Small dense LDL is more susceptible to glycation than more buoyant LDL in Type 2 diabetes

2012 ◽  
Vol 124 (5) ◽  
pp. 343-349 ◽  
Author(s):  
Nahla N. Younis ◽  
Handrean Soran ◽  
Philip Pemberton ◽  
Valentine Charlton-Menys ◽  
Mohamed M. Elseweidy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Free Amino ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Peroxide ◽  
Amino Groups ◽  
Small Dense Ldl ◽  
Ldl Subfractions

Glycation of apoB (apolipoprotein B) of LDL (low-density lipoprotein) increases its atherogenicity. Concentrations of both serum glyc-apoB (glycated apoB) and SD-LDL (small dense LDL) (syn LDL3; D=1.044–1.063 g/ml) are increased in diabetes and are closely correlated. We studied whether SD-LDL is more susceptible to glycation in vitro than more buoyant LDL in statin- and non-statin-treated Type 2 diabetes mellitus. Serum SD-LDL apoB and glyc-apoB on statins was 20±2 (means±S.D.) and 3.6±0.41 compared with 47±3 and 5.89±0.68 mg/dl in those not receiving statins (P<0.001 and <0.01, respectively). There was a dose-dependent increase in glycation on incubation of LDL subfractions with glucose, which was accompanied by an increase in LPO (lipid peroxide) and electrophoretic mobility and a decrease in free amino groups. SD-LDL was more susceptible to these changes than more buoyant LDL. Both SD-LDL and more buoyant LDL from statin-treated patients were less susceptible to glycation. There were fewer free amino groups on LDL subfractions from statin-treated patients, which may contribute to this resistance. In conclusion, greater susceptibility of SD-LDL to glycation is likely to contribute to the raised levels of circulating glyc-apoB in diabetes. Statins are associated with lower levels of both SD-LDL and glyc-apoB.

scholarly journals Pemafibrate decreases triglycerides and small, dense LDL, but increases LDL-C depending on baseline triglycerides and LDL-C in type 2 diabetes patients with hypertriglyceridemia: an observational study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ichiro Komiya ◽  
Akira Yamamoto ◽  
Suguru Sunakawa ◽  
Tamio Wakugami
Keyword(s):  
Type 2 Diabetes ◽  
Disease Risk ◽  
Direct Method ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Small Dense Ldl ◽  
Group I ◽  
Diabetes Patients

Abstract Background Pemafibrate, a selective PPARα modulator, has the beneficial effects on serum triglycerides (TGs) and very low density lipoprotein (VLDL), especially in patients with diabetes mellitus or metabolic syndrome. However, its effect on the low density lipoprotein cholesterol (LDL-C) levels is still undefined. LDL-C increased in some cases together with a decrease in TGs, and the profile of lipids, especially LDL-C, during pemafibrate administration was evaluated. Methods Pemafibrate was administered to type 2 diabetes patients with hypertriglyceridemia. Fifty-one type 2 diabetes patients (mean age 62 ± 13 years) with a high rate of hypertension and no renal insufficiency were analyzed. Pemafibrate 0.2 mg (0.1 mg twice daily) was administered, and serum lipids were monitored every 4–8 weeks from 8 weeks before administration to 24 weeks after administration. LDL-C was measured by the direct method. Lipoprotein fractions were measured by electrophoresis (polyacrylamide gel, PAG), and LDL-migration index (LDL-MI) was calculated to estimate small, dense LDL. Results Pemafibrate reduced serum TGs, midband and VLDL fractions by PAG. Pemafibrate increased LDL-C levels from baseline by 5.3% (− 3.8–19.1, IQR). Patients were divided into 2 groups: LDL-C increase of > 5.3% (group I, n = 25) and < 5.3% (group NI, n = 26) after pemafibrate. Compared to group NI, group I had lower LDL-C (2.53 [1.96–3.26] vs. 3.36 [3.05–3.72] mmol/L, P = 0.0009), higher TGs (3.71 [2.62–6.69] vs. 3.25 [2.64–3.80] mmol/L), lower LDL by PAG (34.2 [14.5, SD] vs. 46.4% [6.5], P = 0.0011), higher VLDL by PAG (28.2 [10.8] vs. 22.0% [5.2], P = 0.0234), and higher LDL-MI (0.421 [0.391–0.450] vs. 0.354 [0.341–0.396], P < 0.0001) at baseline. Pemafibrate decreased LDL-MI in group I, and the differences between the groups disappeared. These results showed contradictory effects of pemafibrate on LDL-C levels, and these effects were dependent on the baseline levels of LDL-C and TGs. Conclusions Pemafibrate significantly reduced TGs, VLDL, midband, and small, dense LDL, but increased LDL-C in diabetes patients with higher baseline TGs and lower baseline LDL-C. Even if pre-dose LDL-C remains in the normal range, pemafibrate improves LDL composition and may reduce cardiovascular disease risk.

scholarly journals Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
David Meyre ◽  
Edward J. Andress ◽  
Tanmay Sharma ◽  
Marjolein Snippe ◽  
Hamza Asif ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Binding ◽  
European Ancestry ◽  
Missense Mutations ◽  
Metabolic Complications ◽  
Mutant Proteins

AbstractWe sequenced coding regions of the cluster of differentiation 36 (CD36) gene in 184 French individuals of European ancestry presenting simultaneously with type 2 diabetes (T2D), arterial hypertension, dyslipidemia, and coronary heart disease. We identified rare missense mutations (p.Pro191Leu/rs143150225 and p.Ala252Val/rs147624636) in two heterozygous cases. The two CD36 mutation carriers had no family history of T2D and no clustering of cardio-metabolic complications. While the p.Pro191Leu mutation was found in 84 heterozygous carriers from five ethnic groups from the genome aggregation database (global frequency: 0.0297%, N = 141,321), only one European carrier of the p.Ala252Val mutation was identified (global frequency: 0.00040%, N = 125,523). The Pro191 and Ala252 amino acids were not conserved (74.8% and 68.9% across 131 animal species, respectively). In vitro experiments showed that the two CD36 mutant proteins are expressed and trafficked to the plasma membrane where they bind modified low-density-lipoprotein (LDL) cholesterol as normal. However, molecular modelling of the recent CD36 crystal structure showed that Pro191 was located at the exit/entrance gate of the lipid binding chamber and Ala252 was in line with the chamber. Overall, our data do not support a major contribution of CD36 rare coding mutations to T2D and its cardio-metabolic complications in the French population.

scholarly journals Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Giuseppina Russo ◽  
Basilio Pintaudi ◽  
Carlo Giorda ◽  
Giuseppe Lucisano ◽  
Antonio Nicolucci ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Diabetes Duration ◽  
Lipid Lowering ◽  
Age And Gender ◽  
Chd Risk ◽  
And Gender

Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men.Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM.Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P<0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups.Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk.

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 Study on health risk factors as a basis to implement programs that promote a nutritional culture in students of the la Sabana University

2021 ◽  
pp. 89-94
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Chemistry ◽  
Monitoring And Control ◽  
The Metabolic Syndrome

Background. Nowadays the importance of lifestyles in the prevention of type 2 diabetes and the metabolic syndrome has been largely accertained. Objective. The purpose of our work is to implement programs that promote a nutritional culture in adolescents and young adults of the La Sabana University. Methods. The methodology entailed, after the corresponding informed consent, taking measures of the triceps and supraescapular skinfolds, waist circumference, body mass index (BMI), lean mass, and fat mass. Fasting blood samples were also taken to quantify cholesterol, triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL). Results. The results obtained show that of the 165 students, 10.3% were underweight, 13.93% were overweight and 0.6% were obese. With regards to gender, 4.8% of the men and 9% of the women were overweight, 3% of the men and 7.2% of the women were underweight, and 0.6% of the women were obese. The blood chemistry showed that 30% had hypercholesterolemia, 18% hypertriglyceridemia, 17% reported low HDL levels and 67% reported high LDL levels. Of all the cases studied, 40% are at risk of a metabolic syndrome. 60% claimed not to practice any physical activity - especially women who reported 44.70%. Conclusions. These findings have allowed us at the institution to implement a culture of healthy habits. The have also allowed us to identify students with risk factors for type 2 diabetes and metabolic syndrome. This is why the cardiometabolic monitoring and control based on healthy eating and physical activity are important.

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