The rs4712527 Polymorphism in the CDKAL1 Gene: A Protective Factor for Proliferative Diabetic Retinopathy Progress in Type 2 Diabetes

2018 ◽  
Vol 2 (4) ◽  
pp. 200-207
Author(s):  
Pablo Yang ◽  
José D. Luna ◽  
Emilio Alcoba ◽  
Aylén Sein ◽  
Ana L. Gramajo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Protective Factor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Regulatory Subunit ◽  
Ophthalmological Examination

Purpose: Diabetic retinopathy (DR) is one of the chronic retinal disorders linked to diabetes and remains the leading cause of blindness in working-age people. Many studies have demonstrated the existence of associations between type 2 diabetes mellitus (T2DM) and variants in the cyclin-dependent kinase 5 regulatory subunit–associated protein 1-like 1 ( CDKAL1) gene. Here, we performed a case-control study in the CDKAL1 gene (rs4712527 polymorphism) to investigate the potential association between this single-nucleotide polymorphism (SNP) and DR risk. Methods: Two hundred thirty-one patients with T2DM (126 patients with proliferative diabetic retinopathy [PDR] and 105 patients without diabetic retinopathy [WDR]), who assisted at the Centro Privado de Ojos Romagosa, Fundación VER, were studied. An independent cohort of 98 patients (56 with PDR and 42 with WDR) from the Hospital Nacional de Clínicas was taken for replication. A complete ophthalmological examination included an external examination of the eye and adnexa, pupil responsiveness, and slit-lamp biomicroscopic examination. Genotyping of rs4712527 was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratio (OR) and 95% CI were calculated by unconditional logistic regression adjusted for diabetes duration, body mass index, insulin therapy, HbA1c, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and systolic and diastolic blood pressure. Results: Analysis from the rs4712527 SNP in the Centro Privado de Ojos Romagosa, Fundación VER, cohort was found to be associated with decreased risk of PDR both before and after adjustment, under the codominant (adjusted OR = 0.16 [95% CI, 0.06-0.44]; P = 4e-04), dominant (adjusted OR = 0.17 [95% CI, 0.07-0.43]; P = 1e-04), overdominant (adjusted OR = 0.20 [95% CI, 0.08-0.52]; P = 5e-04), and log-additive (adjusted OR = 0.28 [95% CI, 0.13-0.59]; P = 4e-04) models. In the combined analysis including both cohorts, the rs4712527 was nominally involved as a protective factor in the development of DR. Conclusions: Our findings suggest that the rs4712527 in the CDKAL1 gene might be involved in the protection to develop PDR in T2DM.

scholarly journals Impact of Adoption of Directly Measured Low-Density Lipoprotein-Cholesterol (LDL-C) on Targets of Lipid Control and Its Comparison With Friedewald Formula-Calculated LDL Cholesterol in People With Type-2 Diabetes Mellitus

2020 ◽  
pp. 263246362097804
Author(s):  
Rejitha Jagesh ◽  
Mathew John ◽  
Manju Manoharan Nair Jalaja ◽  
Tittu Oommen ◽  
Deepa Gopinath
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Friedewald Formula

Objectives: The accurate and precise measurement of low-density lipoprotein-cholesterol (LDL-C) is important in the assessment of atherosclerotic cardiovascular disease risk (ASCVD) in people with diabetes mellitus. This study aimed at comparing directly measured LDL-C with Friedewald formula (FF)-calculated LDL-C (c-LDL-C) in people with type-2 diabetes. Methods: Fasting lipid profiles of 1905 people with type-2 diabetes, whose LDL-C was estimated by direct LDL assay, were chosen for the study. In the same group, LDL-C was calculated with FF. Correlation and agreement between these methods were analyzed at various strata of triglycerides (TGs). The possibility of misclassifying people at various levels of LDL-C targets proposed in literature was calculated. Results: The mean LDL-C levels were lower in the c-LDL-C group across various TG strata. A significant correlation was found between c-LDL-C and direct LDL-C for all the study samples ( r = 0.948, P < .001) and across all TG strata. Analysis of agreement showed a positive bias for direct LDL-C which increased at higher strata of TGs. c-LDL-C underestimated ASCVD by misclassifying people at various LDL-C target levels. Conclusion: There is a difference between direct LDL-C and c-LDL-C values in people with diabetes and this may result in misclassifying ASCVD especially at lower levels of LDL-C and higher levels of TGs.

scholarly journals Correlation of Serum Low Density Lipoprotein Cholesterol and High Density Lipoprotein Cholesterol with Type 2 Diabetes Mellitus

2018 ◽  
Vol 26 (2) ◽  
pp. 140-147
Author(s):  
Nahid Yeasmin ◽  
Qazi Shamima Akhter ◽  
Sayeeda Mahmuda ◽  
Sultana Yeasmin ◽  
Rumana Afroz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Fasting Serum ◽  
Medical College

Background: Diabetes mellitus is one of the most widespread endocrine disorders in female and its complications are increasing all over the world, leading to life threatening medical problems like cardiovascular diseases, stroke and end stage renal diseases. A correlation between hyperlipidemia and type 2 diabetes mellitus has been identified. The study was carried out to observe the correlation of serum low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) level with type 2 diabetes mellitus in adult female subjects.Method: This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka, during the period of January 2011 to December 2011. Total sixty female subjects were selected with age ranging from 30 to 50 years. Among them 30 female subjects with diabetes mellitus were included from out-patient department of Endocrinology, Dhaka Medical College Hospital, Dhaka as study group (B) and 30 apparently healthy females were taken as control group (A) for comparison. Estimation of serum fasting serum LDL-C and HDL-C levels was done by enzymatic method in the department of Physiology, Dhaka Medical College Dhaka in both groups. Fasting serum insulin level was measured by ELISA method in the laboratory of National Institute of ENT, Dhaka and fasting blood glucose was estimated by glucose oxidase method in the department of Physiology, Dhaka Medical College in both groups. Data were analyzed by Unpaired Student’s- test and Pearson’s correlation co-efficient (r) test as applicable.Results: The value of fasting serum LDL-C level was significantly higher in study subjects than those of control. Again, fasting serum HDL-C level was significantly lower in study subjects in comparison to controls. In study subjects fasting serum LDL showed positive correlation and fasting serum HDL-C levels showed negative correlation with fasting blood glucose and serum insulin level.Conclusion: Present study reveals that serum insulin and blood glucose level have positive relationship with low density lipoprotein cholesterol (LDL-C) and negative relationship with high density lipoprotein cholesterol (HDL-C) levels.J Dhaka Medical College, Vol. 26, No.2, October, 2017, Page 140-147

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

Low-density lipoprotein cholesterol levels in adults with type 2 diabetes: An alternative equation for accurate estimation and improved cardiovascular risk classification

2014 ◽  
Vol 11 (6) ◽  
pp. 431-439 ◽  
Author(s):  
Ester Yeoh Chai Kheng ◽  
Sum Chee Fang ◽  
Su Chang ◽  
Serena Low Kiat Mun ◽  
Lim Su Chi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vascular Reactivity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Accurate Estimation ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Therapeutic Decisions

Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic disease. Despite its limitations, Friedewald-calculated LDL-C (F-LDL-C) remains widely used for LDL-C determination. In this observational study of 1999 adults with type 2 diabetes mellitus (T2DM), we compare the accuracy of F-LDL-C to directly measured LDL-C (M-LDL-C) and derived and validated a new [SMART2D (Singapore Study of MAcro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes)] formula to estimate LDL-C. From 1000 randomly selected patients, M-LDL-C was compared to F-LDL-C. Using multiple linear regression to identify independent predictors for M-LDL-C, the SMART2D equation was derived and subsequently validated in the next 981 patients. F-LDL-C was 0.367 (0.216) mmol/L lower than M-LDL-C. This difference was −0.009 (0.189) for SMART2D-LDL-C. Using F-LDL-C, 27% with M-LDL-C ≥2.6 mmol/L were classified as LDL-C <2.6 mmol/L, reduced to 2.1% when using SMART2D-LDL-C. With F-LDL-C, misclassification was greater when triglycerides were ≥2.2 mmol/L, especially for the lower LDL-C cut-offs (1.8 and 2.6 mmol/L), and this was markedly improved with SMART2D-LDL-C. In conclusion, in T2DM, F-LDL-C underestimates M-LDL-C, with misclassifications that may potentially have an impact on therapeutic decisions in T2DM. The SMART2D equation improves accuracy of estimate, reducing misclassifications. Trials will be needed to ascertain the clinical significance of these findings.

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