Consecutive Type 2 Diabetes Mellitus Patients Research Articles

Derivation and validation of the BIMAST score for predicting the presence of fibrosis due to Metabolic dysfunction-associated steatotic liver disease among diabetic patients in the community.

Current screening pathways, developed from tertiary care cohorts, underestimate the presence of Metabolic-dysfunction associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) in the community. We developed, validated, and assessed cost-effectiveness of a new score for screening the presence of fibrosis due to MASLD in primary care. Consecutive T2DM patients underwent screening for liver diseases with transient elastography (TE). Based on predictors of significant/advanced fibrosis, we generated the BIMAST score (based on aspartate aminotransferase (AST) and body mass index (BMI)) and validated it internally and externally (Royal Free Hospital, London and Palermo Hospital). For cost-effectiveness analysis, 6 screening strategies were compared against standard of care: BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, ELF and transient elastography (TE). A Markov model was built based on fibrosis status. Cost per quality-adjusted life year (QALY) gained and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime. Among 300 patients enrolled, 64% (186) had MASLD and 10% (28) other causes of liver disease. In the whole population, patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287), and 3% (8/287), respectively. In primary care, BIMAST performed better than other non-invasive markers at predicting significant and advanced fibrosis. Moreover, BIMAST reduced false negatives from 54% (ELF) and 38% (FIB-4) to 10%. In both validation cohorts, BIMAST performance was as good as FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST. The BIMAST predicts the presence of significant fibrosis in the community, reduces false negatives and is cost-effective. The BIMAST score should be included in the holistic assessment of diabetic patients.

Improved heart failure screening and prevention in type 2 diabetes mellitus by cardiologist in rural areas

Abstract Purpose Guidelines recommend screening in type 2 diabetes mellitus (T2DM) for unrecognised asymptomatic left ventricular systolic dysfunction (LVSD), reduced (HFrEF), mid-range (HFmrEF) or preserved (HFpEF) heart failure (HF) with periodic evaluation of natriuretic peptides (NTproBNP) or echocardiography (echo). Tissue doppler and speckle-tracking echo may be needed to facilitate HF diagnosis at earlier, more treatable stage. Methods 2185 consecutive asymptomatic T2DM (age 62 ±4 years, 62% women) patients (pts) were referred from January 2015 by rural diabetologists (dia) to echolab with elevated NTproBNP (>125 pg/mL) or 5-year HF risk score WATCH-DM ≥14 points. After exclusion of abnormal electrocardiogram or chest x-ray and significant valvular heart disease was compared continued usual care by diabetologist with randomly assigned prospective follow-up by regional cardiologist. Results At referral in both groups were similar baseline characteristics, 20% pts were treated with ACE-inhibitor (ACEi), 2% beta-blockers (BB). After cardiologist consultation ACEi and BB use increased significantly to 96% and 84% in both groups (all p <0.001). Global LVSD (EF≤50%) was detected in 8% at baseline and 29% pts after 5 years in diabetologist group, respectively 9% at baseline and 13% after 5 years in cardiologist group (p <0.001). Systolic dysfunction (S’≤6.0 cm/s) occured in 20% at baseline and 41% pts after 5 years in dia group, respectively 19% at baseline and 24% after 5 years in cardiologist group (p <0.001). Reduced global longitudinal (GLS<16%) observed in 26% at baseline and 59% pts after 5 years in dia group, respectively 26% at baseline and 36% after 5 years in cardiologist group (p <0.001). At baseline we found 1% pts with new-onset HF in both groups (only HFmrEF). After mean follow-up of 54 ±7 months in cardiologist group developed new HF in 4% pts (2% HFmrEF, 2% HFpEF) compared with 25% pts (3% HFrEF, 7% HFmrEF, 15% HFpEF) in diabetologist group (p <0.001). Significant (p <0.001) predictors of incident HFmrEF were systolic dysfunction (S’≤6.0 cm/s), hazard ratio (HR) 3.6, 95% CI 2.96-4.2) and reduced GLS (HR 4.6, 95% CI 3.8-5.2), all p <0.01. The strongest (p <0.001) predictors of incident HFpEF were new-onset atrial fibrillation (HR 2.5, 95% CI 1.2-3.7) and echo-detected left ventricular hypertrophy (septal and posterior wall thickness ≥13 mm, HR 1.7, 95% CI 1.2-2.1), all p <0.01. Conclusions For preventing HF progression is required additional research focused on cooperative care between diabetologists and specialised HF outpatient clinic.

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled type 2 diabetes mellitus: a comparison of cardiovascular effects

Abstract Background Both hyper- and hypo-glycaemia, as well as large glycaemic variability (GV) are associated with increased cardiovascular events in patients with type 2 diabetes mellitus (T2DM); possible contributing mechanisms of the increased cardiovascular risk include endothelial dysfunction and cardiac sympatho-vagal imbalance. Recent studies suggest that continuous subcutaneous insulin infusion (CSII) improves glycaemic control compared to multiple daily insulin injections (MDI). Purpose In this study, we assessed whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI. Methods We enrolled in a small randomized pilot study consecutive T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to CSII (Group 1) or to continue MDI (Group 2); insulin dose was adjusted to achieve optimal glycaemic target ranges. Patients were studied at baseline and after 6 months by: 1) assessment of flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring; 3) a 7-day continuous glucose monitoring (CGM) was performed at baseline and follow-up in 8 and 7 patients of Group 1 and 2, respectively. Results Overall, 21 patients were enrolled, 12 randomized to CSII and 9 to MDI. Daily insulin dose, glycated hemoglobin levels and CGM parameters did not differ significantly between the 2 groups, both at baseline and at follow-up. Both FMD (6.7±2.5 vs 4.6±2.0 %, p=0.51) and NMD (8.9±3.1 vs 7.0±3.0 %, p=0.18), as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up. No relation between GV and both peripheral dilator function and cardiac autonomic function was also detected. Conclusions In this small, randomized pilot study we show that, in T2DM patients, CSII achieves similar medium-term glycaemic control compared to MDI, without any significant adverse effect on the cardiovascular system.

HbA1c control in type 2 diabetes mellitus patients with coronary artery disease: a retrospective study in a tertiary hospital in South Africa.

Type 2 diabetes mellitus (T2DM) patients with coronary artery disease (CAD) have an increased risk of recurrent cardiovascular events. These patients require optimal glucose control to prevent the progression of atherosclerotic cardiovascular disease (ASCVD). Contemporary guidelines recommend an HbA1c ≤7% to mitigate this risk. The aim of this study was to evaluate HbA1c control in T2DM patients with angiographically proven ASCVD. We conducted a cross-sectional, retrospective study on consecutive T2DM patients with acute and chronic coronary syndromes managed in a tertiary academic hospital in South Africa. Glycaemic control was assessed by evaluating the glycated haemoglobin (HbA1c) level measured at index presentation with acute and chronic coronary syndromes and during the most recent follow-up visit. The study population comprised 262 T2DM patients with a mean age of 61.3 ± 10.4 years. At index presentation, 110 (42.0%) T2DM patients presented with ST-segment elevation myocardial infarction, 69 (26.3%) had non-ST-segment elevation myocardial infarction, 43 (16.4%) had unstable angina, and 40 (15.3%) had stable angina. After a median duration of 16.5 months (IQR: 7-29), 28.7% of the study participants had an HbA1c ≤7%. On multivariable logistic regression analysis, females were less likely to have poor glycaemic control (HbA1c above 7%) [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.95, p=0.038]. Also, T2DM patients prescribed metformin monotherapy (OR: 0.34, 95% CI: 0.14-0.82, p=0.017) and patients with ST-segment depression on the electrocardiogram (OR: 0.39, 95% CI: 0.16-0.96, p=0.041) were less likely to have poor glycaemic control. After a median duration of 16.5 months, only 28.7% of T2DM patients with CAD had an HbA1c ≤7%. This finding underscores the substantial unmet need for optimal diabetes control in this very high-risk group.

Evolocumab attenuate pericoronary adipose tissue density via reduction of lipoprotein(a) in type 2 diabetes mellitus: a serial follow-up CCTA study

BackgroundPericoronary adipose tissue (PCAT) density is a biomarker of vessel inflammation, which is supposed to be increased in patients with type 2 diabetes mellitus (T2DM). However, whether the coronary inflammation revealed by this novel index could be alleviated after evolocumab treatment in T2DM remains unknown.MethodsFrom January 2020 to December 2022, consecutive T2DM patients with low-density lipoprotein cholesterol ≥ 70 mg/dL on maximally tolerated statin and taking evolocumab were prospectively included. In addition, patients with T2DM who were taking statin alone were recruited as control group. The eligible patients underwent baseline and follow-up coronary CT angiography with an interval of 48-week. To render patients with evolocumab as comparable to those controls, a propensity-score matching design was used to select the matched pairs with a 1:1 ratio. Obstructive lesion was defined as the extent of coronary artery stenosis ≥ 50%; the numbers inside the brackets were interquartile ranges.ResultsA total of 170 T2DM patients with stable chest pain were included [(mean age 64 ± 10.6 [range 40–85] years; 131 men). Among those patients, 85 were in evolocumab group and 85 were in control group. During follow-up, low-density lipoprotein cholesterol (LDL-C) level (2.02 [1.26, 2.78] vs. 3.34 [2.53, 4.14], p < 0.001), and lipoprotein(a) (12.1 [5.6, 21.8] vs. 18.9 [13.2, 27.2], p = 0.002) were reduced after evolocumab treatment. The prevalence of obstructive lesions and high-risk plaque features were significantly decreased (p < 0.05 for all). Furthermore, the calcified plaque volume were significantly increased (188.3 [115.7, 361.0] vs. 129.3 [59.5, 238.3], p = 0.015), while the noncalcified plaque volume and necrotic volume were diminished (107.5 [40.6, 180.6] vs. 125.0 [65.3, 269.7], p = 0.038; 0 [0, 4.7] vs. 0 [0, 13.4], p < 0.001, respectively). In addition, PCAT density of right coronary artery was significantly attenuated in evolocumab group (− 85.0 [− 89.0, − 82.0] vs. − 79.0 [− 83.5, − 74.0], p < 0.001). The change in the calcified plaque volume inversely correlated with achieved LDL-C level (r = − 0.31, p < 0.001) and lipoprotein(a) level (r = − 0.33, p < 0.001). Both the changes of noncalcified plaque volume and necrotic volume were positively correlated with achieved LDL-C level and Lp(a) (p < 0.001 for all). However, the change of PCATRCA density only positively correlated with achieved lipoprotein(a) level (r = 0.51, p < 0.001). Causal mediation analysis revealed Lp(a) level mediated 69.8% (p < 0.001) for the relationship between evolocumab and changes of PCATRCA.ConclusionsIn patients with T2DM, evolocumab is an effective therapy to decrease noncalcified plaque volume necrotic volume, and increase calcified plaque volume. Furthermore, evolocumab could attenuate PCAT density, at least in part, via the reduction of lipoprotein(a).

Association of D-dimer Level with Renal Parameters and Cardiovascular Events in Type 2 Diabetes Mellitus: A Retrospective Cohort Study

Introduction: D-dimer is a biomarker that can detect early stages of renal and cardiovascular dysfunction in Type 2 Diabetes Mellitus (T2DM). It serves as a key indicator and is readily available in laboratory settings, along with other risk factors. Aim: To investigate the association between D-dimer levels and renal parameters, as well as cardiovascular events, among T2DM subjects. Materials and Methods: This retrospective cohort study was conducted at Visnagar’s Nootan Medical College and Research Centre, Visnagar, Gujarat, India, involving subjects who visited the centre for health checks between September 2021 and December 2022. Screening was performed on all adult individuals with T2DM. Clinical records of 550 consecutive T2DM patients, aged between 18 and 80 years, receiving care at the centre were analysed. After applying exclusion criteria, 155 patients with T2DM diagnosis were enrolled. Parameters such as cystatin C, D-dimer, serum creatinine, urea, estimated Glomerular Filtration Rate (eGFR), and albuminuria were evaluated in all subjects. Bivariate logistic regression analysis was conducted to determine whether renal indicators are associated with high D-dimer levels, generating an odds ratio. Multivariate logistic regression analysis was then performed, correcting for sex and age, to determine which kidney indicators are linked to high D-dimer levels. Results: A total of 155 participants were included in this study, and were divided into high and low D-dimer groups. The mean ages of the low and high D-dimer groups were 40±13 years and 55±10 years, respectively. Compared to the low D-dimer group, the high D-dimer group had a higher frequency of males (p-value &lt;0.001). Patients with high D-dimer levels exhibited significantly increased levels of HbA1c, creatinine, urea, cystatin C, and UAE compared to patients with low D-dimer levels (p-value=0.001, p-value=0.001, p-value &lt;0.001, p-value &lt;0.001, and p-value=0.001, respectively). Conclusion: D-dimer may be beneficial in identifying patients with early-stage diabetic kidney disease, thereby promoting the early adoption of renal and cardioprotective therapy. Additionally, elevated D-dimer levels are associated with an increased risk of cardiovascular disease.

Predictive value of serum irisin for chronic heart failure in patients with type 2 diabetes mellitus

We hypothesize that serum irisin can have additional discriminative potency for heart failure (HF) in individuals with type 2 diabetes mellitus (T2DM). The study group comprised 226 consecutive T2DM patients (153 patients with any HF phenotypes and 30 patients without HF) aged 41 to 65 years. The plasma levels N-terminal brain natriuretic pro-peptide (NT-proBNP) and irisin were detected by ELISA at the baseline of the study. We found that the most appropriate cut-off value of irisin (HF versus non-HF) were 10.4 ng/mL (area under curve [AUC] = 0.96, sensitivity = 81.0%, specificity = 88.0%; P = 0.0001). Cutoff point of NT-proBNP that distinguished patients with HF and without it was 750 pmol/L (AUC = 0.78; sensitivity = 72.7%, specificity 76.5%, p = 0.0001). Using multivariate comparative analysis we established that concentrations of irisin < 10.4 ng/mL (odds ration [OR] = 1.30; P = 0.001) and NT-proBNP > 750 pmol/mL (OR = 1.17; P = 0.042), left atrial volume index (LAVI) > 34 mL/m2 (OR = 1.06; P = 0.042) independently predicted HF. Irisin being added to NT-proBNP improved predictive modality for HF, whereas combination of NT-proBNP and LAVI > 34 mL/m2 did not. In conclusion, we established that irisin had independent predicted potency for HF in patients with established T2DM.

Microvascular complications identify a specific coronary atherosclerotic phenotype in patients with type 2 diabetes mellitus

BackgroundPatients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis.MethodsWe prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up.ResultsWe enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 [73.1%] men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 [53.75%]) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 [63.4%] vs. 68 [45.9%], p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 [14.5%] vs. 12 [8.1%], p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months).ConclusionsThe presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.

Variations in Anthropometric Parameters in Offspring of Type 2 Diabetes Patients

Background: The risk of developing diabetes mellitus for an individual with a positive family history of the disease is two-to fourfold higher in an offspring of a diabetic compared with offspring of non-diabetic. Objectives: This study aimed to assess the anthropometric parameters of offspring of type 2 diabetes mellitus (T2DM) patients in Sagamu, Nigeria. Methods: Study subjects were 100 offspring of consecutive T2DM patients’ attending a hospital endocrinology clinic. Diabetic offspring were exempted from the study. FBS was determined employing enzymatic hexokinase method. Height, weight, waist circumference (WC), and hip circumference (HC) were measured utilizing standard methods while body mass index (BMI) and waist-hip ratio (WHR) were calculated. Results: There were 50 males and 50 females study subjects, aged 16 to 65 years. The most populated aged group was 16 to 25 years of which 48.6% (n=36) were males and 51.4% (n=38) were females. Totally, 18 subjects were either obese or overweight. Significantly, male subjects had a greater mean weight compared to females (P=0.021) while females had greater mean BMI (P=0.037). Mean WHR was significantly higher among male subjects (P=0.018). Conclusion: Common Anthropometric parameters are normal, female subjects tend to have higher BMI while males have higher weight and WHR.

The relationship between hepcidin and anemia in controlled and uncontrolled Type-2 Diabetes Mellitus (T2DM) patients at Sanglah Hospital, Bali, Indonesia

Background: Anemia in patients with diabetes mellitus (DM) is often associated with anemia of chronic disease caused by inflammation or iron metabolism disorders. Hepcidin is known to function in initiating the internalization and degradation of ferroportin. It can inhibit the release of iron from cells where an increase in hepcidin levels will reduce iron absorption in the intestine, resulting in a decrease in serum iron levels. This study aims to determine the relationship between serum hepcidin levels and anemia in patients with Type-2 Diabetes Mellitus (T2DM).Methods: This cross-sectional study was conducted on 77 consecutive T2DM patients who met the inclusion and exclusion criteria and received health services at Sanglah Hospital, Bali, Indonesia, during the study period. The variables assessed in this study included T2DM status (controlled and uncontrolled), anemia, hemoglobin, HbA1c, erythrocyte sedimentation rate, and hepcidin. Data were analyzed with SPSS version 20 for Mac.Results: There was no significant difference in age, sex, disease duration, SGOT, SGPT, leukocytes, platelets, and ESR between controlled and uncontrolled T2DM groups (p&gt;0.05). However, there was a significant difference in eGFR and hemoglobin levels between controlled and uncontrolled T2DM groups (p&lt;0.05). Mann-Whitney U test found a significant difference in hepcidin levels between controlled and uncontrolled T2DM groups (MD=138.14; 95%CI=10.65-286.94; p=0.046). A weak significant negative correlation was found between hemoglobin and hepcidin levels by the Spearman correlation test (r=-0.259; p=0.043).Conclusion: There was a significant difference between the mean hemoglobin and hepcidin levels in the controlled T2DM group compared to uncontrolled T2DM group patients. A weak statistically significant negative correlation was found between hepcidin levels and anemia in T2DM patients.

Dyslipidaemia pattern and prevalence among type 2 diabetes mellitus patients on lipid-lowering therapy at a tertiary hospital in central South Africa

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is a major cause of death worldwide. A large number of deaths due to ASCVD occurs among people with diabetes mellitus (DM). One of the important modifiable risk factors associated with ASCVD is dyslipidaemia and its prevalence is not known in central South Africa (SA). This study aimed to determine the pattern and prevalence of dyslipidaemia among type 2 diabetes mellitus (T2DM) patients on lipid-lowering therapy.MethodsThis descriptive, retrospective study of patients’ records was conducted at Universitas Academic Hospital in Bloemfontein, SA. The study population included 143 consecutive T2DM patients of any age that attended the Diabetes Clinic from 1 January to 31 March 2019. The patients had to be on lipid-lowering therapy for a minimum duration of 3 months. Data were sourced from the clinic files and included the patient’s lipid profile, anthropometric and demographic data. Dyslipidaemia was defined using the 2018 SA dyslipidaemia guidelines.ResultsThe median age of the participants was 63 years (interquartile range [IQR] 52–71 years). The majority of the participants were female (n = 92; 64.3 %). The median duration since the DM diagnosis was 18 years (IQR 13–23 years). The prevalence of dyslipidaemia was 86.7 % (n = 124). Combined dyslipidaemia, namely either triglycerides (TG) + low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) + TG or HDL + LDL, was the most common pattern (n = 51; 42.5 %) largely due to raised TG + LDL contributing 37.2 % (n = 19) to this pattern. The second and third most common patterns were isolated (either LDL, HDL or TG) and mixed dyslipidaemia (TG + HDL + LDL) at 40.8 % (n = 49) and 16.7 % (n = 20), respectively. The most frequent lipid abnormality (n = 84; 70.0 %) was LDL of ≥ 1.8 mmol/L. Of the 140 participants on statin therapy, only 5 % were on high-intensity therapy.ConclusionsA high prevalence of dyslipidaemia among DM patients was observed, despite the use of lipid-lowering therapy in this small observational study. Our findings highlight the need to better educate healthcare providers regarding the intensification of lipid-lowering therapy, along with improved strategies to address poor glycaemic control and other modifiable lifestyle factors.

Impact of compliance with lifestyle recommendations and medication adherence on 1-year prevention of major cardiovascular events in diabetic patients undergoing partial foot amputation

Abstract Funding Acknowledgements Type of funding sources: None. Background Partial foot amputation (PFA) is generally not considered a high-risk surgery. However, 3 years survival rate is less than 50-60%. The purpose of the study was to evaluate the impact of compliance with lifestyle recommendations and medication adherence on 1-year prevention of major cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) after PFA. Methods In this prospective single-center interventional cohort study, 785 consecutive T2DM patients after PFA were included in the 1-year follow-up. Physical examination and laboratory tests were performed at baseline and every month after PFA for 1 year. Patients were considered as compliant with lifestyle recommendations if they followed a healthy diet, smoking cessation, and at least ≥30 min/day physical exercise. Patients were defined as adherent to medication if they followed ≥80% prescribed medication intake. MACE was defined as a composite endpoint including cardiovascular death, myocardial infarction (MI), stent thrombosis, acute stroke, or unstable arrhythmia. Results During 1-year follow-up MACE occurred in 63/535 patients who were medication adherent compared to 137/249 non-adherent patients (Chi square = 167,2, p &amp;lt; 0,001). Among lifestyle compliant patients, 55/498 had MACE compare with 145/286 non-compliant patients (Chi square = 150.3, p &amp;lt; 0,001). The COX regression analysis was conducted to present the adjusted effect of compliance and adherence to the incidence of MACE (B = 0.989, p &amp;lt; 0.001, and B= 1.096, p &amp;lt; 0.001, respectively) (Table). The potential confounders such as age and previous MI were statistically significant (Table). Gender, smoking, diabetes severity, HbA1c, hypertension, symptomatic coronary artery disease, history of ischemic events, heart revascularization were not statistically significant. Conclusion. Failure to follow lifestyle recommendations in T2DM patients after PFA increases the OR of the incidence of MACE 2.7 fold, non-adherence to medication 3 fold. Our results indicate that optimizing preventive interventions is of outmost importance for patients with diabetes undergoing PFA Cox Regression Results for predictors of Indicator Odds ratio B Standard error P-value Age 1.031 0.031 0.009 0.007 History of myocardial infarction 4.017 1.391 0.184 &amp;lt;0.001 Non-compliance to lifestyle changes 2.688 0.989 0.198 &amp;lt;0.001 Medication non-adherence 2.992 1.096 0.186 &amp;lt;0.001

Association of carbamylated high-density lipoprotein with coronary artery disease in type 2 diabetes mellitus: carbamylated high-density lipoprotein of patients promotes monocyte adhesion

BackgroundIncreasing evidence showed that carbamylated lipoprotein accelerated atherosclerosis. However, whether such modification of high-density lipoprotein (HDL) particles alters in type 2 diabetes mellitus (T2DM) patients and facilitates vascular complications remains unclear. We aimed to investigate the alteration of the carbamylation in HDL among T2DM patients and clarify its potential role in atherogenesis.MethodsA total of 148 consecutive T2DM patients undergoning angiography and 40 age- and gender-matched control subjects were included. HDL was isolated from plasma samples, and the concentration of HDL carbamyl-lysine (HDL-CBL) was measured. Furthermore, the HDL from subjects and in-vitro carbamylated HDL (C-HDL) was incubated with endothelial cells and monocyte to endothelial cell adhesion. Adhesion molecule expression and signaling pathway were detected.ResultsCompared with the control group, the HDL-CBL level was remarkably increased in T2DM patients (6.13 ± 1.94 vs 12.00 ± 4.06 (ng/mg), P < 0.001). Of note, HDL-CBL demonstrated a more significant increase in T2DM patients with coronary artery disease (CAD) (n = 102) than those without CAD (n = 46) (12.75 ± 3.82 vs. 10.35 ± 4.11(ng/mg), P = 0.001). Multivariate logistic regression analysis demonstrated that higher HDL-CBL level was independently associated with a higher prevalence of CAD in diabetic patients after adjusting for established cofounders (adjusted odds ratio 1.174, 95% confidence Interval 1.045–1.319, p = 0.017). HDL from diabetic patients with CAD enhanced greater monocyte adhesion than that from the non-CAD or the control group (P < 0.001). Such pro-atherogenic capacity of diabetic HDL positively correlated with HDL-CBL level. Furthermore, in-vitro incubation of carbamylated HDL (C-HDL) with endothelial promoted monocyte to endothelial cell adhesion, induced upregulation of cell adhesion molecules expression, and activated NF-κB/p65 signaling in endothelial cells. Inhibiting carbamylation of HDL or NF-κB activation attenuated the monocyte to endothelial cell adhesion and cell surface adhesion molecules expression.ConclusionsOur study identified elevated carbamylation modification of HDL from T2DM patients, especially in those with concomitant CAD. We also evidenced that C-HDL enhanced monocyte to endothelial cell adhesion, indicating a potential pro-atherogenic role of C-HDL in atherosclerosis among T2DM patients.Trial registrationhttps://register.clinicaltrials.gov, NCT04390711 Registered on 14 May 2020; Retrospectively registered

Prognostic impact of the atherogenic index of plasma in type 2 diabetes mellitus patients with acute coronary syndrome undergoing percutaneous coronary intervention

BackgroundThe association of the atherogenic index of plasma (AIP), an emerging lipid index that can predict the risk for cardiovascular disease, with adverse outcomes in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not been determined. Therefore, the aim of this study was to investigate whether the AIP could independently predict adverse cardiovascular events in T2DM patients with ACS undergoing PCI.MethodsThis study was a retrospective analysis of a single-centre prospective registry involving 826 consecutive T2DM patients who underwent primary or elective PCI for ACS from June 2016 to November 2017. This study ultimately included 798 patients (age, 61 ± 10 years; male, 72.7%). The AIP was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides to high-density lipoprotein-cholesterol (HDL-C). All the patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was a composite of death from any cause, non-fatal spontaneous myocardial infarction (MI), non-fatal ischaemic stroke, and unplanned repeat revascularization. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, and non-fatal ischaemic stroke.ResultsDuring a median follow-up period of 927 days, 198 patients developed at least one event. An unadjusted Kaplan-Meier analysis showed that the incidence of the primary endpoint increased gradually with rising AIP quartiles (log-rank test, P = 0.001). A multivariate Cox proportional hazards analysis revealed that compared with the lowest AIP quartile, the top AIP quartile was associated with significantly increased risk for the primary and key secondary endpoints (hazard ratio [HR]: 2.249, 95% confidence interval [CI]: 1.438 to 3.517, P < 0.001; and HR: 2.571, 95% CI: 1.027 to 6.440, P = 0.044, respectively).ConclusionsA higher AIP value on admission was independently and strongly associated with adverse cardiovascular events in T2DM patients with ACS undergoing PCI.

Major adverse cardiovascular and limb events in patients with diabetes and concomitant peripheral artery disease treated with sodium glucose cotransporter 2 inhibitor versus dipeptidyl peptidase-4 inhibitor

BackgroundWhether sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a lower risk of cardiovascular as well as adverse lower limb events in patients with type-2 diabetes mellitus (T2DM) and concomitant peripheral artery disease (PAD) is unclear.We aimed to evaluate the risk of cardiovascular and limb events, and death associated with the use of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal and national cohort of patients with T2DM.MethodsIn this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, we identified a total of 11,431 and 93,972 consecutive T2DM patients with PAD taking SGLT2i and DPP4i, respectively, from May 1, 2016, to December 31, 2017. We used 1:1 propensity score matching (PSM) to balance covariates across study groups. Patients were followed from the drug index date until the occurrence of clinical outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first.ResultsOverall, 56% and 44% of the patients were treated with dapagliflozin and empagliflozin, respectively. The use of SGLT2i had comparable risks of ischemic stroke and acute myocardial infarction, and was associated with lower risks of congestive heart failure (CHF) [hazard ratio (HR): 0.66; 95% confidence interval (CI) 0.49–0.89; p = 0.0062], lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54–0.98; p = 0.0367) or amputation (HR: 0.43; 95% CI 0.30–0.62; p < 0.0001), and cardiovascular death (HR: 0.67; 95% CI 0.49–0.90; p = 0.0089) when compared with the DDP4i group after PSM. The subgroup analysis revealed consistent results for CHF and major adverse limb outcomes for SGLT2i versus DPP4i among patients aged ≥ 75 years, the presence of chronic kidney disease and established cardiovascular disease was consistent with the main analysis.ConclusionsSGLT2i were associated with lower risks of CHF and adverse lower limb events compared with DPP4i among patients with T2DM and PAD in real-world practice.

Sodium-Glucose Cotransporter-2 Inhibitors at Discharge from Cardiology Hospitalization Department: Decoding A New Clinical Scenario.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) are new glucose-lowering drugs (GLDs) with demonstrated cardiovascular benefits in patients with heart disease and type-2 diabetes mellitus (T2DM). However, their safety and efficacy when prescribed at hospital discharge are unexplored. This prospective, observational, longitudinal cohort study included 104 consecutive T2DM patients discharged from the cardiology department between April 2018 and February 2019. Patients were classified based on SGLT-2 inhibitor prescription and adjusted by propensity-score matching. The safety outcomes included discontinuation of GLDs; worsening renal function; and renal, hepatic, or metabolic hospitalization. The efficacy outcomes were death from any cause, cardiovascular death, cardiovascular readmission, and combined clinical outcome (cardiovascular death or readmission). The results showed that, the incidence rates of safety outcomes were similar in the SGLT-2 inhibitor or non-SGLT-2 inhibitor groups. Regarding efficacy, the SGLT-2 inhibitors group resulted in a lower rate of combined clinical outcomes (18% vs. 42%; hazard ratio (HR), 0.35; p = 0.02), any cause death (0% vs. 24%; HR, 0.79; p = 0.001) and cardiovascular death (0% vs. 17%; HR, 0.83; p = 0.005). No significant differences were found in cardiovascular readmissions. SGLT-2 inhibitor prescription at hospital discharge in patients with heart disease and T2DM was safe, well tolerated, and associated with a reduction in all-cause and cardiovascular deaths.

Predictive Value of Pancreatic Steatosis for Severity of Coronary Atherosclerosis in Patients with Type 2 Diabetes Mellitus

Objective To investigate the association of pancreatic steatosis with coronary atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods Patients with T2DM who underwent coronary computed tomography angiography(CCTA)in our center due to chest pain were enrolled from January 2016 to February 2019. According to the CCTA findings,patients were divided into normal group,mild-to-moderate coronary atherosclerosis group and severe coronary atherosclerosis group. CT attenuation of pancreas and spleen was measured on abdominal non-enhanced CT,and the CT attenuation indexes including the difference between pancreatic and splenic attenuation (P-S) and the ratio of pancreas-to-spleen attenuation (P/S) were calculated. Analysis of variance or Kruskal-Wallis rank test were used to assess differences among each group. Logistic regression analysis was used to analyze the risk factors of severe coronary stenosis. The accuracy of P/S in predicting severe coronary artery stenosis was assessed by receiver operator characteristic (ROC) curve analysis. Results A total of 173 consecutive T2DM patients were enrolled. These patients included 27 patients with normal coronary artery (15.6%),124 patients with mild to moderate stenosis (71.7%),and 22 patients with severe stenosis (12.7%). There were significant differences in CT attenuation of pancreas (Z=11.543,P=0.003),P-S (Z=11.152,P=0.004) and P/S (Z=11.327,P=0.004) among normal coronary artery group,mild and moderate stenosis group,and severe stenosis group. The CT attenuation of pancreatic head,body,and tail significantly differed in patients with coronary artery stenosis (Z=14.737,P=0.001). After adjusting for confounding factors,multiple Logistic regression showed that P/S (OR=0.062,95%CI=0.008-0.487,P=0.008) was still significantly associated with the severe coronary artery stenosis. The area under the ROC curve of P/S for the diagnosis of severe coronary artery stenosis was 0.701,and the optimal cutoff point was 0.660. Conclusion CT attenuation of pancreas and CT attenuation indexes are associated with the severity of coronary stenosis in T2DM patients,suggesting that pancreatic steatosis may be used as one of the indicators for predicting severe coronary artery stenosis.

Evaluation of LVDD by CCTA with Dual-source CT in Type 2 Diabetes Mellitus Patients.

Left ventricular diastolic dysfunction (LVDD) is a common abnormality among patients in T2DM. We aimed to evaluate the feasibility of coronary computed tomography angiography (CCTA) for the assessment of LVDD in type 2 diabetes mellitus (T2DM) patients. 80 consecutive T2DM patients who were referred for a clinically dual-source CCTA examination to evaluate suspected coronary artery disease and also underwent 2D echocardiography within 7 days of CCTA inclusion and exclusion criteria, were performed. Correlation between CCTA and echocardiography was tested through linear regression and Bland-Altman analysis. In total, 60 T2DM patients were included for the analysis. Pearson correlation showed good correlation for E (r = 0.28; P = 0.028), E/A (r = 0.69; P < 0.01); E (r = -0.06; P = 0.776), E/A (r = 0.54; P = 0.003) and E (r = 0.64; P < 0.01), E/A (r = 0.83; P < 0.01) in three groups, respectively. Overall, diagnostic accuracy for assessment in CCTA of diastolic dysfunction was 79.76% (95% CI: 68%-91%), 71.43% (95% CI: 58%-85%) and 87.50 (95% CI: 79%-96%) in three groups. The presented study proved that CCTA showed good correlations in the estimation of LV filling pressures compared with echocardiography in T2DM patients. Accordingly, retrospectively ECG-gated CCTA may provide valuable information on the evaluation of LVDD in T2DM patients.

Left Atrial Phasic Function in Type 2 Diabetes Mellitus Patients with Preserved Left Ventricular Ejection Fraction Assessed by Feature Tracking CMR Imaging

Purposes: Type 2 diabetes mellitus (T2DM) patients are associated with left atrial (LA) function abnormalities. This study aimed to assess LA phasic function in T2DM patients using FT-CMR imaging. Materials and methods: One hundred consecutive Chinese T2DM patients and 20 controls underwent CMR imaging were prospectively enrolled. LA phasic function was determined by volumetric and strain analysis. Total strain (εs) and peak positive strain rate (SRs), passive strain (εe) and peak early negative strain rate (SRe), active strain (εa) and peak late negative strain rate (SRa) were measured reflecting LA reservoir, conduit, and pump function, respectively. Results: LA reservoir, conduit function were decreased in T2DM, while LA pump function were only numerically higher than controls regardless of LA size. The ROC analysis showed superiority of strain parameters (AUC of εs: 0.852, εe: 0.802, p < 0.001 for both) than traditional LAEF parameters (AUC of total LAEF: 0.671, p = 0.014; passive LAEF: 0.642, p = 0.042) to differentiate T2DM from controls. Multivariate regression analysis showed age was independent determinant of εs and εe, DM duration and LV global longitudinal strain (GLS) were independent determinants of εe and εa. Conclusions: Aside from LA pump function, LA reservoir and conduit function determined on FT-CMR are impaired in T2DM patients compared with controls regardless of LA size. Strain parameters are superior in differentiating T2DM from controls. LA phasic function evaluated using FT-CMR may add important information in clinical decisions.

Short and long-term metabolic outcomes in patients with type 1 and type 2 diabetes receiving a simultaneous pancreas kidney allograft

BackgroundIn contrast to insulin-dependent type 1 diabetes mellitus (T1DM), the indication for Simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) is still ambiguous and wisely Eurotransplant (ET) only granted transplant-permission in a selected group of patients. However, with regard to improvement of metabolic conditions SPK might still be a considerable treatment option for lean insulin dependent type 2 diabetics suffering from renal disease.MethodsMedical data (2001–2013) from all consecutive T1DM and T2DM patients who received a SPK or kidney transplant alone (KTA) at the University Hospital of Leipzig were analyzed. Donor, recipients and long-term endocrine, metabolic and graft outcomes were investigated for T1DM and T2DM-SPK recipients (transplanted upon a special request allocation by ET) and T2DM patients who received a KTA during the same period.ResultsEighty nine T1DM and 12 T2DM patients received a SPK and 26 T2DM patients received a KTA. Patient survival at 1 and 5 years was 89.9 and 88.8% for the T1DM group, 91.7 and 83.3% for the T2DM group, and 92.3 and 69.2% for the T2DM KTA group, respectively (p < 0.01). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was 83.1 and 78.7% for the T1DM group and 91.7 and 83.3% for the T2DM group, respectively (p = 0.71). Kidney allograft survival at 5 years was 79.8% for T1DM, 83.3% for T2DM, and 65.4% for T2DM KTA (p < 0.01). Delayed graft function (DGF) rate was significantly higher in type 2 diabetics received a KTA. Surgical, immunological and infectious complications showed similar results for T1DM and T2DM recipients after SPK transplant and KTA, respectively. With regard to the lipid profile, the mean high-density lipoprotein (HDL)- cholesterol levels were significantly higher in T1DM recipients compared to T2DM patients before transplantation (p = 0.02) and remained significantly during follow up period.ConclusionOur data demonstrate that with regard to metabolic function a selected group of patients with T2DM benefit from SPK transplantation. Consensus guidelines and further studies for SPK transplant indications in T2DM patients are still warranted.