Age-specific differences in the association between prediabetes and cardiovascular diseases in China: A national cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, the global burden of which is rising. It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults. To develop a focused screening plan and treatment for Chinese adults with prediabetes, it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age. AIM: To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China. METHODS: The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008. A thorough evaluation was conducted. Individuals with prediabetes were categorized into two groups based on age. Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years. Random forest was established in both age groups. SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution. RESULTS: In total, 6948 people were diagnosed with prediabetes in this study. In pre-diabetes, prevalences of CVD were 5 (0.29%) in the younger group and 148 (2.85%) in the older group. Overall, 11.11% of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years. In the younger age group, the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle, whereas in the older age group, resident status was more closely linked. CONCLUSION: The susceptibility to CVD is age-specific in newly diagnosed prediabetes. It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.

Cardiovascular disease risk in early-onset vs late-onset type 2 diabetes in China: A population-based cross-sectional study.

BACKGROUND: This study investigated the effects of early-onset type 2 diabetes (EOD) vs late-onset type 2 diabetes (LOD) on nonfatal cardiovascular diseases (CVD) in China. METHODS: We conducted a cross-sectional survey of 46 239 participants from 14 provinces in China from 2007 to 2008, selecting 4949 participants with type 2 diabetes for analysis. Participants were categorized as EOD (<40 years) or LOD (≥40 years) based on age at diabetes diagnosis. Sociodemographic and nonfatal CVD information was collected through an interviewer-assisted questionnaire and clinical examination. Logistic regression analysis was used to investigate the nonfatal CVD risk. RESULTS: Out of 4949 participants with type 2 diabetes, 390 (7.88%) had nonfatal CVD. Participants with EOD had a higher age-standardized prevalence of nonfatal CVD than those with LOD (11.4% vs 4.4%). Compared to LOD patients, EOD patients tended to be males and had a higher family history of diabetes, unhealthy lifestyle behaviors, and lower blood pressure levels. After adjustment for age and sex, EOD patients had a higher risk of nonfatal CVD than LOD patients (odds ratio [OR] 2.3, 95% CI 1.5-3.5). After further adjustment for diabetes duration, use of drugs, and other risk factors, the OR of nonfatal CVD was reduced but significant (OR 1.8, 95% CI 1.1-2.9). Sensitivity analysis revealed that EOD patients with metabolic syndrome had an increased nonfatal CVD risk compared to LOD patients (OR 2.0, 95% CI 1.2-3.5). CONCLUSIONS: EOD patients are at increased risk of nonfatal CVD. Individualized intervention and management measures for EOD patients are necessary.

Assessment of Lumbosacral Nerve Roots in Patients with Type 2 Diabetic Peripheral Neuropathy Using Diffusion Tensor Imaging.

BACKGROUND: Diffusion tensor imaging (DTI) has found clinical applications in the evaluation of the central nervous system and has been extensively used to image peripheral neuropathy. However, few studies have focused on lumbosacral nerve root fiber damage in diabetic peripheral neuropathy (DPN). The aim of the study was to evaluate whether DTI of the lumbosacral nerve roots can be used to detect DPN. METHODS: Thirty-two type 2 diabetic patients with DPN and thirty healthy controls (HCs) were investigated with a 3T MRI scanner. DTI with tractography of the L4, L5, and S1 nerve roots was performed. Anatomical fusion with the axial T2 sequences was used to provide correlating anatomical information. Mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured from tractography images and compared between groups. Diagnostic value was assessed using receiver operating characteristic (ROC) analysis. The Pearson correlation coefficient was used to explore the correlation between DTI parameters and clinical data and the nerve conduction study (NCS) in the DPN group. RESULTS: In the DPN group, FA was decreased (p < 0.001) and ADC was increased (p < 0.001) compared with the values of the HC group. FA displayed the best diagnostic accuracy, with an area under the ROC curve of 0.716. ADC was positively correlated with HbA1c level (r = 0.379, p = 0.024) in the DPN group. CONCLUSIONS: DTI of lumbosacral nerve roots demonstrates appreciable diagnostic accuracy in patients with DPN.

Polymorphisms in the Glucagon-Like Peptide 1 Receptor (GLP-1R) Gene Are Associated with the Risk of Coronary Artery Disease in Chinese Han Patients with Type 2 Diabetes Mellitus: A Case-Control Study.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) bestows protective effects upon the cardiovascular system through direct cardiovascular interactions or by improvements to metabolic function. Both these effects are thought to be at least partly mediated by the GLP-1 receptor (GLP-1R). This case-controlled study investigated whether polymorphisms in the GLP-1R gene affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population. METHODS: Eleven haplotype-tagging single nucleotide polymorphisms (SNPs), distributed across 22 kb of the 39 kb GLP-1R gene, were selected and genotyped in diabetic patients from a Chinese Han population. Patients were classified based on the severity of coronary artery stenosis. Coronary artery stenosis was ≥50% in 394 patients (coronary artery disease- (CAD-) positive group), and coronary artery stenosis was <50% in 217 patients (control group). Allele and genotype frequencies were compared between the two groups at all 11 SNPs. RESULTS: When considered in recessive inheritance mode, patients with the GG genotype at rs4714210 had a lower CAD risk than patients with other genotypes (OR = 0.442, 95% CI = 0.258-0.757, p = 0.002), even when other known CAD risk factors were taken into account (ORa = 0.440, 95% CIa = 0.225-0.863, p a = 0.017). In additive inheritance mode, GG genotype carriers at rs4714210 exhibited a lower risk of CAD than AA carriers (ORa = 0.475, CIa = 0.232-0.970, p a = 0.041). CONCLUSION: In type 2 diabetic patients from a Han Chinese population, some variations in the GLP-1R gene were associated with a lower risk of developing CAD.

Genetic Variability in eIF2α Gene Is Associated with Islet ß-Cell Function in the Development of Diabetes in a Chinese Han Population.

AIMS: Protein kinase-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 alpha (eIF2α) pathway mutations lead to failure of ß-cell function. The aim of this article was to assess the association between eIF2α and the risk of glucose metabolism abnormalities. METHODS: Two eIF2α SNPs (rs9840992 T>C and rs13072593 A>G) were selected based on CHB data from HapMap, and 1466 unrelated nondiabetes individuals were genotyped. All subjects were examined by the 75 g oral glucose tolerance test, and 733 participated in a subsequent insulin release test. Various indicators of insulin resistance and islet ß-cell function were examined. RESULTS: There were no significant differences in genotype distribution and allele frequency between the prediabetes and controls. CC genotype carriers at rs9840992 showed higher insulin levels at 120 min after a 75 g glucose load than noncarriers. Also, CC homozygotes had higher ΔI30/ΔG30 and ΔI120/ΔG120 than noncarriers, even after adjusting for insulin resistance. CC homozygotes had greater AUCi values than noncarriers. Subjects aged ≥ 65 yrs, those with a BMI ≥ 24 kg/m2 and those carrying the rs9840992 risk allele, had a 2.5-fold higher risk of glucose abnormalities than subjects who had none of these risk factors. CONCLUSION: The eIF2α polymorphism is associated with islet ß-cell function in a Chinese population.

Association between STK11 Gene Polymorphisms and Coronary Artery Disease in Type 2 Diabetes in Han Population in China.

Background. Recent studies indicated that the Serine threonine kinase 11 (STK11), which is a key regulator of the AMP-activated protein kinase (AMPK), plays a crucial role in cardiovascular system. This study aimed to investigate whether genetic variations in the STK11 gene affect the risk of coronary artery disease (CAD) in Chinese type 2 diabetics. Methods. 5 haplotype-tagging single nucleotide polymorphisms (SNPs) were selected, and 288 CAD-positive cases and 159 CAD-negative controls with type 2 diabetes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results. The carriers of minor allele A at rs12977689 had a higher risk of CAD compared to the homozygotes of CC (OR = 1.572, 95% CI = 1.039-2.376, p = 0.035), and the difference was still significant after adjustment for the other known CAD risk factors (OR' = 1.184, 95% CI' = 1.036-1.353, p' = 0.013). Conclusion. Genetic variability at STK11 locus is associated with CAD risk in type 2 diabetes in the Chinese population.

Genetic variants in PCSK1 gene are associated with the risk of coronary artery disease in type 2 diabetes in a Chinese Han population: a case control study.

BACKGROUND: Insulin and glucagon-like peptide 1 (GLP-1), converted by proprotein convertase 1 (PC1/3) from proinsulin and proglucagon, are associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of PCSK1 gene, which encodes PC1/3, with the risk of CAD in Chinese patients with T2DM. METHODS: We selected and genotyped 5 haplotype-tagging single nucleotide polymorphisms (SNPs) at PCSK1 gene (across 39873bp locus) in a case-control study of Chinese Han population involving 425 diabetic patients (62.1% male, mean age 63.2 years) with CAD as positive cases and 258 diabetic patients (44.2% male, mean age 62.0 years) without CAD as controls. RESULTS: The allele frequencies at rs3811951 were significantly different between cases and controls (30.7% vs. 37.2%), with the allele G associated with decreased risk for CAD (OR = 0.75, 95% CI = 0.59-0.94, p = 0.013). In recessive inheritance mode, the carriers of GG had a lower risk (OR = 0.50, 95%CI = 0.31-0.82, p = 0.005), even after adjusted for gender, age, BMI and smoking (OR = 0.43, 95%CI = 0.24-0.77, p = 0.004). The carriers of the minor allele A at rs156019 had a higher risk (OR = 1.66, 95%CI = 1.10-2.50, p = 0.016 after adjustment) in dominant inheritance mode. The SNP rs6234 was also significantly associated with CAD risk in women, with the carriers of the minor allele G at rs6234 associated with a reduced CAD risk in recessive inheritance mode (OR = 0.42, 95% CI = 0.18-0.95, p = 0.036 after adjustment). CONCLUSIONS: Our results found that common genetic variants in PCSK1 were associated with CAD in Chinese patients with T2DM.

Synergistic effect of smoking with genetic variants in the AMPKα1 gene on the risk of coronary artery disease in type 2 diabetes.

BACKGROUND: Increasing evidence suggests that adenosine monophosphate-activated protein kinase (AMPK) plays a critical physiological role in the cardiovascular system. The objective of this study was to assess the possible correlation between the genetic variability of the AMPKα1 (PRKAA1) gene and the risk of cardiovascular disease, as well as the interactive effects of the genetic variations and environmental factors, on the risk in Chinese patients with type 2 diabetes. METHODS: Five haplotype-tagging single nucleotide polymorphisms (SNPs) at the AMPKα1 locus and 404 unrelated Chinese Han subjects with type 2 diabetes were studied; 260 individuals with coronary artery disease and 144 non-coronary artery disease controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: Minor allele C at rs3805489 was protective from coronary artery disease in type 2 diabetic subjects compared with allele A (OR 0.67, 95% CI 0.48-0.92, p = 0.015). There was no significant correlation between the genotypes at five SNPs and the risk of coronary artery disease. In addition, a significant interaction was identified between smoking status and rs3805489 (p = 0.018 for interaction). The smokers with genotype AA at the SNP had a three-fold higher risk of coronary artery disease compared with non-smokers with genotypes AC or CC (OR' 3.02, 95% CI' 1.39-6.57, p' = 0.005, after adjustment for other known coronary artery disease risk factors). CONCLUSIONS: The genetic variability at the AMPKα1 locus has synergetic effects with smoking to increase the risk of coronary artery disease in the Chinese Han population with type 2 diabetes.