Function In Type 2 Diabetes Mellitus Patients Research Articles

Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients.

Type 2 diabetes mellitus (T2DM) is a leading risk factor for the development and progression of chronic kidney disease (CKD). However, an accurate and convenient marker for early detection and appropriate management of CKD in individuals with T2DM is limited. Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio (NLR) and CKD. Nonetheless, the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied. To investigate the relationship between NLR and renal function in T2DM patients. This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center. The total number of neutrophils and lymphocytes was detected, and NLR levels were calculated. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m². Participants were divided into four groups based on NLR levels. The clinical data and biochemical characteristics were compared among groups. A multivariate logistic regression model was used to analyze the association between NLR levels and CKD. Significant differences were found in terms of sex, serum creatinine, blood urea nitrogen, total cholesterol, and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups (P < 0.0007). T2DM patients in the highest NLR quartile had a higher prevalence of CKD (P for trend = 0.0011). Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters (P = 0.0001, odds ratio = 1.41, 95% confidence intervals: 1.18-1.68). An elevated NLR in patients with T2DM is associated with higher prevalence of CKD, suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

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

BackgroundStudies 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.ObjectiveThis 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.MethodsWe 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).ResultsOur 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).ConclusionWe 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.

Analysis of current situation and influencing factors of cognitive dysfunction associated with type 2 diabetes and follow-up study on treatment effectiveness.

Many studies have explored the risk factors associated with cognitive impairment in patients with Type 2 diabetes mellitus (T2DM). However, research on determining the optimal threshold for these risk factors and comparative studies on the therapeutic effects of insulin and metformin is limited. This study aims to establish the optimal threshold for cognitive impairment risk factors in T2DM patients and compare the efficacy of insulin and metformin in treating mild cognitive impairment (MCI). A total of 308 patients with T2DM were included. The optimal threshold for cognitive impairment risk factors was determined using receiver operating characteristic curve and binary logistic regression models. MCI patients were divided into three groups: insulin, metformin, and insulin with metformin. The treatment effect was evaluated after a 6-month follow-up. The study identified several factors that influenced cognitive function in T2DM patients, including female gender, duration of diabetes >13.50 years, years of education >7.50 years, and serum sodium level > 141.90 mmol/L. Metformin and insulin with metformin showed superior therapeutic effects compared to insulin alone, but no difference was observed between metformin and combination therapy. Special attention should be given to female and those with diabetes duration >13.50 years, as well as to individuals with educational level ≤ 7.50 years and serum sodium concentration ≤ 141.90 mmol/L. Metformin and insulin with metformin effectively improve MCI in patients with T2DM and outperform insulin monotherapy. The efficacy of metformin and combination therapy was found to be comparable.

Evaluation of subclinical left ventricular myocardial systolic dysfunction in type 2 diabetes mellitus patients with and without diabetes peripheral neuropathy by global myocardial work.

Speckle-tracking echocardiography can non-invasively estimate myocardial work (MW) to evaluate left ventricular (LV) myocardial systolic function. The present study evaluated whether MW may detect subclinical LV myocardial systolic dysfunction in type 2 diabetes mellitus (T2DM) patients with and without diabetes peripheral neuropathy (DPN). A total of 127 T2DM patients were included in the present study, including 67 T2DM patients with DPN. In addition, 73 sex- and age- matched healthy individuals served as normal controls. The global myocardial work index (GWI), global constructive work (GCW), global waste work (GWW), global positive work (GPW), global negative work (GNW), global work efficiency (GWE) and GCW/GWW were measured and analysed. Furthermore, the differences in MW parameters among normal controls, T2DM patients, and T2DM patients with DPN were analysed. Multiple regression models were built to explore for the independent influencing factors of GWI and GPW values in T2DM patients with DPN. Receiver operating characteristic curve analysis was performed to evaluate the sensitivity and specificity of MW in evaluating subclinical LV myocardial systolic dysfunction in T2DM patients with DPN. The GWI, GCW and GPW of T2DM patients with DPN were significantly decreased compared with those of T2DM patients and normal controls (P < 0.001) and showed a significant decreasing trend overall (P trend < 0.001). GWE and GCW/GWW were significantly decreased in T2DM patients with DPN compared with normal controls (P < 0.05). Although GWW was not significantly different among the three groups, it showed an increasing trend (Ptrend = 0.033). High-density lipoprotein cholesterol (HDL-C) levels were independent influencing factor for decreased GWI (β = 0.21, P = 0.031) and GPW (β = 0.19, P = 0.043) values in T2DM patients with DPN. The combination of the GWI, GCW, GWE, GPW and GCW /GWW had good sensitivity (62.69%) and specificity (89.04%) when evaluating subclinical LV myocardial systolic dysfunction in T2DM patients with DPN. Non-invasive evaluation of LV myocardial work can detect subclinical LV myocardial systolic dysfunction in T2DM patients with and without DPN. DPN has additive deleterious effects on LV myocardial systolic function in T2DM patients. The reduction of HDL-C levels may indicate the occurrence of subclinical LV myocardial systolic dysfunction in T2DM patients with DPN.

Effects of Incretin-Based Treatment on the Diastolic (Dys)Function in Patients with Uncontrolled Type 2 Diabetes Mellitus: A Prospective Study with 1-Year Follow-Up.

Left ventricular diastolic dysfunction (DD) is a subclinical cardiac abnormality in patients with type 2 diabetes mellitus (T2DM) that can progress to heart failure (HF) and increase cardiovascular risk. This prospective study evaluated the DD in T2DM patients without atherosclerotic cardiovascular disease after one year of incretin-based drugs added to standard treatment. Of the 138 enrolled patients (49.30% male, mean age 57.86 ± 8.82, mean T2DM history 5 years), 71 were started on dipeptidyl peptidase-4 inhibitor sitagliptin/saxagliptin, 21 on glucagon-like peptide-1 receptor agonist exenatide, and 46 formed the control group (metformin and sulphonylurea/acarbose). At baseline, 71 patients had grade 1 DD, another 12 had grade 2 and 3 DD, and 15 had indeterminate DD. After one year, DD was evidenced in 50 cases. Diastolic function improved in 9 cases, and 27 patients went from grade 1 to indeterminate DD. The active group benefited more, especially patients treated with exenatide; their metabolic and inflammation profiles also improved the most. An in-depth analysis of echocardiographic parameters and paraclinical results in the context of literature data justifies the conclusion that early assessment of diastolic function in T2DM patients is necessary and the benefits of affordable incretin-based treatment may extend to subclinical cardiovascular manifestations such as DD.

Examining the Links Between Physical Activity, Sitting Time, and Renal Function in T2DM Patients.

Sitting time and physical activity are related to renal function among type 2 diabetes mellitus (T2DM); however, the mechanism of how it contributes to renal function is not well understood. The current study attempts to explore the relationship between sitting time and renal function among T2DM patients, with a particular focus on the mediating role of physical activity. This research uses the data of 1761 Chinese T2DM patients from Ningxia Province. Sitting time and physical activity were obtained during a face-to-face survey, and renal function was assessed by the estimated glomerular filtration rate (eGFR). The bootstrap method is used to test the mediating effect. The research found that sitting time was negatively associated with eGFR and physical activity after controlling for covariates. Physical activity was positively associated with eGFR. Physical activity has mediated the relationship between sitting time and eGFR among T2DM patients (explaining 16.1% of the total variance). The present findings suggest that sitting time negatively affects eGFR among T2DM patients and provides new evidence that physical activity could attenuate the association between sitting time and eGFR. Hence, intervention strategies focusing on sitting time and physical activity should be paid more attention in the future.

Diagnostic value of serum cathepsin S in type 2 diabetic kidney disease.

Identification of risk factors that have causal effects on the occurrence of diabetic kidney disease (DKD), is of great significance in early screening and intervening for DKD, and in delaying the progression of DKD to end-stage renal disease. Cathepsin S (Cat-S), a novel non-invasive diagnostic marker, mediates vascular endothelial dysfunction. The diagnostic value of Cat-S for DKD has rarely been reported in clinical studies. To analyze whether Cat-S is a risk factor for DKD and evaluate the diagnostic value of serum Cat-S for DKD. Forty-three healthy subjects and 200 type 2 diabetes mellitus (T2DM) patients were enrolled. T2DM patients were divided into subgroups according to various criteria. Enzyme-linked immunosorbent assay was used to detect serum Cat-S levels among different subgroups. Spearman correlation analysis was used to analyze correlations between serum Cat-S and clinical indicators. Multivariate logistic regression analysis was performed to analyze risk factors for the occurrence of DKD and decreased renal function in T2DM patients. Spearman analysis showed that serum Cat-S level was positively correlated with urine albumin creatinine ratio (r=0.76, P<0.05) and negatively correlated with estimated glomerular filtration rate (r=-0.54, P<0.01). Logistic regression analysis showed that increased serum Cat-S and cystatin C(CysC) were independent risk factors for DKD and decreased renal function in T2DM patients (P<0.05). The area under the receiver operating characteristic (ROC) curve was 0.900 of serum Cat-S for diagnosing DKD, and when the best cut-off value was 827.42 pg/mL the sensitivity and specificity were 71.6% and 98.8%, respectively. Thus, serum Cat-S was better than CysC for diagnosing DKD (for CysC, the area under the ROC curve was 0.791, and when the cut-off value was 1.16 mg/L the sensitivity and specificity of CysC were 47.4% and 98.8%, respectively). Increased serum Cat-S were associated with the progression of albuminuria and decreased renal function in T2DM patients. The diagnostic value of serum Cat-S was better than that of CysC for DKD. Monitoring of serum Cat-S levels could be helpful for early screening DKD and assessing the severity of DKD and could provide a new strategy for diagnosing DKD.

Acute effects of different exercise forms on executive function and the mechanism of cerebral hemodynamics in hospitalized T2DM patients: a within-subject study.

This study aimed to investigate the acute effects of aerobic exercise (AE), resistance exercise (RE), and integrated concurrent exercise (ICE; i.e., AE plus RE) on executive function among hospitalized type 2 diabetes mellitus (T2DM) inpatients, and the mechanism of cerebral hemodynamics. A within-subject design was applied in 30 hospitalized patients with T2DM aged between 45 and 70 years in the Jiangsu Geriatric Hospital, China. The participants were asked to take AE, RE, and ICE for 3 days at 48-h intervals. Three executive function (EF) tests, namely, Stroop, More-odd shifting, and 2-back tests, were applied at baseline and after each exercise. The functional near-infrared spectroscopy brain function imaging system was used to collect cerebral hemodynamic data. The one-way repeated measurement ANOVA was used to explore training effects on each test indicator. Compared with the baseline data, the EF indicators have been improved after both ICE and RE (p < 0.05). Compared with the AE group, the ICE and RE groups have demonstrated significant improvements in inhibition (ICE: MD = - 162.92 ms; RE: MD = -106.86 ms) and conversion functions (ICE: MD = -111.79 ms; RE: MD = -86.95 ms). Based on the cerebral hemodynamic data, the beta values of brain activation in executive function related brain regions increased after three kinds of exercise, the EF improvements after the ICE showed synchronous activation of blood flow in the dorsolateral prefrontal cortex (DLPFC), the frontal polar (FPA) and orbitofrontal cortex (OFC), the improvement of inhibitory function after RE displayed synchronous activation of DLPFC and FPA, and AE mainly activates DLPFC. The HbO2 concentration in the pars triangularis Broca's area increased significantly after AE, but the EF did not improve significantly. The ICE is preferred for the improvements of executive function in T2DM patients, while AE is more conducive to the improvements of refresh function. Moreover, a synergistic mechanism exists between cognitive function and blood flow activation in specific brain regions.

Echocardiographic evaluation of the effect of dapagliflozin on epicardial adipose tissue and left ventricular systolic function in type 2 diabetes mellitus

Background and aimsEpicardial adipose tissue (EAT) is associated with cardiovascular disease, and sodium-glucose cotransporter-2 inhibitors (SGLT-2I) have been reported to reduce the occurrence of cardiovascular events. This study was designed to investigate the effect of an SGLT-2 inhibitor (dapagliflozin) on EAT and left ventricular (LV) systolic function in type 2 diabetes mellitus (T2DM) patients during a 6-month follow-up. MethodsTwenty-seven T2DM patients who received dapagliflozin for the first time were enrolled in this study to measure EAT thickness and evaluate LV function before and after 6 months of SGLT-2 administration. The thickness of EAT was measured as the echo-free space between the free wall of the right ventricle and the visceral layer of the pericardium at end-systole by echocardiography. LV systolic function was evaluated by LV global longitudinal strain (LV GLS) obtained through two-dimensional speckle tracking echocardiography (2D-STE) technology. ResultsAfter a 6-month follow-up, twenty-five patients completed this study. The values of EAT thickness, HbA1c, body weight, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly reduced, while the LV GLS value was significantly increased. Moreover, the increase in LV GLS was independently associated with the reduction in EAT thickness, HbA1c, weight, and SBP (all p < 0.05). ConclusionsDapagliflozin can reduce EAT thickness and improve LV systolic function in T2DM patients. 2D-STE can be used for the early evaluation of the beneficial effect of dapagliflozin on LV systolic function. The improvement in LV systolic function is independently associated with a reduction in EAT thickness.

Correlation between Atherogenic Index of Plasma and Various Domains of Cognitive Function in Type 2 Diabetes Mellitus Patients

Cognitive impairment in patients with Type 2 Diabetes Mellitus (T2DM) is related to the lack of blood supply to the brain. Previous studies showed that the atherogenic index of plasma (AIP) is a predictor of vascular abnormalities, but studies investigating its association with cognitive functions in T2DM patients younger than 60 years remain limited. This study aimed to determine the correlation between AIP and various domains of cognitive function in T2DM patients. This study was a cross-sectional study involving 75 T2DM patients selected using a consecutive sampling technique at Haji Adam Malik General Hospital Medan from July 2021 to January 2022. Cognitive function was examined using the Visual Cognitive Assessment Test Indonesian Version (VCAT-INA) on several cognition domains. The AIP value of each patient was measured and categorized into high (AIP&gt;0.21), intermediate (AIP between &gt;0.11 and ≤0.21), or low (≤0.11). The mean triglyceride level was 176±108.3mg/dl, the HDL-C level was 38.3±12.1mg/dl, and the mean AIP value was 0.191±0.25. The mean score of the VCAT-INA was 21.7±2.3, which was lower than normal. The AIP value showed significant negative correlation with global cognition (r=0.432, p&lt;0.001) and various cognitive domains, namely memory (r=-0.375, p=0.001), attention (r=-0.383, p=0.001), executive function (r=-0.051, p=0.663), visuospatial (r=-0.306, p=0.008), and language (r=-0.352, p=0.002). In short, there is a significant correlation between AIP value and domains of cognitive function, such as memory, attention, visuospatial, and language domains, but not with executive domains.

Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes: A systematic review

Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome characterized by insulin resistance and hyperglycemia that may lead to endothelial dysfunction, reduced functional capacity and exercise intolerance. Regular aerobic exercise has been promoted as the most beneficial non-pharmacological treatment of cardiovascular diseases. High intensity interval training (HIIT) seems to be superior than moderate-intensity continuous training (MICT) in cardiovascular diseases by improving brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness to a greater extent. However, the beneficial effects of HIIT in patients with T2DM still remain under investigation and number of studies is limited. To evaluate the effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in patients with T2DM. We performed a search on PubMed, PEDro and CINAHL databases, selecting papers published between December 2012 and December 2022 and identified published randomized controlled trials (RCTs) in the English language that included community or outpatient exercise training programs in patients with T2DM. RCTs were assessed for methodological rigor and risk of bias via the Physiotherapy Evidence Database (PEDro). The primary outcome was peak VO2 and the secondary outcome was endothelial function assessed either by FMD or other indices of microcirculation. Twelve studies were included in our systematic review. The 12 RCTs resulted in 661 participants in total. HIIT was performed in 310 patients (46.8%), MICT to 271 and the rest 80 belonged to the control group. Peak VO2 increased in 10 out of 12 studies after HIIT. Ten studies compared HIIT with other exercise regimens (MICT or strength endurance) and 4 of them demonstrated additional beneficial effects of HIIT over MICT or other exercise regimens. Moreover, 4 studies explored the effects of HIIT on endothelial function and FMD in T2DM patients. In 2 of them, HIIT further improved endothelial function compared to MICT and/or the control group while in the rest 2 studies no differences between HIIT and MICT were observed. Regular aerobic exercise training has beneficial effects on cardiorespiratory fitness and endothelial function in T2DM patients. HIIT may be superior by improving these parameters to a greater extent than MICT.

Preliminary study of the interactive effects of coronary heart disease and lacunar infarction on renal function in patients with type 2 diabetes mellitus by gender

BackgroundCoronary heart disease (CHD) and lacunar infarction (LI) are the most common cardio- cerebrovascular complications of type 2 diabetes mellitus (T2DM) and a recognized risk factor for renal injury. Although a unidirectional association of CHD or LI with T2DM or the kidney has been demonstrated, however, it remains unknown whether there is an interactive effect of the coexistence of CHD and LI on renal function in T2DM patients. The aim of our study was to investigate the interaction between CHD and LI on renal function in gender-specific patients with T2DM and the association between cardio-cerebrovascular disease-related conventional serum markers and the estimated glomerular filtration rate (eGFR). MethodsWe conducted a cross-sectional study in Beijing and Tianjin from April 2019 to August 2021. Participants with T2DM aged ≥18 years were asked to complete a one-to-one questionnaire and physical examination. ResultsIn this study, 389 eligible patients with T2DM were included, with a mean age of 63.04 ± 9.41 years, of whom 200 (51.41 %) were male. The proportions of patients with CHD, LI, and both CHD and LI were 28.53 %, 24.42 %, and 11.05 %, respectively. Compared to T2DM patients without either CHD or LI, those with both CHD and LI were found to have a significantly greater risk of reduced eGFR (OR: 12.82, 95 % CI 5.06–32.52, P < 0.001) than those with CHD alone (OR: 2.42, 95 % CI 1.37–3.00, P = 0.004) or LI alone (OR: 1.15, 95 % CI 0.61–2.18, P = 0.664). The combined presence of CHD and LI is associated with a significantly greater risk of decreased eGFR in female T2DM patients compared to their male counterparts. We found both multiplicative and additive effects in all T2DM patients; however, when stratified by sex, only multiplicative effects were observed. After controlling for interference from CHD, LI, and age, we found that total cholesterol (TC) was negatively correlated with eGFR in females (r = −0.156, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) was negatively correlated with eGFR in males (r = −0.229, P = 0.001). ConclusionThis study provides novel evidence that the synergistic effect of CHD and LI on renal injury in patients with T2DM is significantly greater than their individual effects. Women with T2DM who have both CHD and LI are at a 4.85-fold higher risk of decreased eGFR than men. Therefore, increased clinical attention should be given to preventing and treating vascular complications in T2DM patients, as well as aggressively reducing lipid levels, particularly TC and LDL-C, to delay or prevent renal dysfunction in T2DM patients.

Heterogeneity of circulating CXCR5-PD-1hiTph cells in patients of type 2 and type 1 diabetes in Chinese population.

Circulating peripheral helper T (Tph) cells are shown to promote the progression of autoimmune diseases. However, the role of Tph cells in inflammatory diseases such as type 2 diabetes mellitus (T2DM) and the differences between T2DM and autoimmune diabetes remain unclear. We recruited 92 T2DM patients, 106 type 1 diabetes mellitus (T1DM) patients and 84 healthy control individuals. Peripheral blood mononucleated cells were isolated and examined by multicolor flow cytometry. We further evaluated the correlations between circulating Tph cells and clinical biochemical parameters, islet function, disease progression and islet autoantibodies. Circulating Tph cells were significantly higher in both T2DM and T1DM patients than in healthy control individuals. A significant positive correlation was observed between Tph cells and B cells in T1DM patients and overweight T2DM patients. Furthermore, Tph cells were negatively correlated with the area under the C-peptide curve (C-PAUC), and Tph cells were significantly positively correlated with fasting glucose and glycated hemoglobin levels in T2DM patients. However, no correlation was found between Tph cells and the above clinical indicators in T1DM patients. The frequency of Tph cells positively correlated with the titer of GAD autoantibodies and duration of disease in T1DM patients. In addition, we demonstrated that the frequency of Tph cells was decreased after rituximab therapy in T1DM patients. Circulating Tph cells are associated with blood glucose levels and islet function in T2DM patients. In T1DM patients, circulating Tph cells are associated with B cells and islet autoantibodies. This may suggest that Tph cells have different pathogenic mechanisms in the two types of diabetes. http://ClinicalTrials.gov NCT01280682 (registered July, 2010).

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

The rs3931283/PVT1 and rs7158663/MEG3 polymorphisms are associated with diabetic kidney disease and markers of renal function in patients with type 2 diabetes mellitus.

Long non-coding RNAs (lncRNAs) are key regulators of gene expression. Some studies have reported the association of polymorphisms in lncRNA genes with diabetes mellitus (DM) and its chronic complications, including diabetic kidney disease (DKD); however, the results are still inconclusive. Thus, we investigated the association of the rs3200401/MALAT1, rs1894720/MIAT, rs3931283/PVT1, rs11993333/PVT1, rs5749201/TUG1, and rs7158663/MEG3 polymorphisms with DKD in patients with type 2 DM (T2DM). This study comprised 902 patients with T2DM and DKD (cases) and 394 patients with T2DM without DKD (controls). The six polymorphisms of interest were genotyped by real-time PCR using TaqMan probes. Frequency of the rs3931283/PVT1 G/G genotype was 36.2% in cases and 31.9% in controls (P = 0.331). After adjustment for gender, glycated hemoglobin, HDL cholesterol, ethnicity, hypertension, and diabetic retinopathy, the G/G genotype was associated with risk for DKD (OR = 1.625, 95% CI 1.020-2.588; P = 0.041). The rs3931283/PVT1 G/G genotype was also associated with higher urinary albumin excretion levels compared to A allele carriers (P = 0.017). No difference was found in rs7158663/MEG3 genotype frequencies between T2DM controls and DKD patients (OR = 1.087, 95% CI 0.686-1.724; P = 0.722). However, the rs7158663/MEG3 G/G genotype was associated with protection against severe DKD (OR = 0.694, 95% CI 0.488-0.989; P = 0.043, for patients with severe DKD vs. T2DM controls). The rs7158663/MEG3 G/G genotype was also associated with lower creatinine levels (P = 0.007) and higher estimated glomerular filtration rate (P = 0.010) compared to A allele carriers. No association was found between the rs11993333/PVT1, rs3200401/MALAT1, rs1894720/MIAT, and rs5749201/TUG1 polymorphisms and DKD or its laboratory markers. The rs3931283/PVT1 G/G and rs7158663/MEG3 G/G are associated with DKD and markers of renal function in T2DM patients from a Brazilian population.

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level

BackgroundPatients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels.MethodsThis is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function.ResultsAfter adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053–0.402), an association specific to participants with < 1 year duration of diabetes. RCS analyses demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 144 mmHg corresponding to the best beta-cell function. This higher SBP was “paradoxically” associated with lower 2 h postprandial blood glucose (PBG) when SBP < 150 mmHg that was almost exclusively mediated by ISSI2 (mediating effect = − 0.043, 95%CI − 0.067 to − 0.018; mediating effect percentage = 94.7%, P < 0.01). SBP was however not associated with improvement in ISSI2 or 2 h PBG in participants with HbA1c < 10%.ConclusionsIn early stage of diabetes, a slightly elevated SBP (140–150 mmHg) was transiently associated with better beta-cell function in T2DM patients with HbA1c ≥ 10% but not in those with HbA1c < 10%.

Application of urine C-peptide creatinine ratio in type 2 diabetic patients with different levels of renal function.

This study aims to investigate the effect of single urine C peptide/creatinine (UCPCR) in assessing the islet β Cell function of type 2 diabetes mellitus (T2DM) patients with different renal function. A total of 85 T2DM patients were recruited in this study, all the patients were assigned to one group with estimated glomerular filtration rate (eGFR)≤60 ml·min-1·1.73 m-2 and another group complicated with eGFR>60 ml·min-1·1.73 m-2. Serum creatinine, urine creatinine, serum fasting C-peptide (FCP), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1C) and 24-hour urinary C-peptide (24hUCP) were measured. The modified homeostasis model assessment-islet β cell function [HOMA-islet (CP-DM)], the modified homeostasis model assessment-insulin resistance [HOMA-IR(CP)] and UCPCR were calculated. When compared with group eGFR ≤60 ml·min-1·1.73 m-2, the levels of UCPCR, FCP, the modified HOMA-IR(CP) and HOMA-islet (CP-DM) were promoted and the concentrations of HbA1C, FPG, creatinine were decreased in the patients of eGFR>60 ml·min-1·1.73 m-2 (P<0.05); FCP was uncorrelated with 24hUCP while associated with UCPCR in the patients of eGFR ≤ 60 ml·min-1·1.73 m-2; UCPCR was positively correlated with FCP and HOMA-IR(CP) in the T2DM patients with different levels of renal function; the cut-off (UCPCR ≤ 1.13 nmol/g) had 88.37% sensitivity and 95.24% specificity [95% confidence interval (CI):0.919-0.997] for identifying severe insulin deficiency in T2DM patients[area under the curve (AUC) 0.978]. UCPCR can be used to evaluate islets β Cell function in T2DM patients with different renal function status.

The Effect of SGLT2 Inhibitor Dapagliflozin on Serum Levels of Apelin in T2DM Patients with Heart Failure.

Apelin is a multifunctional peptide that plays a pivotal role in cardiac remodeling and HF manifestation because of counteracting angiotensin-II. We hypothesized that positive influence of sodium-glucose co-transporter-2 (SGLT2) inhibitor on cardiac function in T2DM patients with HF might be mediated by apelin and that its levels seem to be a target of management. A total of 153 type 2 diabetes mellitus (T2DM) patients with II/III HF NYHA class and average left ventricular (LV) ejection fraction (EF) of 46% have been enrolled and treated with dapagliflosin. The serum levels of apelin and N-terminal brain natriuretic pro-peptide (NT-proBNP) were measured at baseline and over a 6-month period of dapagliflosin administration. We noticed that administration of dapagliflozin was associated with a significant increase in apelin levels of up to 18.3% and a decrease in NT-proBNP of up to 41.0%. Multivariate logistic regression showed that relative changes of LVEF, LA volume index, and early diastolic blood filling to longitudinal strain ratio were strongly associated with the levels of apelin, whereas NT-proBNP exhibited a borderline significance in this matter. In conclusion, dapagiflosin exerted a positive impact on echocardiographic parameters in close association with an increase in serum apelin levels, which could be a surrogate target for HF management.

467-P: The Relationship between Diabetic Peripheral Neuropathy and Metformin Treatment in Type 2 Diabetes Mellitus

Background: Metformin is the first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM) . However, the use of metformin may lead to neuropathy by affecting the absorption of vitamin B12. Our objective was to explore the association between the application of metformin and diabetic peripheral neuropathy (DPN) . Methods: The multicenter randomized cross-sectional study was conducted in 13 hospitals in Beijing from October 2015 to April 2016. T2DM Patients were divided into confirmed DPN group, suspected DPN group and non-DPN group by the five physical examinations (Ankle reflex, acupuncture pain, temperature, vibration, and pressure) . Non-parametric Mann-Whitney test was used for the comparison between non-normally distributed variables between two groups. Chi-square test was used for the comparison of categorical variables. The risk factors of DPN in T2DM Patients were assessed using logistic regression. Results: Compared with patients without metformin, patients taking metformin were more likely to suffer from DPN and suspected DPN (P &amp;lt; 0.0for both) . Similar results were obtained after stratifying the data based on age, BMI, and HbA1c. It was shown that the application of metformin was a risk factor for DPN (OR = 5.06, 95%Cl: 3.90-6.56; P &amp;lt; 0.001) and suspected DPN (OR = 3.58, 95%Cl: 2.78-4.62; P &amp;lt; 0.001) in T2DM patients after the adjustment for age, BMI and HbA1c. In addition, prolonged application of metformin, increased cumulative and single doses would also be associated with the risk of DPN (P &amp;lt; 0.0for all) . Conclusion: The application of metformin was observed relate to DPN in T2DM patients. The vitamin B12 concentration and peripheral nerve function of T2DM patients with the application of metformin should be monitored. Disclosure Q.Pan: None. J.Luo: None. L.Guo: None. Funding National Key R&amp;D Program of China (2020YFC2009006)

Cardiac magnetic resonance T1 mapping for evaluating myocardial fibrosis in patients with type 2 diabetes mellitus: correlation with left ventricular longitudinal diastolic dysfunction.

We aimed to evaluate myocardial fibrosis using cardiac magnetic resonance (CMR) T1 mapping in type 2 diabetes mellitus (T2DM) patients and investigate the association between left ventricular (LV) subclinical myocardial dysfunction and myocardial fibrosis. The study included 37 short-term (≤ 5 years) and 44 longer-term (> 5 years) T2DM patients and 41 healthy controls. The LV global strain parameters and T1 mapping parameters were compared between the abovementioned three groups. The association of T1 mapping parameters with diabetes duration, in addition to other risk factors, was determined using multivariate linear regression analysis. The correlation between LV strain parameters and T1 mapping parameters was evaluated using Pearson's correlation. The peak diastolic strain rates (PDSRs) were significantly lower in longer-term T2DM patients compared to those in healthy subjects and short-term T2DM patients (p < 0.05). The longitudinal peak systolic strain rate and peak strain were significantly lower in the longer-term T2DM compared with the short-term T2DM group (p < 0.05). The extracellular volumes (ECVs) were higher in both subgroups of T2DM patients compared with control subjects (all p < 0.05). Multivariate linear regression analysis showed that diabetes duration was independently associated with ECV (β = 0.413, p < 0.001) by taking covariates into account. Pearson's analysis showed that ECV was associated with longitudinal PDSR (r = - 0.441, p < 0.001). T1 mapping could detect abnormal myocardial fibrosis early in patients with T2DM, which can cause a decline in the LV diastolic function. • CMR T1 mapping could detect abnormal myocardial fibrosis early in patients with T2DM. • The diabetes duration was independently associated with ECV. • Myocardial fibrosis can cause a decline in the LV diastolic function in T2DM patients.