Diabetes contributes to the development of heart failure through various metabolic, structural and biochemical changes. The presence of diabetes increases the risk for the development of cardiovascular disease (CVD), and since the introduction of cardiovascular outcome trials to test diabetic drugs, the importance of improving our understanding of the mechanisms by which diabetes increases the risk for heart failure has come under the spotlight. In addition to the coronary vasculature changes that predispose individuals with diabetes to coronary artery disease, diabetes can also lead to cardiac dysfunction independent of ischaemic heart disease. The hyperlipidaemic, hyperglycaemic and insulin resistant state of diabetes contributes to a perturbed energy metabolic milieu, whereby the heart increases its reliance on fatty acids and decreases glucose oxidative rates. In addition to changes in cardiac energy metabolism, extracellular matrix remodelling contributes to the development of cardiac fibrosis, and impairments in calcium handling result in cardiac contractile dysfunction. Lipotoxicity and glucotoxicity also contribute to impairments in vascular function, cardiac contractility, calcium signalling, oxidative stress, cardiac efficiency and lipoapoptosis. Lastly, changes in protein acetylation, protein methylation and DNA methylation contribute to a myriad of gene expression and protein activity changes. Altogether, these changes lead to decreased cardiac efficiency, increased vulnerability to an ischaemic insult and increased risk for the development of heart failure. This review explores the above mechanisms and the way in which they contribute to cardiac dysfunction in diabetes. 

/pdf/metabolic-structural-and-biochemical-changes-in-diabetes-and-3op81ety.pdf

Metabolic, structural and biochemical changes in diabetes and the development of heart failure

The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes. 

https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-023-01875-8

Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions

The effect of comorbid hypertension and type 2 diabetes mellitus (T2DM) on coronary artery plaques examined by coronary computed tomography angiography (CCTA) is not fully understood. We aimed to comprehensively assess whether comorbid hypertension and T2DM influence coronary artery plaques using CCTA.A total of 1100 T2DM patients, namely, 277 normotensive [T2DM(HTN-)] and 823 hypertensive [T2DM(HTN +)] individuals, and 1048 normotensive patients without T2DM (control group) who had coronary plaques detected on CCTA were retrospectively enrolled. Plaque type, coronary stenosis, diseased vessels, the segment involvement score (SIS) and the segment stenosis score (SSS) based on CCTA data were evaluated and compared among the groups.Compared with patients in the control group, the patients in the T2DM(HTN-) and T2DM(HTN +) groups had more partially calcified plaques, noncalcified plaques, segments with obstructive stenosis, and diseased vessels, and a higher SIS and SSS (all P values < 0.001). Compared with the control group, T2DM(HTN +) patients had increased odds of having any calcified and any noncalcified plaque [odds ratio (OR) = 1.669 and 1.278, respectively; both P values < 0.001]; both the T2DM(HTN-) and T2DM(HTN +) groups had increased odds of having any partially calcified plaque (OR = 1.514 and 2.323; P = 0.005 and P < 0.001, respectively), obstructive coronary artery disease (CAD) (OR = 1.629 and 1.992; P = 0.001 and P < 0.001, respectively), multivessel disease (OR = 1.892 and 3.372; both P-values < 0.001), an SIS > 3 (OR = 2.233 and 3.769; both P values < 0.001) and an SSS > 5 (OR = 2.057 and 3.580; both P values < 0.001). Compared to T2DM(HTN-) patients, T2DM(HTN +) patients had an increased risk of any partially calcified plaque (OR = 1.561; P = 0.005), multivessel disease (OR = 1.867; P < 0.001), an SIS > 3 (OR = 1.647; P = 0.001) and an SSS > 5 (OR = 1.625; P = 0.001).T2DM is related to the presence of partially calcified plaques, obstructive CAD, and more extensive coronary artery plaques. Comorbid hypertension and diabetes further increase the risk of partially calcified plaques, and more extensive coronary artery plaques. 

/pdf/the-additive-effect-of-essential-hypertension-on-coronary-2sgyq5ez.pdf

The additive effect of essential hypertension on coronary artery plaques in type 2 diabetes mellitus patients: a coronary computed tomography angiography study

Patients with type 2 diabetes mellitus (T2DM) are highly susceptible to cardiovascular disease, and coronary artery disease (CAD) is their leading cause of death. We aimed to assess whether computed tomography (CT) based imaging parameters and radiomic features of pericoronary adipose tissue (PCAT) can improve the diagnostic efficacy of whether patients with T2DM have developed CAD.We retrospectively recruited 229 patients with T2DM but no CAD history (146 were diagnosed with CAD at this visit and 83 were not). We collected clinical information and extracted imaging manifestations from CT images and 93 radiomic features of PCAT from all patients. All patients were randomly divided into training and test groups at a ratio of 7:3. Four models were constructed, encapsulating clinical factors (Model 1), clinical factors and imaging indices (Model 2), clinical factors and Radscore (Model 3), and all together (Model 4), to identify patients with CAD. Receiver operating characteristic curves and decision curve analysis were plotted to evaluate the model performance and pairwise model comparisons were performed via the DeLong test to demonstrate the additive value of different factors.In the test set, the areas under the curve (AUCs) of Model 2 and Model 4 were 0.930 and 0.929, respectively, with higher recognition effectiveness compared to the other two models (each p < 0.001). Of these models, Model 2 had higher diagnostic efficacy for CAD than Model 1 (p < 0.001, 95% CI [0.129-0.350]). However, Model 4 did not improve the effectiveness of the identification of CAD compared to Model 2 (p = 0.776); similarly, the AUC did not significantly differ between Model 3 (AUC = 0.693) and Model 1 (AUC = 0.691, p = 0.382). Overall, Model 2 was rated better for the diagnosis of CAD in patients with T2DM.A comprehensive diagnostic model combining patient clinical risk factors with CT-based imaging parameters has superior efficacy in diagnosing the occurrence of CAD in patients with T2DM. 

/pdf/diagnosis-of-coronary-artery-disease-in-patients-with-type-2-3kepil79.pdf

Diagnosis of coronary artery disease in patients with type 2 diabetes mellitus based on computed tomography and pericoronary adipose tissue radiomics: a retrospective cross-sectional study

This study aimed to evaluate the effectiveness of ICI of platelet‐rich plasma (PRP) in addition to daily oral tadalafil intake in diabetic erectile dysfunction (ED) patients non‐responding to PDE5 inhibitors. Overall, 48 patients complaining of ED non‐responding to on‐demand PDE5 inhibitors were allocated into 2 equal groups, diabetics and non‐diabetics that were given a daily dose of 5 mg tadalafil plus vardenafil 20 mg on demand during the study besides being subjected to 3 doses of ICI of PRP, 4 weeks apart. Responses to on‐demand PDE5 inhibitors, International index of erectile function‐5 (IIEF‐5) score, erection hardness scores (EHS) and pharmaco‐dynamic duplex studies were assessed. After PRP injections, 33% and 50% of cases were satisfied with on‐demand PDE5 inhibitors, respectively, whereas 41% and 66% of them showed improved EHS response. Compared with baseline scores, the mean IIEF‐5 scores were significantly improved after PRP therapy in the diabetic ED group (12.1 vs. 8.04, p = 0.003) as well as in the non‐diabetic ED group (14.8 vs. 10.2, p = 0.001) linked to pharmaco‐penile duplex readings. Both good and fair diabetic control exhibited significant responses to ICI therapy of PRP compared with bad controlled cases. The significant improvement included; the IIEF‐5 score increase (86.7%, 126% vs. 16.1%), improved EHS as well as penile duplex readings. Baseline HbA1C demonstrated a significant negative correlation with IIEF‐5 score before (p = 0.019) and after PRP therapy (p = 0.002) respectively. It could be concluded that ICI of PRP could be an effective therapy for treating ED patients non‐responding to on‐demand oral PDE5 treatment.

Assessment of the intracavernosal injection platelet‐rich plasma in addition to daily oral tadalafil intake in diabetic patients with erectile dysfunction non‐responding to on‐demand oral PDE5 inhibitors

We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM). In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c). The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P   0.05). Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.

/pdf/impact-of-glycemic-control-on-the-association-of-endothelial-13luxsu371.pdf

Impact of glycemic control on the association of endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus.

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Impact of glycemic control on the association of endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus.