[Correlation between insulin resistance and coronary collateral circulation in patients with chronic total coronary occlusion].

OBJECTIVE: To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism. METHODS: This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis. RESULTS: NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (P<0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways. CONCLUSION: The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.

Biomaterials-Based Strategies to Enhance Angiogenesis in Diabetic Wound Healing.

Amidst the present healthcare issues, diabetes is unique as an emerging class of affliction with chronicity in a majority of the population. To check and control its effects, there have been huge turnover and constant development of management strategies, and though a bigger part of the health care area is involved in achieving its control and the related issues such as the effect of diabetes on wound healing and care and many of the works have reached certain successful outcomes, still there is a huge lack in managing it, with maximum effect yet to be attained. Studying pathophysiology and involvement of various treatment options, such as tissue engineering, application of hydrogels, drug delivery methods, and enhancing angiogenesis, are at constantly developing stages either direct or indirect. In this review, we have gathered a wide field of information and different new therapeutic methods and targets for the scientific community, paving the way toward more settled ideas and research advances to cure diabetic wounds and manage their outcomes.

Diabetes: a review of its pathophysiology, and advanced methods of mitigation.

Diabetes mellitus (DM) is a long-lasting metabolic non-communicable disease often characterized by an increase in the level of glucose in the blood or hyperglycemia. Approximately, 415 million people between the ages of 20 and 79 years had DM in 2015 and this figure will rise by 200 million by 2040. In a study conducted by CARRS, it's been found that in Delhi the prevalence of diabetes is around 27% and for prediabetic cases, it is more than 46%. The disease DM can be both short-term and long-term and is often associated with one or more diseases like cardiovascular disease, liver disorder, or kidney malfunction. Early identification of diabetes may help avoid catastrophic repercussions because untreated DM can result in serious complications. Diabetes' primary symptoms are persistently high blood glucose levels, frequent urination, increased thirst, and increased hunger. Therefore, DM is classified into four major categories, namely, Type 1, Type 2, Gestational diabetes, and secondary diabetes. There are various oral and injectable formulations available in the market like insulin, biguanides, sulphonylureas, etc. for the treatment of DM. Recent attention can be given to the various nano approaches undertaken for the treatment, diagnosis, and management of diabetes mellitus. Various nanoparticles like Gold Nanoparticles, carbon nanomaterials, and metallic nanoparticles are some of the approaches mentioned in this review. Besides nanotechnology, artificial intelligence (AI) has also found its application in diabetes care. AI can be used for screening the disease, helping in decision-making, predictive population-level risk stratification, and patient self-management tools. Early detection and diagnosis of diabetes also help the patient avoid expensive treatments later in their life with the help of IoT (internet of medical things) and machine learning models. These tools will help healthcare physicians to predict the disease early. Therefore, the Nano drug delivery system along with AI tools holds a very bright future in diabetes care.

Could poor glycaemic control be a predictor of walking speed decline in older adults? Evidence from the English Longitudinal Study of Ageing.

AIM: Although diabetes is a risk factor for walking speed decline in older adults, it remains unclear how glycaemic control [assessed by glycated haemoglobin (HbA1c)] might affect the long-term trajectories of walking speed. We investigated whether the glycaemic control status accelerates the walking speed decline and whether this decline differs depending on previous mobility conditions. MATERIALS AND METHODS: In total, 3202 individuals aged ≥60 years from the English Longitudinal Study of Ageing (ELSA) were classified at baseline and after 4 and 8 years of follow-up according to glycaemic control status as 'without diabetes' (no self-reported diabetes and HbA1c <6.5%), 'good glycaemic control' (self-reported diabetes and HbA1c ≥6.5% and <7.0%) and 'poor glycaemic control' (PGC) (self-reported diabetes and HbA1c ≥7.0%). The generalized linear mixed models verified the walking speed trajectories in m/s. A second analysis was performed, including only participants without slowness at baseline (>0.8 m/s). RESULTS: Compared with the status 'without diabetes', the annual walking speed decline was -0.015 m/s for PGC and -0.011 m/s for good glycaemic control, totalling -0.160 and -0.130 m/s, respectively, over 8 years. Among those without slowness at baseline, only PGC had a significant walking speed decline, corresponding to -0.014 m/s per year and -0.222 m/s over 8 years. CONCLUSIONS: Poor glycaemic control is a discriminator of walking speed decline in older adults, regardless of previous mobility conditions. It may serve as an early screening tool for those at risk of decreased functional performance later in life.

Association between dietary inflammatory index and low muscle mass in diabetes/prediabetes patients.

BACKGROUND: Growing evidence has increasingly validated that individuals with diabetes/prediabetes have a higher prevalence of low skeletal muscle mass and function compared to healthy individuals. The anti-inflammatory diet is considered a promising and modifiable approach to optimize skeletal muscle quality. However, current evidence on the relation of dietary inflammatory potential with low muscle mass among diabetic/prediabetic patients is limited. METHODS: Dietary consumption was determined by trained staff using the 24-hour diet recall method, and the Dietary Inflammatory Index (DII) was scored based on a previously validated approach that included 26 food parameters. Dual-energy X-ray absorptiometry was used to assess the mass of skeletal muscle and low muscle mass was defined based on the sarcopenia index. Logistic regression was conducted to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). Restricted cubic spline (RCS) analysis was also performed to visually represent the relationship between DII and low muscle mass. Furthermore, sensitivity and subgroup analyses were conducted. RESULTS: In this study, a total of 4269 eligible participants were registered, comprising 1975 (46.26 %) females and 2294 (53.74 %) males. The mean age was 49.98 ± 0.31 years old, and the mean DII score was 1.53 ± 0.04. Among them, 934 (21.88 %) patients were defined as having low muscle mass, while 3335 (78.12 %) were without low muscle mass. The highest tertile (T3) of DII had an 61 % increased risk of low muscle mass (OR = 1.61, 95%CI: 1.19-2.17, p for trend = 0.004) compared to the lowest tertile. The RCS curve displayed a linear dose-response relationship between DII score and low muscle mass risk in patients with diabetes/prediabetes. Subgroup and sensitivity analyses provided robustness to our results. CONCLUSIONS: Our results indicated that a higher DII score was associated with an increased risk of low muscle mass among diabetes/prediabetes patients. These findings provided a nutritional strategy for diabetes/prediabetes patients to prevent skeletal muscle mass loss.

Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia.

Introduction: Diabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized. Method: The current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Results: A total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant (P < 0.05, VIP > 1, FC > 1.2 or FC < 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased. Discussion: Based on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P < 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.

Understanding and treating ejaculatory dysfunction in men with diabetes mellitus.

Diabetes mellitus is a rapidly rising metabolic disorder with important systemic complications. Global figures have demonstrated the prevalence of diabetes mellitus has almost quadrupled from 108 million in 1980 to 422 million in 2014, with a current prevalence of over 525 million. Of the male sexual dysfunction resulting from diabetes mellitus, significant focus is afforded to erectile dysfunction. Nevertheless, ejaculatory dysfunction constitutes important sexual sequelae in diabetic men, with up to 35%-50% of men with diabetes mellitus suffering from ejaculatory dysfunction. Despite this, aspects of its pathophysiology and treatment are less well understood than erectile dysfunction. The main disorders of ejaculation include premature ejaculation, delayed ejaculation, anejaculation and retrograde ejaculation. Although ejaculatory dysfunction in diabetes mellitus can have complex multifactorial aetiology, understanding its pathophysiological mechanisms has facilitated the development of therapies in the management of ejaculatory dysfunction. Most of our understanding of its pathophysiology is derived from diabetic animal models; however, observational studies in humans have also provided useful information in elucidating important associative factors potentially contributing to ejaculatory dysfunction in diabetic men. These have provided the potential for more tailored treatment regimens in patients depending on the ejaculatory disorder, other co-existing sequelae of diabetes mellitus, specific metabolic factors as well as the need for fertility treatment. However, evidence for treatment of ejaculatory dysfunction, especially delayed ejaculation and retrograde ejaculation, is based on low-level evidence comprising small sample-size series and retrospective or cross-sectional studies. Whilst promising findings from large randomised controlled trials have provided strong evidence for the licensed treatment of premature ejaculation, similar robust studies are needed to accurately elucidate factors predicting ejaculatory dysfunction in diabetes mellitus, as well as for the development of pharmacotherapies for delayed ejaculation and retrograde ejaculation. Similarly, more contemporary robust data are required for fertility outcomes in these patients, including methods of sperm retrieval and assisted reproductive techniques in retrograde ejaculation.

The impact of progredient vessel and tissue stiffening for the development of metabolic syndrome.

Established risk factors for the metabolic syndrome as diabetes and arterial hypertension are believed to be the cause of arteriosclerosis and subsequently following diseases like coronary heart disease, apoplexy, or chronic renal failure. Based on broad evidence from the already available experimental literature and clinical experience, an alternative hypothesis is presented that puts an increased vessel and organ stiffness to the beginning of the pathophysiological scenario. The stiffness itself is caused by a persistent activation of mechano-sensitive cation channels like the epithelial/endothelial sodium channel. A further enhancement takes place by proteins like JACD and RhoA coupled phospholipase C coupled G-protein receptors and integrins. A self-enhancing positive feedback loop by activation of YAP/TAZ signaling is a further central pillar of this theory. Further investigations are necessary to verify this hypothesis. If this hypothesis could be confirmed fundamental changes regarding the pharmacologic therapy of the diseases that are currently summarizes as metabolic syndrome would be the consequence.

Association of Ultra-Widefield Fluorescein Angiography-Identified Retinal Nonperfusion and the Risk of Diabetic Retinopathy Worsening Over Time.

Importance: Presence of predominantly peripheral diabetic retinopathy (DR) lesions on ultra-widefield fluorescein angiography (UWF-FA) was associated with greater risk of DR worsening or treatment over 4 years. Whether baseline retinal nonperfusion assessment is additionally predictive of DR disease worsening is unclear. Objective: To assess whether the extent and location of retinal nonperfusion identified on UWF-FA are associated with worsening in Diabetic Retinopathy Severity Scale (DRSS) score or DR treatment over time. Design, Setting, and Participants: This cohort study was a prospective, multicenter, longitudinal observational study with data for 508 eyes with nonproliferative DR and gradable nonperfusion on UWF-FA at baseline. All images were graded at a centralized reading center; 200° ultra-widefield (UWF) color images were graded for DR at baseline and annually for 4 years. Baseline 200° UWF-FA images were graded for nonperfused area, nonperfusion index (NPI), and presence of predominantly peripheral lesions on UWF-FA (FA PPL). Interventions: Treatment of DR or diabetic macular edema was at investigator discretion. Main Outcomes and Measures: Association of baseline UWF-FA nonperfusion extent with disease worsening, defined as either 2 or more steps of DRSS worsening within Early Treatment Diabetic Retinopathy Study fields on UWF-color images or receipt of DR treatment. Results: After adjusting for baseline DRSS, the risk of disease worsening over 4 years was higher in eyes with greater overall NPI (hazard ratio [HR] for 0.1-unit increase, 1.11; 95% CI, 1.02-1.21; P = .02) and NPI within the posterior pole (HR for 0.1-unit increase, 1.35; 95% CI, 1.17-1.56; P < .001) and midperiphery (HR for 0.1-unit increase, 1.08; 95% CI, 1.00-1.16; P = .04). In a multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95% CI, 1.02-1.22; P = .02) and presence of FA PPL (HR, 1.89; 95% CI, 1.35-2.65; P < .001) remained associated with disease worsening. Conclusions and Relevance: This 4-year longitudinal study has demonstrated that both greater baseline retinal nonperfusion and FA PPL on UWF-FA are associated with higher risk of disease worsening, even after adjusting for baseline DRSS score and known systemic risk. These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research.

Lower limb amputations among individuals living with diabetes mellitus in low- and middle-income countries: A systematic review protocol.

BACKGROUND: The burden of diabetes mellitus (DM) and its associated complications continue to burgeon, particularly in low- and middle-income countries (LMICs). Lower limb amputation (LLA) is one of the most life-altering complications of DM, associated with significant morbidity, mortality and socio-economic impacts. High-income countries have reported a decreasing incidence of DM-associated LLA, but the situation in many LMICs is unknown. We aim to conduct a systematic review to determine the incidence and prevalence of DM-associated LLA in LMICs to better inform appropriate interventions and health system response. METHODS AND ANALYSIS: A systematic search of the literature will be conducted on five databases: MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus and African Journal Online (AJOL). Only observational, quantitative studies reporting the incidence and/or prevalence of DM-related LLA will be considered. A validated study design-specific critical appraisal tool will be used to assess the risk of bias in individual studies. We will determine the incidence of LLA by examining the number of new cases of LLA among individuals with confirmed DM diagnosis during the specified period, while the prevalence will be based on the total number of all new and existing LLAs in a population. LLA will be considered as the resection of the lower limb from just above the knee to any point down to the toe. If heterogeneity is low to moderate, a random-effects meta-analysis will be conducted on extracted crude prevalence/incidence rates, with the median and interquartile range also reported. The systematic review will be performed in accordance with the JBI guideline for prevalence and incidence review. Study reporting will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guideline. PROSPERO REGISTRATION NUMBER: CRD42021238656.

Sex Differences in Peripheral Artery Disease.

Peripheral artery disease (PAD) is a prevalent condition that confers substantial morbidity and mortality and remains underdiagnosed as well as undertreated in the overall population. Although PAD prevalence is similar or higher in women compared with men, associations of traditional and nontraditional risk factors with PAD and clinical manifestations of PAD differ by sex and may contribute to delayed or lack of diagnosis in women. Such sex-based differences in the manifestation of PAD may arise from sexual dimorphism in the vascular substrate in health as well as sex variation in the responses to vascular stressors. Despite the availability of proven therapies for improving symptoms and reducing risk of ischemic cardiovascular and limb events among patients with diagnosed PAD, important sex differences in treatment and outcomes have been observed. We provide an overview of current knowledge regarding sex differences in the epidemiology, pathophysiology, clinical presentation, and management of PAD.

The Impact of Sex and Gender on Stroke.

Women face a disproportionate burden of stroke mortality and disability. Biologic sex and sociocultural gender both contribute to differences in stroke risk factors, assessment, treatment, and outcomes. There are substantial differences in the strength of association of stroke risk factors, as well as female-specific risk factors. Moreover, there are differences in presentation, response to treatment, and stroke outcomes in women. This review outlines current knowledge of impact of sex and gender on stroke, as well as delineates research gaps and areas for future inquiry.

Long-Term Changes in Sarcopenia and Body Composition in Diabetes Patients with and without Charcot Osteoarthropathy.

BACKGROUND: Charcot osteoarthropathy of the foot (COA) can currently only be treated using prolonged periods of immobilization of the affected extremity. Therefore, the hypothesis is that COA leads to altered body composition and increased sarcopenia. OBJECTIVE: To investigate the changes over several years in sarcopenia, body composition, and fat distribution in diabetes patients with previous COA compared to diabetes patients without previous COA. METHODS: Prospective observational clinical study. Twenty-one subjects were included and had two DXA scans done with mean 8.6-year intervals to compare changes in lean mass and fat distribution. The lean mass of limbs was used as an estimate of appendicular lean mass (aLM). Fat mass and aLM were then used to detect sarcopenic individuals using different methods. Results and Conclusions. As compared to baseline, both groups had significant loss of lean mass, and diabetics without COA had significant gain of total fat percentage. No statistically different prevalence of sarcopenia between the groups could be established. Likewise, no difference was found in total lean and fat mass changes. None of the groups had statistically significant changes of android fat distribution. As compared with published data on sarcopenia, people with diabetes might be more prone to sarcopenia than healthy individuals.

Delivering the National Diabetes Prevention Program: Assessment of Enrollment in In-Person and Virtual Organizations.

The aim of the US Centers for Disease Control and Prevention's (CDC) National Diabetes Prevention Program (National DPP) is to make an evidence-based lifestyle change program widely available to the more than 88 million American adults at risk for developing type 2 diabetes. The National DPP allows for program delivery using four delivery modes: in person, online, distance learning, and combination. The objective of this study was to analyze cumulative enrollment in the National DPP by delivery mode. We included all participants who enrolled in CDC-recognized organizations delivering the lifestyle change program between January 1, 2012, and December 31, 2019, and whose data were submitted to CDC's Diabetes Prevention Recognition Program. During this time, the number of participants who enrolled was 455,954. Enrollment, by delivery mode, was 166,691 for in-person; 269,004 for online; 4,786 for distance-learning; and 15,473 for combination. In-person organizations enrolled the lowest proportion of men (19.4%) and the highest proportions of non-Hispanic Black/African American (16.1%) and older (65+ years) participants (28.2%). Online organizations enrolled the highest proportions of men (27.1%), younger (18-44 years) participants (41.5%), and non-Hispanic White participants (70.3%). Distance-learning organizations enrolled the lowest proportion of Hispanic/Latino participants (9.0%). Combination organizations enrolled the highest proportions of Hispanic/Latino participants (37.3%) and participants who had obesity (84.1%). Most in-person participants enrolled in organizations classified as community-centered entities (41.4%) or medical providers (31.2%). Online and distance-learning participants were primarily enrolled (93.3% and 70.2%, respectively) in organizations classified as for-profit businesses or insurers. Participants in combination programs were enrolled almost exclusively in organizations classified as medical providers (89%). The National DPP has reached nearly half a million participants since its inception in 2012, but continued expansion is critical to stem the tide of type 2 diabetes among the many Americans at high risk.