Impact of sustained virologic response on glucose parameters among patients with chronic hepatitis C treated with direct-acting antivirals.

Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

Inulin Reduces Kidney Damage in Type 2 Diabetic Mice by Decreasing Inflammation and Serum Metabolomics.

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.

The unique association between the level of plateletcrit and the prevalence of diabetic kidney disease: a cross-sectional study.

Objective: The activation of platelets in individuals with type 2 diabetes mellitus (T2DM) triggers inflammation and hemodynamic abnormalities, contributing to the development of diabetic kidney disease (DKD). Despite this, research into the relationship between plateletcrit (PCT) levels and DKD is sparse, with inconsistent conclusions drawn regarding the connection between various platelet parameters and DKD. This highlights the necessity for comprehensive, large-scale population studies. Therefore, our objective is to explore the association between PCT levels and various platelet parameters in relation to DKD. Methods: In this cross-sectional study, hematological parameter data were collected from a cohort of 4,302 hospitalized Chinese patients. We analyzed the relationships between PCT, platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR), and DKD, along with the urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic potential of these parameters. Results: DKD patients exhibited significantly higher PCT levels compared to those without DKD. Multivariate regression analysis identified elevated PCT and PLT levels as potential independent risk factors for both DKD and UACR, while lower MPV levels might serve as independent protective factors for eGFR. The areas under the ROC curve for PCT in relation to DKD and UACR (≥30 mg/g) were 0.523 and 0.526, respectively. The area under the ROC curve for PLT in relation to UACR (≥30 mg/g) was 0.523. Conclusion: PCT demonstrates a weak diagnostic value for T2DM patients at risk of developing DKD and experiencing proteinuria, and PLT shows a similarly modest diagnostic utility for detecting proteinuria. These insights contribute to a deeper understanding of the complex dynamics involved in DKD. Additionally, incorporating these markers into routine clinical assessments could enhance risk stratification, facilitating early interventions and personalized management strategies.

The effects of gut microbiome manipulation on glycemic indices in patients with non-alcoholic fatty liver disease: a comprehensive umbrella review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action. METHODS: A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed. RESULTS: Gut microbial therapy significantly decreased HOMA-IR (ES: -0.41; 95%CI: -0.52, -0.31; P < 0.001) and FI (ES: -0.59; 95%CI: -0.77, -0.41; P < 0.001). However, no significant effect was observed on FBS (ES: -0.17; 95%CI: -0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics. CONCLUSION: Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS.

Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort.

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Association between HDL cholesterol with diabetic retinopathy in diabetic patients: a cross-sectional retrospective study.

OBJECTIVE: Diabetic patients are often comorbid with dyslipidemia, however, the relationship between high-density lipoprotein cholesterol(HDL-C) and diabetic retinopathy (DR) in the adult diabetic population remains to be fully elucidated.The aim of this study is to evaluate the associations between HDL-C and DR in the United States adults with diabetes. METHODS: A total of 1708 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008 were enrolled in the present study. Fundus images of all study subjects were captured and evaluated using a digital camera and an ophthalmic digital imaging system, and the diagnosis of DR was made by the severity scale of the Early Treatment Diabetic Retinopathy Study (ETDRS).Roche Diagnostics were used to measure serum HDL-C concentration. The relationship of DR with HDL-C was investigated using multivariable logistic regression. The potential non-line correlation was explored with smooth curve fitting approach. RESULTS: The fully-adjusted model showed that HDL-C positively correlated with DR(OR:1.69, 95%CI: 1.25-2.31).However, an inverted U-shaped association between them was observed by applying the smooth curve fitted method. The inflection point of HDL-C(1.99mmol/l) was calculated by utilizing the two-piecewise logistic regression model. In the subgroup analysis, the inverted U-shaped nonlinear correlation between HDL-C and DR was also found in female, Non-Hispanic White, and lower age groups. CONCLUSION: Our study revealed an inverted U-shaped positive relationship between HDL-C and DR.The findings may provide us with a more comprehensive understanding of the association between HDL-C and DR.

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies.

OBJECTIVE: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related. RESEARCH DESIGN AND METHODS: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC. RESULTS: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (ß-coefficient: 0.02 (0.02, 0.03), p = 3 × 10- 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13)). CONCLUSIONS: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.

Examination of the Complex Molecular Landscape in Obesity and Type 2 Diabetes.

The escalating prevalence of metabolic disorders, notably type 2 diabetes (T2D) and obesity, presents a critical global health challenge, necessitating deeper insights into their molecular underpinnings. Our study integrates proteomics and metabolomics analyses to delineate the complex molecular landscapes associated with T2D and obesity. Leveraging data from 130 subjects, including individuals with T2D and obesity as well as healthy controls, we elucidate distinct molecular signatures and identify novel biomarkers indicative of disease progression. Our comprehensive characterization of cardiometabolic proteins and serum metabolites unveils intricate networks of biomolecular interactions and highlights differential protein expression patterns between T2D and obesity cohorts. Pathway enrichment analyses reveal unique mechanisms underlying disease development and progression, while correlation analyses elucidate the interplay between proteomics, metabolomics, and clinical parameters. Furthermore, network analyses underscore the interconnectedness of cardiometabolic proteins and provide insights into their roles in disease pathogenesis. Our findings may help to refine diagnostic strategies and inform the development of personalized interventions, heralding a new era in precision medicine and healthcare innovation. Through the integration of multi-omics approaches and advanced analytics, our study offers a crucial framework for deciphering the intricate molecular underpinnings of metabolic disorders and paving the way for transformative therapeutic strategies.

Significant elevation of serum CA19-9 and CA242 levels induced by dulaglutide.

The use of dulaglutide, a common medication for managing type 2 diabetes, rarely causes elevated pancreatic tumour markers. Here, we report the case of a woman in her mid-60s with diabetes for over 10 years. The patient presented with markedly elevated serum CA19-9 and CA242 levels revealed during a routine health examination despite being asymptomatic. She had been receiving dulaglutide injections for 16 months. Imaging and interventional assessments did not reveal any hepatobiliary, gastrointestinal or pancreatic neoplasm. After excluding alternate diagnoses, the patient was determined to exhibit an adverse reaction to dulaglutide use. Management involved the discontinuation of dulaglutide, which resulted in normalisation of serum CA19-9 and CA242 levels within 6 weeks. This case underscores the importance of discontinuing dulaglutide and monitoring changes in the biomarker levels in asymptomatic patients receiving dulaglutide, rather than immediately resorting to imaging and endoscopic examinations.

Evaluating the correlation of sclerostin levels with obesity and type 2 diabetes in a multiethnic population living in Kuwait.

Obesity and Type 2 Diabetes Mellitus (T2DM) are intricate metabolic disorders with a multifactorial etiology, often leading to a spectrum of complications. Recent research has highlighted the impact of these conditions on bone health, with a particular focus on the role of sclerostin (SOST), a protein molecule integral to bone metabolism. Elevated circulating levels of SOST have been observed in patients with T2DM compared to healthy individuals. This study aims to examine the circulating levels of SOST in a multiethnic population living in Kuwait and to elucidate the relationship between SOST levels, obesity, T2DM, and ethnic background. The study is a cross-sectional analysis of a large cohort of 2083 individuals living in Kuwait. The plasma level of SOST was measured using a bone panel multiplex assay. The study found a significant increase in SOST levels in individuals with T2DM (1008.3 pg/mL, IQR-648) compared to non-diabetic individuals (710.6 pg/mL, IQR-479). There was a significant gender difference in median SOST levels, with males exhibiting higher levels than females across various covariates (diabetes, IR, age, weight, and ethnicity). Notably, SOST levels varied significantly with ethnicity: Arabs (677.4 pg/mL, IQR-481.7), South Asians (914.6 pg/mL, IQR-515), and Southeast Asians (695.2 pg/mL, IQR-436.8). Furthermore, SOST levels showed a significant positive correlation with gender, age, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, insulin, total cholesterol, triglycerides, HDL, LDL, ALT, and AST (p-Value ≥0.05). South Asian participants, who exhibited the highest SOST levels, demonstrated the most pronounced associations, even after adjusting for age, gender, BMI, and diabetes status (p-Value ≥0.05). The observed correlations of SOST with various clinical parameters suggest its significant role in the diabetic milieu, particularly pronounced in the South Asian population compared to other ethnic groups.

Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study.

Background and Aims: This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects. Methods: Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free thyroxine (fT4)/free triiodothyronine (fT3) ratio. These indices were then categorized into quartiles for analysis. The outcomes were the change rates in VFA, SFA, and BMI among the participants. Result: The present study included 921 patients, with a median follow-up of 2.2 years. In multivariate linear regression, when compared to the first quartile, SFA demonstrated a notable decline in the fourth quartile of TFQI, TSHI, and TT4RI (ß coefficient = -5.78, -7.83, and - 6.84 cm2 per year), while it significantly increased in the fourth quartile of fT4/fT3 ratio (ß coefficient = 6.13 cm2 per year). Similarly, in the fourth quartile of TFQI, TSHI, and TT4RI, VFA decreased significantly, evidenced by ß coefficients of -5.14, -4.80, and -4.08 cm2 per year. Yet, among the quartiles of the fT4/fT3 ratio, no discernible trend in VFA was observed. There was no significant association between indices of thyroid hormone sensitivity and change in BMI. Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

Oral glucose tolerance test clearance in type 2 diabetes patients who underwent remission following intense lifestyle modification: A quasi-experimental study.

Achieving diabetes remission (HbA1c<48mmol/mol without the use of anti-diabetic medication for 3 months) might not assure restoration of a normal glycemic profile [fasting blood sugar level <5.6 mmol/L and Post-Prandial (PP) blood glucose <7.8mmol/L]. The study investigates the factors associated with OGTT clearance in patients under type 2 diabetes remission. Four hundred participants who achieved remission during a one-year online structured lifestyle modification program, which included a plant-based diet, physical activity, psychological support, and medical management (between January 2021 and June 2022), and appeared for the OGTT were included in the study. OGTT clearance was defined by fasting blood glucose < 5.6 mmol/L and 2-hour post-prandial blood glucose <7.8 mmol/L post-consumption of 75g glucose solution. Of the 400 participants, 207 (52%) cleared OGTT and 175 (44%) had impaired glucose tolerance (IGT). A shorter diabetes duration (<5 years) was significantly associated with OGTT clearance (p<0.05). Pre-intervention use of glucose-lowering drugs showed no association with OGTT clearance (p<0.1). Post-intervention, the OGTT-cleared group showed significantly higher weight loss (p<0.05) and a decrease in HbA1c compared to the IGT group (p<0.05). Improvement in Insulin resistance and ß-cell function was also higher in the OGTT-cleared group compared to the IGT group (p<0.05). In conclusion, clearing the OGTT is a possibility for those achieving remission through lifestyle interventions. Higher weight loss, a shorter duration of diabetes, and improvement in insulin resistance were significantly associated with OGTT clearance in participants in remission. Future randomized controlled trials with longer follow-ups may help substantiate our findings.

Association of the longitudinal trajectory of urinary albumin/creatinine ratio in diabetic patients with adverse cardiac event risk: a retrospective cohort study.

Objective: The baseline urinary albumin/creatinine ratio (uACR) has been proven to be significantly associated with the risk of major adverse cardiac events (MACE). However, data on the association between the longitudinal trajectory patterns of uACR, changes in glycated hemoglobin A1c (HbA1c), and the subsequent risk of MACE in patients with diabetes are sparse. Methods: This is a retrospective cohort study including 601 patients with type 2 diabetes mellitus (T2DM; uACR < 300 mg/g) admitted to The First Hospital of Shanxi Medical University and The Second Hospital of Shanxi Medical University from January 2015 to December 2018. The uACR index was calculated as urinary albumin (in milligrams)/creatinine (in grams), and latent mixed modeling was used to identify the longitudinal trajectory of uACR during the exposure period (2016-2020). The deadline for follow-up was December 31, 2021. The primary outcome was the MACE [a composite outcome of cardiogenic death, hospitalization related to heart failure (HHF), non-fatal acute myocardial infarction, non-fatal stroke, and acute renal injury/dialysis indications]. The Kaplan-Meier survival analysis curve was used to compare the risk of MACE among four groups, while univariate and multivariate Cox proportional hazards models were employed to calculate the hazard ratio (HR) and 95% confidence interval (CI) for MACE risk among different uACR or HbA1c trajectory groups. The predictive performance of the model, both before and after the inclusion of changes in the uACR and HbA1c, was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Results: Four distinct uACR trajectories were identified, namely, the low-stable group (uACR = 5.2-38.3 mg/g, n = 112), the moderate-stable group (uACR = 40.4-78.6 mg/g, n = 229), the high-stable group (uACR = 86.1-153.7 mg/g, n = 178), and the elevated-increasing group (uACR = 54.8-289.4 mg/g, n = 82). In addition, five distinct HbA1c trajectories were also identified: the low-stable group (HbA1c = 5.5%-6.8%, n = 113), the moderate-stable group (HbA1c = 6.0%-7.9%, n = 169), the moderate-decreasing group (HbA1c = 7.4%-6.1%, n = 67), the high-stable group (HbA1c = 7.7%-8.9%, n = 158), and the elevated-increasing group (HbA1c = 8.4%-10.3%, n = 94). Compared with the low-stable uACR group, patients in the high-stable and elevated-increasing uACR groups were more likely to be older, current smokers, and have a longer DM course, higher levels of 2-h plasma glucose (PG), HbA1c, N-terminal pro-B-type natriuretic peptide (NT-proBNP), uACR, and left ventricular mass index (LVMI), while featuring a higher prevalence of hypertension and a lower proportion of ß-receptor blocker treatment (p < 0.05). During a median follow-up of 45 months (range, 24-57 months), 118 cases (19.6%) of MACE were identified, including 10 cases (1.7%) of cardiogenic death, 31 cases (5.2%) of HHF, 35 cases (5.8%) of non-fatal acute myocardial infarction (AMI), 18 cases (3.0%) of non-fatal stroke, and 24 cases (4.0%) of acute renal failure/dialysis. The Kaplan-Meier survival curve showed that, compared with that in the low-stable uACR group, the incidence of MACE in the high-stable (HR = 1.337, 95% CI = 1.083-1.652, p = 0.007) and elevated-increasing (HR = 1.648, 95% CI = 1.139-2.387, p = 0.009) uACR groups significantly increased. Similar results were observed for HHF, non-fatal AMI, and acute renal injury/dialysis indications (p < 0.05). The multivariate Cox proportional hazards models indicated that, after adjusting for potential confounders, the HRs for the risk of MACE were 1.145 (p = 0.132), 1.337 (p = 0.007), and 1.648 (p = 0.009) in the moderate-stable, high-stable, and elevated-increasing uACR groups, respectively. In addition, the HRs for the risk of MACE were 1.203 (p = 0.028), 0.872 (p = 0.024), 1.562 (p = 0.033), and 2.218 (p = 0.002) in the moderate-stable, moderate-decreasing, high-stable, and elevated-increasing groups, respectively. The ROC curve showed that, after adding uACR, HbA1c, or both, the AUCs were 0.773, 0.792, and 0.826, which all signified statistically significant improvements (p = 0.021, 0.035, and 0.019, respectively). Conclusion: A long-term elevated uACR is associated with a significantly increased risk of MACE in patients with diabetes. This study implies that regular monitoring of uACR could be helpful in identifying diabetic patients with a higher risk of MACE.

Synchronizing positive effect of vitamin C and chromium on hyper lipidemia, hyperglycemia, liver enzymes and BMI of diabetes mellitus type 2 patients.

This study investigates the combined effect of vitamin C and chromium on BMI, lipid profile, LFTs and HbA1c of Diabetes Mellitus type 2 patients. This is randomized controlled trial study. For this study a total of 60 patients (n=28 female, n=32 male) Diabetes Mellitus type 2 patients were selected. They were divided into treatment group (vitamin C (500mg) Chromium (200µg) and control group (placebo) comprising thirty patients per group. Mean age in control group and treatment group is 33± 5.729 and 33±7.017 respectively. Statistical analysis showed significant results of lipid profile; total cholesterol (mg/dl) 198±66.1 P=0.008, High-Density Lipoprotein 38±7.5, P<0.001, Low Density Lipoprotein (LDL) (mg/dl) 105.1±22.4, P=0.002 and Triglycerides 191±64.3, P=0.02 are respectively. Levels of serum ALT (u/l) (34.7±9.1, P<0.001) and AST (u/l) (31.6 ±8.6, P<0.001) were significantly lower as compared to control group. HbA1c percentages were also normalized (5.45±0.2, P<.001) as compared to group 2. BMI values were also improved (P=0.01) after treatment. Combined supplementation of vitamin C and chromium reduce the plasma lipid percentage, blood glucose levels and also improve the ALT and AST functions.

Association between lipoprotein(a) plasma levels and diabetic nephropathy in Han Chinese patients with type 2 diabetes mellitus.

The goal of this study was to evaluate the relationship between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy (DN) among Han Chinese individuals with type 2 diabetes mellitus (T2DM). This retrospective analysis comprised a consecutive case series of 767 grown-up patients with T2DM (199 among them with DN) hospitalized in the Department of Endocrinology at the The First Affiliated Hospital of Anhui Medical University from February 20220 to February 2021. Clinical data and other laboratory measurements, such as glycated hemoglobin (HbA1c), were extracted from medical records and compared among groups. Clinical characteristics according to Lp(a) quartiles were also studied. Univariate and multivariate regression analysis were used to examine the relationship between serum Lp(a) and DN. Patients with DN had a longer disease duration, higher HbA1c, higher level of Lp(a), and were more likely to have diabetic retinopathy (DR) than those without DN (P < 0.005 for each). With regard to the Lp(a) quartile group, patients with a higher Lp(a) concentration were more likely to have DN and have higher level of HbA1c during the study (P for trend < 0.005 for each). After adjusting for several confounding factors, the development of DN was significantly associated with the serum Lp(a) level (P = 0.026, comparing the 4th vs 1st quartile of Lp(a)) according to multivariate regression analysis. The receiver operating characteristic (ROC) curves for DN development using serum Lp(a) showed that the area under the receiver operating characteristic curves (AUC) was 0.590 (P < 0.001). Findings from this study demonstrated that the DN was independently associated with the serum Lp(a) level in patients with T2DM in this retrospective study.

Untargeted lipidomics analysis in women with morbid obesity and type 2 diabetes mellitus: A comprehensive study.

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women.

Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.