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Real role of growth factor receptor-binding protein 10: Linking lipid metabolism to diabetes cardiovascular complications.

ABSTRACT: Cardiovascular complications of patients with type 2 diabetes mellitus (T2DM) threaten the health and life of numerous individuals. Recently, growth factor receptor-binding protein 10 (GRB10) was found to play a pivotal role in vascular complications of T2DM, which participates in the regulation of lipid metabolism of T2DM patients. The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM. The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients.

SUBMITTER: Yang Y

PROVIDER: S-EPMC9782935 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Real role of growth factor receptor-binding protein 10: Linking lipid metabolism to diabetes cardiovascular complications.

Yang Yang Y Yao Hua-Jie HJ Lin Wei-Jie WJ Huang Si-Chao SC Li Xiao-Dong XD He Fa-Zhong FZ

World journal of clinical cases 20221201 35

Cardiovascular complications of patients with type 2 diabetes mellitus (T2DM) threaten the health and life of numerous individuals. Recently, growth factor receptor-binding protein 10 (GRB10) was found to play a pivotal role in vascular complications of T2DM, which participates in the regulation of lipid metabolism of T2DM patients. The genetic variation of <i>GRB10</i> rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM. The development of GRB10 as a key med ...[more]

PMID: 36569013

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Project description:Sphingolipid metabolism is dysregulated in type 2 diabetes mellitus (T2DM); however, the focus of previous studies was mostly limited to ceramide (Cer), and only few studies have investigated other metabolites, including sphingosine-1 phosphate (So1P). The present study aimed to examine the involvement of 8 major sphingolipid metabolites, including Cer, glucosyl ceramide (GluCer), lactosyl ceramide (LacCer), sphingomyelin (SM), sphinganine (Sa), So1P, sphingosine (So) and sphinganine-1-phosphate (Sa1P), during the progression of T2DM, and to evaluate the ability of serum sphingolipids to predict cases of diabetes with an elevated risk of cardiovascular complications. Blood samples were obtained from 245 participants who were divided into 3 groups: Healthy controls, pre-diabetes (pre-DM) and diagnosed diabetes. The 8 major sphingolipid metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry and blood parameters were determined by routine laboratory assays for all subjects. Among the sphingolipid metabolites, So1P was associated with sex and lean mass index, but not with the body mass index. So1P was highest in healthy controls and gradually decreased when the disease proceeded to pre-DM and T2DM. GluCer, SM, Sa and So decreased in pre-DM and rose again in T2DM, graphically exhibiting a 'U' shape change during the progression of diabetes. So1P and Sa were identified to be significantly associated with cardiovascular complications by multivariate logistic regression analysis. Receiver operating characteristic curve analysis also suggested that So1P and Sa were able to indicate cardiovascular complications in diabetic patients. Pre-DM and diabetes were significantly associated with decreased So1P, SM, Sa and So, compared with the healthy controls. So1P was correlated with the progression of T2DM, and was a predictor of an elevated risk of cardiovascular complications among T2DM patients, along with Sa. The present study was registered with ClinicalTrials.gov (no. NCT02826759; April 2016).

Project description:AimTo examine the associations between variability in lipids and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes based on low-density lipoprotein-cholesterol (LDL-C), the total cholesterol (TC) to high-density lipoprotein-cholesterol (HDL-C) ratio and triglycerides (TG).Materials and methodsA retrospective cohort study included 125 047 primary care patients with type 2 diabetes aged 45-84 years without CVD during 2008-2012. The variability of LDL-C, TC to HDL-C and TG was determined using the standard deviation of variables in a mixed effects model to minimize regression dilution bias. The associations between variability in lipids and CVD and mortality risk were assessed by Cox regression. Subgroup analyses based on patients' baseline characteristics were also conducted.ResultsA total of 19 913 CVD events and 15 329 mortalities were recorded after a median follow-up period of 77.5 months (0.8 million person-years), suggesting a positive linear relationship between variability in lipids and the risk of CVD and mortality. Each unit increase in the variability of LDL-C (mmol/L), the TC to HDL-C ratio and TG (mmol/L) was associated with a 27% (HR: 1.27 [95% CI: 1.20-1.34]), 31% (HR:1.31 [95% CI: 1.25-1.38]) and 9% (HR: 1.09 [95% CI: 1.04-1.15]) increase in the risk of composite endpoint of CVD and mortality, respectively. Age-specific effects were also found when comparing LDL-C variability, with patients aged 45-54 years (HR: 1.70 [95% CI: 1.42-2.02]) exhibiting a 53% increased risk for the composite endpoints than those aged 75-84 years (HR: 1.11 [95% CI: 1.01-1.23]). Similar age effects were observed for both the TC to HDL-C ratio and TG variability. Significant associations remained consistent among most of the subgroups.ConclusionsVariability in respective lipids are significant factors in predicting CVD and mortality in primary care patients with type 2 diabetes, with the strongest effects related to LDL-C and the TC to HDL-C ratio and most significant in the younger age group of patients aged 45-54 years. Further study is warranted to confirm these findings.

Project description:BackgroundInsight in sex disparities in the detection of cardiovascular risk factors and diabetes-related complications may improve diabetes care. The aim of this systematic review is to study whether sex disparities exist in the assessment of cardiovascular risk factors and screening for diabetes-related complications.MethodsPubMed was systematically searched up to April 2020, followed by manual reference screening and citations checks (snowballing) using Google Scholar. Observational studies were included if they reported on the assessment of cardiovascular risk factors (HbA1c, lipids, blood pressure, smoking status, or BMI) and/or screening for nephropathy, retinopathy, or performance of feet examinations, in men and women with diabetes separately. Studies adjusting their analyses for at least age, or when age was considered as a covariable but left out from the final analyses for various reasons (i.e. backward selection), were included for qualitative analyses. No meta-analyses were planned because substantial heterogeneity between studies was expected. A modified Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to assess risk of bias.ResultsOverall, 81 studies were included. The majority of the included studies were from Europe or North America (84%).The number of individuals per study ranged from 200 to 3,135,019 and data were extracted from various data sources in a variety of settings. Screening rates varied considerably across studies. For example, screening rates for retinopathy ranged from 13% to 90%, with half the studies reporting screening rates less than 50%. Mixed findings were found regarding the presence, magnitude, and direction of sex disparities with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, with some evidence suggesting that women, compared with men, may be more likely to receive retinopathy screening and less likely to receive foot exams.ConclusionOverall, no consistent pattern favoring men or women was found with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, and screening rates can be improved for both sexes.

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Real role of growth factor receptor-binding protein 10: Linking lipid metabolism to diabetes cardiovascular complications.

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Real role of growth factor receptor-binding protein 10: Linking lipid metabolism to diabetes cardiovascular complications.

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