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.

The association between trajectories of risk factors and risk of cardiovascular disease or mortality among patients with diabetes or hypertension: A systematic review.

INTRODUCTION: Cardiometabolic risk factors and renal function are monitored regularly for patients with diabetes mellitus (DM)/ hypertension (HT). In addition to risk factor levels at a single time point, their trajectory (changes over time) can also be differentially related to the risk of cardiovascular diseases (CVD) and mortality. This study aimed to systematically examine the evidence regarding the association between risk factor trajectories and risk of CVD/mortality in patients with DM/HT. METHOD: PubMed, MEDLINE, and Embase were searched for articles from January 1963 to April 2021. Inclusion criteria: studies that 1) analyzed trajectories of risk factors including haemoglobin A1c (HbA1c), blood pressure, estimated glomerular filtration rate (eGFR), body mass index (BMI), and blood lipids; 2) were performed in the DM/HT population and, 3) included risk of CVD/mortality as outcomes. Study quality was assessed using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 22,099 articles were identified. After screening by title and abstract, 22,027 articles were excluded by irrelevant outcomes, exposure, population, or type of articles. Following full-text screening, 11 articles investigating the trajectories of HbA1c (N = 7), systolic blood pressure (SBP) (N = 3), and eGFR (N = 1) were included for data extraction and analysis. No studies were identified examining the association of BMI or lipid trajectories with CVD/mortality. All included studies were of good quality based on the NOS criteria. In general, stable trajectories within optimal ranges of the risk factors (HbA1c: <7%, SBP: 120-139mmHg, eGFR: >60mL/min/1.73m2) had the lowest CVD/mortality risk compared to an increasing HbA1c trajectory (from 8% to 10%), an increasing SBP trajectory (from 120-139 to ≥140mmHg), or a decreasing eGFR trajectory (from 90 to 70mL/min/1.73m2). CONCLUSION: A relatively stable and well-controlled trajectory for cardiometabolic risk factors was associated with the lowest risk of CVD/mortality. Risk factor trajectories have important clinical implications in addition to single time point measurements. More attention should be given to patients with suboptimal control and those with unstable trends of cardiometabolic risk factors.

Evidence of plasma biomarkers indicating high risk of dementia in cognitively normal subjects.

Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aß1-42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aß1-42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aß1-42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aß1-42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers.

Can Overnutrition Lead to Wasting?-The Paradox of Diabetes Mellitus in End-Stage Renal Disease Treated with Maintenance Hemodialysis.

BACKGROUND: The population of end-stage renal disease (ESRD) patients with diabetes mellitus (DM) may be at increased risk of protein energy wasting (PEW). The aim of the study was to investigate the impact of DM on selected indicators of PEW in the ESRD population that was undergoing maintenance hemodialysis (MHD). METHODS: A total of 515 MHD patients were divided into two subgroups with and without DM. The evaluation of diet composition, Charlson Comorbidity Index (CCI), SGA, and laboratory and BIS analyses were performed. All-cause and cardiovascular mortality was recorded. RESULTS: DM patients had lower albumin (3.93 (3.61-4.20) vs. 4.10 (3.80-4.30) g/dL, p < 0.01), total cholesterol (158 (133-196) vs. 180 (148-206) mg/dL, p < 0.01), and creatinine (6.34 (5.08-7.33) vs. 7.12 (5.70-8.51) mg/dL, p < 0.05). SGA score (12.0 (10.0-15.0) vs. 11.0 (9.0-13.0) points, p < 0.001), BMI (27.9 (24.4-31.8) vs. 25.6 (22.9-28.8) kg/m2, p < 0.001), fat tissue index (15.0 (11.4-19.6) vs. 12.8 (9.6-16.0) %, p < 0.001), and overhydration (2.1 (1.2-4.1) vs. 1.8 (0.7, 2.7) L, p < 0.001) were higher in the DM group. Increased morbidity, reflected in the CCI and mortality-both all-cause and cardiovascular-were observed in DM patients. CONCLUSIONS: Hemodialysis recipients with DM experience overnutrition with a paradoxically higher predisposition to PEW, expressed by a higher SGA score and lower serum markers of nutrition. This population is also more comorbid and is at higher risk of death, including from cardiovascular causes.

Circulating biomarkers, echocardiographic parameters, and incident subclinical atrial fibrillation in patients with diabetes and hypertension.

BACKGROUND: Long-term rhythm monitoring (LTRM) can detect undiagnosed atrial fibrillation (AF) in patients at high risk of AF and stroke. Biomarkers and echocardiographic parameters could, however, help identify patients benefitting most from LTRM. The aim of this study was to investigate, whether circulating biomarkers of cardiac and vascular function (brain natriuretic peptide (BNP), cardiac troponin I (cTnI), copeptin, and mid-regional proadrenomedullin (MR-proADM)) and echocardiographic parameters were associated with incident subclinical AF (SCAF) in a population at high risk of stroke in the presence of AF. For this purpose, we investigated individuals ≥65 years of age with hypertension and diabetes mellitus, but no history or symptoms of AF or other cardiovascular disease (CVD). METHODS: We included 82 consecutive patients (median age 71.3 years (IQR 67.4-75.1)). All patients received an insertable cardiac monitor (ICM) and were followed for a median of 588 days (IQR 453-712). On the day of ICM implantation, a comprehensive echocardiogram and blood samples were obtained. RESULTS: During a median follow-up of 588 days (IQR: 453-712 days), incident SCAF occurred in 17 patients (20.7%) with a median time to first-detected episode of 91 days (IQR 41-251 days). MR-proADM (median 0.87 nmol/L (IQR 0.76-1.02) vs 0.78 nmol/L (IQR 0.68-0.98)) and copeptin (median 13 pmol/L (IQR 9-17) vs 8 pmol/L (IQR 4-18)) levels were insignificantly higher in patients with incident SCAF. BNP and cTnI concentrations and echocardiographic parameters were similar in the two groups. CONCLUSIONS: MR-proADM, BNP, cTnI, copeptin, and several echocardiographic parameters were not associated with incident SCAF in this cohort of patients with hypertension and diabetes, but without any underlying CVD.

Comparison of bovine serum albumin glycation by ribose and fructose in vitro and in vivo.

Advanced glycation end products (AGEs) play a critical pathogenic role in the development of diabetic complications. Recent studies have shown that diabetes is associated with not only abnormal glucose metabolism but also abnormal ribose and fructose metabolism, although glucose is present at the highest concentration in humans. The glycation ability and contribution of ribose and fructose to diabetic complications remain unclear. Here, the glycation ability of ribose, fructose and glucose under a mimic physiological condition, in which the concentration of ribose or fructose was one-fiftieth that of glucose, was compared. Bovine serum albumin (BSA) was used as the working protein in our experiments. Ribose generated more AGEs and was markedly more cytotoxic to SH-SY5Y cells than fructose. The first-order rate constant of ribose glycation was found to be significantly greater than that of fructose glycation. LC-MS/MS analysis revealed 41 ribose-glycated Lys residues and 12 fructose-glycated residues. Except for the shared Lys residues, ribose reacted selectively with 17 Lys, while no selective Lys was found in fructose-glycated BSA. Protein conformational changes suggested that ribose glycation may induce BSA into amyloid-like monomers compared with fructose glycation. The levels of serum ribose were correlated positively with glycated serum protein (GSP) and diabetic duration in type 2 diabetes mellitus (T2DM), respectively. These results indicate that ribose has a greater glycation ability than fructose, while ribose largely contributes to the production of AGEs and provides a new insight to understand in the occurrence and development of diabetes complications.

Diabetic Pneumopathy-A New Diabetes-Associated Complication: Mechanisms, Consequences and Treatment Considerations.

Patients with diabetes are over-represented among the total cases reported with "idiopathic" pulmonary fibrosis (IPF). This raises the question, whether this is an association only or whether diabetes itself can cause pulmonary fibrosis. Recent studies in mouse models of type 1 and type 2 diabetes demonstrated that diabetes causes pulmonary fibrosis. Both types of diabetes trigger a cascade, starting with increased DNA damage, an impaired DNA repair, and leading to persistent DNA damage signaling. This response, in turn, induces senescence, a senescence-associated-secretory phenotype (SASP), marked by the release of pro-inflammatory cytokines and growth factors, finally resulting in fibrosis. Restoring DNA repair drives fibrosis into remission, thus proving causality. These data can be translated clinically to patients with type 2 diabetes, characterized by long-term diabetes and albuminuria. Hence there are several arguments, to substitute the term "idiopathic" pulmonary fibrosis (IPF) in patients with diabetes (and exclusion of other causes of lung diseases) by the term "diabetes-induced pulmonary fibrosis" (DiPF). However, future studies are required to establish this term and to study whether patients with diabetes respond to the established therapies similar to non-diabetic patients.

Vitamin D Deficiency in Patients with Diabetes in French Guiana: Epidemiology and Relation with Microvascular and Macrovascular Complications.

Vitamin D (VD) insufficiency is common among patients with diabetes in French Guiana. The study aimed to evaluate the prevalence of VD deficiency in the different type of diabetes encountered and to analyze the relationship between VD deficiency and diabetes complications. METHODS: An observational study was conducted between May 2019 and May 2020 in French Guiana, based on data from the CODIAM study (Diabetes Cohort in French Amazonia), describing the characteristics of patients with diabetes mellitus. Among 600 patients enrolled with diabetes, 361 had an available VD assay. RESULTS: The mean 25(OH)VD (hydroxycalciferol) level was 27.9 ng/mL. The level of VD was inversely proportional to the HbA1c (glycated hemoglobin) level. Patients with angina pectoris had a greater proportion of deficiencies VD < 20 ng/mL than those without angina. By contrast, patients with retinopathy had higher vitamin D concentrations than those without retinopathy. There was no association between vitamin D and arteriopathy, stroke, nephropathy and polyneuropathy. VD deficiency was more frequent in women, and in patients with a high school education. CONCLUSION: The prevalence of VD deficiency was high in patients with diabetes in French Guiana, emphasizing the importance of VD supplementation.

CT Image Features of the FBP Reconstruction Algorithm in the Evaluation of Fasting Blood Sugar Level of Diabetic Pulmonary Tuberculosis Patients and Early Diet Nursing.

The study was aimed at exploring the application value of the CT image based on a filtered back projection (FBP) algorithm in the diagnosis of patients with diabetes complicated with tuberculosis and at analyzing the influence of dietary nursing on patients with diabetes complicated with tuberculosis. In this study, the FBP algorithm was used to optimize CT images to effectively obtain reconstructed ROI images. Then, the deviation from measurement values of reconstructed images at different pixel levels was analyzed. 138 patients with diabetes complicated with tuberculosis were selected as research subjects to compare the number of lung segments involved and the CT imaging manifestations at different fasting glucose levels. All patients were divided into the control group (routine drug treatment) and observation group (diet intervention on the basis of drug treatment) by random number table method, and the effect of different nursing methods on the improvement of patients' clinical symptoms was discussed. The results showed that the distance measurement value decreased with the increase in pixel level, there was no significant difference in the number of lung segments involved in patients with different fasting glucose levels (P > 0.05), and there were statistically significant differences in the incidence of segmental lobar shadow, bronchial air sign, wall-less cavity, thick-walled cavity, pulmonary multiple cavity, and bronchial tuberculosis in patients with different fasting glucose levels (P < 0.05). Compared with the control group, 2 h postprandial blood glucose level in the observation group was significantly improved (P < 0.05), there was a statistical significance in the number with reduced pleural effusion and the number with reduced tuberculosis foci in the two groups (P < 0.05), and the level of hemoglobin in the observation group was 7.1 ± 1.26, significantly lower than that in the control group (8.91 ± 2.03, P < 0.05). It suggested that the changes of CT images based on the FBP reconstruction algorithm were correlated with fasting blood glucose level. Personalized diet nursing intervention can improve the clinical symptoms of patients, which provides a reference for the clinical diagnosis and treatment of patients with diabetes complicated with tuberculosis.

Achievement of treatment targets predicts progression of vascular complications in type 1 diabetes.

BACKGROUND AND AIM: To study the association between achievement of guideline-defined treatment targets on HbA1c, low-density lipoproteins (LDL-C), and blood pressure with the progression of diabetic complications in patients with type 1 diabetes (T1D). METHODS: The study included 355 patients at baseline and 114 patients with follow-up data after 3-5 years. Outcome variables were the progression of diabetic kidney disease, retinopathy, or cardiovascular disease (CVD). We used logistic regression and other machine learning algorithms (MLA) to model the association of achievement of treatment targets and probability of progression of complications. RESULTS: Achievement of the target blood pressure was associated with 96% lower odds of a new CVD event (0.04 (95% CI 0.00, 0.53), p = 0.016), and 72% lower odds of progression of any complication (0.28 (95% CI 0.09, 0.89), p = 0.027. Achievement of HbA1c target was associated with lower odds of composite complication progression by 82% (0.18 (95% CI 0.04, 0.88), p = 0.034.) None of the patients who achieved HbA1c target progressed in CVD. MLA demonstrated good accuracy for the prediction of progression of CVD (AUC 0.824), and lower accuracy for other complications. CONCLUSION: The achievement of blood pressure and HbA1c treatment targets is associated with lower odds of vascular complication of T1D in a real life study.

Inferior survival outcomes of pancreas transplant alone in uremic patients.

Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal.

HSP70 as a biomarker of the thin threshold between benefit and injury due to physical exercise when exposed to air pollution.

Physical exercise has acute and chronic effects on inflammatory balance, metabolic regulation, and redox status. Exercise-induced adaptations are mediated by enhanced 70-kDa heat shock protein (HSP70) levels and an improved heat shock response (HSR). Therefore, exercise could be useful against disease conditions [obesity, diabetes mellitus (DM), and exposure to atmospheric pollutants] marked by an impaired HSR. However, exercise performed by obese or diabetic subjects under pollution conditions might also be dangerous at certain intensities. Intensity correlates with an increase in HSP70 levels during physical exercise until a critical point at which the effort becomes harmful and impairs the HSR. Establishing a unique biomarker able to indicate the exercise intensity on metabolism and cellular fatigue is essential to ensure adequate and safe exercise recommendations for individuals with obesity or DM who require exercise to improve their metabolic status and live in polluted regions. In this review, we examined the available evidence supporting our hypothesis that HSP70 could serve as a biomarker for determining the optimal exercise intensity for subjects with obesity or diabetes when exposed to air pollution and establishing the fine threshold between anti-inflammatory and pro-inflammatory exercise effects.

D-dimer Level and Diabetes in the COVID-19 Infection.

INTRODUCTION: Diabetes is the most common of comorbidity in patients with SARS-COV-2 pneumonia. Coagulation abnormalities with D-dimer levels are increased in this disease. OBJECTIFS: We aimed to compare the levels of D-dimer in diabetic and non-diabetic patients with COVID 19. A link between D-dimer and mortality has also been established. MATERIALS: A retrospective study was carried out at the University Hospital Center of Oujda (Morocco) from November 01st to December 01st, 2020. Our study population was divided into two groups: a diabetic group and a second group without diabetes to compare clinical and biological characteristics between the two groups. In addition, the receiver operator characteristic curve was used to assess the optimal D-dimer cut-off point for predicting mortality in diabetics. RESULTS: 201 confirmed-COVID-19-patients were included in the final analysis. The median age was 64 (IQR 56-73), and 56% were male. Our study found that D-dimer levels were statistically higher in diabetic patients compared to non-diabetic patients. (1745 vs 845 respectively, P = 0001). D-dimer level > 2885 ng/mL was a significant predictor of mortality in diabetic patients with a sensitivity of 71,4% and a specificity of 70,7%. CONCLUSION: Our study found that diabetics with COVID-19 are likely to develop hypercoagulation with a poor prognosis.

Alcohol use and dysglycemia among people living with human immunodeficiency virus (HIV) in the Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions (ALIVE-Ex) study.

BACKGROUND: At-risk alcohol use is a common and costly form of substance misuse that is highly prevalent among people living with HIV (PLWH). The goal of the current analysis was to test the hypothesis that PLWH with at-risk alcohol use are more likely to meet the clinical criteria for prediabetes/diabetes than PLWH with low-risk alcohol use. METHODS: A cross-sectional analysis was performed on measures of alcohol and glycemic control in adult PLWH (n = 105) enrolled in a prospective, interventional study (the ALIVE-Ex Study (NCT03299205)) that investigated the effects of aerobic exercise on metabolic dysregulation in PLWH with at-risk alcohol use. The Alcohol Use Disorders Identification Test (AUDIT), Timeline Followback, and phosphatidylethanol (PEth) level were used to measure alcohol use. Participants were stratified into low-risk (AUDIT score < 5) and at-risk alcohol use (AUDIT  score ≥ 5). All participants underwent an oral glucose tolerance test and measures of glycemic control- the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Matsuda Index - were correlated with alcohol measures and compared by AUDIT score group using mixed-effects linear and logistic regression models, adjusting for age, sex, race, body mass index (BMI), and viral load. RESULTS: In response to the glucose challenge, participants with at-risk alcohol use (n = 46) had higher glucose levels and were five times more likely to meet criteria for prediabetes/diabetes (OR: 5.3 (1.8, 15.9)) than participants with an AUDIT score < 5. Two-hour glucose values were positively associated with AUDIT score and PEth level and a higher percentage of PLWH with at-risk alcohol use had glucose values ≥140 mg/dl than those with low-risk alcohol use (34.8% vs. 10.2%, respectively). CONCLUSION: In this cohort of PLWH, at-risk alcohol use increased the likelihood of meeting the clinical criteria for prediabetes/diabetes (2-h glucose level ≥140 mg/dl). Established determinants of metabolic dysfunction (e.g., BMI, waist-hip ratio) were not associated with greater alcohol use and dysglycemia, suggesting that other mechanisms may contribute to the impaired glycemic control observed in this cohort.

Calculated plasma osmolality at hospital admission correlates well with eGFR and D-Dimer, a simple outcome predictor and guiding tool for management of severe COVID-19 patients.

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.

Aldose Reductase: a cause and a potential target for the treatment of diabetic complications.

Diabetes mellitus, a disorder of metabolism, results in the elevation of glucose level in the blood. In this hyperglycaemic condition, aldose reductase overexpresses and leads to further complications of diabetes through the polyol pathway. Glucose metabolism-related disorders are the accumulation of sorbitol, overproduction of NADH and fructose, reduction in NAD+, and excessive NADPH usage, leading to diabetic pathogenesis and its complications such as retinopathy, neuropathy, and nephropathy. Accumulation of sorbitol results in the alteration of osmotic pressure and leads to osmotic stress. The overproduction of NADH causes an increase in reactive oxygen species production which leads to oxidative stress. The overproduction of fructose causes cell death and non-alcoholic fatty liver disease. Apart from these disorders, many other complications have also been discussed in the literature. Therefore, the article overviews the aldose reductase as the causative agent and a potential target for the treatment of diabetic complications. So, aldose reductase inhibitors have gained much importance worldwide right now. Several inhibitors, like derivatives of carboxylic acid, spirohydantoin, phenolic derivatives, etc. could prevent diabetic complications are discussed in this article.

Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients.

The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.

Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce SARS-CoV2-Induced Inflammatory Cytokines Under High Glucose and Uremic Toxin Conditions.

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

A Serum Resistin and Multicytokine Inflammatory Pathway Is Linked With and Helps Predict All-cause Death in Diabetes.

CONTEXT: Type 2 diabetes (T2D) shows a high mortality rate, partly mediated by atherosclerotic plaque instability. Discovering novel biomarkers may help identify high-risk patients who would benefit from more aggressive and specific managements. We recently described a serum resistin and multicytokine inflammatory pathway (REMAP), including resistin, interleukin (IL)-1ß, IL-6, IL-8, and TNF-α, that is associated with cardiovascular disease. OBJECTIVE: We investigated whether REMAP is associated with and improves the prediction of mortality in T2D. METHODS: A REMAP score was investigated in 3 cohorts comprising 1528 patients with T2D (409 incident deaths) and in 59 patients who underwent carotid endarterectomy (CEA; 24 deaths). Plaques were classified as unstable/stable according to the modified American Heart Association atherosclerosis classification. RESULTS: REMAP was associated with all-cause mortality in each cohort and in all 1528 individuals (fully adjusted hazard ratio [HR] for 1 SD increase = 1.34, P < .001). In CEA patients, REMAP was associated with mortality (HR = 1.64, P = .04) and a modest change was observed when plaque stability was taken into account (HR = 1.58; P = .07). REMAP improved discrimination and reclassification measures of both Estimation of Mortality Risk in Type 2 Diabetic Patients and Risk Equations for Complications of Type 2 Diabetes, well-established prediction models of mortality in T2D (P < .05-< .001). CONCLUSION: REMAP is independently associated with and improves predict all-cause mortality in T2D; it can therefore be used to identify high-risk individuals to be targeted with more aggressive management. Whether REMAP can also identify patients who are more responsive to IL-6 and IL-1ß monoclonal antibodies that reduce cardiovascular burden and total mortality is an intriguing possibility to be tested.