Relationship between small dense low density lipoprotein and cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Residual risk remained significant despite effective low density lipoprotein cholesterol (LDL-C) lowering treatment. Small dense low density lipoprotein cholesterol (sdLDL-C) as part of LDL-C has been found to be predictor of coronary heart disease (CHD) and cardiovascular (CV) events in patients with stable CHD independently of LDL-C. However, to date, few studies have explored the role of sdLDL-C in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Accordingly, this study aimed to evaluate the association of sdLDL-C with CV events in patients with ACS undergoing PCI. METHODS: Patients hospitalized with ACS undergoing PCI were enrolled and followed up for 18 months. The risk of sdLDL-C for CV events was compared according to sdLDL-C quartiles. The primary outcome was major cardiovascular and cerebrovascular adverse events (MACCE), which was the composite of all cause of death, nonfatal myocardial infarction (MI), nonfatal stroke or unplanned repeat revascularization. A Cox proportional hazards regression model was performed to estimate the risk of CV events. Subgroup analysis according to diabetes status and LDL-C were performed separately for MACCE. RESULTS: A total of 6092 patients were included in the analysis (age: 60.2 ± 10.13 years, male: 75.3%, BMI: 25.9 ± 3.33 kg/m2, dyslipidemia: 74.1% and diabetes: 44.5%). During 18 months of follow-up, 320 (5.2%) incident CV events occurred. Compared to the lowest sdLDL-C quartile group, patients in the highest quartile had a greater risk of CV events after multivariable adjustment (HR 1.92; 95% CI 1.37-2.70). In addition, it was mainly due to the increase of unplanned repeat revascularization. In the subgroup analyses, significant association was observed regardless of level of LDL-C and diabetes status. CONCLUSIONS: Patients with elevated sdLDL-C have a higher risk of CV events in Chinese patients with ACS undergoing PCI, providing additional value for better risk assessment.

Effects of androgenic properties of progestin combined with ethinyl estradiol on vascular endothelial reactivity, plasma lipids and free radical production in women with endometriosis.

AIM: Endothelial reactivity is inhibited and oxidative stress is enhanced in women with endometriosis. Testosterone may adversely affect lipids and endothelium. We investigated the effects of androgenic properties of progestins combined with ethinyl estradiol (EE) on endothelial function, lipids and free radical production in such women. METHODS: Women with endometriosis were treated with 20 µg EE + 3 mg drospirenone (DRSP) or 35 µg EE + 1 mg norethisterone (NET) for 3 months. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, copper (Cu), derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), nitrite/nitrate, endothelin-1 and asymmetrical dimethylarginine (ADMA) were measured before and after treatment. Flow-mediated vasodilation (FMD) of the brachial artery was measured by ultrasonography. RESULTS: DRSP group, but not NET group, significantly increased FMD and concentrations of nitrite/nitrate and small dense LDL cholesterol, while decreased endothelin-1 concentrations. In both groups, ADMA and LDL cholesterol concentrations were significantly decreased, but triglyceride, SHBG, d-ROMs, Cu and ceruloplasmin concentrations increased, and BAP concentrations did not change. DRSP group significantly increased HDL cholesterol concentrations, whereas NET group decreased its concentrations. Changes in triglyceride correlated positively either with changes in SHBG (r = 0.57, P < 0.001) or with small dense LDL cholesterol (r = 0.45, P = 0.005). Changes in Cu correlated positively with changes in d-ROMs (r = 0.87, P < 0.001). CONCLUSION: Androgenic properties of progestin may counteract EE's favorable effects on endothelial function and HDL cholesterol, while eliminating its adverse effects on increased triglyceride-induced small dense LDL cholesterol in women with endometriosis.

Protection of the kidney with sodium-glucose cotransporter 2 inhibitors: potential mechanisms raised by the large-scaled randomized control trials.

This communication provides a current overview on the renal protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in diabetics. Following the epoch-making publications, the CANVAS Program and the EMPA-REG OUTCOME trial, numerous literature has discussed the mechanisms by which SGLT2 inhibition exerts its cardio-renal protective effects. Some of them reached agreement, while others did not. This review focuses on the hemodynamic aspect and the remaining potential factors relevant to the renal protection which have not been so much taken up by other review papers. Questions unanswered include factors of uric acid, lipids, erythropoiesis and oxidative stress, salt and sympathetic nerve, and the Na-H exchanger in heart and kidney.

Association of small, dense low-density lipoprotein cholesterol and galectin-3 in patients with chronic kidney disease.

BACKGROUND: Dyslipidemia is a common feature of chronic kidney disease (CKD). Although it has been observed that the pattern of lipid abnormalities can vary according to the stage of CKD, there is lack of data concerning the distribution of lipoprotein subclasses at various stages of the disease. In addition, association of proatherogenic small, dense low-density lipoprotein (sdLDL) subclasses with markers of inflammation, such is galectin-3, is not sufficiently explored. The aim of this study was to analyze concentrations and relative proportions of sdLDL-cholesterol (sdLDL-C) and galectin-3 in patients with CKD, with respect to the stage of the disease. Also, we sought possible independent associations of galectin-3 and sdLDL-C. METHODS: The study involved 100 hemodialysis (HD) and 50 pre-dialysis patients, together with 94 healthy individuals. SdLDL-C was measured by heparin-magnesium precipitation method. Galectin-3 was measured by ELISA technique. RESULTS: Galectin-3 levels were higher in pre-dialysis and HD patients than in the control group (p < 0.01). The concentration of sdLDL-C was highest in the pre-dialysis group and lowest in HD patients (p < 0.01). CKD patients with increased galectin-3 concentrations had significantly higher relative proportions of cholesterol in sdLDL (% sdLDL-C) than their counterparts with lower galectin-3 levels (p < 0.05). Relative proportion of sdLDL-C was shown to be an independent determinant of galectin-3 concentration. CONCLUSIONS: Our results demonstrated alterations in concentrations and proportions of sdLDL-C according to the stages of CKD. The observed independent associations of % sdLDL-C and galectin-3 provide further insight into their complex interaction during the progression of atherosclerosis in CKD.

Plasma proprotein convertase subtilisin kexin type 9 levels are related to markers of cholesterol synthesis in familial combined hyperlipidemia.

BACKGROUND AND AIMS: Two recent independent studies showed that patients with familial combined hyperlipidemia (FCHL) have elevated plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) and markers of cholesterol synthesis. Both PCSK9 expression and cholesterol synthesis are downstream effects of hepatic activation of sterol regulatory element binding protein 2 (SREBP2). The present study was conducted to study the relationship between plasma PCSK9 and markers of cholesterol synthesis in FCHL. METHODS AND RESULTS: Markers of cholesterol synthesis (squalene, desmosterol, lathosterol), cholesterol absorption (campesterol, sitosterol, cholestanol) and PCSK9 were measured in plasma of FCHL patients (n = 103) and their normolipidemic relatives (NLR; n = 240). Plasma PCSK9, lathosterol and desmosterol levels were higher in FCHL patients than their NLR (p < 0.001, age and sex adjusted). Heritability calculations demonstrated that 35% of the variance in PCSK9 levels could be explained by additive genetic effects (p < 0.001). Significant age- and sex-adjusted correlations were observed for the relationship between PCSK9 and lathosterol, both unadjusted and adjusted for cholesterol, in the overall FCHL population (both p < 0.001). Multivariate regression analyses, with PCSK9 as the dependent variable, showed that the regression coefficient for FCHL status decreased by 25% (from 0.8 to 0.6) when lathosterol was included. Nevertheless, FCHL status remained an independent contributor to plasma PCSK9 (p < 0.001). CONCLUSIONS: The present study confirms the previously reported high and heritable PCSK9 levels in FCHL patients. Furthermore, we now show that high PCSK9 levels are, in part, explained by plasma lathosterol, suggesting that SREBP2 activation partly accounts for elevated PCSK9 levels in FCHL.

Small Dense Low-Density Lipoprotein Cholesterol and Cardiovascular Risk in Statin-Treated Patients with Coronary Artery Disease.

AIM: We investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy. METHODS: This was a prospective case-cohort study within the Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study, a randomized trial of high- or low-dose (4 or 1 mg/d pitavastatin, respectively) statin therapy, in patients with stable coronary artery disease (CAD). Serum sdLDL-C was determined using an automated homogenous assay at baseline (randomization after a rule-in period, ＞1 month with 1 mg/d pitavastatin) and 6 months after randomization, in 497 MACE cases, and 1543 participants randomly selected from the REAL-CAD study population. RESULTS: High-dose pitavastatin reduced sdLDL-C by 20% than low-dose pitavastatin (p for interaction ＜0.001). Among patients receiving low-dose pitavastatin, baseline sdLDL-C demonstrated higher MACE risk independent of LDL-C (hazard ratio [95% confidence interval], 4th versus 1st quartile, 1.67 [1.04-2.68]; p for trend=0.034). High-dose (versus low-dose) pitavastatin reduced MACE risk by 46% in patients in the highest baseline sdLDL-C quartile (＞34.3 mg/dL; 0.54 [0.36-0.81]; p=0.003), but increased relative risk by 40% in patients with 1st quartile (≤ 19.5 mg/dL; 1.40 [0.94-2.09]; p=0.099) and did not alter risk in those in 2nd and 3rd quartiles (p for interaction=0.002). CONCLUSIONS: These findings associate sdLDL-C and cardiovascular risk, independent of LDL-C, in statin-treated CAD patients. Notably, high-dose statin therapy reduces this risk in those with the highest baseline sdLDL-C.

Metabolic Properties of Lowdensity Lipoprotein (LDL) Triglycerides in Patients with Type 2 Diabetes, Comparison with Small Dense LDL-Cholesterol.

AIMS: Abnormal compositional changes in low-density lipoprotein (LDL) particles, such as triglyceride (TG) enrichment and size reduction, are common in patients with diabetes. Several cohort studies have demonstrated that LDL-TG and sdLDL-cholesterol (C) are sensitive biomarkers for predicting atherosclerotic cardiovascular diseases beyond LDL-C. Although sdLDL has been extensively studied, little is known about the properties of LDL-TG. We investigated similarities or differences between LDL-TG and sdLDL-C. METHODS: Fasting plasma was obtained from 1,085 patients with type 2 diabetes who were enrolled in the diabetes regional cohort study (ViNA Cohort). LDL-TG and sdLDL-C concentrations were measured using a homogeneous assay established by us. In a subset of subjects, LDL-TG and sdLDL-C levels were measured postprandially or after treatment with lipid-lowering drugs. RESULTS: In a quartile analysis, higher LDL-TG quartiles were associated with higher frequency of female and fibrate users, whereas sdLDL-C quartiles were associated with frequency of men, drinking, and metabolic syndrome-related measurements. Higher quartiles of LDL-TG/LDL-C were associated with smoking, drinking, fibrate users, and statin users. LDL-TG was significantly correlated with TG, LDL-C, sdLDL-C, and apolipoprotein (apo) B, with apoB being the primary determinant. LDL-TG correlated to high sensitive C-reactive protein (CRP) independently of other lipids. Mean LDL-TG did not change with fasting/non-fasting. Statin treatment reduced LDL-TG, whereas fibrates increased it, but these drugs reduced sdLDL-C equally. CONCLUSIONS: LDL-TG levels were more tightly regulated by the number of LDL particles than plasma TG levels were. SdLDL-C was closely associated with metabolic syndrome-related factors, whereas LDL-TG was associated with low-grade systemic inflammation.

Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia.

Dyslipidemia is a risk factor for cardiovascular disease (CVD), a major cause of death worldwide. Angiopoietin-like protein 3 (ANGPTL3), recognized as a new therapeutic target for dyslipidemia, regulates the metabolism of low-density lipoprotein-cholesterol (LDL-C) and triglycerides. Here, we design 3 epitopes (E1-E3) for use in development of a peptide vaccine targeting ANGPTL3 and estimate effects of each on obesity-associated dyslipidemia in B6.Cg-Lepob /J (ob/ob) mice. Vaccination with the E3 (32EPKSRFAMLD41) peptide significantly reduces circulating levels of triglycerides, LDL-C, and small dense (sd)-LDL-C in ob/ob mice and decreases obese-induced fatty liver. Moreover, E3 vaccination does not induce cytotoxicity in ob/ob mice. Interestingly, the effect of E3 vaccination on dyslipidemia attenuates development of atherosclerosis in B6.KOR/StmSlc-Apoeshl mice fed a high-cholesterol diet, which represent a model of severe familial hypercholesterolemia (FH) caused by ApoE loss of function. Taken together, ANGPTL3 vaccination could be an effective therapeutic strategy against dyslipidemia and associated diseases.

The Association of Small Dense Low-Density Lipoprotein Cholesterol and Coronary Heart Disease in Subjects at High Cardiovascular Risk.

AIM: The present study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in subjects at high cardiovascular risk. METHODS: A total of 3,080 participants without prior cardiovascular disease (CVD), aged ≥ 40 years, were followed up for a median of 8.3 years, which were divided into two groups, those with serum sdLDL cholesterol levels of ＜35 mg/dL or ≥ 35 mg/dL. Then, subjects were stratified by the status of diabetes, CVD-related comorbidities (defined as the presence of diabetes, chronic kidney disease, or peripheral artery disease), and the CVD risk assessment according to the Japan Atherosclerosis Society Guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using a Cox proportional hazards model. RESULTS: During the follow-up, 79 subjects developed CHD. The risk for incident CHD was higher in subjects with serum sdLDL cholesterol of ≥ 35 mg/dL than those with sdLDL cholesterol of ＜35 mg/dL (HR 2.09, 95%CI 1.26-3.45) after adjusting for traditional risk factors. In the subgroup analyses, the multivariable-adjusted HR for incident CHD increased significantly in those with serum sdLDL cholesterol of ≥ 35 mg/dL among subjects with diabetes (HR 2.76, 95%CI 1.09-7.01), subjects with CVD-related comorbidities (HR 2.60, 95%CI 1.21-5.58), and high-risk category defined as the presence of CVD-related comorbidities or a Suita score of ≥ 56 points (HR 1.93, 95%CI 1.02-3.65). CONCLUSIONS: Elevated serum sdLDL cholesterol was associated with the development of CHD even in subjects at high cardiovascular risk.

Small Dense Low-Density Lipoprotein Cholesterol and the Risk of Coronary Heart Disease in a Japanese Community.

AIMS: This study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in a Japanese community. METHODS: A total of 3,080 participants without prior cardiovascular disease, aged 40 years or older, were followed up for 8 years. The participants were divided into the quartiles of serum sdLDL cholesterol levels. The risk estimates were computed using a Cox proportional hazards model. RESULTS: During the follow-up period, 79 subjects developed CHD. Subjects in the highest quartile had a 5.41- fold (95% confidence interval, 2.12-13.82) higher risk of CHD than those in the lowest quartile after controlling for confounders. In the analysis classifying the participants into four groups according to the levels of serum sdLDL cholesterol and serum low-density lipoprotein (LDL) cholesterol levels, the risk of CHD almost doubled in subjects with sdLDL cholesterol of ≥ 32.9 mg/dL (median), regardless of serum LDL cholesterol levels, as compared with subjects with serum sdLDL cholesterol of ＜32.9 mg/dL and serum LDL cholesterol of ＜120.1 mg/dL (median). When serum sdLDL cholesterol levels were incorporated into a model with known cardiovascular risk factors, c-statistics was significantly increased (from 0.77 to 0.79; p=0.02), and the net reclassification improvement was also significant (0.40; p＜0.001). CONCLUSIONS: The present findings suggest that the serum sdLDL cholesterol level is a relevant biomarker for the future development of CHD that offers benefit beyond the serum LDL cholesterol level and a possible therapeutic target to reduce the burden of CHD in a Japanese community.

Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression.

AIM: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan. METHODS: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression. RESULTS: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C ＜100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population. CONCLUSIONS: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

Small dense LDL cholesterol is associated with metabolic syndrome traits independently of obesity and inflammation.

BACKGROUND: Small dense LDL cholesterol (sdLDL-c) has been established to be highly associated with metabolic disorder. However, the relationship between circulating sdLDL-c and the presence of metabolic syndrome (MetS) has not been fully established. METHODS: A total of 1065 Chinese males (45.07 ± 11.08 years old) without diabetes and general obesity was recruited into a population-based, cross-sectional study. The MetS was defined based on the updated National Cholesterol Education Program/ Adult Treatment Panel III criteria for Asian Americans. Serum sdLDL-c concentration was measured by a homogeneous assay method and its relationship with MetS and its traits was investigated. RESULTS: Serum sdLDL-c concentrations increased gradually with increasing numbers of MetS components (p < 0.001) and the proportion of patients with MetS increased gradually with increasing sdLDL-c levels (p for trend< 0.001). For the second, third, and fourth sdLDL-c quartiles versus the first, the OR (95% CI) for MetS were 4.47(2.41,8.28), 5.47(2.97,10.07) and 8.39(4.58,15.38) (p < 0.001 for trend) after multivariate adjustment. The stratified analysis conducted according to LDL-c levels showed that the OR between serum sdLDL-c levels and MetS was greater in those LDL-c levels lower than 3.3 mmol/L (OR = 22.97; 95% CI, 7.64-69.09) than in those LDL-c levels higher than 3.3 mmol/L (OR = 17.49; 95% CI, 4.43-68.98). Mediation analysis showed sdLDL-c mediated 38.6% of the association of waist circumference with triglycerides, while the association between sdLDL-c and MetS components did not mediate by hsCRP. CONCLUSIONS: This study found that high sdLDL-c concentrations were associated with the presence of MetS independently of central obesity and inflammation.

Cardiovascular disease prevalence and insulin resistance in the Kyushu-Okinawa Population Study and the Framingham Offspring Study.

BACKGROUND: Age-adjusted cardiovascular disease (CVD) prevalence rates are significantly lower in Japan than in the United States. OBJECTIVE: Our aim was to compare CVD risk in participants in Fukuoka and Framingham. METHODS: We measured glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, and triglycerides in men and women from Fukuoka (n = 1108), and age (median, 53 years) and gender-matched subjects from Framingham (n = 1101). Blood pressure, body mass index, use of medications, and history of CVD were also assessed. RESULTS: CVD prevalence rates were more than 6-fold higher in Framingham men and women than their Fukuoka counterparts (P < .001). Median body mass index, LDL-C, insulin levels, and insulin resistance assessment in Fukuoka men and women were significantly (P < .01) lower than in Framingham; however, diabetes prevalence in Fukuoka men was significantly (P < .01) higher than in Framingham men, whereas female rates were similar, as were levels of systolic blood pressure. High-density lipoprotein cholesterol and surprisingly small dense LDL-C levels were significantly (P < .001) higher in Fukuoka than in Framingham. Standard risk factors do not account for the large differences in CVD prevalence rates between the 2 populations, and population differences in insulin resistance may explain some of these differences. CONCLUSIONS: Our data are consistent with the concept that the CVD prevalence rate in a Japanese population is much lower than those observed in the United States, and that these differences cannot be explained by standard CVD risk factors, but may relate to marked population differences in insulin resistance.

Ipragliflozin lowers small, dense low-density lipoprotein cholesterol levels in Japanese patients with type 2 diabetes mellitus.

AIMS: This preliminary randomized, parallel-group comparative study evaluated the efficacy of ipragliflozin for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Sixty-two patients with T2DM (age, 56 ± 8 years; hemoglobin A1c levels, 8.1 ± 0.9%; BMI, 27.5 ± 3.3 kg/m2) were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day) (treatment group; n = 40) or continued treatment (control group; n = 22) for 12 weeks. The primary endpoints were changes in sd LDL-C levels detected using the LipoPhor AS® system; the secondary endpoints included changes in the sd LDL-C/large buoyant LDL-C (lb LDL-C) ratio, a surrogate marker for LDL particle size, and percent changes in routine lipid parameters. RESULTS: The treatment group exhibited a statistically significant reduction from baseline for LDL-C levels (-0.37 mg/dL vs. 14.4 mg/dL, p = 0.038), sd LDL-C levels (-1.28 mg/dL vs. 2.81 mg/dL, p = 0.012), and sd LDL-C/lb LDL-C ratio (-3.20% vs. 4.58%, p = 0.040) compared with the control group. Multiple regression analysis among all subjects revealed change in TG levels (p = 0.011) and LDL-C levels (p = 0.024) as well as change in body weight (p = 0.006) as independent factors contributing to the reduction in sd LDL-C. CONCLUSIONS: Ipragliflozin may have a potential for lowering sd LDL-C levels associated with increasing LDL particle size in Japanese patients with T2DM.

Effect of Omega-3 Fatty Acids on Low Density Lipoprotein Subfraction, Adiponectin and Apolipoprotein B in Type 2 Diabetic Patients

BACKGROUND: Omega-3 fatty acids derived from fish oil have been reported to exert a beneficial effect on reducing cardiovascular disease. Reports about their mechanism have generated several interesting findings, including a change in small dense low density lipoprotein (sdLDL) cholesterol proportion, adiponectin, and apolipoprotein B (apoB), in addition to changes in the lipid profile. The principal objective of our study was to evaluate the effects of omega-3 fatty acids on plasma sdLDL, adiponectin, apoB100, and B48 in type 2 diabetic patients with hypertriglyceridemia. METHODS: We randomized 28 type 2 diabetic patients in a placebo-controlled, double-blind trial to receive either omega-3 fatty acids or placebo, both administered at a dose of 4 g daily for 12 weeks. LDL subfractions prior to and after treatment were separated via low-speed ultracentrifugation and analyzed via immunoelectrophoresis. Adiponectin, apoB100, and B48 levels were measured using an ELISA kit. RESULTS: sdLDL proportions were reduced in the omega-3 fatty acids group by 11% after 12 weeks of treatment (n = 17, P = 0.001), and were reduced by 4% in the control group (n = 11, P = 0.096). The patients receiving the omega-3 fatty acids evidenced a significant reduction in the levels of triglyceride (P = 0.001), apoB100, and B48 after 12 weeks (P = 0.038 and P = 0.009, respectively) relative to the baseline. Omega-3 fatty acids supplementation increased fasting blood glucose (P = 0.011), but the levels of HbA1c in each group did not change to a statistically significance degree. The adiponectin value was not reduced in the omega-3 fatty acids group (P = 0.133); by way of contrast, the placebo group evidenced a significant reduction in adiponectin value after 12 weeks (P = 0.002). CONCLUSION: Omega-3 fatty acid treatment proved effective in the reduction of atherogenic sdLDL and apoB in type 2 diabetic patients (Clinical trials reg. no. NCT 00758927, clinicaltrials.gov).