Effects of Xuezhikang vs. Pravastatin on Triglyceride Level in Patients with Type 2 Diabetes Mellitus and Dyslipidemia: A Research Protocol for a Randomized Controlled Study

Background: Diabetes often accompanies with increase in triglyceride(TG) as well as small dense low density lipoprotein(sdLDL). Statins are difficult to completely correct this dyslipidemia. Xuezhikang, an extract of cholestin, is better than some statins in reducing TG. Under the condition of the similar decrease in LDL-cholesterol (LDL-C), it is not clear whether there is any difference in the effect of XZK and statins on TG reduction in patients with Type 2 DM(T2DM). Methods: An open-label multicenter study is planned to estimate the effects of Xuezhikang(1.2 g/d) and pravastatin(20 mg/d) on TG level and other blood lipids in T2DM patients with dyslipidemia and moderate to high risk of cardiovascular diseases. A total of 114 patients will be enrolled and randomly assigned (1:1 ratio) to accept Xuezhikang or pravastatin therapy for 6 weeks. The primary outcome measure is the change in fasting TG level after 6 weeks. The changes in other fasting lipids and postprandial lipids at 1, 2, 4 h after a nutritious breakfast will also be explored. The planned duration for enrollment is between November 2021 and December 2022. Conclusion: This study will evaluate the effect of 6-week treatment of Xuezhikang(1.2 g/d) and pravastatin(20 mg/d) on fasting TG level and other blood lipids in T2DM patients with dyslipidemia, which may provide a more optimized schedule for lipid control in patients with diabetes and dyslipidemia in primary prevention.

Change in Postprandial Level of Remnant Cholesterol After a Daily Breakfast in Chinese Patients With Hypertension

Background: Hypertension (HBP) is usually accompanied by hypertriglyceridemia that represents the increased triglyceride-rich lipoproteins and cholesterol content in remnant lipoproteins [i.e., remnant cholesterol (RC)]. According to the European Atherosclerosis Society (EAS), high RC (HRC) is defined as fasting RC ≥0.8 mmol/L and/or postprandial RC ≥0.9 mmol/L. However, little is known about postprandial change in RC level after a daily meal in Chinese patients with HBP.Methods: One hundred thirty-five subjects, including 90 hypertensive patients (HBP group) and 45 non-HBP controls (CON group), were recruited in this study. Serum levels of blood lipids, including calculated RC, were explored at 0, 2, and 4 h after a daily breakfast. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff point of postprandial HRC.Results: Fasting TG and RC levels were significantly higher in the HBP group (P < 0.05), both of which increased significantly after a daily meal in the two groups (P < 0.05). Moreover, postprandial RC level was significantly higher in the HBP group (P < 0.05). ROC curve analysis showed that the optimal cutoff point for RC after a daily meal to predict HRC corresponding to fasting RC of 0.8 mmol/L was 0.91 mmol/L, which was very close to that recommended by the EAS, i.e., 0.9 mmol/L. Fasting HRC was found in 31.1% of hypertensive patients but not in the controls. According to the postprandial cutoff point, postprandial HRC was found in approximately half of hypertensive patients and ~1-third of the controls.Conclusion: Postprandial RC level increased significantly after a daily meal, and hypertensive patients had higher percentage of HRC at both fasting and postprandial states. More importantly, the detection of postprandial lipids could be helpful to find HRC.

Important Food Sources of Fructose-Containing Sugars and Postprandial Lipids: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

Objectives Fructose providing excess calories has been shown to increase postprandial triglycerides (TAG). Whether this effect holds for different food sources of fructose-containing sugars is unclear. We conducted a systematic review and meta-analysis of controlled feeding trials on the effect of different food sources of fructose-containing sugars at different levels of energy control on postprandial blood lipids (NCT02716870). Methods MEDLINE, EMBASE, and Cochrane Library were searched through June 1st, 2020 for controlled feeding trials ≥7-days assessing the effect of food sources of fructose-containing sugars on postprandial lipids. Trial designs were prespecified based on energy control: substitution (energy matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients) trials. Independent reviewers extracted data and assessed risk of bias. Outcomes were postprandial TAG and apoB48. Certainty of evidence was assessed using GRADE. Results We included 29 trials (60 trial comparisons, N = 943) assessing 5 food sources (SSBs, fruit, sweets and desserts, added caloric sweetener and mixed sources) across 4 levels of energy control. Total fructose-containing sugars increased postprandial TAG in substitution (MD: 0.17 mmol/L [95% CI: 0.05, 0.30], P = 0.007), addition (0.38 mmol/L [0.13, 0.62], P = 0.003), and ad libitum (0.17 mmol/L [0.02, 0.31], P = 0.024) trials and increased apoB48 in addition trials (0.12 g/L [0.07, 0.18], P < 0.001).There was evidence of interaction by food source with SSBs increasing postprandial TAG and apoB48 in addition trials and mixed sources increasing postprandial TAG in ad libitum trials. The certainty of the evidence was “moderate” for SSBs increasing TAG in addition trials and mixed sources increasing TAG in ad libitum trials and “low” for all other comparisons. Conclusions Food source more than energy control appears to mediate fructose-containing sugars on postprandial lipids. Good evidence suggests that SSBs and mixed sources increase postprandial lipids while evidence is less certain for the lack of effect of other food sources. More high-quality trials of different food sources are needed. Funding Sources Primary: Diabetes Canada.

Change in Postprandial Level of Remnant Cholesterol After a Daily Breakfast in Chinese Patients With Hypertension

Background: Hypertension(HBP) is usually accompanied by hypertriglyceridemia that represents the increased triglyceride-rich lipoproteins(TRLs) and their cholesterol content(i.e. remnant cholesterol, RC). According to the European Atherosclerosis Society(EAS), high RC(HRC) is defined as fasting RC ≥ 0.8mmol/L or/and postprandial RC ≥ 0.9mmol/L. However, little was known about postprandial change in RC level after a daily meal in Chinese patients with HBP. Methods: One hundred and thirty-five subjects, including 90 hypertensive patients(HBP group) and 45 non-HBP controls(CON group), were recruited in this study. Serum levels of blood lipids, including calculated RC, were explored at 0, 2, and 4 h after a daily breakfast. Receiver operating characteristic(ROC) curve analysis was used to determine the cut-off point of postprandial HRC.Results: TG and RC levels increased significantly after a daily meal in two groups(P<0.05). However, postprandial RC level was significantly higher in HBP group( P<0.05). ROC curve analysis showed that the optimal cut-off point for RC after a daily meal to predict HRC in corresponding to fasting RC 0.8 mmol/L was 0.91 mmol/L, which was very close to that recommended by the EAS, i.e. 0.9mmol/L. Fasting HRC was found in 31.1% hypertensive patients but not in the controls. According to the postprandial cut-off point, postprandial HRC was found in about half of hypertensive patients and about one third of controls. Conclusion: Postprandial RC level increased significantly after a daily meal and hypertensive patients had higher percentage of HRC. More importantly, the detection of postprandial lipids is helpful to find HRC.

Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method

Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90–94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m2; fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-13C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis.