ABSTRACT
Objectives: This study aimed to investigate the link between 25-hydroxy vitamin D and serum asprosin in individuals with type 2 diabetes within the community. The goal was to provide a foundation for clinical interventions. Methods: Between November 2019 and July 2021, data from 463 patients with type 2 diabetes were consistently gathered at a community health service station in Southeast Shanxi Province. General information and laboratory metrics were compiled, including serum asprosin levels. The participants were categorized based on three serum asprosin quantiles, allowing for a comparison of various factors among the groups. The correlation between serum asprosin levels and other factors was analyzed. Employing a general linear model, the connection between 25-hydroxy vitamin D and serum asprosin levels was studied. Utilizing three quantiles of 25-hydroxy vitamin D, serum asprosin was treated as the dependent variable, while 25-hydroxy vitamin D served as the independent variable for linear regression analysis. Results: As serum asprosin increased, there were gradual increments in age, disease duration, SBP, BMI, WC, creatinine, and SUA levels (P<0.05). Conversely, HbA1c, HDL-C, GFR, and 25-hydroxy vitamin D levels exhibited gradual declines (P<0.05). Age, 25-hydroxy vitamin D, SUA, creatinine, and LDL-C emerged as independent influencing factors for serum asprosin. Across the 1st to 3rd 25-hydroxy vitamin D quantiles, elevated 25-hydroxy vitamin D levels correlated with a gradual reduction in mean serum asprosin (P<0.05). Conclusion: Serum asprosin levels demonstrate an inverse correlation with 25-hydroxy vitamin D levels in community-dwelling individuals with type 2 diabetes. Serum asprosin levels might independently contribute to 25-hydroxy vitamin D levels.
Subject(s)
Diabetes Mellitus, Type 2 , Fibrillin-1 , Vitamin D , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Vitamin D/blood , Vitamin D/analogs & derivatives , Female , Male , Middle Aged , Fibrillin-1/blood , Aged , Biomarkers/blood , Adult , AdipokinesABSTRACT
Islet amyloid polypeptide (IAPP) is co-secreted with insulin from pancreatic ß-cells. Its oligomerisation is regarded as disease driving force in type 2 diabetes (T2D) pathology. Up to now, IAPP oligomers have been detected in affected tissues. IAPP oligomer concentrations in blood have not been analysed so far. Using the IAPP single-oligomer-sensitive and monomer-insensitive surface-based fluorescence intensity distribution analysis (sFIDA) technology, levels of IAPP oligomers in blood plasma from healthy controls and people with T2D in different disease stages where determined. Subsequently, the level of IAPP oligomerisation was introduced as the ratio between the IAPP oligomers determined with sFIDA and the total IAPP concentration determined with ELISA. Highest oligomerisation levels were detected in plasma of people with T2D without late complication and without insulin therapy. Their levels stand out significantly from the control group. Healthy controls presented with the lowest oligomerisation levels in plasma. In people with T2D without complications, IAPP oligomerisation levels correlated with disease duration. The results clearly demonstrate that IAPP oligomerisation in insulin-naïve patients correlates with duration of T2D. Although a correlation per se does not identify, which is cause and what is consequence, this result supports the hypothesis that IAPP aggregation is the driving factor of T2D development and progression. The alternative and conventional hypothesis explains development of T2D with increasing insulin resistance causing exhaustion of pancreatic ß-cells due to over-secretion of insulin, and thus IAPP, too, resulting in subsequent IAPP aggregation and fibril deposition in the pancreas. Further experiments and comparative analyses with primary tissues are warranted.
Subject(s)
Diabetes Mellitus, Type 2 , Islet Amyloid Polypeptide , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Islet Amyloid Polypeptide/blood , Islet Amyloid Polypeptide/metabolism , Male , Middle Aged , Female , Aged , Protein Multimerization , Adult , Case-Control Studies , Insulin/blood , Insulin/metabolism , Insulin-Secreting Cells/metabolismABSTRACT
OBJECTIVE: To elucidate the impact and predictive value of the Triglyceride Glucose Index (TyG) and the ratio of Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) in identifying the risk of diabetes progression in Chinese individuals with prediabetes. METHODS: This longitudinal study enrolled 15,012 prediabetic adults from the Rich Healthcare Group between 2010 and 2016. Diabetes was defined as self-reported diabetes or a fasting glucose level ≥ 7.0 mmol/L. The Cox proportional hazards models was utilized to assess the relationship between the two indices and the risk of developing diabetes. The predictive efficacy of the two markers was gauged by the area under the curve (AUC). RESULTS: Over a median follow-up period of 2.87 years, 1,730 (11.5%) prediabetic participants developed diabetes. The adjusted hazard ratios for the top quartile of the TyG index and the TG/HDL-C ratio were 2.03 (95% confidence interval [CI]: 1.71-2.40) and 2.59 (95% CI: 2.20-3.05), respectively, compared to the lowest quartile. A significant trend of increasing diabetes risk with higher quartiles of both indices was observed. The AUC for the adjusted prediction model for prediabetes-to-diabetes transition was 0.726 for the TyG index and 0.710 for the TG/HDL-C ratio. The difference in AUCs was statistically significant (P = 0.03). CONCLUSIONS: The baseline TyG index or TG/HDL-C ratio was significantly associated with an increased risk of diabetes in prediabetic individuals. The TyG index demonstrated superior predictive accuracy, underscoring its importance in preventing diabetes in prediabetic individuals.
Subject(s)
Blood Glucose , Cholesterol, HDL , Diabetes Mellitus, Type 2 , Prediabetic State , Triglycerides , Humans , Prediabetic State/blood , Prediabetic State/epidemiology , Prediabetic State/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Female , Male , Middle Aged , Longitudinal Studies , Cholesterol, HDL/blood , Triglycerides/blood , Blood Glucose/metabolism , Risk Factors , Adult , China/epidemiology , Aged , Proportional Hazards Models , Asian People , Biomarkers/blood , East Asian PeopleABSTRACT
BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.
Subject(s)
Biomarkers , Blood Coagulation Factors , Blood Coagulation , Cause of Death , Coronary Angiography , Prediabetic State , Humans , Prediabetic State/blood , Prediabetic State/mortality , Prediabetic State/diagnosis , Male , Middle Aged , Female , Risk Assessment , Aged , Biomarkers/blood , Blood Coagulation Factors/metabolism , Blood Coagulation Factors/analysis , Prognosis , Coronary Artery Disease/mortality , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Blood Glucose/metabolism , Risk Factors , Mediation Analysis , Predictive Value of Tests , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosisABSTRACT
The increased utilization of continuous glucose monitors (CGM) and smart insulin pens (SIP) among people with type 2 diabetes generates significant health data. This study explored possible patterns in long term CGM and SIP data.
Subject(s)
Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 2 , Insulin Infusion Systems , Insulin , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Insulin/therapeutic use , Blood Glucose/analysis , Hypoglycemic Agents/therapeutic useABSTRACT
Advanced glycation end-products (AGEs) formation increases with metabolic disorders, leading to higher serum AGE levels in patients with progressive vascular complications. Measuring AGE levels in biological samples requires multiple pre-analytical processing steps, rendering analysis of multiple samples challenging. This study evaluated the progression of diabetic complications by analyzing AGE levels using a pre-analytical processing strategy based on a fully automated solid phase-extraction system. Serum samples from patients with diabetes, with or without macrovascular complications (Mac or non-Mac) or microvascular complications (Mic or non-Mic), were processed with the established methods. Free and total AGE levels in sera were measured using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In patients with diabetes, both free and total AGE levels were elevated in those with complications compared to those without complications. In Mac and Mic groups, free and total AGE levels and z-scores (the sum of normalized AGE levels) also increased. AGE z-scores were markedly higher than those of single AGE levels in distinguishing each complication. Our study demonstrated that the free AGE z-score, measured using a new analytical method without hydrolysis, correlated with the presence of vascular complications and may serve as a marker of disease complications.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Angiopathies , Glycation End Products, Advanced , Tandem Mass Spectrometry , Humans , Glycation End Products, Advanced/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Female , Male , Middle Aged , Aged , Tandem Mass Spectrometry/methods , Diabetic Angiopathies/blood , Diabetic Angiopathies/etiology , Chromatography, Liquid/methods , Biomarkers/bloodABSTRACT
BACKGROUND: The triglyceride glucose (TyG) index is a cutting-edge and highly effective marker of insulin resistance, a crucial factor in the development and exacerbation of diabetic kidney disease (DKD). To date, there has been limited research on how the triglyceride-glucose (TyG) index affects the outlook for patients suffering from DKD. METHODS: In this multicenter retrospective cohort study, the analysis recruited 2,203 DKD patients from the National Health and Nutrition Examination Survey (NHANES) dataset, which covers the US from 2001 to 2018. The research applied a Cox proportional hazards model with multiple variables to investigate the association of the TyG index with mortality outcomes. Restricted cubic splines (RCS) and methods for analyzing threshold effects were employed to identify possible non-linear relationships. RESULTS: Over nearly 19 years of follow-up, this study captured data on 753 all-cause and 231 cardiovascular disease-specific fatalities. Sophisticated statistical methods, including RCS and smoothing curve adjustments via penalized splines, helped identify distinctive patterns: The baseline TyG index was observed to have a U-shaped pattern related to overall mortality and an L-shape with cardiovascular diseases(CVD) mortality among individuals with DKD. Notably, TyG index below 9.15 for overall mortality and 9.27 for CVD mortality were linked to reduced death rates (HR = 0.65, 95% CI = 0.52-0.82 for all-cause; HR = 0.58, 95% CI = 0.43-0.83 for CVD). On the other hand, TyG index exceeding these benchmarks (greater than 9.15 for all-cause and 9.27 for CVD) correlated with increased all-cause mortality risks (HR = 1.21, 95% CI = 1.02-1.43) and showed a non-significant change in CVD mortality risks (HR = 1.07, 95% CI = 0.83-1.38). CONCLUSIONS: This study emphasizes the non-linear linkage involving the TyG index and death rates due to CVD and other factors in patients with DKD, demonstrating its effectiveness in estimating potential adverse events within this demographic.
Subject(s)
Blood Glucose , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Nutrition Surveys , Triglycerides , Humans , Triglycerides/blood , Diabetic Nephropathies/mortality , Diabetic Nephropathies/blood , Male , Female , Middle Aged , Retrospective Studies , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Blood Glucose/analysis , Aged , Proportional Hazards Models , Adult , Risk FactorsABSTRACT
BACKGROUND: The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear. METHODS: We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure). RESULTS: 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50-1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37-10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27-4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27-5.03; p = 0.008). CONCLUSIONS: In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.
Subject(s)
Biomarkers , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Hepcidins , Up-Regulation , Humans , Female , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Male , Aged , Prospective Studies , Hepcidins/blood , Middle Aged , Biomarkers/blood , Risk Assessment , Time Factors , Risk Factors , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Prognosis , Ferritins/blood , Incidence , Aged, 80 and over , Cause of DeathABSTRACT
BACKGROUND: Neuregulin 4 (Nrg4) is a brown adipose tissue-derived adipokine that greatly affects systemic metabolism and improves metabolic derangements. Although abnormal circulating levels of Nrg4 are common in obesity, it remains elusive whether low or elevated levels of this batokine are associated with the onset of metabolic diseases. AIM: To assess Nrg4 levels and its role as a feasible biomarker to predict the severity of obesity, gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). METHODS: A search for relevant studies was performed systematically using prominent search engines, including PubMed, Google Scholar, and Embase, by following PRISMA guidelines. RESULTS: Ample clinical evidence reported low serum/plasma levels of Nrg4 in obesity and these were inversely proportional to the indices of metabolic syndrome, including body mass index, waist circumference, triglycerides, fasting plasma glucose, and homoeostatic model assessment for insulin resistance as well as high-sensitivity C-reactive protein. Low circulating Nrg4 levels may aid in the prediction of morbid obesity, and subsequent GDM, T2DM, NAFLD, and CVD. CONCLUSION: Current clinical evidence emphasizes that the circulating levels of Nrg4 are decreased in morbid obesity, and it also highlights that Nrg4 May serve as a potential prognostic biomarker for obesity-related metabolic diseases.
Subject(s)
Biomarkers , Neuregulins , Obesity , Humans , Neuregulins/blood , Neuregulins/metabolism , Biomarkers/blood , Obesity/blood , Obesity/metabolism , Prognosis , Metabolic Diseases/blood , Metabolic Diseases/metabolism , Metabolic Diseases/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/metabolism , Female , Pregnancy , Severity of Illness Index , Diabetes, Gestational/blood , Diabetes, Gestational/metabolismABSTRACT
The COVID-19 pandemic has revealed that viruses can have multiple receptor properties, penetrating various tissues and causing mutations in various genes, thus promoting a range of metabolic disorders. The purpose of this study was to investigate the connection between three factors: diabetic status, pre-hospitalization oxygen therapy, and saturation levels, to the values of morphological, inflammatory, and biochemical parameters in the blood serum of COVID-19 patients. The study group consisted of 2139 patients, 1076 women (50.30%) and 1063 men (49.70%), with an average age of 63.73 ± 15.69 years. The population was divided into three groups based on a three-stage scale, taking into account patients with either type 2 diabetes/prediabetes (473 patients), those who received oxygen therapy before hospitalization, and those with a saturation value of below 95% (cut-off value). Among patients who did not receive pre-hospitalization oxygen therapy, those with diabetes and a SpO2 level < 95% had significantly higher levels of D-dimers, procalcitonin, albumin, lymphocytes, RDW-SD ≥ 47, potassium, creatinine, and troponin T when compared to diabetic patients with a SpO2 level ≥ 95%. Similarly, in the same group of patients without pre-hospitalization oxygen therapy, those without diabetes but with a SpO2 level < 95% showed significantly increased levels of IL-6, CRP, albumin, lymphocytes, RDW-SD ≥ 47, glucose, potassium, sodium, creatinine, and ALT, compared to patients without diabetes and with a SpO2 level ≥ 95%. The findings suggest that lower saturation levels may result in increased potassium and glucose levels in patients who did not receive any oxygen therapy before hospitalization due to COVID-19. It is hypothesized that this may be caused by damage to pancreatic ß-cells by SARS-CoV-2, and disturbances in the potassium channel, leading to cell membrane depolarization and insulin secretion.
Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Oxygen Inhalation Therapy , Oxygen Saturation , Humans , COVID-19/therapy , COVID-19/blood , Male , Middle Aged , Female , Aged , Oxygen Inhalation Therapy/methods , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , SARS-CoV-2/isolation & purification , Glucose Metabolism Disorders/therapy , Glucose Metabolism Disorders/blood , Hospitalization , Oxygen/metabolismABSTRACT
To explore the corn silk's effect and possible mechanism on patients with type 2 diabetes mellitus (T2DM) by untargeted metabolomics. Newly diagnosed patients with T2DM admitted to the endocrinology department of the author's hospital from March 2020 to September 2021 were chosen and then allocated to either the intervention or the control group (NC) randomly. Patients in the intervention group were administered corn silk in the same way as the patients in the NC were given a placebo. A hypoglycemic effect was observed, and an untargeted metabolomics study was done on patients of both groups. Compared with the NC, the glycosylated hemoglobin and fasting blood glucose of patients in the intervention group significantly decreased after 3 months of treatment (Pâ <â .05), identified using tandem mass spectrometry, and analyzed by orthogonal partial least squares-discriminant analysis. A total of 73 differential metabolites were screened under the conditions of variable important in projection value >1.0 and Pâ <â .05. Differential metabolites are mainly enriched in signaling pathways such as oxidative phosphorylation, purine metabolism, and endocrine resistance. Through untargeted metabolomic analysis, it is found that corn silk water extract may reduce blood glucose in patients with T2DM through multiple pathways, including oxidative phosphorylation and purine metabolism.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Metabolomics , Zea mays , Humans , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Middle Aged , Male , Female , Metabolomics/methods , Blood Glucose/metabolism , Blood Glucose/drug effects , Blood Glucose/analysis , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Hypoglycemic Agents/therapeutic use , Aged , AdultABSTRACT
This study aimed to investigate and analyze the medication use, fasting blood glucose control, and associated risk factors among residents with type 2 diabetes at the grassroots level in Xinjiang Production and Construction Corps. A multi-stage cluster sampling method was employed to conduct a questionnaire survey among residents aged 45 and above in battalions (communities) as the smallest unit. The medication use was recorded, and fasting blood glucose control was considered as the dependent variable. Logistic regression analysis was performed to identify the risk factors influencing fasting blood glucose control among different population characteristics. A total of 2316 participants were included in the study, of which 1072 were male (45.12%), 1418 were aged 65 and above (61.23%), 2031 were Han Chinese (87.69%), and 1551 were from the surrounding areas of Urumqi (66.97%). The main medications used among the top three classes were metformin, insulin, and α-glucosidase inhibitors. The treatment rate for type 2 diabetes was 71.80%, and the fasting blood glucose control rate was 27.98%. Multivariate analysis identified living outside the Urumqi surrounding area, age 65 and above, body mass indexâ ≥â 24, abnormal blood lipids, and untreated hypertension as independent risk factors for poor fasting blood glucose control, while treatment was a protective factor for achieving blood glucose control. The treatment rate and fasting blood glucose control rate among grassroots residents with type 2 diabetes in Xinjiang Production and Construction Corps need improvement. Efforts should be made to enhance patient medication adherence and health management awareness through education. Targeted interventions should be implemented for high-risk populations with identified risk factors to reduce or delay the occurrence of diabetes and its complications, ultimately aiming to reduce mortality rates and improve quality of life.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Glycemic Control , Hypoglycemic Agents , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Male , Middle Aged , Aged , Female , Risk Factors , Blood Glucose/analysis , China/epidemiology , Hypoglycemic Agents/therapeutic use , Glycemic Control/methods , Fasting/blood , Metformin/therapeutic use , Insulin/therapeutic use , Surveys and Questionnaires , Age Factors , Cross-Sectional Studies , Body Mass IndexABSTRACT
BACKGROUND: Beta 2-microglobulin (ß2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of ß2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum ß2-MG and LVH in T2DM patients. METHODS: The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum ß2-MG levels were measured, and participants were categorized into four groups (Q1-Q4) by their serum ß2-MG quartile. The relationship of serum ß2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. RESULTS: The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum ß2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]. When considering ß2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09-1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36-2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between ß2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of ß2-MG for LVH in T2DM patients. CONCLUSION: Elevated serum ß2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.
Subject(s)
Diabetes Mellitus, Type 2 , Hypertrophy, Left Ventricular , beta 2-Microglobulin , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Hypertrophy, Left Ventricular/blood , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/etiology , beta 2-Microglobulin/blood , Cross-Sectional Studies , Female , Male , Middle Aged , Retrospective Studies , Aged , Prevalence , Echocardiography , Biomarkers/blood , Risk FactorsABSTRACT
INTRODUCTION: Syndecan (SDC)-1 is a transmembrane heparan sulfate proteoglycan and is a major component of endothelial glycocalyx (EG). This study aimed to investigate the association of serum SDC-1 concentration as a marker of EG degradation with albuminuria in type 2 diabetes. METHODS: We included 370 patients with type 2 diabetes and 219 individuals with no diabetes. The individuals with estimate glomerular filtration rate <30 mL/min/1.73 m2 were excluded. RESULTS: Serum SDC-1 concentration was higher in type 2 diabetes than in no diabetes. The presence of diabetes was independently associated with log [SDC-1] in multivariate analysis. In type 2 diabetes, serum SDC-1 concentration was correlated with log [urinary albumin-to-creatinine ratio (ACR)]. Moreover, log [SDC-1] was an independent determinant of log [ACR] after adjustment for known risk factors of albuminuria. CONCLUSIONS: Serum SDC-1 concentration was higher in patients with type 2 diabetes compared to individuals with no diabetes and an independent determinant of ACR. This study implicates the role of the EG degradation in albuminuria in type 2 diabetes.
Subject(s)
Albuminuria , Biomarkers , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Syndecan-1 , Humans , Syndecan-1/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Albuminuria/blood , Albuminuria/diagnosis , Female , Male , Middle Aged , Biomarkers/blood , Aged , Diabetic Nephropathies/blood , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/etiology , Risk Factors , Up-Regulation , Case-Control Studies , Cross-Sectional Studies , Glomerular Filtration Rate , Glycocalyx/metabolismABSTRACT
Type 2 diabetes mellitus (T2DM) is accompanied by halogenative stress resulting from the excessive activation of neutrophils and neutrophilic myeloperoxidase (MPO) generating highly reactive hypochlorous acid (HOCl). HOCl in blood plasma modifies serum albumin (Cl-HSA). We studied the formation of neutrophil extracellular traps (NETs) in the whole blood and by isolated neutrophils under the action of Cl-HSA. It was found that Cl-HSA induces neutrophil priming and NETosis. MPO-containing as well as MPO-free NETs were found. These NETs with different composition can be a product of NETosis of one and the same neutrophil. NET formation in neutrophils with vacuolated cytoplasm was detected. In the presence of Cl-HSA, acceleration of NET degradation was observed. Accelerated NET degradation and neutrophil priming can be the factors contributing to the development of complications in T2DM.
Subject(s)
Extracellular Traps , Hypochlorous Acid , Neutrophils , Peroxidase , Hypochlorous Acid/metabolism , Hypochlorous Acid/pharmacology , Neutrophils/metabolism , Neutrophils/drug effects , Extracellular Traps/metabolism , Extracellular Traps/drug effects , Humans , Peroxidase/metabolism , Diabetes Mellitus, Type 2/blood , Serum Albumin/metabolism , MaleABSTRACT
(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.
Subject(s)
Amino Acids, Aromatic , Amino Acids, Branched-Chain , Cardiometabolic Risk Factors , Diabetes Mellitus, Type 2 , Hispanic or Latino , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/blood , Female , Male , Middle Aged , Amino Acids, Branched-Chain/blood , Amino Acids, Aromatic/blood , Adult , Hispanic or Latino/statistics & numerical data , Longitudinal Studies , Puerto Rico/epidemiology , Puerto Rico/ethnology , Aged , Prevalence , Boston/epidemiology , Incidence , Obesity/epidemiology , Obesity/ethnologyABSTRACT
The present study aimed to explore the association between serum cystatin C (Cys-C) levels and visceral fat area (VFA) in patients with type 2 diabetes mellitus (T2DM). A total of 208 previously diagnosed T2DM patients who visited our hospital from September 2019 to December 2021 were included and divided into three groups based on tertiles of Cys-C levels, namely, Groups C1, C2, and C3. The clinical data of the subjects were collected, biochemical parameters such as Cys-C levels were determined, and bioelectrical impedance analysis was applied to determine the VFA and subcutaneous fat area (SFA). The VFA in Group C1 was lower than that in Groups C2 and C3 (all P < 0.05), with no significant difference in VFA between Groups C2 and C3 (P > 0.05). Spearman's correlation analysis revealed that the serum Cys-C level was positively correlated with age, VFA, SFA, insulin resistance index, waist circumference, body mass index, systolic blood pressure, serum creatinine level, and blood uric acid level (r = 0.543, 0.353, 0.168, 0.148, 0.365, 0.264, 0.25, 0.497, and 0.155, respectively; P < 0.05) and negatively correlated with glycated haemoglobin levels (r = -0.175, P < 0.05). Univariate linear regression analysis revealed that VFA was positively correlated with the Cys-C level (ß = 0.002, 95% CI = 0.001-0.003, P < 0.05), with an increase of 0.002 mg/L in the Cys-C level for each 1 cm2 increase in VFA. Further multivariate linear regression analysis was performed with the serum Cys-C level as the dependent variable and age, VFA, SFA, insulin resistance (HOMA-IR), WC, BMI, SBP, Cr, UA, and HbA1c as the independent variables. The results suggested that VFA was positively correlated with serum Cys-C level (ß = 0.001, 95% CI = 0.000-0.002, P < 0.05), with serum Cys-C levels increasing by 0.001 mg/L for every 1 cm2 increase in VFA. Using a VFA ≥ 100 cm2 as the criterion for visceral obesity, ROC analysis revealed that the Cys-C level was a better predictor of visceral obesity, with an area under the ROC curve (AUC) of 0.701 (95% CI = 0.631-0.771, P < 0.05), an optimal cut-off of 0.905 mg/L, and a sensitivity and specificity of 58.3% and 75.2%, respectively. The results suggested that the serum Cys-C level was correlated with the VFA in patients with T2DM and that Cys-C may play a vital role in T2DM patients with visceral obesity.
Subject(s)
Cystatin C , Diabetes Mellitus, Type 2 , Intra-Abdominal Fat , Humans , Cystatin C/blood , Diabetes Mellitus, Type 2/blood , Male , Middle Aged , Intra-Abdominal Fat/metabolism , Female , Insulin Resistance , Aged , Body Mass Index , Waist Circumference , Adult , Biomarkers/bloodABSTRACT
Free Fatty Acids (FFAs) are vital for energy homeostasis and the pathogenesis of a variety of diseases, including diabetes. For the first time, we presumed and investigated the types and levels of FFAs and their links to Insulin Resistance (IR) and Oxidative Stress (OS) in T2DM. A case-control study was conducted on 60 individuals with diabetes, 60 prediabetics with IFG, and 60 control groups. A Gas Chromatography Flame Ionization Detector (GC-FID) was used to estimate FFAs, which were then classified based on length and saturation. Indeed, antioxidant parameters such as TAC, MDA levels, PON-1, SOD-3, and CAT activity were assessed. Higher levels of LCFFA, SFFA, USFFA, and total FFA were found in people with diabetes and prediabetes. These levels were also linked to higher levels of HOMA-IR, BMI, FBS, HbA1C, and MDA, but lower levels of antioxidants. Furthermore, adjusting the above FFAs with age, sex, and antihypertensive medication increased T2DM development. SCFFA and ω3/6 fatty acids had a negative relationship with HOMA-IR, FBS, and insulin and a positive relationship with TAC. Adjusted SCFFA reduces T2DM risk. According to our models, total FFA is utilized to diagnose diabetes (AUC = 83.98, cut-off > 919 µM) and SCFFA for prediabetes (AUC = 82.32, cut-off < 39.56 µM). Total FFA (≥ 776 µM), LCFFA (≥ 613 µM), SFFA (≥ 471 µM), and USFFA (≥ 398 µM) all increase the risk of T2DM by increasing OS, BMI, and HOMA-IR. On the other hand, SCFFAs (≥ 38.7 µM) reduce the risk of T2DM by reducing BMI, HOMA-IR, and OS. SCFFAs and total FFAs can be used for the diagnosis of prediabetes and diabetes, respectively.
Subject(s)
Diabetes Mellitus, Type 2 , Fatty Acids, Nonesterified , Insulin Resistance , Oxidative Stress , Humans , Fatty Acids, Nonesterified/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Male , Case-Control Studies , Female , Middle Aged , Adult , Prediabetic State/blood , Prediabetic State/metabolism , Antioxidants/metabolism , AgedABSTRACT
Introduction: Waist circumference (WC) and fasting plasma glucose (FPG) have been demonstrated as risk factors for type 2 diabetes mellitus (T2DM). Evidence is limited regarding the association of the combination of WC and FPG (WyG) with the risk of T2DM. The primary aim of the study was to investigate the relationship between WyG and T2DM. Research design and methods: The current study was a population-based cohort study using data from the NAGALA database. Participants were divided into tertiles based on WyG. Cox proportional hazard regression model was applied to identify the association of WyG with T2DM. Results: During a median follow-up of 6.19 years in the normoglycemia group and 5.58 years in the prediabetes group, respectively, 88 and 285 individuals in the two groups received a diagnosis of T2DM. After full adjustment, risk of T2DM increased in step-wise fashion with increasing tertiles of WyG. For a per-SD increase in WyG, the hazard ratios for T2DM were 3.05 (95% CI 2.64 - 3.51) in all populations, 1.94 (95% CI 1.46 - 2.58) in the normoglycemia group and 1.63 (95% CI 1.40 - 1.90) in the prediabetes group. The interaction between WyG and fatty liver on T2DM was statistically significant in the prediabetes group (P for interaction = 0.034). Conclusions: Elevated WyG was independently associated with incident T2DM in Japan. Baseline WyG help identify individuals at high risk of T2DM and implement effective preventive measures.