Cause Of Death In Type Research Articles

Assessment of glycemic control and correlation of HbA1c level with lipid profile and duration of diabetes in type 2 diabetes mellitus patients

Background & Objectives: The prevalence of Type 2 diabetes mellitus, or Type 2 DM, is rising globally. A periodic estimation of HbA1c has been recommended to track the state of glycemic control of Type 2 DM patients, in order to control the diabetes associated disorders. The main consequence and cause of death in Type 2 diabetes has been identified as cardiovascular disease (CVD).Optimization of glycemic status along with decreasing CVD risk factors are critical to preventing morbidity and mortality in patients with Type 2 DM. Since there is a lack of data on these CVD risk factors, in Madhesh Province, Nepal, we aimed to evaluate the glycemic status, estimate the lipid profile, and ascertain their correlation, including duration of Type 2 DM among patients in tertiary care hospitals in Madhesh Province, Nepal. Materials and Methods: The tertiary care hospital based cross-sectional study was conducted on 139 Type 2 DM patients, in Madhesh Province, Nepal. In order to gather information of the participants, a systematic questionnaire was introduced. A physical and clinical examination was performed, and an appropriate volume of blood was drawn with prior written consent. The lipid profile parameters, HbA1C, Fasting and post prandial serum glucose were estimated. Results: In 84 (60.3%) and 106 (76.3%) cases, there was an increased fasting and postprandial blood sugar. The mean±SD HbA1c level was 8.40±0.8%. More than half (52.5%) of the patients had poor glycemic control, while 22.3% had inadequate glycemic control, in reference to HbA1c >8% and 7 to 8%, respectively. A substantial increased level of LDL-C, triglycerides and total cholesterol was observed in 122 patients and 85.6% had reduced HDL-C. A significant strong positive association was found between HbA1c level and total cholesterol and triglycerides, in contrast, no discernible association with duration of disease observed. Conclusion: Glycemic control was inadequate. Triglycerides and total cholesterol were significantly positively correlated with HbA1c, but not with HDL-C, LDL-C, or the course of diabetes.

EFFECT OF DAPAGLIFLOZIN AND EMPAGLIFLOZIN ON BODY WEIGHT, LIPID PROFILE AND BLOOD PRESSURE IN TYPE 2 DIABETICS

Background: Cardiovascular disease (CVD) is a leading cause of death in type 2 diabetes mellitus (T2DM) patients with risk factors including weight, lipid profile, and blood pressure. Evidence suggests sodium-glucose co-transporter 2 (SGLT-2) inhibitors benefit T2DM patients. This study investigated the effects of SGLT-2 inhibitors on these risk factors in T2DM patients. Methods: This quasi-experimental study at Sheikh Zayed Medical College/Hospital, Rahim Yar Khan randomized T2DM patients with inadequate glycaemic control. First group received dapagliflozin 5?10 mg and second group received empagliflozin 10-25 mg as add-on therapy to conventional antidiabetic drugs for 12 weeks. The dose was adjusted based on serum blood sugar, with primary endpoints assessing changes in glycaemic control (blood sugar and HbA1c) from baseline. Secondary endpoints included recording additional glycaemic effects (body weight, BMI, lipid profile, and blood pressure) from baseline to endpoint. Results: Both drugs showed excellent tolerability and safety profiles with no major adverse effects. Significant reductions in body weight (empagliflozin 86.7±18 to 78±16.5 Kg, p=0.001; dapagliflozin 89.8±12 to 83±10 Kg, p=0.005), and BMI (empagliflozin 28±5.5 to 26.5±4.2 Kg/m², p=0.003; dapagliflozin 29.6±4.2 to 25.7±5.8 Kg/m², p=0.002) were observed. Both drugs significantly improved glycaemic control, fasting blood sugar (empagliflozin 180±32 to 140±44 mg/dL, p=0.003; dapagliflozin 190±48 to 150±33 mg/dL, p=0.005) and HbA1c (empagliflozin 9.7±2.6 to 7.5±1.8%, p=0.004; dapagliflozin 9.0±1.82 to 7.0±2.2%, p=0.001). Neither drug showed significant improvements in blood pressure or serum lipid profile. Conclusion: Empagliflozin and dapagliflozin have a modest effect on CVD risk factors in T2DM patients. Pak J Physiol 2024;20(2):36-40

Manipulation of Post-Prandial Hyperglycaemia in Type 2 Diabetes: An Update for Practitioners.

This review paper explores post-prandial glycemia in type 2 diabetes. Post-prandial glycemia is defined as the period of blood glucose excursion from immediately after the ingestion of food or drink to 4 to 6 hours after the end of the meal. Post-prandial hyperglycemia is an independent risk factor for cardiovascular disease with glucose "excursions" being more strongly associated with markers of oxidative stress than the fasting or pre-prandial glucose level. High blood glucose is a major promoter of enhanced free radical production and is associated with the onset and progression of type 2 diabetes. Oxidative stress impairs insulin action creating a vicious cycle where repeated post-prandial glucose spikes are key drivers in the pathogenesis of the vascular complications of type 2 diabetes, both microvascular and macrovascular. Some authors suggest post-prandial hyperglycemia is the major cause of death in type 2 diabetes. Proper management of post-prandial hyperglycemia could yield up to a 35% cut in overall cardiovascular events, and a 64% cut in myocardial infarction. The benefits of managing post-prandial hyperglycemia are similar in magnitude to those seen in type 2 diabetes patients receiving secondary prevention with statins - prevention which today is regarded as fundamental by all practitioners. Given all the evidence surrounding the impact of post-prandial glycemia on overall outcome, it is imperative that any considered strategy for the management of type 2 diabetes should include optimum dietary, pharma, and lifestyle interventions that address glucose excursion. Achieving a low post-prandial glucose response is key to prevention and progression of type 2 diabetes and cardiometabolic diseases. Further, such therapeutic interventions should be sustainable and must benefit patients in the short and long term with the minimum of intrusion and side effects. This paper reviews the current literature around dietary manipulation of post-prandial hyperglycemia, including novel approaches. A great deal of further work is required to optimize and standardize the dietary management of post-prandial glycemia in type 2 diabetes, including consideration of novel approaches that show great promise.

KORELASI HbA1c DAN GULA DARAH PUASA TERHADAP RASIO TG/HDL-K PASIEN DIABETES MELLITUS TIPE 2 BERETNIS JAWA

Background : Most of the causes of death in type 2 Diabetes Mellitus (T2DM) are coronary heart disease (CHD) with dyslipidemia as one of its risk factors. The best marker for early detection of dyslipidemia is the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C). In T2DM patients, glycemic control in the form of Fasting Blood Sugar (GDP) and HbA1c can be done to avoid the risk of CHD. This study aims to identify the correlation of Hba1c and GDP with the ratio of TG/HDL-K in T2DM patients with Javanese ethnicity.Methods : This research was a cross sectional study involving 107 respondents from several health centers in Semarang City with consecutive sampling method. GDP, HbA1c, and TG/HDL-K ratio were obtained from medical records. Spearman correlation statistical test was used with a significance value of p <0.05. Results: The average HbA1c (7.86 ±1.97%), GDP (160.36± 76.82gr/dL), and the TG/HDL-K ratio (3.50± 2.22) exceeded the normal number. There was a weak significant correlation between GDP and the TG/HDL-K ratio (p=0.020; r=0.224) and there was no correlation between HbA1c and the TG/HDL-K ratio (p=0.549; r=0.059) in T2DM patients with Javanese ethnicity.Conclusion: The GDP of Javanese T2DM patients is weakly correlated with the TG/HDL-K ratio but not with HbA1c. Glycemic control is needed as an early marker of CHD risk in T2DM.

More new cancers in type 2 diabetes with diabetic foot disease: A longitudinal observational study

ObjectiveCancer has been proposed as the primary cause of death in type 2 diabetes (T2D).The life expectancy is reduced after a diabetic foot ulcer. We investigated whether Diabetic Foot Disease related to an increased risk of developing a new cancer.Research design and methods: We conducted a retrospective analysis on a cohort of patients hospitalized for T2D between 2009 and 2017, stratified for the risk of diabetic foot ulcer (International Working Group on Diabetic Foot classification). We highlighted new cancers in their medical records until December 2020. The relationship between Diabetic Foot Disease and later cancers was analyzed by multivariable Cox regression and survival curves were compared. ResultsAmong 519 patients, 27% had a Diabetic Foot Disease, and 159 were classified as grades 1 or 2 (at risk). As compared to the 218 patients graded 0 according to the IWGDF, they were more men, older, with a longer duration of diabetes, more vascular complications, a greater incidence of insulin use, and a higher skin autofluorescence. During the 54 months of follow-up, 63 (12.1%) new cancers were diagnosed. Baseline Diabetic Foot Disease was significantly associated with a higher risk of cancer (multivariable adjusted Hazard ratio: 2.08, 95%CI: 1.02–4.25), whereas the relation was not significant for subjects at risk of DFU (HR: 1.65, 95%CI:0.81–3.35) ConclusionThe risk of cancer was increased twofold in T2D with Diabetic Foot Disease.

1582-P: Association of Low eGFR with Novel Liver Fibrosis Biomarker Mac-2 Binding Protein Glycosylation Isomer in Type 2 Diabetes Patients

Objective: Advanced liver fibrosis, which leads to liver cirrhosis and cancer, has been one of the major causes of death in type 2 diabetes (T2D). Efficient screening system is needed to detect liver fibrosis early and prevent its progression. A novel serum fibrosis biomarker Mac-2 binding protein glycan isomer (M2BPGi) has high sensitivity plus specificity, and can be used in combination with FIB-4 screening index (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]/platelet ratio). This study aimed to investigate the predictive factors for the early detection of liver fibrosis using a combination of these two approaches. Methods: This cross-sectional study consisted of T2D patients, with negative results for hepatitis viruses and no history of heavy drinking. FIB-4 high patients were divided into two groups based on M2BPGi (high, M2BPGi > 1.00; normal level, M2BPGi < 1.00. The levels of clinical biomarkers were measured among two groups and predictive factors were calculated for M2BPGi high patients. Results: From July to December 2021, a total of 311 FIB-4 high T2D patients (male/female, 202/109; age, 71.1 + 9.8; Body Mass Index, 24.5 + 3.9; HbA1c 7.4 + 3.3 %) were enrolled in this study. The M2BPGi high group (44,3%, n=138) showed a significantly longer duration of diabetes, high alkaline phosphatase (ALP), AST, ALT, and low eGFR than M2BPGi normal group (55.7%, n=173). In multiple logistic regression analysis, eGFR < 60 mL/min/1.73m2 was independently identified as a predictive factor for M2BPGi high (Odds Ratio [OR] 2.61, 95% C.I. 1.55-4.39 P < 0.01) as well as AST > 30 IU/ml (OR, 3.37) and ALP > 113 IU/ml (OR, 1.88). Conclusions: low eGFR is associated with liver fibrosis in type 2 diabetes patients, and requires more careful attention to liver related disease. Disclosure E.Suzuki: None. Y.Shinya: None. B.Kanari: None. M.Kambara: None. H.Takahashi: None.

Плейотропные эффекты ипраглифлозина

Type 2 diabetes mellitus and its complications is a serious threat to the health and lives of the world's population. Among the causes of death in type 2 diabetes mellitus are both cardiovascular and non-vascular causes. Sodium-glucose cotransporter type 2 inhibitors are well-established drugs for the treatment of type 2 diabetes mellitus with various hemodynamic and metabolic effects. The range of pleiotropic effects is quite wide and includes an improvement in the lipid profile, a decrease in insulin resistance and body weight, a decrease in the risk of adverse cardiovascular outcomes, nephroprotection, as well as a positive effect on the course of non-alcoholic fatty liver disease. Recent data also testify to the antiproliferative effects of this group of drugs. Ipragliflozin is one of the representatives of the class of sodium-glucose cotransporter type 2 inhibitors, which is effective in terms of glycemic control in monotherapy and in combination with other hypoglycemic drugs. The BRIGHTEN and SPOTLIGHT studies have shown an association of ipragliflozin with increased HDL and lower triglycerides. Ipragliflozin contributes to the reduction of insulin resistance and body weight, as confirmed by the PRIME-V and ILLUMINATE studies. In some cases, regression of LV hypertrophy and a decrease of NT-proBNP were shown when taking ipragliflozin. The effect on the course of non-alcoholic fatty liver disease and the reduction of fibrosis, confirmed by liver biopsy, in patients with type 2 diabetes is the advantage of ipragliflozin. There is also evidence of the antiproliferative efficacy of ipragliflozin in various types of malignant neoplasms. The review highlights the effectiveness of ipragliflozin in relation to dyslipidemia, insulin resistance, cardiovascular outcomes in patients with type 2 diabetes mellitus, presents data on the positive effect of the drug on the course of NAFLD and type 2 diabetes, and also considers possible mechanisms of the antiproliferative effect of the drug.

Cardiovascular Magnetic Resonance Imaging as an Adjunct to the Evaluation of Cardiovascular Involvement in Diabetes Mellitus.

Diabetes mellitus (DM) is a new epidemic which has presented an immense increase in recent decades, due to the rapid increase in obesity. Cardiovascular disease (CVD) significantly reduces life expectancy and is the main cause of death in type 2 diabetes mellitus (T2DM). Strict glycemic control is a well-established method to combat microvascular CVD of type 1 diabetes mellitus (T1DM); its role against CVD of the T2DM risk has not been well documented. Therefore, the most efficient prevention is multifactorial risk factor reduction. Recently, the European Society of Cardiology published its 2019 recommendations on CVD in DM. Although all clinical points were discussed in this document, only a few comments were presented about when and how we should recommend cardiovascular (CV) imaging. Currently, CV imaging is the "must" in CV noninvasive evaluation. Alterations in CV imaging parameters can lead to early recognition of various types of CVD. In this paper, we briefly discuss the role of noninvasive imaging modalities, emphasizing the benefits of including cardiovascular magnetic resonance (CMR) in the evaluation of DM. CMR, in the same examination, can provide an assessment of tissue characterization, perfusion and function, with excellent reproducibility and without radiation or limitations, due to the body habitus. Therefore, it can play a dominant role in the prevention and risk stratification of DM. The suggested protocol for DM evaluation should include routine annual echocardiographic evaluation of all DM patients and CMR assessment of those with poorly controlled DM, microalbuminuria, heart failure, arrhythmia and recent alterations in clinical or echocardiographic evaluation.

MiR-132-3p and KLF7 as novel regulators of aortic stiffening-associated EndMT in type 2 diabetes mellitus

BackgroundThe prevalence of diabetes mellitus has risen considerably and currently affects more than 422 million people worldwide. Cardiovascular diseases including myocardial infarction and heart failure represent the major cause of death in type 2 diabetes (T2D). Diabetes patients exhibit accelerated aortic stiffening which is an independent predictor of cardiovascular disease and mortality. We recently showed that aortic stiffness precedes hypertension in a mouse model of diabetes (db/db mice), making aortic stiffness an early contributor to cardiovascular disease development. Elucidating how aortic stiffening develops is a pressing need in order to halt the pathophysiological process at an early time point.MethodsTo assess EndMT occurrence, we performed co-immunofluorescence staining of an endothelial marker (CD31) with mesenchymal markers (α-SMA/S100A4) in aortic sections from db/db mice. Moreover, we performed qRT-PCR to analyze mRNA expression of EndMT transcription factors in aortic sections of db/db mice and diabetic patients. To identify the underlying mechanism by which EndMT contributes to aortic stiffening, we used aortas from db/db mice and diabetic patients in combination with high glucose-treated human umbilical vein endothelial cells (HUVECs) as an in vitro model of diabetes-associated EndMT.ResultsWe demonstrate robust CD31/α-SMA and CD31/S100A4 co-localization in aortic sections of db/db mice which was almost absent in control mice. Moreover, we demonstrate a significant upregulation of EndMT transcription factors in aortic sections of db/db mice and diabetic patients. As underlying regulator, we identified miR-132-3p as the most significantly downregulated miR in the micronome of db/db mice and high glucose-treated HUVECs. Indeed, miR-132-3p was also significantly downregulated in aortic tissue from diabetic patients. We identified Kruppel-like factor 7 (KLF7) as a target of miR-132-3p and show a significant upregulation of KLF7 in aortic sections of db/db mice and diabetic patients as well as in high glucose-treated HUVECs. We further demonstrate that miR-132-3p overexpression and KLF7 downregulation ameliorates EndMT in high glucose-treated HUVECs.ConclusionsWe demonstrate for the first time that EndMT contributes to aortic stiffening in T2D. We identified miR-132-3p and KLF7 as novel EndMT regulators in this context. Altogether, this gives us new insights in the development of aortic stiffening in T2D.

ЛЕТАЛЬНОСТЬ В ТЕЧЕНИЕ ГОДА У БОЛЬНЫХ САХАРНЫМ ДИАБЕТОМ II ТИПА ПОСЛЕ ОСТРОГО ПЕРЕДНЕГО ИНФАРКТА МИОКАРДА С ЗУБЦОМ Q

Abstract. Introduction. Type II diabetes is now a global epidemic, its prevalence has significantly increased globally. Myocardial infarction is the primary cause of death in type II diabetes patients. Aim. The aim is to study one-year mortality in patients with diabetes mellitus type II after acute anterior myocardial infarction with Q-wave, receiving one of the sulfonylureas. Material and methods. Participated in the study 246 patients with type II diabetes and acute anterior Q-wave myocardial infarction receiving sulfonylureas. The patients were divided into 2 groups: control group (n=156) and the main group (n=90). All patients received standard examination and treatment of acute myocardial infarction. Patients from the main group were given a second breakfast 2 hours after taking sulfonylurea to prevent hypoglycemic reactions. Results and discussion. One year after acute anterior Q-wave myocardial infarction in patients with type II diabetes mellitus mortality in the control group was 26,2% (n=41), and in the main group – 1,1% (n=1). The mortality rate in the control group was significantly higher, which was statistically significant (p<0,05). The main cause of mortality in patients in control was a severe degree of chronic heart failure (31,7%, n=13), in second place are episodes of heart arrhythmia (24,3%, n=10), and repeated myocardial infarction (24,3%, n=10), and the rarest cause was pulmonary embolism (3,7%, n=3). The greatest mortality in the control group was observed in the glibenclamide subgroup (39%, n=16), then in the glimepiride subgroup (34,1%, n=14) and gliclazide (26,9%, n=11). In the control group, hypoglycemia was higher (49,3%, n=78) than in the main group (15,5%, n=14), which was statistically significant (p<0,05). The incidence of hypoglycemia in the glibenclamide subgroup was statistically higher (p<0,05) than in the gliclazide and glimepiride subgroups. Conclusion. Mortality in patients with type II diabetes within a year after an acute anterior myocardial infarction with a Q-wave in a group of patients where the risk of receiving repeated hypoglycemic reactions is minimized is significantly less.

Effects of RAS inhibitors on all-site cancers and mortality in the Hong Kong diabetes surveillance database (2002-2019).

SummaryBackgroundCancer is replacing cardiovascular-disease as a leading cause of death in type 2 diabetes (T2D). The association of RAS-inhibitors (RASi) and cancer, including differences between angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) as well as their associations independent of blood pressure lowering, remains inconclusive in T2D.MethodsWe conducted a cohort study with new-user design in 253,491 patients in the Hong-Kong-Diabetes-Surveillance-Database (HKDSD) in 2002-2019. We evaluated the associations of time-varying RASi use (ACEi and ARBs) with all-site cancer, diabetes-related cancers, and cancer-specific mortality including comparison with new-users of calcium-channel-blockers (CCBs) as an active-comparator group.FindingsOf 253,491, 133,730 (52.8%) were new-RASi and 119,761 (47.2%) were non-RASi users with a median follow-up period of 6.3 (interquartile ragne: 3.4-9.2) years (1,678,719 patient-years). After propensity-score weighting and adjustment for time-varying covariables, RASi use was associated with lower risk of all-site cancer (HR=0.76, 95%CI: 0.74-0.79), diabetes-related cancer (HR=0.79, 95%CI: 0.75-0.84), cancer-specific mortality (HR=0.50, 95%CI: 0.47-0.53), and diabetes-related cancer mortality (HR=0.49, 95%CI: 0.45-0.54) versus non-RASi. Amongst RASi users, ARBs use was associated with lower risk of cancer-specific mortality versus ACEi (HR=0.77, 95%CI: 0.66-0.91). Use of RASi was associated with an estimated-prevention of 2.6 (95%CI: 2.3-3.0) all-site cancer per-1000-person-years and 2.2 (95%CI: 2.0-2.5) cancer-related mortality per-1000-person-years. Lower risk of cancer-specific mortality was similarly observed in new-RASi compared with new-CCBs users.InterpretationRASi use was independently associated with lower cancer risk in T2D with stronger associations in users of ARBs than ACEi. The benefits of RASi in patients with diabetes might go beyond cardiovascular-renal protection if confirmed by other real-world studies and trials.FundingDr. Aimin Yang was supported by a CUHK Impact-Research-Fellowship Scheme.

Tumor Necrosis Factor Receptor Superfamily Member 21 Induces Endothelial-Mesenchymal Transition in Coronary Artery Endothelium of Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is an increasing threat to human health and regarded as an important public issue. Coronary artery disease is one of the main causes of death in type 2 DM patients. However, the effect of hyperglycemia on coronary artery endothelial cells (CAECs) and the pathophysiologic mechanisms are still not well-explored. This study aims to explore the signal pathway and novel biomarkers of injury of CAECs in DM in understanding the microenvironment changes and mechanisms of diabetic heart disease. Next-generation sequence (NGS) and bioinformatics analysis to analyze the CAECs of one type 2 DM patient and one normal individual was performed, and it was found that tumor necrosis factor receptor superfamily member 21 (TNFRSF21) was a soluble factor in circulating system. Further experiments confirmed that advanced glycation end products (AGEs), the metabolite derived by hyperglycemia, increased the expression of TNFRSF21 in CAECs. TNFRSF21 induced endothelial–mesenchymal transition (EndoMT) in CAECs, resulting in increased permeability of CAECs. In addition, levels of serum TNFRSF21 were higher in type 2 DM patients with left ventricular hypertrophy (LVH) than those without LVH. Serum TNFRSF21 levels were also positively correlated with the LV mass index and negatively with LV systolic function. Serum TNFRSF21 levels were associated with changes in cardiac structure and function in patients with type 2 DM. In conclusion, TNFRSF21 plays a pathogenic role in heart disease of type 2 DM, and can be used as a biomarker of the impairment of cardiac structure and function in type 2 DM patients.

IDF21-0540 HbA1c as a marker of HDL cholesterol in Indian subjects with type 2 diabetes

Background: HbA1c is the gold standard means of accessing long term glycemia and for diagnosing diabetes. Cardiovascular disease (CVD) is the leading cause of death in type 2 diabetes (T2DM). HDL‐c has been considered as a surrogate marker of CVD. Aim: In this study we aimed to find the relationship between HbA1c and HDL‐c in Odia subjects with T2DM. Method: T2DM adults, who visited Diabetic OPD were requested to participate. Subjects with type 1 diabetes, secondary diabetes, GDM, nourishing mothers, pregnant women, as well as individuals who were on lipid lowering medicines, thyroid hormone therapy, steroids, immunosupressants were excluded. Comprehensive medical and drug history were recorded. After consent, participants underwent overnight fasting for estimation of HbA1c and lipid panel measurement. Results: Mean age and duration of diabetes for the sample (n = 1352, M/F = 832/520) were 51.8 ± 10.5 and 9.8 ± 6.0 years respectively. Mean HbA1c and HDL‐c values were 8.7 ± 2.4% and 40.6 ± 8.7mg/dl in order. The prevalence of low HDL (n = 697, 51.6%) and hypertriglyceridemia (n = 689, 51.0%) were almost similar. Uncontrolled HbA1c (≥7%) was documented in two third (66.7%) of persons with low HDL. While HDL was seen to be inversely related to HbA1c values, triglyceride level was found to be proportionate to HbA1c. Discussion: The study shows that elevated HbA1c is associated with low HDL and high triglyceride levels in Odia T2DM subjects and warrants the use of statins for prevention of cardiovascular events in this resource restricted community.

The Role of Peroxisome Proliferator-Activated Receptor Gamma and Atherosclerosis: Post-translational Modification and Selective Modulators.

Atherosclerosis is the hallmark of cardiovascular disease (CVD) which is a leading cause of death in type 2 diabetes patients, and glycemic control is not beneficial in reducing the potential risk of CVD. Clinically, it was shown that Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are insulin sensitizers with reducing risk of CVD, while the potential adverse effects, such as weight gain, fluid retention, bone loss, and cardiovascular risk, restricts its use in diabetic treatment. PPARγ, a ligand-activated nuclear receptor, has shown to play a crucial role in anti-atherosclerosis by promoting cholesterol efflux, repressing monocytes infiltrating into the vascular intima under endothelial layer, their transformation into macrophages, and inhibiting vascular smooth muscle cells proliferation as well as migration. The selective activation of subsets of PPARγ targets, such as through PPARγ post-translational modification, is thought to improve the safety profile of PPARγ agonists. Here, this review focuses on the significance of PPARγ activity regulation (selective activation and post-translational modification) in the occurrence, development and treatment of atherosclerosis, and further clarifies the value of PPARγ as a safe therapeutic target for anti-atherosclerosis especially in diabetic treatment.

Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review.

Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.

Cardiovascular outcomes after simultaneous pancreas kidney transplantation compared to kidney transplantation alone: a propensity score matching analysis

BackgroundCoronary heart disease due to arteriosclerosis is the leading cause of death in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to evaluate the effect of simultaneous pancreas kidney transplantation (SPKT) compared to kidney transplantation alone (KTA) on survival, cardiovascular function and metabolic outcomes.MethodsA cohort of 127 insulin-dependent diabetes mellitus (IDDM) patients with ESRD who underwent either SPKT (n = 100) or KTA (n = 27) between 1998 and 2019 at the University Hospital of Leipzig were retrospectively evaluated with regard to cardiovascular and metabolic function/outcomes as well as survival rates. An additional focus was placed on the echocardiographic assessment of systolic and diastolic cardiac function pretransplant and during follow-up. To avoid selection bias, a 2:1 propensity score matching analysis (PSM) was performed.ResultsAfter PSM, a total of 63 patients were identified; 42 patients underwent SPKT, and 21 patients received KTA. Compared with the KTA group, SPKT recipients received organs from younger donors (p < 0.05) and donor BMI was higher (p = 0.09). The risk factor-adjusted hazard ratio for mortality in SPKT recipients compared to KTA recipients was 0.63 (CI: 0.49–0.89; P < 0.05). The incidence of pretransplant cardiovascular events was higher in the KTA group (KTA: n = 10, 47% versus SPKT: n = 10, 23%; p = 0.06), but this difference was not significant. However, the occurrence of cardiovascular events in the SPKT group (n = 3, 7%) was significantly diminished after transplantation compared to that in the KTA recipients (n = 6, 28%; p = 0.02). The cardiovascular death rate was higher in KTA recipients (19%) than in SPK recipients with functioning grafts (3.3%) and comparable to that in patients with failed SPKT (16.7%) (p = 0.16).In line with pretransplant values, SPKT recipients showed significant improvements in Hb1ac values (p = 0.001), blood pressure control (p = < 0.005) and low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (p = < 0.005) 5 years after transplantation. With regard to echocardiographic assessment, SPKT recipients showed significant improvements in left ventricular systolic parameters during follow-up.ConclusionsNormoglycaemia and improvement of lipid metabolism and blood pressure control achieved by successful SPKT are associated with beneficial effects on survival, cardiovascular outcomes and systolic left ventricular cardiac function. Future studies with larger samples are needed to make predictions regarding cardiovascular events and graft survival.

Патогенетичні механізми та ознаки серцево-судинних уражень при цукровому діабеті 2-го типу

Актуальність. Висока захворюваність та поширеність цукрового діабету (ЦД) зумовлює ранню інвалідизацію та смертність через розвиток хронічних ускладнень. При цьому головна причина смерті при ЦД 2-го типу пов’язана із серцево-судинними захворюваннями. Мета дослідження: з’ясувати частоту, механізми та прояви уражень серцево-судинної системи у хворих на ЦД 2-го типу. Матеріали та методи. Обстежено 49 пацієнтів з ЦД 2-го типу віком понад 50 років, у тому числі 25 чоловіків, 24 жінки. Визначали показники метаболізму, зміни електрокардіограми. Результати. У групі спостереження у 55,1 % пацієнтів виявлена ішемічна хвороба серця (ІХС), у 77,6 % — артеріальна гіпертензія, у 28,6 % — перенесені кардіоваскулярні події. Переважали хворі (83,7 %) з надлишковою масою тіла і ожирінням. У 57,1 % виявлені порушення ліпідного обміну за наявної декомпенсації ЦД в 61,2 %, що підтверджено збільшенням рівня глікованого гемоглобіну до 8,8 ± 0,3 %. Зареєстровані порушення процесів автоматизму, збудливості та провідності серця: у 12,2 % — синусова тахікардія, у 6,1 % — синусова брадикардія, у 4,1 % — синусова аритмія, у 10,2 % — миготлива аритмія, у 8,2 % — суправентрикулярна і шлуночкова екстрасистолія, у 30,6 % — внутрішньошлуночкові блокади. Прояви гіпоксії мали 32,7 % пацієнтів, зміни зубця Q — 8,2 %, зміни інтервалу ST — 8,2 %. Висновки. Дисметаболічні порушення є підґрунтям для розвитку хронічних діабетичних ускладнень, що формують, зокрема, кардіальну автономну нейропатію, діабетичну кардіоміопатію та атеросклеротичні ураження серцево-судинної системи з маніфестацією ІХС, артеріальної гіпертензії, синдрому порушень ритму і провідності, гіпоксії.

Role of Selective Sodium-Glucose Co-Transporter-2 Inhibitors in Managing Cardio-Renal Complications in Type 2 Diabetes Mellitus: Beyond Glycemic Control.

Chronic kidney disease (CKD) and cardiovascular complications are the leading causes of death in type 2 diabetes mellitus. Apart from the standard therapy, which includes angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), lipid-lowering medication, and anti-platelet therapy, the new group of drugs termed the 'sodium-glucose co-transporter-2 (SGLT2) inhibitors' have shown promising results in managing complications arising from the cardiovascular and renal systems in diabetics. This article attempts to highlight the role and mechanism of action of this class of drugs. We reviewed 127 articles and analyses of randomized controlled trials using several drugs in the SGLT2 inhibitor family (sotagliflozin, canagliflozin, dapagliflozin, tofogliflozin) over the past five years, out of which 58 met the criteria and aim of the study. These articles were retrieved from PubMed, Google Scholar, and Medline data sources and assessed for quality using the assessment of multiple systematic reviews (AMSTAR) checklist and Cochrane risk-of-bias tool. Results from the review showed significant benefits in reducing progressive renal decline, blood pressure control, heart failure hospitalization, death from renal or cardiovascular complications, myocardial infarction, and stroke. This benefit is also seen in non-diabetic patients, hence postulating that these effects may not be solely due to glycemic control. There are several mechanisms with which it achieves this benefit with the most significant being its role on intraglomerular pressure. Other pathways include blood pressure control, natriuresis, ventricular remodeling, erythropoiesis, lipid metabolism, plasma volume, and electrolyte imbalance. It is clear that the role of SGLT2 inhibitors isn’t limited to glycemic control and they can achieve a wide array of functions by affecting different systems. More studies need to be done to completely understand this medication to improve the quality of life in diabetic and non-diabetic patients living with CKD and cardiovascular complications. The pharmacokinetics of this drug could also help set the basis for newer medications.

Dyslipidaemia in Type 1 Diabetes: Molecular Mechanisms and Therapeutic Opportunities

Cardiovascular disease (CVD) is the leading cause of death in Type 1 Diabetes (T1D). The molecular basis for atherosclerosis in T1D is heavily influenced by hyperglycaemia and its atherogenic effects on LDL. Ongoing research into the distinct pathophysiology of atherosclerosis in T1D offers exciting opportunities for novel approaches to calculate CVD risk in patients with T1D and to manage this risk appropriately. Currently, despite the increased risk of CVD in the T1D population, there are few tools available for estimating the risk of CVD in younger patients. This poses significant challenges for clinicians in selecting which patients might benefit from lipid-lowering therapies over the long term. The current best practice guidance for the management of dyslipidaemia in T1D is generally based on evidence from patients with T2D and the opinion of experts in the field. In this review article, we explore the unique pathophysiology of atherosclerosis in T1D, with a specific focus on hyperglycaemia-induced damage and atherogenic LDL modifications. We also discuss the current clinical situation of managing these patients across paediatric and adult populations, focusing on the difficulties posed by a lack of strong evidence and various barriers to treatment.

The main etiological reasons of fatal type 2 myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Purpose the assessment of the proportion of myocardial infarction (MI) type 2 in the structure of mortality in a multidisciplinary hospital Material and methods. A retrospective study was made of 1,574 autopsy protocols carried out in a multidisciplinary hospital in the period from 01.01.10 to 31.12.16, of which a group with postmortem type II MI was identified. The control group was composed of persons who died from proven atherothrombotic type 1 MI Results. In 360 cases (22.87%), the cause of death was MI. Of these, 137 cases were due to type 2 MI. The ratio of men and women was the same. Type 2 MI more often developed in elderly (48.2%) and senile (34.3%) ages; the average age of patients with type 2 MI was 71.7 ± years (68.2 ± 3 years among men and 75.3 ± 4 years among women p &amp;lt;0.05), which did not differ from the group with fatal type 1 MI. The main causes of death in type 2 MI were tachysystolic arrhythmias - 59.12% of cases, severe hypoxia of any etiology - 35.04%. The absence of significant stenoses of coronary artery (CA) is significantly more common in type 2 MI, and multivessel disease - in type 1 MI. In the group of patients with type 1 MI, 67.29% had multivessel lesions (Table 1). When comparing mortality in different departments of a multidisciplinary hospital, it turned out that only 29.2% of patients with type 2 MI were initially hospitalized in the cardiology department; 45.3% of patients - therapeutic, 25.5% of patients – surgical. Conclusion. Nearly one in four patients die as a result of MI, with more than 1/3 of fatal MIs occurring in type 2 MI. The main reasons for the development of type 2 MI: tachysystolic arrhythmias - 59.12%, hypoxia of various origins - 35.04%, sepsis - 2.2%. 25% of fatal type 2 MIs occurred in surgical patients. Table 1. CA in type 1 and 2 MI Sign Type 1 MY n = 223 Type 2 MY n = 137 p No significant stenosis 2,24% 32,85% 0,001 Single CA significant stenosis 8,07% 12,41% 0,193 2-CA significant stenosis 23,3% 23,36% 0,272 Multivessel stenosis 66,4% 31,38% 0,005 Occlusion of at least one CA 48,9% 4,38% 0,001