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The prevalence of diabetes mellitus is rising among children and adolescents worldwide. Cardiovascular diseases are the main cause of morbidity and mortality in diabetic patients. We review the impact of diabetes on establishing, during childhood and adolescence, the premises for cardiovascular diseases later in life. Interestingly, it seems that h...
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Context 1
... are several old and new CV risk factors that appear to be relevant for pediatric patients with diabetes and that can be targeted. We classify them as modifiable and unmodifiable factors (Table 1). Among those unmodifiable factors are the age at onset and the disease duration [18,21,24,27]. ...Citations
... In another study [27], Katz et al. showed lack of knowledge and parental concerns of using antihypertensives and lipidlowering medications at young age as patient-related reasons of undertreatment of CVD risk factors in youth with T1D. Despite concerns about the use of lipid-lowering agents and antihypertensive drugs limit the treatment of cardiovascular risk factors in young adults with diabetes, early risk recognition and treatment of cardiovascular risk factors are still critical to reducing the risk of developing cardiovascular disease [28]. ...
Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, and for this reason, all guidelines for CV risk management provide the same targets in controlling traditional CV risk factors in patients with type 1 or type 2 diabetes at equal CV risk class. Aim of our study was to evaluate and compare CV risk management in patients with type 1 and type 2 diabetes included in AMD Annals Database paying particular attention to indicators of clinical inertia.
This was a multicenter, observational, retrospective study of AMD Annals Database during year 2022. Patients with diabetes were stratified on the basis of their cardiovascular risk, according to ESC-EASD guidelines. The proportion of patients not treated with lipid-lowering despite LDL cholesterol > to 100 mg/dl or the proportion of patients not treated with antihypertensive drug despite BP > 140/90 mmhg and proportion of patients with proteinuria not treated with angiotensin converting enzyme inhibitors or angiotensinogen receptor blockers (ACE/ARBs) were considered indicators of clinical inertia. The proportion of patients reaching at the same time HbA1c < 7% LDL < 70 mg/dl and BP < 130/80 mmhg were considered to have good multifactorial control. Overall quality of health care was evaluated by the Q-score.
Using the inclusion criteria and stratifying patients by ESC/EASD Cardiovascular Risk categories, we included in the analysis 118.442 patients at High Cardiovascular risk and 416.246 patients at Very High Cardiovascular risk. The proportion of patients with good multifactorial risk factor control was extremely low in both T1D and T2D patients in each risk class. At equal risk class, the patients with T1D had lower proportion of subjects reaching HbA1c, LDL, or Blood Pressure targets. Indicators of clinical inertia were significantly higher compared with patients with T2D at equal risk class. Data regarding patients with albuminuria not treated with RAAS inhibitors were available only for those at Very High risk and showed that the proportion of patients not treated was again significantly higher in patients with T1DM.
In conclusion, this study provides evidence of wide undertreatment of traditional cardiovascular risk factors among patients with diabetes included in AMD Annals Database. Undertreatment seems to be more pronounced in individuals with T1D compared to those with T2D and is frequently due to clinical inertia.
... Study has shown that smoking, alcohol abuse, a history of hypertension and diabetes are risk factors that increase the likelihood of developing cardiovascular disease. 53 A study has found that the incidence of arterial disease may be different between men and women. 54 It can be seen that the occurrence of atherosclerosis is the result of genetic factors, environmental factors, living habits and other comprehensive effects. ...
Background
Vascular diseases such as atherosclerosis usually affect multiple organs. Genetic factors have a certain proportion in the risk factors of atherosclerosis. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with multi-site atherosclerosis.
Methods
The study included 410 patients with single-site atherosclerosis and 529 patients with multi-site atherosclerosis. The relationship between CYP2C19 rs4244285 and rs4986893 polymorphisms and single-site atherosclerosis and multi-site atherosclerosis was analyzed.
Results
The proportion of CYP2C19 rs4244285 A allele (35.9% vs 29.9%, P=0.007) and rs4986893 G allele (97.7% vs 94.8%, P=0.001) in multi-site atherosclerosis group was significantly higher than that in single-site atherosclerosis group. The distribution of CYP2C19 genotypes was significantly different between the two groups (P=0.002). The results of univariate logistic regression indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: odds ratio (OR) 0.456, 95% confidence interval (CI): 0.231–0.902, P=0.024) may decrease risk of multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.780, 95% CI: 1.100–2.880, P=0.019) may increase risk of multi-site atherosclerosis. Multivariate logistic regression (adjusted for gender, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: OR 0.459, 95% CI: 0.231–0.909, P=0.026) may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.767, 95% CI: 1.091–2.864, P=0.021) may be an independent risk factor for multi-site atherosclerosis.
Conclusion
CYP2C19 *1/*3 genotype may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype may be an independent risk factor for multi-site atherosclerosis.
... Low ABI is known to be a strong predictor of cardiovascular morbidity and mortality in people with diabetes [33]. In agreement with the current results, Pastore and colleagues reported increased subclinical vascular diseases among children with T1DM compared to healthy controls manifested as reduced brachial artery flow-mediated dilatation reactivity and increased carotid-femoral pulse wave velocity [34]. ...
Aim
Although macrovascular complications represent the leading cause of mortality in type 1 diabetes mellitus (T1DM), the prevalence of subtle macrovascular affection including peripheral artery disease (PAD) among children with T1DM and its genetic predictors remains to be unraveled. Increasing evidence suggests a link between adiponectin rs1501299 and chemerin rs17173608 gene polymorphism and atherogenesis, and insulin resistance. Hence, this study assess the prevalence of these variants among children with T1DM in comparison to healthy controls and their association with macrovascular complications, namely PAD and hyperlipidemia.
Methods
Fifty children with T1DM and 50 matched controls underwent a thorough assessment including adiponectin rs1501299 and chemerin rs17173608 gene polymorphisms, fasting lipids, glycated hemoglobin (HbA1c), and ankle–brachial index (ABI). Cochran–Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and PAD using a case–control design.
Results
Children with T1DM were found to have significantly higher ABI ( p = 0.011) than controls. Chemerin gene polymorphism was detected in 41 children with T1DM (82.0%), while adiponectin gene polymorphism was detected in 19 children (38.0%). Children with T1DM having GG chemerin variant and those having TT adiponectin variant had significantly higher cholesterol with significantly lower HDL-C and ABI than those having the other two variants ( p < 0.005). Children with T1DM having abnormal ABI had significantly higher chemerin G ( p = 0.017) and adiponectin T ( p = 0.022) alleles than those with normal ABI. Cholesterol and ABI were independently associated with chemerin and adiponectin gene polymorphism by multivariable regression analysis.
Conclusion
Children with T1DM having chemerin and adiponectin gene polymorphisms have significantly higher cholesterol and ABI than those without these polymorphisms and controls.
Trial registration
The Research Ethics Committee of Ain Shams University, approval number R 31/2021.
... In another study [27], Katz et al. showed lack of knowledge and parental concerns of using antihypertensives and lipidlowering medications at young age as patient-related reasons of undertreatment of CVD risk factors in youth with T1D. Despite concerns about the use of lipid-lowering agents and antihypertensive drugs limit the treatment of cardiovascular risk factors in young adults with diabetes, early risk recognition and treatment of cardiovascular risk factors are still critical to reducing the risk of developing cardiovascular disease [28]. ...
Background and aims: Aim of this study was to evaluate cardiovas-
cular (CV) risk management in a large cohort of "real life" patients
focusing on differencies in indicators of clinical inertia among
patients with type 1 and type 2 diabetes.
Materials and methods: Multicenter, observational, retrospective
study including a large sample of patients cared for by 258 Italian
diabetes clinics participating in the Annals initiative of the Italian
Association of Clinical Diabetologists during 2019. Patients were
stratified on the basis of their CV risk, according to ESC-EASD 2019
guidelines. General descriptive indicators, intermediate outcome
measures regarding intensity and appropriateness of diabetes phar-
macological therapy, cardiovascular risk factors and overall health
care quality were evaluated. The proportion of patients not treated
with lipid lowering despite LDL cholesterol > to 130 mg/dl, propor-
tion of patients not treated with antihypertensive drug despite BP >
140/90 mmhg and proportion of patients with micro/macroalbuminu-
ria not treated with ACE/ARBs were considered Indicators of Clinical
Inertia. Overall quality of health care was evaluated by the Q score.
Results: By using the inclusion criteria and stratifying patients by ESC/
EASD CV Risk categories we included in the analysis 107.142 patients at
High CV and 391.140 patients at Very High CV risk. At equal risk class
the proportion of patients with type 1 diabetes with LDL cholesterol > 130
mg/dl not treated with statin or with blood pressure >140/90 mmHg not
treated with antihypertensive drugs were significantly higher compared with patients with type 2 diabetes (figure 1). In both CV risk class, the proportion
of patients with LDL cholesterol >130 despite statin treatment were signifi-
cantly higher in patients with T1D (23.0% vs 16.9% and 13.1% vs 9.7% p
<0.001). Proportion of patients with BP > 140/90 despite treatment were
higher among T2D independently to CV risk class (46.8% vs 40.6% and
48.8% vs 46,8% p <0.001). Proportion of patients with good multifactorial
risk factor control were significantly higher in patients with T2D in both
high and very high-risk class (24.3 vs 15.2 and 18.6 vs 10.6 p < 0.001).
Mean Q score did not differ significantly in the two groups however propor-
tion of patients with Q score > 25 was higher among patients with T1D.
Conclusion: This study shows clearly that in patients included in
AMD Annals database there is a substantial undertreatment of lipids
and blood pressure in diabetic patients at high or very high CV risk.
The undertreatment seem to be more pronounced in individuals with
type 1 diabetes compared to those with type 2 diabetes and is fre-
quently due to clinical inertia.
... Given that T1DM is an autoimmune disease and previous studies have revealed that inflammatory factors and hypertension caused by T1DM might mediate the development of cardiovascular disease [5,7,12,[31][32][33][34], we performed a mediation MR analysis using the twostep MR method [35]. In the first step, we calculated the causal effect of T1DM on mediators (β 1 ), and in the second step, we estimated the causal effect of mediators on CVDs (β 2 ). ...
Background
The presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies.
Methods
Summary statistics of T1DM and seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry and FinnGen biobank were extracted for the primary MR analysis, and the analysis was replicated using UK biobank (UKBB) for validation. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs.
Results
Causal effects of T1DM on peripheral atherosclerosis (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02–1.10; p = 0.002)] and coronary atherosclerosis (OR = 1.03, 95% CI: 1.01–1.05; p = 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23–19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35–28.33%). We didn’t find significant causal relationships between T1DM and other CVDs, including heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), myocardial infarction (MI) and stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified.
Conclusion
This MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.
... The increasing incidence of diabetes in children leads to prolonged exposure to hyperglycemia and other metabolic abnormalities; early diabetes onset carries an elevated risk of cardiovascular complications. 8,9 These disease dynamics, which constitute a heavy burden on patients and their families, have become global public health problems. ...
Importance:
Diabetes in children is a global epidemic that causes various medical conditions associated with an increased incidence of premature death.
Objective:
To investigate the trends in diabetes incidence, mortality, and disability-adjusted life-years (DALYs) in children, with risk factors for diabetes-associated death, from 1990 to 2019.
Design, setting, and participants:
This was a cross-sectional study that used data from the Global Burden of Diseases (GBD) 2019 in 204 countries and territories. Children with diabetes who were aged 0 to 14 years were included in the analysis. Data were analyzed from December 28, 2022, to January 10, 2023.
Exposure:
Childhood diabetes from 1990 to 2019.
Main outcome measures:
Incidence, all-cause and cause-specific deaths, DALYs, and corresponding estimated annual percentage changes (EAPCs). These trends were stratified according to region, country, age, sex, and Sociodemographic Index (SDI).
Results:
A total of 1 449 897 children (738 923 male [50.96%]) were included in the analysis. In 2019, there were 227 580 incident cases of childhood diabetes worldwide. Cases of childhood diabetes increased by 39.37% (95% uncertainty interval [UI], 30.99%-45.45%) from 1990 to 2019. Over 3 decades, diabetes-associated deaths decreased from 6719 (95% UI, 4823-8074) to 5390 (95% UI, 4450-6507). The global incidence rate increased from 9.31 (95% UI, 6.56-12.57) to 11.61 (95% UI, 7.98-15.98) per 100 000 population; however, the diabetes-associated death rate decreased from 0.38 (95% UI, 0.27-0.46) to 0.28 (95% UI, 0.23-0.33) per 100 000 population. Among the 5 SDI regions, the low SDI region had the highest childhood diabetes-associated mortality rate in 2019. Regionally, North Africa and the Middle East had the largest increase in incidence (EAPC, 2.06; 95% CI, 1.94-2.17). Among 204 countries, Finland had the highest national incidence of childhood diabetes in 2019 (31.60 per 100 000 population; 95% UI, 22.65-40.36), Bangladesh had the highest diabetes-associated mortality rate (1.16 per 100 000 population; 95% UI, 0.51-1.70), and the United Republic of Tanzania had the highest DALYs rate (100.16 per 100 000 population; 95% UI, 63.01-155.88). Globally, environmental/occupational risk, nonoptimal temperature, high temperature, and low temperature were key risk factors for childhood diabetes-associated mortality in 2019.
Conclusions and relevance:
Childhood diabetes is an increasing global health challenge with rising incidence. Results of this cross-sectional study suggest that despite the global decline in deaths and DALYs, the number of deaths and DALYs remains high among children with diabetes, especially in low SDI regions. Improved understanding of the epidemiology of diabetes in children may facilitate prevention and control.
... The most frequent comorbidities include insulin resistance, dyslipidemia, altered glucose tolerance and arterial hypertension, carrying an increased risk of developing a variety of chronic disorders, such as type 2 diabetes mellitus (T2DM) and cardiovascular and renal diseases [2][3][4]. The spread of the western lifestyle is leading to an increase in the prevalence of prediabetes and T2DM in childhood, which are important risk factors for cardiovascular diseases that represent the main cause of morbidity and mortality in diabetic patients [5]. Obesity is also frequently associated with non-alcoholic fatty liver disease (NAFLD) in children and adults. ...
... This constitutes an important public health problem in the context of population aging and increased prevalence of diabetes worldwide (7), hence, early-life prevention of CVD has been advocated (2,54). Multiple factors seem to contribute to their higher CVD risk, such as hyperglycemia, hypertension, dyslipidemia, or insulin resistance (55). Our meta-analysis suggests that the use of metformin as an adjunctive therapy may hold promise in CVD risk reduction in children with type 1 diabetes through improvements in CIMT. ...
IntroductionHyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a systematic review and meta-analysis to assess the effect of pharmacological or non-pharmacological interventions on CIMT in children and adolescents with prediabetes or diabetes.Methods
We conducted systematic searches of MEDLINE, EMBASE, and CENTRAL, together with supplementary searches in trial registers and other sources for studies completed up to September 2019. Interventional studies assessing ultrasound CIMT in children and adolescents with prediabetes or diabetes were considered for inclusion. Where appropriate, data were pooled across studies using random-effect meta-analysis. Quality was assessed using The Cochrane Collaboration’s risk-of-bias tool and a CIMT reliability tool.ResultsSix studies involving 644 children with type 1 diabetes mellitus were included. No study involved children with prediabetes or type 2 diabetes. Three randomized controlled trials (RCTs) evaluated the effects of metformin, quinapril, and atorvastatin. Three non-randomized studies, with a before-and-after design, evaluated the effects of physical exercise and continuous subcutaneous insulin infusion (CSII). The mean CIMT at baseline ranged from 0.40 to 0.51 mm. The pooled difference in CIMT was -0.01 mm (95% CI: -0.04 to 0.01) for metformin compared to placebo (2 studies; 135 participants; I2: 0%). The difference in CIMT was -0.01 mm (95% CI: -0.03 to 0.01) for quinapril compared to placebo (1 study; 406 participants). The mean change from baseline in CIMT was -0.03 mm (95% CI: -0.14 to 0.08) after physical exercise (1 study; 7 participants). Inconsistent results were reported for CSII or for atorvastatin. CIMT measurement was rated at a higher quality on all reliability domains in 3 (50%) studies. The confidence in results is limited by the low number of RCTs and their small sample sizes, as well as the high risk of bias in before-and-after studies.Conclusions
Some pharmacological interventions may decrease CIMT in children with type 1 diabetes. However, there is great uncertainty with respect to their effects and no strong conclusions can be drawn. Further evidence from larger RCTs is required.Systematic Review RegistrationPROSPERO, CRD42017075169
... In the Middle East, the prevalence is reported to be among the highest in the world, with an average of 11.4% (48). The prevalence of cardiovascular risk factors is high among patients with diabetes and in those with earlier onset of the disease, where higher cardiovascular risks and poorer cardiovascular outcomes and mortality are seen (49). In fact, the leading cause of mortality among patients with diabetes is cardiovascular disease (50). ...
The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes.
... Both T2D morbidity and mortality are increasing from year to year, affecting dramatically the health-care systems and quality of life [2][3][4]. This metabolic condition, characterized by elevated levels of blood glucose, can lead to development of chronic diseases affecting the cardiovascular, renal, and nervous systems [5][6][7][8]. Nowadays, the management of T2D aims to reduce blood glucose levels through both pharmacological and non-pharmacological (healthy lifestyle and balanced diet) treatments. To overcome the high costs and side effects of drug therapies, dietary supplementation with natural anti-diabetic agents is becoming increasingly crucial [9][10][11][12]. ...
The intake of phenolic-rich foods is an emerging preventive approach for the management of type 2 diabetes, thanks to the ability of these compounds to inhibit some key metabolic enzymes. In this study, the influence of cooking and in vitro digestion on the α-glucosidase, α-amylase, and dipeptidyl-peptidase IV (DPP-IV) inhibitory activity of red-skinned onion (RSO) and dark purple eggplant (DPE) phenolic fractions was assessed. The applied cooking procedures had different influences on the total and individual phenolic compounds gastrointestinal bioaccessibility. DPE in vitro digested phenolic fractions displayed no inhibitory activity versus α-amylase and DPP-IV, whereas the fried DPE sample exhibited moderate inhibitory activity against α-glucosidase. This sample mainly contained hydroxycinnamic acid amides that can be responsible for the observed effect. Contrariwise, raw and cooked in vitro digested RSO phenolic fractions inhibited all three enzymes but with different effectiveness. Fried and raw RSO samples were the most active against them. Statistical analysis pointed out that quercetin mono-hexosides (mainly quercetin-4′-O-hexoside) were responsible for the inhibition of α-glucosidase, whereas quercetin di-hexosides (mainly quercetin-3-O-hexoside-4′-O-hexoside) were responsible for the DPP-IV-inhibitory activity of RSO samples. An accurate design of the cooking methods could be essential to maximize the release of individual phenolic compounds and the related bioactivities.
