 1.34-2.33, P < 0.01). This association was most prominent in patients with a diagnosis of deficiency syndrome (predominantly qiyin deficiency, accounting for 74.8% of cases) and a disease duration of less than 5 years (OR = 2.28, 95% CI: 1.21-4.29, P = 0.03). However, TCM decoctions did not exert a statistically significant effect on hospitalization duration among patients with T2DM (OR = 0.96, 95% CI: 0.91-1.01, P = 0.22). Conclusion: This study suggests that TCM decoctions may be effective in improving within-day GV stability in hospitalized patients with T2DM. This effect appears to be most pronounced in patients diagnosed with deficiency syndrome, particularly those with qi-yin deficiency and a shorter disease course. Further investigation is warranted to confirm these findings and elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide's dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure. [ABSTRACT FROM AUTHOR]

Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic effect, exert multiple beneficial effects at a metabolic and cardiovascular level, through mechanisms other than antihyperglycemic agents. This review aims to discuss the effects of these new antidiabetic drugs, highlighting cardiovascular and metabolic benefits, through the description of their action mechanisms as well as available data by preclinical and clinical studies. Moreover, new innovative tools in the T2D field will be described which may help to advance towards a better targeted T2D personalized care in future. [ABSTRACT FROM AUTHOR]

The escalating prevalence of carbohydrate metabolism disorders (CMDs) prompts the need for early diagnosis and effective markers for their prediction. Hyperglycemia, the primary indicator of CMDs including prediabetes and type 2 diabetes mellitus (T2DM), leads to overproduction of reactive oxygen species (ROS) and oxidative stress (OxS). This condition, resulting from chronic hyperglycemia and insufficient antioxidant defense, causes damage to biomolecules, triggering diabetes complications. Additionally, aging itself can serve as a source of OxS due to the weakening of antioxidant defense mechanisms. Notably, previous research indicates that miR-196a, by downregulating glutathione peroxidase 3 (GPx3), contributes to insulin resistance (IR). Additionally, a GPx3 decrease is observed in overweight/obese and insulin-resistant individuals and in the elderly population. This study investigates plasma GPx3 levels and miR-196a expression as potential CMD risk indicators. We used ELISA to measure GPx3 and qRT-PCR for miR-196a expression, supplemented by multivariate linear regression and receiver operating characteristic (ROC) analysis. Our findings included a significant GPx3 reduction in the CMD patients (n = 126), especially in the T2DM patients (n = 51), and a decreasing trend in the prediabetes group (n = 37). miR-196a expression, although higher in the CMD and T2DM groups than in the controls, was not statistically significant, potentially due to the small sample size. In the individuals with CMD, GPx3 levels exhibited a negative correlation with the mass of adipose tissue, muscle, and total body water, while miR-196a positively correlated with fat mass. In the CMD group, the analysis revealed a weak negative correlation between glucose and GPx3 levels. ROC analysis indicated a 5.2-fold increased CMD risk with GPx3 below 419.501 ng/mL. Logistic regression suggested that each 100 ng/mL GPx3 increase corresponded to a roughly 20% lower CMD risk (OR = 0.998; 95% CI: 0.996–0.999; p = 0.031). These results support the potential of GPx3 as a biomarker for CMD, particularly in T2DM, and the lack of a significant decline in GPx3 levels in prediabetic individuals suggests that it may not serve reliably as an early indicator of CMDs, warranting further large-scale validation. [ABSTRACT FROM AUTHOR]

Patient empowerment is crucial for promoting and strengthening health. We aimed to assess patient empowerment and diabetes-specific health-related quality of life (HRQoL) in adults with type 2 diabetes (T2D). A multi-centre, cross-sectional survey was conducted among adults with T2D in urban and rural primary care settings in Slovenia between April and September 2023. The survey utilised convenience sampling and included sociodemographic and clinical data, the Diabetes Empowerment Scale (DES), and the Audit of Diabetes-Dependent QoL (ADDQoL). The study included 289 people with T2D and a mean age of 67.2 years (SD 9.2). The mean overall DES score was 3.9/5 (SD 0.4). In a multivariable linear regression model, higher empowerment was significantly associated with residing in a rural region (p = 0.034), higher education (p = 0.028), and a lack of comorbid AH (p = 0.016). The median overall ADDQoL score was −1.2 (IQR [−2.5, −0.6]). The greatest negative influence of diabetes on HRQoL was observed in the domain 'Freedom to eat', followed by 'Freedom to drink', 'Leisure activities', and 'Holidays'. Despite high empowerment among adults with T2D, the condition still imposes a personal burden. Integrated primary care models should prioritise the importance of implementing targeted interventions to enhance diabetes empowerment, address comorbidities, and improve specific aspects of QoL among individuals with T2D. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes is estimated to reach almost 630million casesworldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM2.5) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes. Air pollution exposure is a driver of cardiovascular disease onset and exacerbation and can increase cardiovascular risk among those with diabetes. In this review, we summarize the literature describing the relationships between air pollution exposure, diabetes and cardiovascular disease, highlighting how airborne pollutants can disrupt glucose homeostasis. We discuss how air pollution and diabetes, via shared mechanisms leading to endothelial dysfunction, drive increased cardiovascular disease risk. We identify portable air cleaners as potentially useful tools to prevent adverse cardiovascular outcomes due to air pollution exposure across the diabetes spectrum, while emphasizing the need for further study in this particular population. Given the enormity of the health and financial impacts of air pollution exposure on patients with diabetes, a greater understanding of the interventions to reduce cardiovascular risk in this population is needed. [ABSTRACT FROM AUTHOR]

Purpose: Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes Mellitus (T2DM). However, whether these effects prevent electrocardiographic changes associated with T2DM altogether remain unknown. Our aim was to investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) model of T2DM. Methods: Twenty-five (25) rats were randomized into five (5) groups: normal control receiving a normal diet while the other groups received an 8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), electrocardiograms (ECGs), paracardial adipose mass, and left ventricular fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, with the level of significance at p < 0.05. Results: Compared to the diabetic control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 0.0463). Furthermore, the high dose dapagliflozin group had the lowest paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In contrast, while metformin showed favorable effects on OGT (p = 0.0025), paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did not demonstrate significant antiarrhythmic effects. Conclusion: Pretreatment with higher doses of Dapagliflozin exhibits prophylactic cardioprotective characteristics against diabetic cardiomyopathy that include antifibrotic and antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could be a more effective initial therapeutic option in T2DM. [ABSTRACT FROM AUTHOR]

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Aims: Frequent and extensive within-day glycemic variability (GV) in blood glucose levels may increase the risk of hypoglycemia and long-term mortality in hospitalized patients with diabetes. We aimed to assess the amplitude and frequency of within-day GV in inpatients with type 2 diabetes and to explore the factors influencing within-day GV. Methods: We conducted a single-center, retrospective observational study by analyzing hospital records and 10-day real-time continuous glucose monitoring data. Within-day GV was assessed using the coefficient of variation (%CV). The primary outcome was the amplitude and frequency of within-day GV. The frequency of within-day GV was assessed by the consecutive days (CD) of maintaining within the target %CV range after first reaching it (CD after first reaching the target) and the maximum consecutive days of maintaining within the target %CV range (Max-CD). The target %CV range was less than 24.4%. We evaluated the factors influencing within-day GV using COX regression and Poisson regression models. Results: A total of 1050 cases were analyzed, of whom 86.57% reduced the amplitude of within-day GV before the sixth day of hospitalization. Of the 1050 hospitalized patients, 66.57% stayed within the target %CV range for less than two days after first reaching the target and 69.71% experienced a Max-CD of fewer than four days. Reducing the average postprandial glucose excursion (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.77–0.85; incidence rate ratios [IRR]: 0.72, 95% CI: 0.69–0.74) and the use of α-glucosidase inhibitors (IRR: 1.1, 95% CI: 1.01–1.18) and glucagon-like peptide-1 agonist (IRR: 1.30, 95% CI: 1.02–1.65) contributed to reducing the amplitude and decreasing the frequency of within-day GV. However, the use of insulin (HR: 0.64, 95% CI: 0.55–0.75; IRR: 0.86, 95% CI: 0.79–0.93) and glinide (HR: 0.47, 95% CI: 0.31–0.73; IRR: 0.84, 95% CI: 0.73–0.97) may lead to an increased frequency of within-day GV. Conclusions: An increasing frequency of within-day GV was observed during the hospitalization in patients with type 2 diabetes, despite the effective reduction in the amplitude of within-day GV. Using medications designed to lower postprandial blood glucose could contribute to minimize the risk of frequent within-day GV. [ABSTRACT FROM AUTHOR]

Background: Although studies have shown that glycemic variability is positively associated with an increased risk of cardiovascular disease, few studies have compared hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) variability with adverse cardiovascular events in patientswith type 2 diabetes mellitus (T2DM). Methods: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional hazards models were used to explore the relationship between HbA1c or FPG variability and the incidence of major adverse cardiovascular events (MACEs). Results: In total, 9,547 patients with T2DM were enrolled in this study. During the median 4.6 ± 1.5 years follow-up period, 907 patients developed MACEs. The risk of MACEs increased in the HbA1c variability group in each higher quartile of HbA1c variability (P < 0.01). Compared with those in the first quartile of HbA1c variability, patients in the fourth quartile had a hazard ratio of 1.37 (Model 2, 95% confidence interval: 1.13-1.67) for MACEs. Higher FPG variability was not associated with a higher risk of MACEs in patients with T2DM (P for trend=0.28). A U-shaped relationship was observed between HbA1c and FPG variability, and MACEs. Glucose control therapy modified the relationship between HbA1c and MACEs; participants with higher HbA1c variability receiving intensive glucose control were more likely to develop MACEs (P for interaction <0.01). Conclusion: In adults with T2DM, the relationship between glycemic variability evaluated using HbA1c and FPG was U-shaped, and an increase in HbA1c variability rather than FPG variability was significantly associated with MACEs. The relationship between HbA1c variability and MACEs was affected by the glucose control strategy, and a higher HbA1c variability was more strongly associated with MACEs in patients receiving an intensive glucose control strategy. [ABSTRACT FROM AUTHOR]

Purpose: More than 90% of patients with diabetes worldwide are type 2 diabetes (T2D), which is caused by insulin resistance or impaired producing insulin by pancreatic β cells. T2D and its complications, mainly large cardiovascular (LCV) and kidney (Ne) complications, are the major cause of death in diabetes patients. Recently, the dysregulation of peripheral T cell immune homeostasis was found in most T2D patients. However, the characteristics of T-cell receptors (TCR) remain largely unexplored in T2D patients. Patients and methods: Here we investigated the TCR repertoire using high-throughput sequencing in peripheral blood collected from T2D patient with (8 LCV and 7 Ne) or without complications. Results: Our analysis of TCR repertoires in peripheral blood samples showed that TCR profiles in T2D patients with complications tended to be single and specific compared to controls, according to the characteristics of TCR repertoire in V-J combination number, diversity, principal component analysis (PCA) and differential genes. And we identified some differentially expressed V-J gene segments and amino acid clonotypes, which had the potential to contribute to distinguishing T2D patient with or without complications. As the progression of the disease, we found that the profiling of TCR repertoire was also differential between T2D patients with LVD and Ne complications base on this pilot analysis. Conclusion: This study demonstrated the protentional unique property of TCR repertoire in peripheral blood of T2D patient with and without complications, or T2D patients with LVD and Ne complications, which provided the possibility for future improvements in immune-related diagnosis and therapy for T2D complications. [ABSTRACT FROM AUTHOR]

In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention (n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period (n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders (p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (−0.19, 95% CI −0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (−0.35; 95% CI, −0.54 to −0.16; p < 0.001), and a low disposition index (−0.25; 95% CI, −0.47 to −0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline (p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, −0.06–0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings. [ABSTRACT FROM AUTHOR]

Aims: How the pathology of type 2 diabetes (T2D), including hyperglycaemia and obesity, affects liver enzymes has not been clinically demonstrated. Thus, we compared time courses of gamma‐glutamyltransferase (GGT) and alanine aminotransferase (ALT) with those of fasting plasma glucose (FPG) and body weight (BW) during treatment with the SGLT2 inhibitor tofogliflozin for T2D. Materials and Methods: We post‐hoc analysed preexisting data on 1046 people with T2D administered tofogliflozin or placebo for 24 weeks in four tofogliflozin studies. First, time courses of percent changes in variables during the intervention were analysed using a mixed effect model to explore the similarity of the time courses and to evaluate time‐treatment interactions. Second, clinical factors related to the percent changes in GGT and ALT were clarified using multivariate analyses. Results: GGT levels and FPG values rapidly and significantly decreased via tofogliflozin as early as week 4, with decreases maintained until week 24. Conversely, BW and ALT decreased progressively until week 24. Time courses of FPG (p =.365, time‐treatment interaction) and GGT (p =.510) reductions were parallel between tofogliflozin and placebo from weeks 4 to 24, while BW and ALT reductions (p <.001, respectively) were not. Reductions in GGT at week 24 were associated with reductions in FPG and BW at week 24, whereas ALT reductions were only associated with reductions in BW. Conclusions: Reductions in GGT and ALT were associated with the anti‐hyperglycaemic and anti‐obesity effects of tofogliflozin, respectively, in people with T2D. Therefore, GGT and ALT may be surrogate markers for hyperglycaemia and obesity in T2D. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is now regard as a worldwide health issue affecting hundreds millions of people. It is a metabolic disease targeting glucose metabolism and insulin homeostasis, Type 2 diabetes mellitus (T2DM) is the most prevent type of this disease accounting about 90-95% of the disease as whole. microRNAs (miRNAs) which are a small non-coding RNAs, they revolutionized as potential new biomarkers for the diagnosis and prognosis of a wide range of disorders. Recent studies prove the relationship between miR-21 and inflammatory process and insulin resistance, our emphasis suggest there is a role of miR-21 in insulin resistance in T2DM. Studies have explored the potential of miR-21 as diagnostic biomarkers for T2DM. The purpose of this study is to compare the sera levels of miRNA-21 among newly diagnosed patients e with T2DM patients with their levels in apparently healthy subjects using blood samples. The time frame for this case-control research is August 2022 through March 2023, and it took place at Al-Sadr Teaching Hospital/Masin / Iraq. There were 100 patients home recent diagnosed with T2DM (50 females and 50 males) with age ranged between (20 -70 years) and 100 apparently healthy subject who dealt with as control group. 2 ml of blood drown from each patient and healthy person, putted it in EDTA tube with 1 ml of Trizole as a preservative, and put the tubes in the freezer at -70 degrees Celsius until analyze the samples. [ABSTRACT FROM AUTHOR]

Epidemiological studies have indicated that the consumption of whole-grain products is associated with a reduced risk of cardiovascular diseases, type II diabetes, and cancer. In the case of bread, high amounts of antioxidants and advanced glycation end products (AGEs) are formed during baking by the Maillard reaction in the bread crust; however, the formation of potentially harmful compounds such as acrylamide also occurs. This study investigated the antioxidant responses of different soluble extracts from whole-grain wheat bread crust extracts (WBCEs) in the context of the asparagine, AGE, and acrylamide content. For that, we analyzed nine bread wheat cultivars grown at three different locations in Germany (Hohenheim, Eckartsweier, and Oberer Lindenhof). We determined the asparagine content in the flour of the 27 wheat cultivars and the acrylamide content in the crust, and measured the antioxidant potential using the induced expression of the antioxidant genes GCLM and HMOX1 in HeLa cells. Our study uncovered, for the first time, that the wheat crust's antioxidant potential correlates with the AGE content, but not with the acrylamide content. Mass spectrometric analyses of WBCEs for identifying AGE-modified proteins relevant to the antioxidant potential were unsuccessful. However, we did identify the wheat cultivars with a high antioxidant potential while forming less acrylamide, such as Glaucus and Lear. Our findings indicate that the security of BCEs with antioxidative and cardioprotective potential can be improved by choosing the right wheat variety. [ABSTRACT FROM AUTHOR]

Various animal and cell culture models of diabetes mellitus (DM) have been established and utilized to study diabetic peripheral neuropathy (DPN). The divergence of metabolic abnormalities among these models makes their etiology complicated despite some similarities regarding the pathological and neurological features of DPN. Thus, this study aimed to review the omics approaches toward DPN, especially on the metabolic states in diabetic rats and mice induced by chemicals (streptozotocin and alloxan) as type 1 DMmodels and by genetic mutations (MKR, db/db and ob/ob) and high-fat diet as type 2 DM models. Omics approaches revealed that the pathways associated with lipid metabolism and inflammation in dorsal root ganglia and sciatic nerves were enriched and controlled in the levels of gene expression among these animal models. Additionally, these pathways were conserved in human DPN, indicating the pivotal pathogeneses of DPN. Omics approaches are beneficial tools to better understand the association of metabolic changes with morphological and functional abnormalities in DPN. [ABSTRACT FROM AUTHOR]

As we are aging, a number of cutaneous and extracutaneous disorders will be developed. Although the pathogenesis of these aging-associated disorders is not clear yet, abnormalities in the skin are linked to some aging-associated disorders at least to some extent. Inflammatory dermatoses such as psoriasis and atopic dermatitis predispose to the development of cardiovascular diseases, obesity and type 2 diabetes. In addition, both chronologically aged skin and individuals with some aging-associated systemic conditions display altered epidermal function, such as reduced stratum corneum hydration levels, which can provoke cutaneous inflammation. Because aged skin exhibits higher expression levels of inflammatory cytokines, which play a pathogenic role in a variety of aging-associated health condition, the association of the skin with some aging-associated disorders is likely mediated by inflammation. This postulation is supported by the evidence that improvement in either epidermal function or inflammatory dermatoses can mitigate some aging-associated disorders such as mild cognitive impairment and insulin sensitivity. This perspective discusses the association of the skin with aging-associated disorders and highlights the potential of improvement in cutaneous conditions in the management of some health conditions in the elderly. [ABSTRACT FROM AUTHOR]

Background: Increasing prevalence of morbid obesity accompanied by comorbidities like type 2 diabetes mellitus (T2DM) led to a demand for improving therapeutic strategies and pharmacological intervention options. Apart from genetics, inflammation processes have been hypothesized to be of importance for the development of obesity and related aspects like insulin resistance. Main text: Within this review, we provide an overview of the intricate interplay between chronic inflammation of the adipose tissue and the hypothalamus and the development of obesity. Further understanding of this relationship might improve the understanding of the underlying mechanism and may be of relevance for the establishment of new treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Trehalose is a naturally occurring disaccharide of 2 glucose molecules, which has been suggested as a potential therapeutic agent to reduce blood glucose and ameliorate diabetes-related complications in type 2 diabetes (T2D). This study aimed to determine the efficacy of medium-term trehalose treatment in patients with T2D. Material and methods: A double-blind, randomized, placebo-controlled trial in 40 patients with T2D was undertaken; 20 ingested trehalose 3.3 g/day and 20 placebo (sucrose), for 3 months. Parameters of glycaemic indices, high-sensitivity C-reactive protein (CRP), mood status, and quality of life were measured. Results: CRP was significantly lower with trehalose treatment (-0.62 ±0.3 mg/l, p = 0.02); however, no differences in glycaemic indices of fasting blood glucose (FBG) (-7.1 ±10.7 mg/dl, p = 0.15), glycated hemoglobin (HbA1c) (-0.1 ±0.4%, p = 0.73), insulin (0.73 ±0.8 µU/ml, p = 0.39), or insulin resistance (HOMA-IR) (0.19 ±0.33, p = 0.56) were seen between groups after 12 weeks. Depression and stress scores were lower with trehalose compared to the placebo group (p = 0.02 and p = 0.05, respectively), whilst the quality-of-life score was higher with trehalose compared to placebo (p = 0.03) at the end of study. Between-group differences in these indices did not reach statistical significance (-2.36 ±1.20, -2.21 ±1.39 and 3.00 ±1.76 for depression, stress, and quality-of-life score, respectively) (p > 0.05). The pro-oxidant antioxidant balance (PAB) did not differ between groups (-4.6 ±12.8, p = 0.72). Conclusions: 12 weeks of treatment with 3.3 g/day of oral trehalose significantly improves CRP as a marker of inflammation, with potential favourable effects on quality of life, depression, and stress levels, but overall glycaemic control and pro-oxidant-antioxidant balance were unaltered during this time frame. [ABSTRACT FROM AUTHOR]

The fight against aging is an eternal pursuit of humankind. The aging rate of patients with type 2 diabetes mellitus (T2DM) is higher than that of healthy individuals. Reducing the aging rate of patients with T2DM and extending their life expectancy are challenges that endocrinologists are eager to overcome. Many studies have shown that antidiabetic medications have potent anti-aging potential. Telomeres are repetitive DNA sequences located at the ends of chromosomes, and telomere shortening is a hallmark of aging. This review summarizes clinical trials that have explored the association between antidiabetic medications and telomere length (TL) in patients with T2DM and explore the mystery of delaying aging in patients with T2DM from the perspective of telomeres. Various antidiabetic medications may have different effects on TL in patients with T2DM. Metformin and sitagliptin may protect telomeres in patients with T2DM, while exogenous insulin may promote telomere shortening in patients with T2DM. The effect of acarbose and glyburide on TL in patients with T2DM is still uncertain due to the absence of evidence from longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design. Methods: The participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively. Results: In the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation. Conclusions: In this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients. [ABSTRACT FROM AUTHOR]

Hypoglycemia occurs frequently in people with type 1 and type 2 diabetes. Hypoglycemia activates the counter-regulatory response. Besides peripheral glucose sensors located in the pancreas, mouth, gastrointestinal tract, portal vein, and carotid body, many brain regions also contain glucose-sensing neurons that detect this fall in glucose. The autonomic nervous system innervates the heart, and during hypoglycemia, can cause many changes. Clinical and animal studies have revealed changes in electrocardiograms during hypoglycemia. Cardiac repolarization defects (QTc prolongation) occur during moderate levels of hypoglycemia. When hypoglycemia is severe, it can be fatal. Cardiac arrhythmias are thought to be the major mediator of sudden death due to severe hypoglycemia. Both the sympathetic and parasympathetic nervous systems of the brain have been implicated in regulating these arrhythmias. Besides cardiac arrhythmias, hypoglycemia can have profound changes in the heart and most of these changes are exacerbated in the setting of diabetes. A better understanding of how the brain regulates cardiac changes during hypoglycemia will allow for better therapeutic intervention to prevent cardiovascular death associated with hypoglycemia in people with diabetes. The aim of this paper is to provide a narrative review of what is known in the field regarding how the brain regulates the heart during hypoglycemia. [ABSTRACT FROM AUTHOR]

Obesity is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. Even a modest weight loss of 5–15% improves metabolic health, but circulating markers to indicate weight loss efficiency are lacking. MicroRNAs, small non-coding post-transcriptional regulators of gene expression, are secreted from tissues into the circulation and may be potential biomarkers for metabolic health. However, it is not known which specific microRNA species are reproducibly changed in levels by weight loss. In this study, we performed a systematic review and meta-analysis to investigate the microRNAs associated with weight loss by comparing baseline to follow-up levels following intervention-driven weight loss. This systematic review was performed according to the PRISMA guidelines with searches in PubMed and SCOPUS. The primary search resulted in a total of 697 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 27 full-text articles, which were evaluated for quality and the risk of bias. We performed systematic data extraction, whereafter the relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: miR-26a, miR-126, and miR-223 were overall significantly increased following weight loss, while miR-142 was significantly decreased after weight loss. miR-221, miR-140, miR-122, and miR-146 were not significantly changed by intervention-driven weight loss. These results indicate that few miRNAs are significantly changed during weight loss. [ABSTRACT FROM AUTHOR]

Purpose: Studies have demonstrated a high prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients. The aim was to review the effect of tofogliflozin on hepatic outcomes in T2DM patients. Methods: A literature search in PubMed, Science Direct and Cochrane Central Register of Controlled Trials was conducted for randomised clinical trials of tofogliflozin by applying predetermined inclusion and exclusion criteria. Results: A total number of four randomised clinical trials, including 226 subjects, were included in the review. There was a significant decrease in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in the tofogliflozin group as compared to the control or active comparator groups. Additionally, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) levels were also significantly decreased in the tofogliflozin group. However, no significant difference was observed in levels of adiponectin. Conclusion: Overall, an improvement in levels of hepatic parameters was observed in T2DM patients with concurrent liver disorders. However, a large number of clinical trials are needed to prove the efficacy of tofogliflozin on hepatic outcomes in patients with T2DM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a commonly diagnosed condition that has been extensively studied. The composition and activity of gut microbes, as well as the metabolites they produce (such as short-chain fatty acids, lipopolysaccharides, trimethylamine N-oxide, and bile acids) can significantly impact diabetes development. Treatment options, including medication, can enhance the gut microbiome and its metabolites, and even reverse intestinal epithelial dysfunction. Both animal and human studies have demonstrated the role of microbiota metabolites in influencing diabetes, as well as their complex chemical interactions with signaling molecules. This article focuses on the importance of microbiota metabolites in type 2 diabetes and provides an overview of various pharmacological and dietary components that can serve as therapeutic tools for reducing the risk of developing diabetes. A deeper understanding of the link between gut microbial metabolites and T2D will enhance our knowledge of the disease and may offer new treatment approaches. Although many animal studies have investigated the palliative and attenuating effects of gut microbial metabolites on T2D, few have established a complete cure. Therefore, conducting more systematic studies in the future is necessary. [ABSTRACT FROM AUTHOR]

Introduction: Migrants, especially from the Middle East, experience poorer health outcomes and face greater difficulties in accessing healthcare compared to native populations and there is a need for culturally appropriate education for this vulnerable group. The purpose of this study is to describe the process of developing a culturally appropriate tool to support self-care in migrants with type 2 diabetes.Methods: In this Co-design study, a tool for supporting self-care in migrants with type 2 diabetes was developed. Migrant patients with type 2 diabetes, healthcare providers and researchers participated in the process, which was based on six elements; engage, plan, explore, develop, decide and change. From February 2021 to December 2022, idea groups were conducted, and a tool was developed through brainstorming, prioritizing and prototyping.Results: In total, 14 migrant patients, ten health care providers and four researchers participated in the Co-design process. The patients wished to receive information about type 2 diabetes self-care behaviour in their own languages. The healthcare providers asked for clear instructions on where to guide their patients regarding reliable information about diabetes in the patient's own language. All participants agreed that information can be presented in different formats, either: text (paper or online), audio-visual via recorded videos and/or lectures and pictures.Discussion: The Co-design process led to several important insights and experiences related to the importance of diverse cultural backgrounds. When conducting a Co-design study with end-users as stakeholders, it is significant that the stakeholders have a diverse background in experiences, both as patients as well as those who deliver or implement the health service. In this study it was of great importance to include patients with diverse backgrounds regarding; gender, age, health literacy, occupation, years living in Sweden and duration of diabetes. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality, being twofold to fourfold more common in patients with type 2 diabetes mellitus (T2DM) than in individuals without diabetes. However, despite this decade-old knowledge, the identification of a specific prognostic risk biomarker remains particularly challenging. Methods: Taking advantage of a large sample of Caucasian patients (n = 529) with a diagnosis of T2DM followed for a median of 16.8 years, the present study was aimed at testing the hypothesis that fasting serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could be prognostic for major adverse cardiovascular events (MACE) and all-cause mortality. Results: Median levels of PCSK9 were 259.8 ng/mL, being higher in women compared to men and increasing even more in the presence of a complication (e.g., diabetic kidney disease). PCSK9 positively correlated with markers of blood glucose homeostasis (e.g., HbA1c, fasting insulin and HOMA-IR) and the atherogenic lipid profile (e.g., non-HDL-C, apoB and remnant cholesterol). Serum PCSK9 predicted new-onset of MACE, either fatal or non-fatal, only in women (Odds Ratio: 2.26, 95% CI 1.12–4.58) and all-cause mortality only in men (Hazard Ratio: 1.79, 95% CI 1.13–2.82). Conclusions: Considering that up to two-thirds of individuals with T2DM develop ASCVD in their lifetime, the assessment of circulating PCSK9 levels can be envisioned within the context of a biomarker-based strategy of risk stratification. However, the sex difference found highlights an urgent need to develop sex-specific risk assessment strategies. Trial registration: It is a retrospective study. [ABSTRACT FROM AUTHOR]

Diabetes is one of the greatest healthcare problems; it requires an appropriate approach to the patient, especially when it concerns pregnant women. Gestational diabetes mellitus (GDM) is a common metabolic condition in pregnancy that shares many features with type 2 diabetes mellitus (T2DM). T2DM and GDM induce oxidative stress, which activates cellular stress signalling. In addition, the risk of diabetes during pregnancy can lead to various complications for the mother and foetus. It has been shown that physical activity is an important tool to not only treat the negative effects of diabetes but also to prevent its progression or even reverse the changes already made by limiting the inflammatory process. Physical activity has a huge impact on the immune status of an individual. Various studies have shown that regular training sessions cause changes in circulating immune cell levels, cytokine activation, production and secretion and changes in microRNA, all of which have a positive effect on the well-being of the diabetic patient, mother and foetus. [ABSTRACT FROM AUTHOR]

Simple Summary: No clinical studies have investigated the effect of radioiodine (131I)-targeted therapy on the potential markers of ongoing inflammation in patients with DTC associated with T2DM and obesity. To our knowledge, this is the first study to report the relationship between prescribed 131I activity, blood radioactivity, BMI, and neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios measured three days after 131I intake in DTC with/without T2DM patients. The strong correlation measured between blood radioactivity and high BMI, without a correlation between blood radioactivity and the 131I dose, proves a possible connection between 131I uptake in the bloodstream and chronic inflammation, the so-called "perfect storm", specific to T2DM. Considering the immune response to 131I therapy, the two groups of patients can be seen as a synchronous portrait of two sides: in patients without T2DM, if 131I therapy has immunosuppressive effects, in the chronic inflammation context of T2DM, 131I therapy amplifies immune metabolism. No clinical studies have investigated the effect of radioiodine (131I)-targeted therapy on the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as inflammatory response markers in patients with differentiated thyroid cancer (DTC) associated with type 2 diabetes mellitus (T2DM) and obesity. This study aimed to assess the relationship between blood radioactivity, body mass index (BMI), and peripheral blood cells three days after 131I intake in 56 female patients without T2DM (DTC/−T2DM) vs. 24 female patients with T2DM (DTC/+T2DM). Blood radioactivity, measured three days after 131I intake, was significantly lower in the DTC/+T2DM than in the DTC/−T2DM patients (0.7 mCi vs. 1.5 mCi, p < 0.001). The relationship between blood radioactivity and BMI (r = 0.83, p < 0.001), blood radioactivity and NLR (r = 0.53, p = 0.008), and BMI and NLR (r = 0.58, p = 0.003) indicates a possible connection between the bloodstream 131I uptake and T2DM-specific chronic inflammation. In patients without T2DM, 131I therapy has immunosuppressive effects, leading to increased NLR (19.6%, p = 0.009) and PLR (39.1%, p = 0.002). On the contrary, in the chronic inflammation context of T2DM, 131I therapy amplifies immune metabolism, leading to a drop in NLR (10%, p = 0.032) and PLR (13.4%, p = 0.021). Our results show that, in DTC/+T2DM, the bidirectional crosstalk between neutrophils and obesity may limit 131I uptake in the bloodstream. Considering the immune response to 131I therapy, the two groups of patients can be seen as a synchronous portrait of two sides. The explanation could lie in the different radiosensitivity of T and B lymphocytes, with T lymphocytes being predominant in patients with DTC/−T2DM and, most likely, B lymphocytes being predominant in T2DM. [ABSTRACT FROM AUTHOR]