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Introduction: Cholesteryl ester transfer protein (CETP) inhibitors, initially developed for treating hyperlipidemia, have shown promise in reducing the risk of new-onset diabetes during clinical trials. This positions CETP inhibitors as potential candidates for repurposing in metabolic disease treatment. Given their oral administration, they could complement existing oral medications like sodium-glucose cotransporter 2 (SGLT2) inhibitors, potentially delaying the need for injectable therapies such as insulin. Methods: We conducted a 2x2 factorial Mendelian Randomization analysis involving 233,765 participants from the UK Biobank. This study aimed to evaluate whether simultaneous genetic inhibition of CETP and SGLT2 enhances glycemic control compared to inhibiting each separately. Results: Our findings indicate that dual genetic inhibition of CETP and SGLT2 significantly reduces glycated hemoglobin levels compared to controls and single-agent inhibition. Additionally, the combined inhibition is linked to a lower incidence of diabetes compared to both the control group and SGLT2 inhibition alone. Discussion: These results suggest that combining CETP and SGLT2 inhibitor therapies may offer superior glycemic control over SGLT2 inhibitors alone. Future clinical trials should investigate the potential of repurposing CETP inhibitors for metabolic disease treatment, providing an oral therapeutic option that could benefit high-risk patients before they require injectable therapies like insulin or glucagon-like peptide-1 (GLP-1) receptor agonists. [ABSTRACT FROM AUTHOR]

A pilot randomized, double-blind placebo-controlled trial was conducted to assess the effects of orticumab, a monoclonal antibody that targets oxidized low-density lipoprotein (oxLDL), on coronary inflammation in patients with psoriasis. The study found that treatment with orticumab reduced the Fat Attenuation Index (FAI) score, a measure of coronary inflammation, in patients with high levels of inflammation but had no effect in those with low levels of inflammation. The study suggests that targeting oxLDL with orticumab may reduce coronary inflammation and potentially lower the risk of fatal cardiac events in patients with elevated inflammation. However, further research is needed to fully understand the mechanisms and clinical implications of this treatment. [Extracted from the article]

This randomized, double-blind, controlled trial evaluated the influence of low fat, low saturated fat food products that contained free tall oil-based phytosterols (TOP) and oat [beta]-glucan (from whole oats and bran concentrate) on serum lipid concentrations in adults with mild-to-moderate hypercholesterolemia. After a 5-wk National Cholesterol Education Program Step I diet lead-in period, 112 subjects incorporated one of two treatments into their diets for 6 wk: food products (cereal, snack bar and beverage) that provided 1.8 g TOP and 2.8 g [beta]-glucan/d and contained [less than or equal to] 3.0 g total fat and [less than or equal to] 1.0 g saturated fat (TOP/ [beta]-glucan treatment) or similar control foods. The serum LDL cholesterol response from baseline to the end of study was significantly larger in the TOP/[beta]-glucan treated group than in the control group, in which there was no change (-3.7 vs. 0.4%; P = 0.013). Likewise, total cholesterol decreased in the TOP/[beta]-glucan treatment group and did not change significantly in the controls (-2.3 vs. 0.8%; P = 0.043). Serum HDL cholesterol and triglyceride responses did not differ between the groups. The results of this trial suggest that consumption of a group of low fat, TOP and [beta]-glucan- containing foods is a useful adjunct in the dietary management of hypercholesterolemia. KEY WORDS: * hypercholesterolemia * lipids * tall oil * phytosterols * [beta]-glucan

Inulin is a carbohydrate belonging to a class of compounds known as fructans. Because inulin is resistant to digestion in the upper gastrointestional tract it reaches the large intestine essentially intact, where it is fermented by indigenous bacteria. Thus, it may be classified as a soluble dietary fiber. Soluble fibers have been shown to modulate serum lipids. A recent study examined the effect of consuming three servings per day of inulin-containing foods, compared with the effect of similar foods without inulin, on serum lipid profiles among hypercholesterolemic men and women. In addition, the practicality of including 18 g/d of inulin in a low fat diet was investigated. The recent study randomized, double-blind, crossover trial with two 6-wk treatment periods, separated by a 6-wk washout. Men and women (n = 21) with baseline LDL increased significantly (7.4 and 12.3%, respectively) during the control phase. There were small, nonsignificant declines in total (1.3%) and LDL-C (2.1%) during the inulin phase. Thus, differences in response between periods (inulin - control) were significant (P < 0.05) for LDL-C (-14.4%) and total cholesterol (-8.7%). Mild gastrointestinal discomfort was more common during the inulin than the control food phase; however, the gastrointestinal side-effect profile of inulin was similar to that of other soluble fibers. Although it was not possible to draw firm conclusions, inulin may have blunted the hypercholesterolemic effects observed during consumption of control foods. Additional research will be required to confirm the possible lipid-modulating properties of dietary inulin in humans. KEY WORDS * inulin * oligosaccharide * dietary fiber * hyperlipidemia * lipoproteins

Dyslipidemia promotes atherosclerosis and causes cardiovascular diseases. Statins are potent lipid-lowering medications with a cardiovascular mortality benefit. They are generally safe and well tolerated but sometimes can be associated with side effects of variable severity. The most common side effect is statin-associated muscle symptoms. Uncommon side effects include new-onset diabetes mellitus and elevation in liver enzymes. These effects can lead to noncompliance and premature discontinuation of the medication. Hence, it is crucial to identify patients with true statin-associated side effects (SASE) to ensure optimal statin use. The appropriate evaluation of the patient before starting statins and proactive utilization of available diagnostic tests to rule out alternate etiologies mimicking adverse effects are essential for accurate diagnosis of SASE. In patients with true SASE, timely intervention with modified statin or non-statins is beneficial. Herein, we discuss key clinical trial data on statins and non-statins, and describe our center's approach toward patients with SASE. [ABSTRACT FROM AUTHOR]

This study was designed to determine whether a soluble dietary fiber supplement containing gum arabic and pectin in apple juice would lower serum lipids in 110 hypercholesterolemic men and women. Subjects were stabilized on an American Heart Association Phase I Diet for 8 wk. Those with elevated low density lipoprotein cholesterol levels, despite dietary modification, continued to follow the diet and were randomly assigned to receive 720 mL/d of apple juice containing 0 (control), 5, 9 or 15 g of gum arabic and pectin (4:1 ratio) for 12 wk, followed by a 6-wk apple juice-only washout phase. Serum lipid profiles, body weight and 3-day diet records were collected at 3-wk intervals. No significant differences among groups were observed in serum lipid responses during treatment or washout. During the treatment phase, mean serum total cholesterol and triglyceride concentrations increased by 3.5 and 28.5%, respectively (all groups combined, P < 0.0001). The high density lipoprotein cholesterol level did not change significantly from baseline in any group. During washout, mean total cholesterol concentration rose by an additional 2.4% (P < 0.05) compared with the value at the end of the treatment period, suggesting that the apple juice used to deliver the fiber supplement may have contributed to the adverse changes observed in the serum lipid profile. These findings do not support the hypothesized hypocholesterolemic effect of the gum arabic/pectin (4:1) mixture studied, but do underline the importance of selecting appropriate vehicles for delivery of dietary fiber mixtures. KEY WORDS: * hypercholesterolemia * water-soluble dietary * fiber * viscosity * fructose * humans