A non-linear association between low-density lipoprotein cholesterol and the risk of diabetic kidney disease in patients with type 2 diabetes in China
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SUBMITTER: Xiang X
PROVIDER: S-EPMC11339054 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is a novel marker related to atherosclerosis, but its role in diabetic kidney disease (DKD) remains unclear. This study investigated the relationship between NHHR and DKD risk in patients with type 2 diabetes mellitus (T2DM) and evaluated its potential as a marker for early DKD screening.MethodsData from adults with T2DM participating in the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2018 were analyzed. Demographic information, laboratory tests, and other relevant information were collected. To evaluate the correlation between NHHR levels and DKD risk, weighted multivariable logistic regression and weighted restricted cubic spline (RCS) analyses were employed. Furthermore, threshold effect analysis was employed to further explore the relationship at different NHHR levels, and subgroup analyses validated the results.ResultsThe study enrolled a total of 3,243 participants, comprising 1,258 individuals with DKD (38.79%) and 1,985 individuals without DKD (61.21%). The multivariable logistic regression analysis showed that T2DM patients with higher NHHR levels exhibited a 45% reduction in the risk of developing DKD in comparison to those with lower NHHR levels (Q2 vs. Q1: OR 0.55, 95% CI 0.40-0.76). The weighted RCS analysis revealed a nonlinear correlation between NHHR and the risk of DKD in patients with T2DM (P for nonlinear = 0.003), with the RCS plot exhibiting an L-shaped association. A negative association was observed between NHHR levels and the risk of DKD when NHHR was ≤2.82 (OR 0.63, 95% CI 0.49-0.83). A statistically significant correlation between NHHR and DKD risk was not observed when NHHR was >2.82. The subgroup analyses indicated that age may have an interaction effect on this association at higher NHHR levels (p for interaction<0.05).ConclusionOur findings revealed a non-linear relationship between the NHHR levels and the risk of DKD in adult T2DM patients in the United States. Managing the NHHR levels in the right range in T2DM patients can help reduce the risk of DKD. This suggests that NHHR may be a valuable and easily measurable biomarker for identifying those at risk for DKD, thereby promoting early intervention and improved disease management.
| S-EPMC11880278 | biostudies-literature
Project description:Patients undergoing maintenance hemodialysis are at high cardiovascular risk. Lowering LDL-cholesterol with statins reduces the incidence rate of cardiovascular events in patients with chronic kidney disease. In contrast, two randomized, prospective, placebo-controlled trials have been completed in hemodialysis patients that showed no significant effects of statins on cardiovascular outcomes.A post hoc analysis was conducted of the 4D (Die Deutsche Diabetes Dialyze) study to investigate whether LDL-cholesterol at baseline is predictive of cardiovascular events and whether the effect of atorvastatin on clinical outcomes depends on LDL-cholesterol at baseline.High concentrations of LDL-cholesterol by tendency increased the risks of cardiac endpoints and all-cause mortality. Concordantly, atorvastatin significantly reduced the rates of adverse outcomes in the highest quartile of LDL-cholesterol (?145 mg/dl, 3.76 mmol/L). The hazard ratios and 95% confidence intervals were 0.69 (0.48 to 1.00) for the composite primary endpoint, 0.58 (0.34 to 0.99) for cardiac death, 0.48 (0.25 to 0.94) for sudden cardiac death, 0.62 (0.33 to 1.17) for nonfatal myocardial infarction, 0.68 (0.47 to 0.98) for all cardiac events combined, and 0.72 (0.52 to 0.99) for death from all causes, respectively. No such decrease was seen in any of the other quartiles of LDL-cholesterol at baseline.In patients with type 2 diabetes mellitus undergoing hemodialysis, atorvastatin significantly reduces the risk of fatal and nonfatal cardiac events and death from any cause if pretreatment LDL-cholesterol is >145 mg/dl (3.76 mmol/L).
| S-EPMC3109927 | biostudies-literature
Project description:BackgroundPrevious research has linked elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) with diabetes mellitus (DM). The present study aims to estimate the RC-related DM risk beyond LDL-C, and to investigate the extent to which the association of RC and DM is mediated via insulin resistance and inflammation.MethodsWe enrolled 7308 individuals without previous history of DM into the present study from the China Health and Nutrition Survey. Fasting RC was calculated as total cholesterol minus LDL-C and high-density lipoprotein cholesterol. Subjects were divided into four groups according to their LDL-C (100 mg/dL) and RC (24 mg/dL) levels to evaluate the role of LDL-C vs. RC on DM. A logistic regression analysis was then employed to evaluate the relationships between the discordant/concordant LDL-C and RC and DM. A mediation analysis was undertaken to identify potential mediators.ResultsOf all the participants, a total of 625 (8.55%) patients were newly diagnosed with DM. Compared to the high LDL-C/low RC group, the low LDL-C/high RC group was more common in DM patients. After a multivariate adjustment, elevated LDL-C and RC were associated with DM. Moreover, the low LDL-C/high RC group and the high LDL-C/low RC group manifested a 4.04-fold (95% CI 2.93-5.56) and 1.61-fold (95% CI 1.21-2.15) higher risk of DM, relative to those with low LDL-C/low RC. The subgroup analysis indicated that low LDL-C/high RC was more likely to be related to DM in females. Similar results were also shown when the sensitivity analyses were performed with different clinical cut-points of LDL-C. Insulin resistance and inflammation partially mediated the association between RC and DM.ConclusionsOur findings provided evidence for RC beyond the LDL-C associations with DM that may be mediated via insulin resistance and the pro-inflammatory state. In addition, women are more susceptible to RC exposure-related DM.
| S-EPMC9238255 | biostudies-literature
Project description:BackgroundSmall dense low-density lipoprotein (sdLDL) possesses atherogenic potential and is predicted to be susceptible to atherogenic modifications, which further increases its atherogenicity. However, studies on the association between measured or estimated sdLDL cholesterol (sdLDL-C) levels and atherogenic modification in diverse population groups are lacking.MethodsSurplus serum samples were collected from male subjects with type 2 diabetes mellitus (DM) under treatment (n = 300) and without DM (non-DM; n = 150). sdLDL and oxidized LDL (oxLDL) levels were measured using the Lipoprint LDL subfractions kit (Quantimetrix Corporation) and the Mercodia oxidized LDL competitive enzyme-linked immunosorbent assay kit (Mercodia), respectively. The estimated sdLDL-Cs were calculated from two relevant equations. The effects of sdLDL-C on oxLDL were assessed using multiple linear regression (MLR) models.ResultsThe mean (±SD) of measured sdLDL-C and oxLDL concentrations were 11.8 ± 10.0 mg/dl and 53.4 ± 14.2 U/L in the non-DM group and 0.20 ± 0.81 mg/dl and 46.0 ± 15.3 U/L in the DM group, respectively. The effects of measured sdLDL-Cs were significant (p = 0.031), whereas those of estimated sdLDL-Cs were not (p = 0.060, p = 0.116) in the non-DM group in the MLR models. The effects of sdLDL-Cs in the DM group were not significant.ConclusionIn the general population, high level of sdLDL-C appeared to be associated with high level of oxLDL. The equation for estimating sdLDL-C developed from a general population should be applied with caution to a special population, such as patients with DM on treatment.
| S-EPMC9833976 | biostudies-literature
Project description:ImportanceLimited evidence supports the association between low-density lipoprotein cholesterol (LDL-C) and mortality across different atherosclerotic cardiovascular disease (ASCVD) risk stratifications.ObjectiveTo explore the associations between LDL-C levels and mortality and to identify the optimal ranges of LDL-C with the lowest risk of mortality in populations with diverse ASCVD risk profiles.Design, setting, and participantsThe ChinaHEART project is a prospective cohort study that recruited residents aged 35 to 75 years from 31 provinces in mainland China between November 2014 and December 2022. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts on the basis of their medical history and ASCVD risk. Data analysis was performed from December 2022 to October 2023.Main outcomes and measuresThe primary end point was all-cause mortality, and secondary end points included cause-specific mortality. Mortality data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed by using Cox proportional hazard regression models with various adjusted variables.ResultsA total of 4 379 252 individuals were recruited, and 3 789 025 (2 271 699 women [60.0%]; mean [SD] age, 56.1 [10.0] years) were included in the current study. The median (IQR) LDL-C concentration was 93.1 (70.9-117.3) mg/dL overall at baseline. During a median (IQR) follow-up of 4.6 (3.1-5.8) years, 92 888 deaths were recorded, including 38 627 cardiovascular deaths. The association between LDL-C concentration and all-cause or cardiovascular disease (CVD) mortality was U-shaped in both the low-risk cohort (2 838 354 participants) and the primary prevention cohort (829 567 participants), whereas it was J-shaped in the secondary prevention cohort (121 104 participants). The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C concentration associated with the lowest all-cause mortality (90.9 mg/dL vs 117.0 mg/dL) and CVD mortality (87 mg/dL vs 114.6 mg/dL) were both lower in individuals with diabetes than in individuals without diabetes in the overall cohort.Conclusions and relevanceThis study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes.
| S-EPMC11258592 | biostudies-literature
Project description:BackgroundType 2 diabetes is emerging in Sudan and is associated with obesity. Deregulated lipid metabolism and inflammatory states are suggested risk factors for cardiovascular disease, which is a leading cause of diabetic death. This study aimed to investigate C-reactive protein (CRP) levels and the lipid profile in type 2 diabetic adult Sudanese compared with nondiabetics, and to test their associations with other characteristics.MethodsA cross-sectional study including 70 diabetics and 40 nondiabetics was conducted. Anthropometric measurements were assessed, and demographic and medical data were obtained using a structured questionnaire. Blood specimens were collected and biochemical parameters were analyzed applying standard methods.ResultsCRP and triglycerides were significantly higher in the diabetic group (P<0.001 and P=0.01, respectively). Differences in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were not statistically significant between the diabetic and nondiabetic groups. In the diabetic group, correlation analysis revealed that the CRP level had a significant positive correlation with LDL-C (r=0.255, P=0.034) and body mass index (r=0.29, P=0.016). Body mass index showed a significant positive correlation with triglycerides (r=0.386, P=0.001). Within the lipid parameters, a number of significant correlations were observed. Elevated levels of CRP, LDL-C, and triglycerides were markedly more prevalent in the diabetic group of patients. Diabetics showed significantly higher CRP levels compared with nondiabetics (odds ratio 5.56, P=0.001).ConclusionThe high prevalence of obesity among diabetics, together with elevated levels of triglycerides and CRP, suggest coexistence of dyslipidemia and inflammation in diabetes. Our findings emphasize that diabetics were 5.6 times more likely to have high CRP levels than nondiabetics; as CRP is a predictor of cardiovascular disease risk, it can be recognized that diabetics are at more risk of cardiovascular disease than nondiabetics. Considering evaluation of CRP together with the lipid profile in prediction of cardiovascular disease risk in Sudanese diabetics should be further tested in large-scale studies.
| S-EPMC4567170 | biostudies-literature
Project description:BackgroundThis paper investigated the link between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease (DKD) in adult diabetic patients and identified the optimal NHHR value for impacting DKD.MethodsThis cross-sectional research made use of records from the National Health and Nutrition Examination Survey (NHANES) executed between 2005 and 2016. The link of NHHR to DKD risk was analyzed by logistic regression and restricted cubic spline (RCS) models. The stability and reliability of the results were assessed by subgroup analysis and sensitivity analysis.ResultsIn total, 4,177 participants were involved. As a continuous variable, NHHR was markedly connected to an increased risk of DKD (OR 1.07, 95% CI 1.02, 1.12, P < 0.01). When NHHR was grouped in quartiles, relative to the reference set, the highest NHHR group was also linked to a heightened risk of DKD (OR 1.23, 95% CI 1.01, 1.50, P < 0.05). The outcome of RCS show a "J" shaped correlation between NHHR and DKD risk (P for nonlinear = 0.0136). The risk of developing DKD was the lowest when NHHR equals 2.66. Subgroup analysis revealed that the link of NHHR to DKD persisted in participants aged below 40, females, non-smokers, and those without hyperuricemia. Sensitivity analysis demonstrated a certain robustness in this association.ConclusionA meaningful link is present between NHHR and DKD. An NHHR value of around 2.66 could represent the ideal cutoff for assessing DKD risk.
| S-EPMC11437633 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of ?-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy.
| S-EPMC4094576 | biostudies-other
Project description:BackgroundThe risk association between low-density lipoprotein (LDL) cholesterol and cancer remains controversial and largely unexplored for people not receiving statin therapy.MethodsWe examined the risk association between LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were free of cancer at enrolment and whose statin use was known. We considered a variety of nonlinear relationships in our analysis.ResultsDuring a median follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients. Among the 3800 patients who did not receive statin therapy, the risk association between LDL cholesterol and cancer was represented by a V-shaped curve. Compared with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80 mmol/L, the risk of cancer, death from any cause or the composite outcome of cancer or death was greater among those with an LDL cholesterol level of less than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20-2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard ratio for cancer 1.87, 95% CI 1.29-2.71). Using 3.8 mmol/L as a reference point, we found that the hazard ratio for cancer for every millimole per litre absolute change in LDL cholesterol was 1.54 (95% CI 1.19-1.99) among patients not using statins; the hazard ratio was reduced to 1.24 (1.01-1.53) for the entire sample (statin users and those not using statins). These associations persisted after adjustment for covariates and exclusion of patients with less than 2.5 years of follow-up.InterpretationAmong patients with type 2 diabetes, the association between LDL cholesterol and cancer was V-shaped, whereby both low and high levels of LDL cholesterol were associated with elevated risk of cancer.
| S-EPMC2518179 | biostudies-literature
Project description:Aims/introductionDyslipidemia plays a critical role in the pathogenesis of metabolic syndrome and diabetes. Evidence has increasingly shown that the ratio of low- to high-density lipoprotein cholesterol (LDL-C/HDL-C) is a novel marker for increased risk of insulin resistance and cardiovascular diseases. However, the correlation between the LDL-C/HDL-C ratio and diabetes risk is rarely reported. This is the first study to investigate the association between the LDL-C/HDL-C ratio and new-onset diabetes in a large community-based cohort.Materials and methodsIn this retrospective cohort study, a total of 116,661 adults without baseline diabetes were enrolled. Participants were stratified into four groups based on LDL-C/HDL-C ratio quartiles. The outcome of interest was new-onset diabetes.ResultsDuring a median follow-up period of 2.98 years, 2,681 (2.3%) new diabetes cases were recorded. The total cumulative incidence of diabetes progressively increased alongside LDL-C/HDL-C ratio quartiles (0.31, 0.43, 0.68 and 0.88%, respectively, P-value for trend <0.001). After adjusting for potential confounders, using the lowest quartile of the LDL-C/HDL-C ratio as the reference, the risk of diabetes increased with LDL-C/HDL-C ratio quartiles (P-value for trend <0.001); in particular, from the second to fourth quartile, hazard ratios were 1.18 (95% confidence interval 0.87-1.59), 1.42 (95% confidence interval 1.07-1.90) and 1.92 (95% confidence interval 1.43-2.59), respectively. The results were also robust to challenges in multiple sensitivity analyses.ConclusionsAmong the Chinese population, elevated LDL-C/HDL-C ratio might be an independent risk factor for new-onset diabetes.
| S-EPMC7779276 | biostudies-literature