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Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition)

  • Yang Xiao , Bilian Yu , Chen Chao , Shuai Wang , Die Hu , Chao Wu , Yonghong Luo , Lingxiang Xie , Chenyu Li , Daoquan Peng ORCID logo EMAIL logo , Zhiguang Zhou ORCID logo EMAIL logo , Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association and National Society of Cardiometabolic Medicine
Published/Copyright: October 1, 2024
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Journal of Translational Internal Medicine
From the journal Journal of Translational Internal Medicine Volume 12 Issue 4

Abstract

Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts’ Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.

Key words: diabetes mellitus; type 1; type 2; dyslipidemia; atherosclerotic cardiovascular disease

The prevalence of diabetes in China is on a continuous upward trend. From 2011 to 2021, the number of diabetic patients in China increased from 90 million to 140 million.[1] Diabetes poses a tremendous threat and is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), a common complication and the primary cause of death in diabetic patients. The prevalence of dyslipidemia is significantly higher in diabetic patients, especially those with type 2 diabetes mellitus (T2DM) than in nondiabetic populations.[2] Dyslipidemia is the primary risk factor for the occurrence, development, and progression of ASCVD.

For diabetic patients, the primary goal of dyslipidemia prevention is to reduce the risk of ASCVD. However, there is currently a lack of guidelines or consensus specific to dyslipidemia related to atherosclerotic risk in all diabetic populations (type 1 diabetes mellitus [T1DM] and T2DM patients, patients aged ≥ 40 years, and patients aged < 40 years). In recent years, a large number of epidemiological and clinical intervention research results have been published, and related clinical research evidence continues to advance and accumulate. To better regulate the management of blood lipids in diabetic patients in China, the Endocrinology and Metabolism Branch of the Chinese Medical Doctor Association and the Cardiovascular Metabolism Committee of the National Cardiovascular Disease Expert Committee have brought together experts in the relevant fields to summarize domestic and international research progress and expert experience, and have formulated the Chinese Expert Consensus on Blood Lipid Management in Patients with Diabetes (2024 Edition). The evidence has been classified into Levels A, B, and C: Level A evidence is based on multiple randomized controlled trials or meta-analyses; Level B evidence is based on single randomized controlled trials or multiple nonrandomized controlled trials; and Level C evidence is based on expert consensus opinions, as well as small-scale research, retrospective research, and registry research results.

Lipid spectrum characteristics and cardiovascular harms in diabetic patients

Lipid spectrum characteristics of T2DM patients

Characteristics of dyslipidemia

The lipid spectrum of T2DM patients is mainly characterized by mixed dyslipidemia, including (1) fasting and postprandial hypertriglyceridemia and decreased levels of high-density lipoprotein cholesterol (HDL-C), (2) normal or slightly elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and (3) changes in low-density lipoprotein (LDL) particle subtypes, with an increase in small dense low-density lipoprotein (sdLDL) particles.[3,4,5]

Main causes of dyslipidemia

The main cause of dyslipidemia in T2DM patients is the presence of insulin resistance and relative insulin deficiency, which increase levels of free fatty acids in the body. This process results in an increase in the substrates available for the liver to synthesize very LDL (VLDL) and a decrease in the activity of insulin-dependent lipoprotein lipase (LPL), reducing the clearance of VLDL. These chances ultimately lead to increased levels of triglycerides (TG) and TG-rich lipoproteins (TRL). Poor blood glucose control in diabetic patients tends to further elevate TG levels. Hypertriglyceridemia stimulates the activity of the cholesterol ester transfer protein, which significantly increases the exchange of TG and cholesteryl esters between TRL and LDL and high-density lipoprotein (HDL), leading to an increase in TG content and a decrease in cholesteryl esters in LDL and HDL particles. Subsequently, when the TG in LDL and HDL is hydrolyzed by LPL and hepatic esterase, the process not only promotes sdLDL generation but also accelerates HDL metabolism, thereby decreasing HDL-C levels.[6,7]

Lipid spectrum characteristics of T1DM patients

T1DM patients with poor blood glucose control

The dyslipidemia of T1DM patients is usually similar to that of T2DM patients, and is characterized by mixed dyslipidemia, which mainly involves fasting and postprandial hypertriglyceridemia, accompanied by decreased HDL-C levels and increased sdLDL levels.[8] T1DM often starts with diabetic ketoacidosis (DKA). During DKA, due to severe insulin deficiency, the condition can manifest as a significant increase in TG levels, accompanied by a decrease in HDL-C and LDL-C levels. These lipid abnormalities can be quickly restored with sufficient insulin treatment.

T1DM patients with good blood glucose control

Due to the long-term use of exogenous insulin, which leads to peripheral hyperinsulinemia, the resulting condition can cause an increase in LPL activity, normal or reduced TG levels, and normal or elevated HDL-C levels. Hyperinsulinemia may upregulate LDL receptors, thereby promoting the clearance of LDL, and LDL-C levels may decrease.[9] However, some studies have shown that even if T1DM patients have good blood glucose control, their sdLDL levels are still higher than those of the normal population.[8]

Dyslipidemia in diabetic patients and ASCVD risk

LDL-C Levels

Among the cardiovascular risks brought about by dyslipidemia in diabetic patients, LDL-C is recognized as the primary risk factor. In 2008, the United Kingdom prospective diabetes study (UKPDS) on T2DM patients showed that for every 1.0 mmol/L increase in LDL-C levels, the risk of coronary artery events increased by 57%.[10] In 2016, the diabetes control and complications trial (DCCT) study on T1DM patients also suggested that after correcting for risk factors, such as age and glycated hemoglobin (HbA1c), for every 0.56 mmol/L increase in LDL-C levels, the risk of major adverse cardiovascular events (MACE) in T1DM patients increased by 7%.[11] In addition to higher LDL-C levels, diabetic patients also demonstrate elevated sdLDL levels. Because sdLDL circulates in the blood for a long time, it is likely to enter and stay underneath the arterial intima, and is ultimately phagocytosed by macrophages to form foam cells. Therefore, sdLDL has a stronger atherogenic effect than LDL.

Non-HDL-C Levels

Clinical epidemiological studies have shown that high TG levels are closely related to atherosclerosis in diabetic patients, making it one of the main factors in residual cardiovascular risk.[11,12,13] Increased TG levels in diabetic patients reflect an increase in TRL particles and non- HDL-C levels, and non-HDL-C indicates cholesterol in all atherogenic lipoprotein particles. Previous studies have shown that non-HDL-C levels can better predict ASCVD risk than LDL-C levels.[14] A meta-analysis suggested that non-HDL-C levels are associated with cardiovascular disease risk in male and female T2DM patients with hazard ratio values of 1.98 (95% confidence Interval [CI]: 1.70-2.30) and 1.63 (95% CI: 1.35-1.96), respectively.[15]

Epidemiology of lipid abnormalities related to ascvd in diabetic patients

T2DM patients

The prevalence of lipid abnormalities in Chinese T2DM patients is higher than in the general population, while rates of awareness, treatment, and control of lipid abnormalities are low. Patients often do not receive adequate treatment due to a lack of noticeable symptoms. In the China cardiovascular and metabolic research network-3B (CCMR-3B) study assessing cardiovascular risk factors in Chinese T2DM patients, a survey of lipid abnormalities in 25,817 outpatient T2DM patients from 104 hospitals nationwide showed that 42% of T2DM patients had lipid abnormalities, of which only 55% received lipid-lowering treatment. The proportion of patients who met all four lipid criteria (TC < 4.5 mmol/L, TG < 1.5 mmol/L, LDL-C < 2.6 mmol/L, and HDL-C > 1.04 mmol/L) was only 12%, with TC, TG, HDL-C, and LDL-C control rates of 36.1%, 46.6%, 71.9%, and 42.9%, respectively.[16] Another cross-sectional study of 4,807 T2DM patients aged 40-75 years from endocrinology clinics in 20 tertiary hospitals in major cities nationwide showed that the proportion of lipid abnormalities was as high as 67.1%; among T2DM patients with lipid abnormalities, the rates of awareness and treatment were 68.7% and 55.9%, respectively, and the rates of achieving LDL-C (< 2.6 mmol/L) and non- HDL-C (< 3.37 mmol/L) targets were 39.4% and 35.9%, respectively.[17]

The results of several national multicenter studies conducted in China are generally unoptimistic about the prevalence and control of lipid abnormalities in T2DM patients (Supplementary Table 1). These patients should pay special attention to the overall management of blood lipids and intervene in lipid abnormalities early to prevent ASCVD.

In addition to the overall high prevalence of lipid abnormalities among T2DM patients in China, there are also regional differences that may be related to different levels of economic development, natural conditions, and lifestyle habits in various parts of the country. In the Northwest, the prevalence of lipid abnormalities in T2DM patients is higher than in other regions, likely due to relatively poor economic levels and accessibility of care in this region, which inhibit patients’ health awareness, as well as factors such as high carbohydrate and high-fat diets.[18]

T1DM patients

Cardiovascular disease is one of the main causes of death in T1DM patients. A meta-analysis of 26 studies showed that compared with the nondiabetic population, the rates of death from coronary heart disease in male and female T1DM patients are 5.62 and 11.32 times higher than the standard, respectively.[19] Although ASCVD risk in T1DM patients is increasing, relatively few large-scale studies have been conducted on the prevalence, awareness, and treatment rates of lipid abnormalities in this population. A cross-sectional survey of 18,976 newly diagnosed diabetic patients in 24 of China’s provincial administrative regions included 1158 adult T1DM patients. The results showed that 29.0% of newly diagnosed adult T1DM patients had TG > 1.7 mmol/L, 50.3% had LDL-C > 2.6 mmol/L, and 39.6% had abnormal HDL-C (men < 1.0 mmol/L; women < 1.3 mmol/L, Supplementary Table 1).[20]

Ascvd risk stratification and treatment goals in diabetic patients

Cardiovascular risk assessment in diabetic patients

Since diabetes is an important independent risk factor of ASCVD, and lipid abnormalities have the greatest impact on ASCVD risk in diabetic patients, their lipid management target values are set more strictly than in nondiabetic populations. To emphasize lipid control in diabetic patients and assess ASCVD risk, it is recommended to divide diabetic patients into extremely high-risk, very high-risk, and high-risk groups (Table 1) according to the length of their disease course, whether they have ASCVD, and the condition of damage to the major target organ.

Table 1

ASCVD risk stratification in diabetic patients[21]

Risk stratification Evaluation indicators
Extremely high-risk Concurrent ASCVD
Very high-risk Without ASCVD, but with any of the following conditions: (1) ≥ 40 years old; (2) < 40 years old and with a long course of DM (T2DM course ≥ 10 years, T1DM course ≥ 20 years); (3) < 40 years old and with ≥ 3 risk factors*; (4) < 40 years old and with target organ damage△
High-risk < 40 years old and absence of characteristics in the extremely high-risk and very high-risk group

  1. ASCVD: atherosclerotic cardiovascular disease; T2DM: type 2 diabetes mellitus; HDL-C: high-density lipoprotein cholesterol; CKD: chronic kidney disease. ASCVD refers to a clear diagnosis of coronary atherosclerotic cardiovascular disease, including past or current diagnosis of acute coronary syndrome (myocardial infarction or unstable angina), stable angina, or coronary artery revascularization (percutaneous coronary intervention, stent implantation, or coronary artery bypass grafting); a clear diagnosis of stroke and transient ischemic attack; and a clear diagnosis of peripheral arterial disease. *Risk factors include: (1) smoking; (2) hypertension; (3) obesity (body mass index ≥ 28 kg/m2); (4) family history of early onset coronary heart disease (male < 55 years old; female < 65 years old); (5) non-HDL-C ≥ 4.9 mmol/L; (6) lipoprotein (a) ≥ 300 mg/L;[22,23] (7) high-sensitivity C-reactive protein ≥ 2.0 mg/L.[24,25] The risk factor levels stated here all reflect values before intervention. △Target organ damage includes CKD Stages 3b and above (estimated glomerular filtration rate < 45 mL/min/1.73 m2), proteinuria (urinary albumin/creatinine ratio > 300 mg/g), an ankle-brachial index of < 0.9, and left ventricular systolic/diastolic dysfunction.

Lipid intervention targets and target values in diabetic patients

Lipid intervention targets

The lipid intervention targets and target values for diabetic patients are shown in Table 2.

Table 2

Recommended targets and target values of lipid intervention in diabetic patients

Recommendations Recommendation level
LDL-C and non-HDL-C are both primary lipid-lowering targets for ASCVD risk control Level A
For extremely high-risk patients, the LDL-C goal is < 1.4 mmol/L, and it should be reduced by > 50% from baseline[26,27,28] Level A
For very high-risk patients, the LDL-C goal is < 1.8 mmol/L, and it should be reduced by > 50% from baseline[29] Level A
For high-risk patients, the LDL-C goal is < 2.6 mmol/L Level A
The non-HDL-C target value is the corresponding LDL-C target value + 0.8 mmol/L Level B
ApoB can be used as a secondary target for ASCVD risk control in diabetic patients. For extremely high-risk, very high-risk, and high-risk patients, the ApoB target values are less than 0.7, 0.8, and 0.9 g/L respectively Level C

  1. LDL-C: low-density lipoprotein; HDL-C: high-density lipoprotein cholesterol; ASCVD: atherosclerotic cardiovascular disease; ApoB: apolipoprotein B.

LDL-C

Most lipid-lowering intervention studies use LDL-C as an indicator to observe the relationship between lipid-lowering effects and decreased ASCVD risk. A meta-analysis by the Cholesterol Treatment Trialists’ Collaboration showed that for each 1.0 mmol/L decrease in LDL-C, the risks of MACE, cardiovascular death, and ischemic stroke in diabetic patients decreased by 21%, 13%, and 21%, respectively, regardless of baseline LDL-C levels.[29]

Several clinical studies have shown that T2DM patients aged 40-75 can benefit from taking statin drugs. In primary prevention studies, compared with placebos, moderate-intensity statins can significantly reduce the risk of ASCVD or all-cause death by lowering LDL-C to less than 2.6 mmol/L.[30,31] T2DM patients with multiple ASCVD risk factors or target organ damage are considered to have ASCVD. It is recommended that LDL-C be reduced by more than 50% from baseline for these diabetic patients, and the LDL-C target value should be set at less than 1.8 mmol/L.[32,33,34] In secondary prevention studies, stratified analysis of several intensified lipid-lowering studies that used statin drugs in combination with ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors showed that reducing LDL-C to below 1.4 mmol/L can further reduce ASCVD risk among T2DM patients and that ASCVD patients with T2DM can benefit significantly from intensified lipid-lowering treatment.[26,27,28]

Lipid-lowering interventions for T1DM patients are currently understudied. In the heart protection study (HPS), the benefits of statin treatment in T1DM patients over 40 years old were found to be similar to those in T2DM patients,[30] so it is recommended that the lipid-lowering targets and target values for T1DM patients be the same as those for T2DM patients.

Clinical evidence for the cardiovascular benefits of lipid-lowering treatment for T2DM and T1DM patients under 40 years of age is also scarce. Considering that, despite the low 10-year cardiovascular risk for diabetic patients under 40 years old, the lifetime risk is high, the LDL-C of diabetic patients under 40 years old should also be maintained at a lower level. At this time, the course of diabetes, other cardiovascular risk factors, and the condition of damage to the target organ should be considered comprehensively. Statin treatment should be initiated in a timely manner after a thorough discussion of treatment risks and benefits.[35,36]

Non-HDL-C

Using only LDL-C as a lipid-lowering target for diabetic patients may lead to underestimating ASCVD risk, and non- HDL-C is also a primary lipid-lowering target that diabetic patients must manage. Non-HDL-C is the cholesterol in plasma TC minus the cholesterol in HDL, which represents the cholesterol in all atherogenic lipoprotein particles. Whether or not statin therapy is administered, non-HDL-C reflects ASCVD risk better than LDL-C.[14,37,38] A metaanalysis found that the correlation between the reduction of both non-HDL-C and lowered ASCVD risk was stronger than that between the reduction of LDL-C and lowered ASCVD risk.[39] Currently, the Friedewald formula is widely used to calculate LDL-C levels; however, when plasma TG > 4.5 mmol/L or LDL-C < 1.8 mmol/L, this method faces certain challenges.[40,41] Since lipid abnormalities in diabetic patients are characterized by hypertriglyceridemia, using LDL-C as the primary target has certain limitations. Calculating non-HDL-C is simple, and the results are stable and minimally affected by plasma TG levels. Therefore, along with LDL-C, non-HDL-C is suitable for use as a primary lipid-lowering target for diabetic patients.

Apolipoprotein B (ApoB)

Regardless of particle size, all atherogenic lipoprotein particles contained one molecule of ApoB. Theoretically, ApoB detection more accurately reflects the number of atherogenic lipoprotein particles. Diabetic patients are prone to hypertriglyceridemia, a condition in which ApoB content is high but LDL-C levels not reach the high threshold. Therefore, simultaneous measurement of ApoB and LDL-C levels is a useful method for assessing ASCVD risk in diabetic patients.[14,39] Recent studies on more intense lipid-lowering methods suggest that after controlling for the effects of LDL-C and non-HDL-C, reducing ApoB can independently predict a decrease in ASCVD risk.[42] ApoB testing is currently expensive and not widely used in clinical contexts; thus, it should be considered a secondary target for ASCVD risk interventions in diabetic patients.

Potential Lipid-Modifying Targets

Abnormalities in TG, lipoprotein (a) (Lp [a]), and HDL-C are all associated with an increased ASCVD risk. However, there is currently a lack of strong evidence to support drug intervention based on these lipid indicators as a means of reducing ASCVD risk. Therefore, they may be potential lipid-modifying targets for ASCVD risk management in diabetic patients and require clinical attention.

TG

Hypertriglyceridemia is common in diabetic patients. Most plasma TG is located in the TRL, and diabetic patients show an increase in remnant cholesterol and non-HDL-C levels. For this reason, a mild to moderate increase in TG levels increases the risk of ASCVD. Increased TG levels and increased remnant cholesterol in TRL are risk factors for myocardial infarction.[43] Lifestyle interventions and optimized hypoglycemic drugs can reduce the TG levels and ASCVD risk of diabetic patients,[44,45,46,47] but controversy remains over whether lipid-lowering drugs targeting TG (e.g., fibrates, niacin, and prescription fish oil preparations) can reduce the risk of MACE in high-risk ASCVD diabetic patients.[48,49,50,51,52,53] Therefore, TG is currently recommended solely as a potential indicator of ASCVD risk in diabetic patients.

LP (a)

In T2DM patients, elevated Lp (a) levels are independent risk factors for coronary heart disease and ischemic stroke.[32,54,55,56] For diabetic patients with stable angina, elevated Lp (a) levels significantly increase the risk of MACE.[57] It is recommended that adults have their Lp (a) levels checked at least once in their lifetime.[32,54,55,56] Based on research data obtained from Chinese populations,[57,58,59,60,61,62] it is suggested that Lp (a) > 300 mg/L be used as a cutoff value for increased ASCVD risk.[63]

HDL-C

One of the characteristics of lipids in diabetic patients is a reduction in HDL-C levels. Although low HDL-C levels are independent risk factors for ASCVD, the predictive effect of HDL-C on coronary heart disease is influenced by HDL function, and HDL function predicts ASCVD risk better than HDL-C levels. Moreover, genetic evidence has not yet proven a relationship between HDL-C levels and ASCVD risk, and treatment to raise HDL-C levels via medication has not resulted in cardiovascular event risk reduction. Therefore, HDL-C has not been included in lipid intervention targets for ASCVD risk management and is used only as a management indicator.[32,64]

Lipid-lowering treatment strategies for diabetic patients

The lipid-lowering standardization strategy for diabetic patients also includes lifestyle interventions and drug treatment. Specific recommendations are shown in Table 3.

Table 3

Recommendations for lipid-lowering strategies for diabetic patients

Recommendations Recommendation level
All diabetic patients should engage in lifestyle interventions as a basic lipid-lowering treatment[65,66,67,68] Level A
Moderate-intensity statins should be used for initial pharmaceutical lipid-lowering treatment in diabetic patients[30,69,70,71,72,73,74,75,76,77,78] Level A
When the use of moderate-intensity statins does not reach the LDL-C goal in diabetic patients, cholesterol absorption inhibitors should be added to the treatment[79,80] Level A
When the combined use of moderate-intensity statins and cholesterol absorption inhibitors does not reach the LDL-C goal in diabetic patients, PCSK9 inhibitors should be added to the treatment[81,82] Level A
To achieve > 50% LDL-C reduction in extremely high-risk and very high-risk patients, directly initiating treatment with moderate-intensity statins combined with cholesterol absorption inhibitors may be considered Level C
For extremely high-risk diabetic patients with high baseline LDL-C levels*, where it is expected that reaching the LDL-C goal using moderate-intensity statins combined cholesterol absorption inhibitors will be difficult, directly initiating moderate-intensity statins combined with PCSK9 inhibitors may be considered[81,82] Level B
For patients who cannot tolerate statins, the use of cholesterol absorption inhibitors, as well as PCSK9 inhibitors should be considered[28,83,84,85] Level C
If the non-HDL-C goal is not achieved after the LDL-C goal is reached and TG levels are elevated, further reinforcement of lifestyle management (e.g., diet, exercise, weight loss) and optimizing glucose-lowering and TG-lowering strategies should be considered△ Level A

  1. LDL-C: low-density lipoprotein cholesterol; PCSK9: proprotein convertase subtilisin/kexin type 9; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; SGLT2i, sodium-glucose cotransporter-2 inhibitors. *High baseline LDL-C levels: LDL-C ≥2.6 mmol/L for those taking statins and LDL-C ≥4.9 mmol/L for those not taking statins. △To optimize glucose-lowering and TG-lowering strategies, prioritize the use of glucose-lowering drugs that can improve the lipid spectrum or cardiac prognosis (e.g., metformin, SGLT2i, and glucagon-like peptide-1 receptor agonists), and use TG-lowering drugs when necessary.

Lifestyle intervention

For T1DM and T2DM patients, lifestyle intervention is the foundation of lipid management. In addition to lowering lipid levels, lifestyle changes also benefit blood pressure, blood sugar, and overall cardiovascular health. Healthy, well-regulated lifestyle interventions are discussed below.

Healthy Balanced Diet

Limiting one’s intake of total fat, cholesterol, trans fatty acids, and saturated fatty acids is an important measure for preventing hyperlipidemia and ASCVD.[36,73,86] Dietary fat intake should not exceed 20%-30% of total daily calories, and saturated fatty acid intake should not exceed 10% of total daily calories. Diabetic patients with high cholesterol should minimize their intake of saturated fatty acids to less than 7% of total daily calories, avoid cholesterol-rich food (e.g., animal offal), and limit their daily cholesterol intake to less than 300 mg. Trans fatty acids (e.g., hydrogenated vegetable oils) should account for less than 1% of total daily calories (i.e., not exceeding 2 g/day. The intake of unsaturated fatty acids (e.g., vegetable oils), especially foods rich in ω-3 polyunsaturated fatty acids, should be increased.[87]

Adopting the mediterranean diet,[88] the dietary approaches to stop hypertension diet, or other dietary patterns that increase the consumption of vegetables, fruits, coarse fiber foods, and fish rich in ω-3 fatty acids is recommended. Dietary fiber intake should be no less than 25-30 g/day or 14 g/1000 kcal, and it is recommended to consume 35 g/day. The proportion of carbohydrates and proteins should be the same as for ordinary diabetic patients. In addition to limiting fatty acid intake, patients with high TG levels should pay particular attention to reducing the intake of refined carbohydrates and increasing the intake of fiber-rich, low-sugar foods (e.g., whole grains).

Moderate exercise

At least 150 min of moderate-intensity exercise should be conducted weekly according to individualized exercise prescriptions. Those advised to lose weight should increase their current weekly exercise intensity and duration. However, exercise is not suitable when fasting blood glucose is higher than 16.7 mmol/L, in cases of recurrent hypoglycemia or large fluctuations in blood glucose, acute complications such as DKA, concurrent acute infections, proliferative retinopathy, severe kidney disease, and severe cardiovascular and cerebrovascular diseases (e.g., unstable angina, severe arrhythmia, or transient ischemic attack). It is recommended to gradually resume exercise once the condition stabilizes.[73]

Maintain ideal weight

It is recommended to control total calorie intake and increase exercise to maintain a body mass index of < 24 kg/m2. For those who are overweight or obese, the recommended initial weight loss goal is a 5%-10% reduction in body weight in 3-6 months. Those who are underweight should restore and maintain their ideal weight over the long term through a reasonable nutritional plan.[73]

Controlling other risk factors

It is recommended that smokers quit smoking (including e-cigarettes). Those without a habit of drinking are advised not to start drinking, and those with a habit of drinking should limit alcohol intake (men < 25 g/day; women < 15 g/day). Alcohol consumption plays a significant role in increasing TG, and those with high TG should strictly limit alcohol intake.

In summary, regardless of the type of lipid abnormality, maintaining a healthy, balanced diet is recommended as a lifestyle intervention. For patients who need to better control TC and LDL-C, regular exercise and weight control are suggested on the basis of a healthy diet. It is recommended that patients who need to increase HDL-C should quit smoking and those who need to lower TG should limit alcohol consumption, exercise regularly, and manage their weight.[68]

Cholesterol-lowering drug treatment strategy

Although healthy lifestyle interventions are the foundation of lipid-lowering treatment for all adult diabetic patients, it is often difficult to reach lipid-lowering targets through lifestyle interventions alone. Therefore, it is recommended that drug treatment be initiated alongside lifestyle interventions to achieve lipid-lowering targets as early as possible, thereby reducing the risk of ASCVD events.

The cholesterol-lowering treatment strategy and process for diabetic patients are shown in Figure 1. Cholesterol-lowering drugs can be divided into three major categories according to their mechanisms: statins, cholesterol absorption inhibitors, and PCSK9 inhibitors. Other cholesterol-lowering drugs used in clinical practice include Xuezhikang, bile acid sequestrants, probucol, Zhibitai, and policosanol. This consensus focuses on the three cholesterol-lowering drugs most commonly used in clinical practice (Table 4).

Figure 1 Cholesterol-lowering strategies and procedures for diabetic patients. ASCVD: atherosclerotic cardiovascular disease; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; T2DM: type 2 diabetes mellitus; T1DM: type 1 diabetes mellitus; PCSK9: proprotein convertase subtilisin/ kexin type 9; TG: triglyceride; IPE: icosapent ethyl; SGLT2i, sodium-glucose cotransporter-2 inhibitors. *Risk factors include: (1) smoking; (2) hypertension; (3) obesity (body mass index ≥ 28 kg/m2); (4) family history of early onset coronary heart disease (male < 55 years old; female < 65 years old); (5) non-HDL-C ≥ 4.9 mmol/L; (6) lipoprotein (a) ≥ 300.0 mg/L;[22,23] (7) high-sensitivity C-reactive protein ≥ 2.0 mg/L.[24,25] The risk factor levels stated here all reflect values before intervention. △Target organ damage includes CKD Stages 3b and above (estimated glomerular filtration rate < 45 mL/min/1.73 m2), proteinuria (urinary albumin/creatinine ratio > 300 mg/g), an ankle-brachial index of < 0.9, and left ventricular systolic/diastolic dysfunction. ▲Moderate-intensity statins refer to a daily dose that can reduce LDL cholesterol by 25%-50%. #Moderate-intensity statins combined with cholesterol absorption inhibitors may choose statin/ ezetimibe single-pill combination. △Optimize blood glucose management includes enhancing diet control, exercise, and weight loss and/or initiating glucose-lowering drugs that improve the lipid spectrum or cardiac prognosis, such as metformin, SGLT2i, and glucagon-like peptide-1 receptor agonists. ◆ω-3 fatty acids refer to fish oil preparations containing eicosapentaenoic acid and docosahexaenoic acid.
Figure 1

Cholesterol-lowering strategies and procedures for diabetic patients. ASCVD: atherosclerotic cardiovascular disease; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; T2DM: type 2 diabetes mellitus; T1DM: type 1 diabetes mellitus; PCSK9: proprotein convertase subtilisin/ kexin type 9; TG: triglyceride; IPE: icosapent ethyl; SGLT2i, sodium-glucose cotransporter-2 inhibitors. *Risk factors include: (1) smoking; (2) hypertension; (3) obesity (body mass index ≥ 28 kg/m2); (4) family history of early onset coronary heart disease (male < 55 years old; female < 65 years old); (5) non-HDL-C ≥ 4.9 mmol/L; (6) lipoprotein (a) ≥ 300.0 mg/L;[22,23] (7) high-sensitivity C-reactive protein ≥ 2.0 mg/L.[24,25] The risk factor levels stated here all reflect values before intervention. △Target organ damage includes CKD Stages 3b and above (estimated glomerular filtration rate < 45 mL/min/1.73 m2), proteinuria (urinary albumin/creatinine ratio > 300 mg/g), an ankle-brachial index of < 0.9, and left ventricular systolic/diastolic dysfunction. ▲Moderate-intensity statins refer to a daily dose that can reduce LDL cholesterol by 25%-50%. #Moderate-intensity statins combined with cholesterol absorption inhibitors may choose statin/ ezetimibe single-pill combination. △Optimize blood glucose management includes enhancing diet control, exercise, and weight loss and/or initiating glucose-lowering drugs that improve the lipid spectrum or cardiac prognosis, such as metformin, SGLT2i, and glucagon-like peptide-1 receptor agonists. ◆ω-3 fatty acids refer to fish oil preparations containing eicosapentaenoic acid and docosahexaenoic acid.

Table 4

Types, usage, and adverse effects of commonly used cholesterol-lowering drugs in clinical practice*

Types Medication dosage Impact on blood sugar Adverse effects
Moderate-intensity statins△ Atorvastatin 10-20 mg, once/day Risk of new-onset diabetes or elevated glycosylated hemoglobin, especially for high-intensity and lipophilic statins Abnormal liver function, myopathy, gastrointestinal symptoms, headaches, etc.
Rosuvastatin 5-10 mg, once/day
Fluvastatin 40-80 mg, once/day
Lovastatin 40 mg, once/day
Simvastatin 20-40 mg, once/day
Pravastatin 40 mg, once/day
Pitavastatin 1-4 mg, once/day
Cholesterol absorption inhibitors Xuezhikang▲ 0.6 g, twice/day Neutral effects Rare, similar to the abovementioned statins
Ezetimibe 10 mg, once/day Neutral effects Headache, gastrointestinal Hybutimibe 10-20 mg, once/day Neutral effects symptoms, insomnia, rash, etc.
Hybutimibe 10-20 mg, once/day Neutral effects
PCSK9 inhibitors Evolocumab 140 mg, once/2 weeks or 420 mg, once/month Neutral effects Injection site reactions, hypersensitivity reactions, and flulike symptoms, etc.
Alirocumab 75-150 mg, once/2 weeks Neutral effects
Inclisiran 284 mg, once/6 months Neutral effects
Others Zhibitai 0.24-0.48 g, twice/day Neutral effects Rare
Policosanol 10-20 mg, once/day Neutral effects Rare
Probucol 0.5 g, twice/day Neutral effects Prolonged QT interval, headache, gastrointestinal symptoms, insomnia, rash, etc.

  1. PCSK9: proprotein convertase subtilisin/kexin type 9; LDL: low-density lipoprotein. *Refer to the chinese lipid management guidelines (2023).[68] △Moderateintensity statins refer to a daily dose that can reduce LDL cholesterol by 25%-50%. ▲The main component of Xuezhikang is a natural compound of 13 statins.

Statins

Statins are the most common drugs used in cholesterol-lowering treatments. By inhibiting the rate-limiting enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, statins reduce cholesterol synthesis, thereby upregulating LDL receptors on the surface of liver cells and encouraging liver cells to take up and clear LDL particles in the blood, thereby significantly lowering serum TC, LDL-C, and ApoB levels. Numerous studies have confirmed that statins can significantly reduce ASCVD events in diabetic patients (Supplementary Table 2), and the clinical benefits are linearly correlated with the extent of LDL-C reduction. However, when statin doses are doubled, the reduction in LDL-C increases by just 6%, while potential adverse reactions, including liver function damage, myopathy, and newly diagnosed diabetes, increase.

Chinese populations tolerate high-dose statins less well than Western populations. Therefore, in addition to concerns about safety, efficacy, and treatment costs, poor tolerance contraindicates the use of high-intensity statins, and moderate-intensity statins are instead recommended for use as part of an initial lipid-lowering plan.[30,69,70,71,72,73,74,75,76,77,78] The cholesterol-lowering potential of different types and doses of statins varies. Moderate intensity refers to a daily dose of statin capable of reducing LDL-C by 25%–50% (Table 4). Currently, lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, and pitavastatin are used in clinical practice in China. The lipid-lowering mechanism of Xuezhikang, a lipid-lowering medicine with a Chinese patent, is similar to that of statins. The China coronary secondary prevention study (CCSPS) subgroup analysis of diabetes confirmed that Xuezhikang capsules lowers LDL-C levels effectively, improve the lipid spectrum, significantly reduce the incidence of cardiovascular events in diabetic patients and the mortality rate of coronary heart disease, and have fewer side effects.[89] If LDL-C does not reach the target within 4-6 weeks of treatment with moderate-intensity statins, combination therapy with cholesterol absorption inhibitors, as well as PCSK9 inhibitors should be considered.[26,27,28,79,80,81,82]

Cholesterol absorption inhibitors

Cholesterol absorption inhibitors include ezetimibe and hybutimibe, which work mainly by acting selectively on Niemann-Pick C1-like protein 1 on the brush border of the small intestinal mucosa and inhibiting the intestinal absorption of dietary and biliary cholesterol. Studies have confirmed that when ezetimibe is used in combination with different types of statins, LDL-C can be further reduced by about 18%-20%, thus making the total LDL-C reduction greater than 50% without increasing the risk of adverse reactions to statins.[79,80,90] Subgroup analysis of the improved reduction of outcomes: vytorin efficacy international trial (IMPROVE-IT) study showed that a combination of statins and ezetimibe may enhance benefits for patients with acute coronary syndrome complicated by diabetes by reducing the risk of myocardial infarction, ischemic stroke, and major endpoint events by 24%, 29%, and 15%, respectively.[26,79]

Additionally, subgroup analyses of other clinical studies suggest that combining ezetimibe with statins can reduce adverse cardiovascular events in diabetic patients. A study based on an East Asian population showed that in ASCVD patients, the single-pill combination of rosuvastatin and ezetimibe (10 mg and 10 mg) had a higher LDL-C target achievement rate and better tolerance than high-intensity statin monotherapy. In terms of achieving further reductions in the risk of cardiovascular and cerebrovascular events, the single-pill combination of rosuvastatin and ezetimibe is not inferior to high-intensity statin monotherapy,[80] and the subgroup analysis conducted in this study showed that the efficacy and safety of this combined lipid-lowering treatment are retained in diabetic patients.[91] A single-pill combination of statin/ezetimibe may improve patient compliance. Therefore, to achieve an LDL-C reduction of > 50% in extremely high-risk and very high-risk patients, treatment that combines moderate-intensity statins and cholesterol absorption inhibitors should be initiated. Primary evidence for the use of cholesterol absorption inhibitors in cholesterol-lowering treatment in diabetic patients is shown in Supplementary Table 3.

PCSK9 inhibitors

PCSK9 inhibitors lower LDL-C levels primarily by inhibiting LDL receptor degradation, thereby increasing the clearance of serum LDL. Currently approved PCSK9 inhibitors include two fully human monoclonal antibodies, alirocumab and evolocumab, which bind competitively to PCSK9 in circulation, and inclisiran, a small interfering RNA targeting PCSK9. Research results show that PCSK9 inhibitors (including evolocumab, alirocumab, and inclisiran) can significantly reduce the average LDL-C level of diabetic patients within a range of 50%-70%.[92] At the same time, PCSK9 inhibitors also significantly improve other lipid components, reducing TG levels by 10%-30%, ApoB levels by 35%-41%, and Lp (a) levels by 20%-30%.[93,94,95] The results of the BANTING[96] and BERSON studies[97,98] further confirm that PCSK9 monoclonal antibodies can help high-risk and very high-risk ASCVD T2DM patients quickly achieve lipid control, with good safety and tolerability, without affecting blood glucose levels.

Several large-scale clinical studies, including the further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk (FOURIER) study,[81] the ODYSSEY OUTCOMES diabetes subgroup analysis,[27] and the ODYSSEY DM-INSULIN subgroup analysis,[99] confirm that PCSK9 inhibitors can significantly reduce the risk of cardiovascular events in diabetic patients and are positively correlated with LDL-C reduction.[93,100] Therefore, for diabetic patients with ASCVD and high baseline LDL-C levels (LDL-C ≥ 4.9 mmol/L for patients not using statins and LDL-C ≥ 2.6 mmol/L for patients using statins), or when it is expected that combining statins and cholesterol absorption inhibitors will be difficult to achieve, the combination of PCSK9 inhibitors may be considered.[81,82] The main evidence for the use of PCSK9 inhibitors in cholesterol-lowering treatment in diabetic patients is shown in Supplementary Table 4.

For patients who cannot tolerate statins, typically indicated by clinical adverse reactions or abnormal laboratory test indicators related to statins following their administration, cholesterol absorption inhibitors and PCSK9 inhibitors should also be considered.[28,83,84,85] In addition to these two types of non-statin drugs, a new lipid-lowering drug, bempedoic acid,[101,102] can reduce LDL-C levels by up to 30% by inhibiting adenosine triphosphate-citrate lyase and hepatic cholesterol synthesis.[103,104] The CLEAR-Outcomes study confirmed that bempedoic acid can reduce the risk of MACE with overall good safety and tolerability without leading to related myopathy, abnormal blood glucose, or other adverse reactions.[102] Bempedoic acid may also be an option for future statin-intolerant patients. Zhibitai, policosanol, and other well-tolerated cholesterol-lowering drugs may also be used as alternative drugs when statins are not tolerated.

After using the abovementioned cholesterol-lowering drugs to achieve the LDL-C target in diabetic patients, it is important to clarify whether non-HDL-C targets have been reached. Non-HDL-C contains LDL-C and remnant cholesterol, and an increase in remnant cholesterol levels in diabetic patients is closely related to increased TG levels; thus, the primary method of reducing remnant cholesterol levels is to reduce TG levels. The most recommended measures for reducing TG levels in diabetic patients include strict lifestyle intervention, optimized blood glucose management, and the use of TG-lowering drugs when necessary.

TG-lowering treatment strategy

The TG management strategy for diabetic patients is shown in Table 5.

Table 5

Recommendations for TG management strategies for diabetic patients

Recommendations Recommendation level
Correct other secondary causes of hypertriglyceridemia (including hypothyroidism, nephrotic syndrome, chronic liver disease, and drugs that raise TG levels) Level A
Enhance lifestyle management (e.g., diet, exercise, avoiding alcohol, and weight loss) Level A
Optimize glucose-lowering strategies (prioritizing the use of glucose-lowering drugs that improve the lipid spectrum or cardiac prognosis, such as metformin, SGLT2i, and GLP-1 RA) Level B
Based on treatment with moderate-intensity statins, if TG levels are still 2.3-5.6 mmol/L, it is recommended to combine treatment with a large dose of IPE (2 g, twice/day) to reduce ASCVD risk[51,105] Level B
Based on treatment with moderate-intensity statins, if TG levels are still 2.3-5.6 mmol/L, a combined treatment with high-purity ω-3 fatty acids* or with fenofibrate may be considered to reduce ASCVD risk[48,49] Level C
When TG is > 5.6 mmol/L, fibrates, high-purity ω-3 fatty acids*, or niacin drugs can be used to reduce the risk of pancreatitis[106] Level C

  1. TG: triglyceride; SGLT2i: sodium-glucose cotransporter-2 inhibitors; GLP-1 RA: glucagon-like peptide-1 receptor agonists; ASCVD: atherosclerotic cardiovascular disease; IPE. icosapent ethyl. *ω-3 fatty acids refer to fish oil preparations containing eicosapentaenoic acid and docosahexaenoic acid.

When diabetic patients have hypertriglyceridemia, it is necessary to evaluate other secondary causes of hypertriglyceridemia, including hypothyroidism, nephrotic syndrome, chronic liver disease, and drugs that raise TG levels. Correcting the above secondary causes should be undertaken alongside strict lifestyle management. Studies show that improving diet and exercise, weight loss, and other lifestyle changes not only help control blood sugar but also lower TG levels and may reduce LDL-C and non-HDL-C levels by as much as 5%-15%.[65,107] Metabolic surgery, an invasive weight management strategy, can significantly reduce TG and non-HDL-C levels, as well as the risk of ASCVD.[108,109]

If diabetic patients’ blood sugar, which can also affect TG and non-HDL-C control, does not reach the target levels even with strict lifestyle management, further optimization of the glucose-lowering strategy should be considered to reduce TG levels, thereby helping non-HDL-C to reach the goal.[110,111,112] The optimized glucose-lowering strategy recommends prioritizing the use of glucose-lowering drugs that can improve the lipid spectrum or cardiac prognosis,[113] such as metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). These three types of hypoglycemic drugs, each with specific characteristics, can all improve the lipid spectrum and can be used clinically according to the specific situation of each patient. Metformin and GLP-1 RA have obvious advantages in cases where weight loss is indicated and can reduce the TC, TG, and LDL-C levels of diabetic patients.[114,115] SGLT2i promotes the breakdown and oxidation of fatty acids, reduces fat synthesis and TG levels, increases HDL-C levels,[110,111,116] and also functions to prevent heart failure.

According to the results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCEIT) and the Japan EPA lipid intervention study (JELIS) studies, if lifestyle changes and glucose-lowering strategy optimization do not sufficiently reduce TG levels to < 2.3 mmol/L, adding a large dose of icosapent ethyl (IPE) to the lipid-lowering treatment plan is recommended to reduce the risk of ASCVD.[51,105] Since fenofibrate only shows cardiovascular benefits in a subgroup analysis of the action control cardiovascular risk diabetes (ACCORD) study,[49] and high-purity ω-3 fatty acids (containing EPA and docosahexaenoic acid [DHA]) only shows a trend to reduce ASCVD risk in a meta-analysis,[48] fenofibrate and high-purity ω-3 fatty acids are indicated as second-choice drugs, after IPE, for managing ASCVD risks.

Epidemiological research suggests that when TG levels are significantly increased (> 5.6 mmol/L), the risk of pancreatitis increases.[106] A combination treatment plan of fibrates, large doses of high-purity ω-3 fatty acids, or niacin drugs can be used[106] to reduce TG levels as much as possible while reducing the risk of pancreatitis.

In recent years, new TG-lowering drugs have emerged, including angiopoietin-like protein 3 inhibitors (e.g., Evinacumab, a fully human monoclonal antibody) and apolipoprotein C3 inhibitors (e.g., Volanesorsen, an antisense oligonucleotide). Clinical research suggests that both the above drugs can reduce TG levels significantly while also reducing non-HDL-C and ApoB levels,[117,118] which is promising for improving overall cardiovascular health.

Treatment strategy for reducing Lp (a)

New drugs for reducing Lp (a) mainly include an antisense oligonucleotide of apo-Lp (a) (Pelacarsen) and small interfering RNAs of apo-Lp (a) (Olpasiran and SLN360). Although Phase I studies show that both can significantly reduce Lp (a) levels, large-scale international multicenter clinical studies with cardiovascular benefit endpoints are still ongoing. Therefore, no drugs for the treatment of Lp (a) are currently used in clinical contexts. For patients with elevated Lp (a) levels, further reducing cholesterol levels remains the primary focus. Of the cholesterol-lowering drugs discussed above, PCSK9 inhibitors can reduce the Lp (a) levels of diabetic patients by about 20%-30%, significantly reduce the occurrence of MACE and are available for clinical use.[119] Although niacin drugs and ApoB100 inhibitor mipomersen can also reduce Lp (a) levels by 20%-30%, both drugs lack evidence of cardiovascular benefits, and mipomersen was no longer recommended for use after being withdrawn from the market in 2019.[120,121,122]

The impact of lipid-lowering drugs on blood sugar and treatment strategies

Currently, the mechanism by which lipid-lowering drugs affect blood sugar is not fully understood. On one hand, it may be related to the impact of lipid-lowering drugs on the secretion of insulin by pancreatic β cells; on the other hand, it may be related to the impact of lipid-lowering drugs on insulin sensitivity and the subsequent impact on glucose metabolism in tissues and organs other than the pancreas (e.g., fat and muscle).[123] At present, the results of large-scale clinical studies and meta-analyses suggest that statins and niacin are unfavorable for blood sugar control and increase the risk of new-onset diabetes.[72,123,124,125,126] Conversely, cholesterol absorption inhibitors, PCSK9 inhibitors, probucol, bempedoic acid, fibrates, and high-purity ω-3 fatty acids have a neutral effect on blood sugar regulation. Some research also suggests that these drugs can improve glucose metabolism and, to some extent, alleviate insulin resistance and fatty liver.[26,80,123] Although bile acid sequestrants can improve both sugar and lipid metabolism, because of their weak lipid-lowering effect[27,28,127] and significant gastrointestinal side effects, their clinical use in China is rare. Clinical research on new drugs that lower Lp (a) is ongoing, and the impact of their long-term use on blood sugar is not yet clear.

Given that the cardiovascular protective effect of statins is far greater than its unfavorable effects on blood sugar control (an average increase in HbA1c of 0.3% or less) and the risk of new-onset diabetes, it is not recommended that diabetic patients stop taking statins due to poor blood sugar control. The unfavorable effects of statins on blood sugar control and the risk of new-onset diabetes are dose-related, and different types of statins have different effects on blood sugar. For example, atorvastatin, rosuvastatin, simvastatin, and fluvastatin have similar adverse effects on blood sugar regulation in normal populations and T2DM patients, while pitavastatin and pravastatin have a more neutral effect on blood sugar regulation.[72,124,125,128] Therefore, to control blood lipids in diabetic patients clinically, in addition to monitoring blood sugar or HbA1c before and during the use of statins, it is recommended to introduce cost-effective, medium-intensity statins and those that have a more neutral effect on blood sugar to reduce the associated metabolic abnormalities. If blood lipid control does not reach the desired goals, consider combining cholesterol absorption inhibitors or PCSK9 inhibitors. It is not recommended to increase the dose of statins.[27,28,80]

Research shows that statins cause metabolic abnormalities and insulin resistance in the body by reducing Clostridium-rich microbiota in the intestines and inhibiting the conversion of chenodeoxycholic acid to ursodeoxycholic acid, which leads to a decrease in intestinal GLP-1 secretion.[26,80,123,129] The combination of ursodeoxycholic acid and statins can reverse the glucose tolerance abnormalities caused by statins without changing their lipidlowering efficacy, suggesting that combining statins and ursodeoxycholic acid may show promise as a future lipidlowering treatment strategy.[26,80,123,129] At the same time, for diabetic patients, attention should be paid to reducing weight, maintaining a reasonable diet, and optimizing the hypoglycemic treatment plan. Niacin can cause abnormal glucose metabolism or worsen glucose tolerance, has no cardiovascular benefits for diabetic patients, and is generally not recommended for use in this population. If it is to be used, blood sugar levels should be monitored regularly.[68,123]

Monitoring during lipid-lowering treatment

For first-time users of lipid-lowering drugs, blood lipids, liver enzymes, creatine kinase, and other indicators should be checked 4-6 weeks after medication. If the blood lipid indicators reach the goals and there are no adverse drug reactions, gradually increase the recheck frequency to every 3-6 months. If the blood lipids do not reach the goals after 4-6 weeks of treatment, the dose or type of lipid-lowering drugs should be adjusted promptly, or lipid-lowering drugs with different mechanisms of action should be used in combination. Whenever the type or dose of lipid-lowering drugs is adjusted, the indicators should be rechecked 4-6 weeks after treatment. Given that long-term use of statins may cause abnormal glucose metabolism, blood sugar and HbA1c monitoring should be increased.[130]

Lipid-lowering treatment in special populations with diabetes

Children and adolescents

It is recommended to test and evaluate blood lipids after blood sugar is controlled or after three months of hypoglycemic drug treatment in > 10 year-old children and adolescents diagnosed with diabetes. The ideal blood lipid levels for children and adolescent diabetic patients are LDL-C < 2.6 mmol/L, HDL-C > 0.9 mmol/L, TG < 1.7 mmol/L, and non-HDL-C < 3.4 mmol/L.[131] Interventions should be carried out for those with persistent lipid abnormalities to maintain blood lipids within the ideal range. Intervention measures include introducing a low-fat and high-fiber diet, regular exercise, maintaining an ideal weight, maintaining adequate sleep, and optimizing blood sugar control. For those with familial hypercholesterolemia, lipid-lowering treatment with statins, ezetimibe, bile acid sequestrants, or PCSK9 inhibitors may be considered, but evidence for the long-term safety of these drugs in children and adolescents is limited.

People aged ≥ 75 years

Diabetes has become one of the most common diseases among elderly populations, and the prevalence of diabetes in elderly populations in China has reached 30%.[132] Patients aged ≥ 75 years are rarely included in clinical trials; thus, evidence on whether diabetic patients aged ≥ 75 years can benefit from LDL-C lowering treatment is inadequate. A recent meta-analysis of 29 clinical studies on both primary and secondary prevention showed that patients aged ≥ 75 years may also benefit from LDL-C lowering treatment and that the reduction in the risk of cardiovascular and cerebrovascular events brought about by statin treatment and non-statin drugs (e.g., ezetimibe and PCSK9 inhibitors) were not significantly different from each other. In terms of safety, lipidlowering treatment did not increase the risk of tumors, hemorrhagic stroke, cognitive impairment, and new-onset diabetes in patients aged ≥ 75 years.[133]

Diabetic patients aged ≥ 75 years are considered to be at very high-risk for ASCVD, and vigorous lipid-lowering treatment is recommended for this population. Few randomized controlled trials have established targets for statin lipid-lowering treatment in elderly patients; therefore, this consensus does not make clear recommendations for LDL-C target values in this population. However, randomized control studies of non-statin drugs (e.g., ezetimibe or PCSK9 inhibitors) have included patients aged ≥ 75 years as participants.[28,134] Taking into consideration concurrent liver and kidney diseases, combined medication, and expected lifespans for very high-risk patients aged ≥ 75 years, it is advisable to consider medium-intensity statins in combination with non-statin drugs as a means of intensifying lipid-lowering treatment. During treatment with medication, the monitoring of liver and kidney function, muscle damage, and other adverse reactions should be enhanced.

Patients with chronic kidney disease (CKD)

Approximately 30% of T1DM patients and 40% of T2DM patients have CKD.[135] The risk of cardiovascular death significantly increases in diabetic patients with CKD, who are directly classified as being at very high-risk for ASCVD. Reducing ASCVD risk with statin treatment is affected by renal function. For patients with mild to moderate renal dysfunction but who are not on dialysis, statin treatment can significantly reduce the risk of all-cause mortality.[136] Additionally, these patients may experience cardiovascular benefits with a combination of cholesterol absorption inhibitors or PCSK9 inhibitors based on statin treatment. [137,138,139] Statin treatment has not been shown to significantly reduce the risk of cardiovascular disease in hemodialysis patients.[139,140,141]

CKD patients are at high risk for statin-related myopathy, especially when renal function is progressively declining or the estimated glomerular filtration rate is < 30 mL/ min/1.73 m2, and the risk significantly increases in relation to the dose of statin drugs. Therefore, high doses of statin drugs should be avoided. The dose adjustment plan for statin drugs at different stages of CKD is shown in Table 6. Cholesterol absorption inhibitors and PCSK9 inhibitors are safe for patients with impaired renal function and do not require dose adjustments.

Table 6

Dose adjustment plan for statin drugs at different stages of CKD

eGFR (mL/min/1.73 m2) Atorvastatin Simvastatin Fluvastatin Rosuvastatin Pitavastatin Pravastatin
≥ 60 No reduction No reduction No reduction No reduction No reduction No reduction
needed needed needed needed needed needed
30-59 No reduction needed No reduction needed No reduction needed No reduction needed Restricted use Restricted use
15-29 No reduction needed Reduce the dosage Restricted use Restricted use Restricted use Restricted use
< 15 Restricted use Restricted use Restricted use Restricted use Restricted use Restricted use

  1. CKD: chronic kidney disease; eGFR: estimated glomeruar filtration rate.

Patients with metabolic-associated fatty liver disease (MAFLD)

MAFLD refers to patients with evidence of fatty liver based on pathology or imaging and who have one of the three following conditions: T2DM, metabolic dysfunction, and overweight/obese. Diabetes and MAFLD are risk factors for each other, and the prevalence of MAFLD in T2DM patients can be as high as 55.5%.[142] MAFLD patients with T2DM have a higher risk of liver damage progressing to cirrhosis and liver cancer.[143,144] MAFLD is an independent risk factor for ASCVD,[145] and diabetics with MAFLD have a higher ASCVD risk than those without MAFLD.[146,147,148,149]

At present, there is no evidence to suggest that lipid control for T2DM patients with MAFLD should be stricter. During the use of lipid-lowering drugs, blood lipids and liver function should be monitored closely. Statins can cause elevated liver enzymes at an incidence rate of about 1%, which usually occurs within 12 weeks of starting medication or increasing the dose; such elevation is dose-dependent and rarely causes liver failure. In MAFLD patients with normal liver function, medium-intensity statins can be used. If serum alanine transaminase (ALT) or aspartate transaminase (AST) elevation does not exceed three times the normal upper limit and the total bilirubin level is normal, observation can be carried out on the basis of the original dose or reduced dose of statin use.

If ALT or AST elevation exceeds three times the normal upper limit, statins should be discontinued. Patients with mild liver impairment (i.e., a Child-Pugh score of 5-6) can use cholesterol absorption inhibitors or PCSK9 inhibitors as alternatives. Decompensated cirrhosis and acute liver failure are contraindications for the use of statins,[68,150] and the use of other types of lipid-lowering drugs in these patients is not supported by evidence.

Patients with pregnancy

Pregnancy can cause a physiological increase in blood cholesterol levels, with LDL-C levels increasing by 50%, and abnormal elevation of cholesterol levels during pregnancy increases the risk of preterm birth and fetal atherosclerosis.[151] With choices of lipid-lowering drugs highly limited during pregnancy, lipid management should focus on screening, lifestyle changes (e.g., dietary management, appropriate exercise, and eliminating smoking and alcohol consumption), and keeping blood sugar within an appropriate range.[152]

Based on animal experiments and case reports of fetal malformations caused by statins, it is generally not recommended to use statins during pregnancy. However, two recent randomized controlled studies and cohort studies related to pravastatin found no increased risk of birth defects from statins.[153,154] Meta-analysis results also suggest that statins do not increase the risk of birth defects, but that they are associated with an increased risk of spontaneous abortion.[155,156] Based on this evidence, the United States Food and Drug Administration requested the removal of the “Pregnancy X Class” label for statins in 2021. During pregnancy, for diabetic women who have previously had coronary events or have familial hypercholesterolemia, blood lipoprotein isolation technology to reduce LDL-C is relatively safe and effective, and statins may be chosen with caution after multidisciplinary consultation and a full assessment of the pros and cons.[68]

Diabetic patients with pregnancy have increased liver TG synthesis due to increased nutrient intake and estrogen secretion, which leads to abnormal TG elevation. Especially in late pregnancy, decreased LPL activity increases the risk of developing severe hypertriglyceridemia and acute pancreatitis. Pharmaceutical options for lowering TG during pregnancy are limited, and there is insufficient evidence regarding the safe use of fibrate drugs during pregnancy.

For pregnant patients with diabetes and hypertriglyceridemia, lifestyle improvement and dietary management are the primary recommendations. For patients still with severe hypertriglyceridemia (TG > 5.6 mmol/L) on the basis of blood sugar control, ω-3 fatty acids can effectively and relatively safely lower TG levels. Besides, insulin and heparin can lower TG levels by activating LPL, which is relatively safe for pregnant patients.[157] If a patient with pancreatitis still has a serum TG level of > 11.3 mmol/L or a decrease of less than 50% after 24-48 h of drug treatment, lipoprotein apheresis treatment may be considered.[158]

Conclusion and prospects

China has the highest number of diabetic patients in the world; thus, the effective management of lipid abnormalities and the reduction of cardiovascular event risks in diabetic patients have profound implications for implementing the Healthy China strategy. Performing ASCVD risk stratification for diabetic patients, determining lipid target values, and developing lipid-lowering treatment plans for different risk stratifications are key to lipid management in diabetic patients.

Several problems related to the lipid management of diabetic patients remain, including how to decide lipid-lowering treatment targets and goals, more randomized controlled studies needed for the novel lipid-lowering drugs, and how to make lipid-lowering treatment plans for special populations (e.g., T1DM patients, elderly patients, children, and adolescents). In the future, larger-scale multicenter clinical studies that include T1DM and T2DM patients are recommended to provide more high-quality evidence for lipid management in diabetic patients.

Secondary Publication Declaration

This article was translated with permission from the Chinese language version first published by the Chinese Journal of Diabetes Mellitus and the Chinese Circulation Journal. The original publication is detailed as:

Endocrinology and Metabolism Physician Branch of Chinese Medical Doctor Association, National Society of Cardiometabolic Medicine. [Expert consensus on the lipid management of diabetic patients (2024 edition)]. Chin J Diabetes Mellit. 2024;16(4):383-403.

Endocrinology and Metabolism Physician Branch of Chinese Medical Doctor Association, National Society of Cardiometabolic Medicine. [Expert Consensus on the Lipid Management of Diabetic Patients (2024 Edition)]. Chin Circ J. 2024;39(4):322-341.

Address for Correspondence: Zhou Zhiguang, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China
Peng Daoquan, Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China

#These authors contributed equally to this work.

  1. Author Contributions

    Yang Xiao and Bilian Yu: Conceptualization, Supervision, Writing-Reviewing ang editing. Chen Chao, Shuai Wang, Die Hu, Chao Wu, Yonghong Luo, Lingxiang Xie, Chenyu Li, Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, and National Society of Cardiometabolic Medicine: Writing—Original draft preparation, Writing—Reviewing and Editing. Daoquan Peng and Zhiguang Zhou: Writing-Reviewing and editing, Supervision, Project administration.

  2. Informed Consent

    Not applicable.

  3. Ethical Approval

    Not applicable.

  4. Conflict of Interest

    The authors declare no competing interest.

  5. Data Availability Statement

    Not applicable.

References

1 Magliano DJ, Boyko EJ, IDF Diabetes Atlas 10th edition Scientific Committee. IDF diabetes atlas. 10th ed. Brussels: International Diabetes Federation, 2021.Search in Google Scholar

2 Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. The metabolic syndrome and cardiovascular risk: a systematic review and meta-analysis. J Am Coll Cardiol 2010;56:1113-1132.10.1016/j.jacc.2010.05.034Search in Google Scholar PubMed

3 Khavandi M, Duarte F, Ginsberg HN, Reyes-Soffer G. Treatment of dyslipidemias to prevent cardiovascular disease in patients with type 2 diabetes. Curr Cardiol Rep 2017;19:7.10.1007/s11886-017-0818-1Search in Google Scholar PubMed PubMed Central

4 Hiukka A, Fruchart-Najib J, Leinonen E, Hilden H, Fruchart JC, Taskinen MR. Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes. Diabetologia 2005;48:1207-1215.10.1007/s00125-005-1753-zSearch in Google Scholar PubMed

5 Dunn FL. Management of dyslipidemia in people with type 2 diabetes mellitus. Rev Endocr Metab Disord 2010;11:41-51.10.1007/s11154-010-9132-6Search in Google Scholar PubMed

6 Vergès B. New insight into the pathophysiology of lipid abnormalities in type 2 diabetes. Diabetes Metab 2005;31:429-439.10.1016/S1262-3636(07)70213-6Search in Google Scholar PubMed

7 Wu L, Parhofer KG. Diabetic dyslipidemia. Metabolism 2014;63:1469-1479.10.1016/j.metabol.2014.08.010Search in Google Scholar PubMed

8 Guy J, Ogden L, Wadwa RP, Hamman RF, Mayer-Davis EJ, Liese AD, et al. Lipid and lipoprotein profiles in youth with and without type 1 diabetes: the SEARCH for Diabetes in Youth case-control study. Diabetes Care 2009;32:416-420.10.2337/dc08-1775Search in Google Scholar PubMed PubMed Central

9 Vergès B. Lipid disorders in type 1 diabete. Diabetes Metab 2009;35:353-360.10.1016/j.diabet.2009.04.004Search in Google Scholar PubMed

10 Adler AI. UKPDS-modelling of cardiovascular risk assessment and lifetime simulation of outcomes. Diabet Med 2008;25:41-46.10.1111/j.1464-5491.2008.02498.xSearch in Google Scholar PubMed

11 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group. Risk factors for cardiovascular disease in type 1 diabetes. Diabetes 2016;65:1370-1379.10.2337/db15-1517Search in Google Scholar PubMed PubMed Central

12 Fan W, Philip S, Granowitz C, Toth PP, Wong ND. Residual hypertri-glyceridemia and estimated atherosclerotic cardiovascular disease risk by statin use in U.S. adults with diabetes: national health and nutrition examination survey 2007-2014. Diabetes Care 2019;42:2307-2314.10.2337/dc19-0501Search in Google Scholar PubMed

13 Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. Increased residual cardiovascular risk in patients with diabetes and high versus normal triglycerides despite statin-controlled LDL cholesterol. Diabetes Obes Metab 2019;21:366-371.10.1111/dom.13537Search in Google Scholar PubMed PubMed Central

14 Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 2012;307:1302-1309.10.1001/jama.2012.366Search in Google Scholar PubMed

15 Cao Y, Yan L, Guo N, Yu N, Wang Y, Cao X, et al. Non-high-density lipoprotein cholesterol and risk of cardiovascular disease in the general population and patients with type 2 diabetes: a systematic review and metaanalysis. Diabetes Res Clin Pract 2019;147:1-8.10.1016/j.diabres.2018.11.002Search in Google Scholar PubMed

16 Ji L, Hu D, Pan C, Weng J, Huo Y, Ma C, et al. Primacy of the 3B approach to control risk factors for cardiovascular disease in type 2 diabetes patients. Am J Med 2013;126:925.e11-e22.10.1016/j.amjmed.2013.02.035Search in Google Scholar PubMed

17 Yan L, Xu MT, Yuan L, Chen B, Xu ZR, Guo QH, et al. Prevalence of dyslipidemia and its control in type 2 diabetes: a multicenter study in endocrinology clinics of China. J Clin Lipidol 2016;10:150-160.10.1016/j.jacl.2015.10.009Search in Google Scholar PubMed

18 Li J, Nie Z, Ge Z, Shi L, Gao B, Yang Y. Prevalence of dyslipidemia, treatment rate and its control among patients with type 2 diabetes mellitus in Northwest China: a cross-sectional study. Lipids Health Dis 2022;21:77.10.1186/s12944-022-01691-1Search in Google Scholar PubMed PubMed Central

19 Huxley RR, Peters SAE, Mishra GD, Woodward M. Risk of all-cause mortality and vascular events in women versus men with type 1 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2015;3:198-206.10.1016/S2213-8587(14)70248-7Search in Google Scholar PubMed

20 Tang X, Yan X, Zhou H, Huang G, Niu X, Jiang H, et al. Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes. Chin Med J (Engl) 2022;135:2554-2562.10.1097/CM9.0000000000002075Search in Google Scholar PubMed PubMed Central

21 Samson SL, Vellanki P, Blonde L, Christofides EA, Galindo RJ, Hirsch IB, et al. American association of clinical endocrinology consensus statement: comprehensive type 2 diabetes management algorithm - 2023 update. Endocr Pract 2023;29:305-340.10.1016/j.eprac.2023.02.001Search in Google Scholar PubMed

22 Willeit P, Ridker PM, Nestel PJ, Simes J, Tonkin AM, Pedersen TR, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet 2018;392:1311-1320.10.1016/S0140-6736(18)31652-0Search in Google Scholar PubMed

23 Langsted A, Nordestgaard BG, Kamstrup PR. Elevated lipoprotein(a) and risk of ischemic stroke. J Am Coll Cardiol 2019;74:54-66.10.1016/j.jacc.2019.03.524Search in Google Scholar PubMed

24 Lin JS, Evans CV, Johnson E, Redmond N, Coppola EL, Smith N. Nontraditional risk factors in cardiovascular disease risk assessment: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2018;320:281-297.10.1001/jama.2018.4242Search in Google Scholar PubMed

25 Ridker PM, Bhatt DL, Pradhan AD, Glynn RJ, MacFadyen JG, Nissen SE, et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet 2023;401:1293-1301.10.1016/S0140-6736(23)00215-5Search in Google Scholar PubMed

26 Giugliano RP, Cannon CP, Blazing MA, Nicolau JC, Corbalán R, Špinar J, et al. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results from IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation 2018;137:1571-1582.10.1161/CIRCULATIONAHA.117.030950Search in Google Scholar PubMed

27 Ray KK, Colhoun HM, Szarek M, Baccara-Dinet M, Bhatt DL, Bittner VA, et al. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol 2019;7:618-628.10.1016/S2213-8587(19)30158-5Search in Google Scholar PubMed

28 Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P, De Ferrari GM, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol 2017;5:941-950.10.1016/S2213-8587(17)30313-3Search in Google Scholar PubMed

29 Kearney PM, Blackwell L, Collins R, Collins R, Keech A, Simes J, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117-125.10.1016/S0140-6736(08)60104-XSearch in Google Scholar PubMed

30 Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5 963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:2005-2016.10.1016/S0140-6736(03)13636-7Search in Google Scholar PubMed

31 Taylor F, Huffman MD, Macedo AF, Moore THM, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;2013:CD004816.10.1002/14651858.CD004816.pub5Search in Google Scholar PubMed PubMed Central

32 Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-188.10.15829/1560-4071-2020-3826Search in Google Scholar

33 Newman CB, Blaha MJ, Boord JB, Cariou B, Chait A, Fein HG, et al. Lipid management in patients with endocrine disorders: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2020;105:dgaa674.10.1210/clinem/dgaa674Search in Google Scholar PubMed

34 Goldberg RB, Stone NJ, Grundy SM. The 2018 AHA/ACC/AACVPR/ AAPA/ABC/ACPM/ADA/AGS/APHA/ASPC/NLA/PCNA guidelines on the management of blood cholesterol in diabetes. Diabetes Care 2020;431673-1678.10.2337/dci19-0036Search in Google Scholar PubMed

35 Elsayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 10. Cardiovascular disease and risk management: standards of care in diabetes-2023. Diabetes Care 2023;46: S158-S190.10.2337/dc23-S010Search in Google Scholar PubMed PubMed Central

36 The Chinese Society of Endocrinology, the Chinese Medical Association Diabetes Branch, the Chinese Medical Doctor Association Endocrinology and Metabolism Branch, and others. [Guidelines for the diagnosis and treatment of type 1 diabetes mellitus in China (2021 edition)]. Chin J Diabetes 2022;14:1143-1250.Search in Google Scholar

37 Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol 2009;53:316-322.10.1016/j.jacc.2008.10.024Search in Google Scholar PubMed

38 Charlton-Menys V, Betteridge DJ, Colhoun H, Fuller J, France M, Hitman GA, et al. Targets of statin therapy: LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS). Clin Chem 2009;55:473-480.10.1373/clinchem.2008.111401Search in Google Scholar PubMed

39 Thanassoulis G, Williams K, Ye K, Brook R, Couture P, Lawler PR, et al. Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk reduction from statin therapy: a meta-analysis of randomized trials. J Am Heart Assoc 2014;3:e000759.10.1161/JAHA.113.000759Search in Google Scholar PubMed PubMed Central

40 Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA 2013;310:2061-2068.10.1001/jama.2013.280532Search in Google Scholar PubMed PubMed Central

41 Whelton SP, Meeusen JW, Donato LJ, Jaffe AS, Saenger A, Sokoll LJ, et al. Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol < 70 mg/dL compared with a novel low-density lipoprotein estimation method. J Clin Lipidol 2017;11:1065-1072.10.1016/j.jacl.2017.05.005Search in Google Scholar PubMed

42 Hagström E, Steg PG, Szarek M, Bhatt DL, Bittner VA, Danchin N, et al. Apolipoprotein B, residual cardiovascular risk after acute coronary syndrome, and effects of alirocumab. Circulation 2022;146:657-672.10.1161/CIRCULATIONAHA.121.057807Search in Google Scholar PubMed PubMed Central

43 Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration; Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 2010;375:1634-1639.10.1016/S0140-6736(10)60545-4Search in Google Scholar PubMed PubMed Central

44 McGuire DK, Shih WJ, Cosentino F, Charbonnel B, Cherney DZI, Dagogo-Jack S, et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol 2021;6:148-158.10.1001/jamacardio.2020.4511Search in Google Scholar PubMed PubMed Central

45 Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a doubleblind, randomised placebo-controlled trial. Lancet 2019;394:121-130.10.1016/S0140-6736(19)31149-3Search in Google Scholar PubMed

46 Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834-1844.10.1056/NEJMoa1607141Search in Google Scholar PubMed

47 Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311-322.10.1056/NEJMoa1603827Search in Google Scholar PubMed PubMed Central

48 Hu Y, Hu FB, Manson JE. Marine omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials involving 127477 participants. J Am Heart Assoc 2019;8:e013543.10.1161/JAHA.119.013543Search in Google Scholar PubMed PubMed Central

49 ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR, Leiter LA, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362:1563-1574.10.1056/NEJMoa1001282Search in Google Scholar PubMed PubMed Central

50 Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM, et al. Triglyceride lowering with pemafibrate to reduce cardiovascular risk. N Engl J Med 2022;387:1923-1934.10.1056/NEJMoa2210645Search in Google Scholar PubMed

51 Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.10.1056/NEJMoa1812792Search in Google Scholar PubMed

52 Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369:1090-1098.10.1016/S0140-6736(07)60527-3Search in Google Scholar PubMed

53 Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA 2020;324:2268-2280.10.1001/jama.2020.22258Search in Google Scholar PubMed PubMed Central

54 Saeed A, Sun W, Agarwala A, Virani SS, Nambi V, Coresh J, et al. Lipoprotein(a) levels and risk of cardiovascular disease events in individuals with diabetes mellitus or prediabetes: The Atherosclerosis Risk in Communities study. Atherosclerosis 2019;282:52-56.10.1016/j.atherosclerosis.2018.12.022Search in Google Scholar PubMed PubMed Central

55 Waldeyer C, Makarova N, Zeller T, Schnabel RB, Brunner FJ, Jørgensen T, et al. Lipoprotein(a) and the risk of cardiovascular disease in the European population: results from the BiomarCaRE consortium. Eur Heart J 2017;38:2490-2498.10.1093/eurheartj/ehx166Search in Google Scholar PubMed PubMed Central

56 Zhang Y, Jin JL, Cao YX, Zhang HW, Guo YL, Wu NQ, et al. Lipoprotein (a) predicts recurrent worse outcomes in type 2 diabetes mellitus patients with prior cardiovascular events: a prospective, observational cohort study. Cardiovasc Diabetol 2020;19:111.10.1186/s12933-020-01083-8Search in Google Scholar PubMed PubMed Central

57 Jin JL, Cao YX, Zhang HW, Sun D, Hua Q, Li YF, et al. Lipoprotein(a) and cardiovascular outcomes in patients with coronary artery disease and prediabetes or diabetes. Diabetes Care 2019;42:1312-1318.10.2337/dc19-0274Search in Google Scholar PubMed

58 Liu HH, Cao YX, Jin JL, Zhang HW, Hua Q, Li YF, et al. Predicting cardiovascular outcomes by baseline lipoprotein(a) concentrations: a large cohort and long-term follow-up study on real-world patients receiving percutaneous coronary intervention. J Am Heart Assoc 2020;9:e014581.10.1161/JAHA.119.014581Search in Google Scholar PubMed PubMed Central

59 Fu H, Zhang D, Zhu R, Cui L, Qiu L, Lin S, et al. Association between lipoprotein(a) concentration and the risk of stroke in the Chinese Han population: a retrospective case-control study. Ann Transl Med 2020;8:212.10.21037/atm.2020.01.38Search in Google Scholar PubMed PubMed Central

60 Liu HH, Cao YX, Jin JL, Zhang HW, Hua Q, Li YF, et al. Association of lipoprotein(a) levels with recurrent events in patients with coronary artery disease. Heart 2020;106:1228-1235.10.1136/heartjnl-2020-316586Search in Google Scholar PubMed

61 Cui FM, Fang F, He YM, Cai DP, He J, Yang XJ. Establishing age and sex dependent upper reference limits for the plasma lipoprotein (a) in a Chinese health check-up population and according to its relative risk of primary myocardial infarction. Clin Chim Acta 2018;484:232-236.10.1016/j.cca.2018.06.004Search in Google Scholar PubMed

62 Zhang J, Du R, Peng K, Wu X, Hu C, Li M, et al. Serum lipoprotein (a) is associated with increased risk of stroke in Chinese adults: a prospective study. Atherosclerosis 2019;289:8-13.10.1016/j.atherosclerosis.2019.07.025Search in Google Scholar PubMed

63 Beijing Heart Association. [Expert scientific suggestions on the relationship between lipoprotein(a) and cardiovascular disease risk and its clinical management]. Chin Circ J 2021;36:1158-1167.Search in Google Scholar

64 Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur J Prev Cardiol 2022;29:5-115.10.1093/eurjpc/zwab154Search in Google Scholar PubMed

65 Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller ER 3rd, et al. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA 2005;294:2455-2464.10.1001/jama.294.19.2455Search in Google Scholar PubMed

66 Committee AHAN, Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 2006;114:82-96.10.1161/CIRCULATIONAHA.106.176158Search in Google Scholar PubMed

67 Carson JAS, Lichtenstein AH, Anderson CAM, Appel LJ, Kris-Etherton PM, Meyer KA, et al. Dietary cholesterol and cardiovascular risk: a science advisory from the American heart association. Circulation 2020;141:e39-e53.10.1161/CIR.0000000000000743Search in Google Scholar PubMed

68 Joint Committee on the Chinese Guidelines for Lipid Management. [Chinese guidelines for lipid management (2023)]. Chin Circ J 2023;38:237-271.Search in Google Scholar

69 Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2021-2031.10.1056/NEJMoa1600176Search in Google Scholar PubMed

70 Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696.10.1016/S0140-6736(04)16895-5Search in Google Scholar PubMed

71 Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, Toyota T, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study):a prospective randomised controlled trial. Lancet 2006;368:1155-1163.10.1016/S0140-6736(06)69472-5Search in Google Scholar PubMed

72 Endocrinology Branch of the Chinese Medical Association, Lipid Metabolism Group. [Chinese expert consensus on the prevention and treatment of dyslipidemia in type 2 diabetes (revised edition 2017)]. Chin J Endocrinol Metab 2017;33:925-936.Search in Google Scholar

73 Chinese Diabetes Society. [Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition)]. Chin J Diabetes Mellit 2021;13:315-409.Search in Google Scholar

74 Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-1307.10.1056/NEJM199511163332001Search in Google Scholar PubMed

75 Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA):a multicentre randomised controlled trial. Lancet 2003;361:1149-1158.10.1016/S0140-6736(03)12948-0Search in Google Scholar PubMed

76 Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-1009.10.1056/NEJM199610033351401Search in Google Scholar PubMed

77 Zhao SP, Yu BL, Peng DQ, Huo Y. The effect of moderate-dose versus double-dose statins on patients with acute coronary syndrome in China: Results of the CHILLAS trial. Atherosclerosis 2014;233:707-712.10.1016/j.atherosclerosis.2013.12.003Search in Google Scholar PubMed

78 Diaz R, Li QH, Bhatt DL, Bittner VA, Baccara-Dinet MT, Goodman SG, et al. Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial. Eur J Prev Cardiol 2021;28:33-43.10.1177/2047487320941987Search in Google Scholar PubMed

79 Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372:2387-2397.10.1056/NEJMoa1410489Search in Google Scholar PubMed

80 Kim BK, Hong SJ, Lee YJ, Hong SJ, Yun KH, Hong BK, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING):a randomised, openlabel, non-inferiority trial. Lancet 2022;400:380-390.10.1016/S0140-6736(22)00916-3Search in Google Scholar PubMed

81 Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-1722.10.1056/NEJMoa1615664Search in Google Scholar PubMed

82 Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-2107.10.1056/NEJMoa1801174Search in Google Scholar PubMed

83 Moriarty PM, Thompson PD, Cannon CP, Guyton JR, Bergeron J, Zieve FJ, et al. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol 2015;9:758-769.10.1016/j.jacl.2015.08.006Search in Google Scholar PubMed

84 Schreml J, Gouni-Berthold I. Role of anti-PCSK9 antibodies in the treatment of patients with statin intolerance. Curr Med Chem 2018;25:1538-1548.10.2174/0929867324666170616111647Search in Google Scholar PubMed

85 Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, et al. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA 2016;315:1580-1590.10.1001/jama.2016.3608Search in Google Scholar PubMed

86 American Diabetes Association Professional Practice Committee. 10. cardiovascular disease and risk management: standards of medical care in diabetes-2022. Diabetes Care 2022;45:S144-S174.10.2337/dc22-S010Search in Google Scholar PubMed

87 National Health Commission of the People’s Republic of China. Dietary guidelines for adults with hyperlipemia (2023 edition). Gen Pract Clin Edu 2023;21:581-583.Search in Google Scholar

88 Clinical Nutrition and Health Branch of the China Health Management Association, Clinical Nutrition Branch of the Chinese Nutrition Society, Editorial Committee of the “Chinese Journal of Health Management”. [Expert consensus on medical nutrition management of dyslipidemia]. Chin J Health Manag 2023;17:561-573.Search in Google Scholar

89 Lu Z, Du B, Chen Z, Wu Y, Yu X, Zhao Y. [Chinese coronary heart disease secondary prevention research - intervention outcome analysis for patients with diabetes]. Chin J Cardiovasc Dis 2005;33:1067-1070.Search in Google Scholar

90 Morrone D, Weintraub WS, Toth PP, Hanson ME, Lowe RS, Lin J, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis 2012;223:251-261.10.1016/j.atherosclerosis.2012.02.016Search in Google Scholar PubMed

91 Lee YJ, Cho JY, You SC, Lee YH, Yun KH, Cho YH, et al. Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial. Eur Heart J 2023;44:972-983.10.1093/eurheartj/ehac709Search in Google Scholar PubMed

92 Sabatine MS. PCSK9 inhibitors: clinical evidence and implementation. Nat Rev Cardiol 2019;16:155-165.10.1038/s41569-018-0107-8Search in Google Scholar PubMed

93 Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1489-1499.10.1056/NEJMoa1501031Search in Google Scholar PubMed

94 Stein EA, Turner TA. Are the PCSK9 inhibitors the panacea of atherosclerosis treatment? Expert Rev Cardiovasc Ther 2017;15:491-494.10.1080/14779072.2017.1348231Search in Google Scholar PubMed

95 Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, et al. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/ kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 Mg every two weeks dosing from phase 2 trials). Am J Cardiol 2014;114:711-715.10.1016/j.amjcard.2014.05.060Search in Google Scholar PubMed

96 Rosenson RS, Daviglus ML, Handelsman Y, Pozzilli P, Bays H, Monsalvo ML, et al. Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus: primary results of the randomised controlled BANTING study. Diabetologia 2019;62:948-958.10.1007/s00125-019-4856-7Search in Google Scholar PubMed PubMed Central

97 Lorenzatti AJ, Monsalvo ML, López JAG, Wang H, Rosenson RS. Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: an analysis from BANTING and BERSON. Cardiovasc Diabetol 2021;20:94.10.1186/s12933-021-01287-6Search in Google Scholar PubMed PubMed Central

98 Chen Y, Yuan Z, Lu J, Eliaschewitz FG, Lorenzatti AJ, Monsalvo ML, et al. Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial. Diabetes Obes Metab 2019;21:1464-1473.10.1111/dom.13700Search in Google Scholar PubMed PubMed Central

99 Leiter LA, Cariou B, Müller-Wieland D, Colhoun HM, Del Prato S, Tinahones FJ, et al. Efficacy and safety of alirocumab in insulin-treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM-INSULIN randomized trial. Diabetes Obes Metab 2017;19:1781-1792.10.1111/dom.13114Search in Google Scholar PubMed PubMed Central

100 Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500-1509.10.1056/NEJMoa1500858Search in Google Scholar PubMed

101 Ballantyne CM, Banach M, Mancini GBJ, Lepor NE, Hanselman JC, Zhao X, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study. Atherosclerosis 2018;277:195-203.10.1016/j.atherosclerosis.2018.06.002Search in Google Scholar PubMed

102 Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med 2023;388:1353-1364.10.1056/NEJMoa2215024Search in Google Scholar PubMed

103 Huynh K. Targeting ATP citrate lyase to reduce LDL cholesterol. Nat Rev Cardiol 2019;16:385.10.1038/s41569-019-0201-6Search in Google Scholar PubMed

104 Ray KK, Bays HE, Catapano AL, Lalwani ND, Bloedon LT, Sterling LR, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med 2019;380:1022-1032.10.1056/NEJMoa1803917Search in Google Scholar PubMed

105 Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA 2016;316:1289-1297.10.1001/jama.2016.13985Search in Google Scholar PubMed

106 Christian JB, Arondekar B, Buysman EK, Johnson SL, Seeger JD, Jacobson TA. Clinical and economic benefits observed when follow-up triglyceride levels are less than 500 mg/dL in patients with severe hypertriglyceridemia. J Clin Lipidol 2012;6:450-461.10.1016/j.jacl.2012.08.007Search in Google Scholar PubMed

107 Cicero AFG, Colletti A, Bajraktari G, Descamps O, Djuric DM, Ezhov M, et al. Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Nutr Rev 2017;75:731-767.10.1093/nutrit/nux047Search in Google Scholar PubMed

108 Heffron SP, Parikh A, Volodarskiy A, Ren-Fielding C, Schwartzbard A, Nicholson J, et al. Changes in lipid profile of obese patients following contemporary bariatric surgery: a meta-analysis. Am J Med 2016;129:952-959.10.1016/j.amjmed.2016.02.004Search in Google Scholar PubMed PubMed Central

109 Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, et al. Bariatric surgery versus intensive medical therapy for diabetes - 5-year outcomes. N Engl J Med 2017;376:641-651.10.1056/NEJMoa1600869Search in Google Scholar PubMed PubMed Central

110 Muzurovic E, Mikhailidis DP. Impact of glucagon-like peptide 1 receptor agonists and sodium-glucose transport protein 2 inhibitors on blood pressure and lipid profile. Expert Opin Pharmacother 2020;21:2125-2135.10.1080/14656566.2020.1795132Search in Google Scholar PubMed

111 Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Furtado RHM, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019;139:2022-2031.10.1161/CIRCULATIONAHA.118.038868Search in Google Scholar PubMed

112 Wilson JM, Nikooienejad A, Robins DA, Roell WC, Riesmeyer JS, Haupt A, et al. The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diabetes Obes Metab 2020;22:2451-2459.10.1111/dom.14174Search in Google Scholar PubMed PubMed Central

113 Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J 2023;44:4043-4140.10.1093/eurheartj/ehad192Search in Google Scholar PubMed

114 Expert Group for Updating Chinese Expert Consensus on Metformin in Clinical Practice. [Chinese expert consensus on metformin in clinical practice: 2023 update]. Chin J Int Med 2023;43:345-356.Search in Google Scholar

115 Ussher JR, Drucker DJ. Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nat Rev Cardiol 2023;20:463-474.10.1038/s41569-023-00849-3Search in Google Scholar PubMed

116 Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol 2020;17:761-772.10.1038/s41569-020-0406-8Search in Google Scholar PubMed

117 Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, et al. Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med 2020;383:711-720.10.1056/NEJMoa2004215Search in Google Scholar PubMed

118 Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med 2019;381:531-542.10.1056/NEJMoa1715944Search in Google Scholar PubMed

119 Imbalzano E, Ilardi F, Orlando L, Pintaudi B, Savarese G, Rosano G. The efficacy of PCSK9 inhibitors on major cardiovascular events and lipid profile in patients with diabetes: a systematic review and meta-analysis of randomized controlled trials. Eur Heart J Cardiovasc Pharmacother 2023;9:318-327.10.1093/ehjcvp/pvad019Search in Google Scholar PubMed

120 Sahebkar A, Reiner Ž, Simental-Mendía LE, Ferretti G, Cicero AFG. Effect of extended-release niacin on plasma lipoprotein(a) levels: a systematic review and meta-analysis of randomized placebo-controlled trials. Metabolism 2016;65(11):1664-1678.10.1016/j.metabol.2016.08.007Search in Google Scholar PubMed

121 Group HC, Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. N Engl J Med 2017;377:1217-1227.10.1056/NEJMoa1706444Search in Google Scholar PubMed

122 Bell DA, Hooper AJ, Watts GF, Burnett JR. Mipomersen and other therapies for the treatment of severe familial hypercholesterolemia. Vasc Health Risk Manag 2012;8:651-689.10.2147/VHRM.S28581Search in Google Scholar PubMed PubMed Central

123 Zafrir B, Jain M. Lipid-lowering therapies, glucose control and incident diabetes: evidence, mechanisms and clinical implications. Cardiovasc Drugs Ther 2014;28:361-377.10.1007/s10557-014-6534-9Search in Google Scholar PubMed

124 Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735-742.10.1016/S0140-6736(09)61965-6Search in Google Scholar PubMed

125 Preiss D, Seshasai SRK, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011;305:2556-2564.10.1001/jama.2011.860Search in Google Scholar PubMed

126 Elam MB, Hunninghake DB, Davis KB, Garg R, Johnson C, Egan D, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. JAMA 2000;284:1263-1270.10.1001/jama.284.10.1263Search in Google Scholar PubMed

127 Mazidi M, Rezaie P, Karimi E, Kengne AP. The effects of bile acid sequestrants on lipid profile and blood glucose concentrations: a systematic review and meta-analysis of randomized controlled trials. Int J Cardiol 2017;227:850-857.10.1016/j.ijcard.2016.10.011Search in Google Scholar PubMed

128 Teramoto T, Shimano H, Yokote K, Urashima M. New evidence on pitavastatin: efficacy and safety in clinical studies. Expert Opin Pharmacother 2010;11:817-828.10.1517/14656561003641990Search in Google Scholar PubMed

129 She J, Tuerhongjiang G, Guo M, Liu J, Hao X, Guo L, et al. Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner. Cell Metab 2024;36:408-421.e5.10.1016/j.cmet.2023.12.027Search in Google Scholar PubMed

130 Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of statin therapy initiation with diabetes progression: a retrospective matched-cohort study. JAMA Intern Med 2021;181:1562-1574.10.1001/jamainternmed.2021.5714Search in Google Scholar PubMed PubMed Central

131 Shah AS, Zeitler PS, Wong J, Pena AS, Wicklow B, Arslanian S, et al. ISPAD clinical practice consensus guidelines 2022: type 2 diabetes in children and adolescents. Pediatr Diabetes 2022;23:872-902.10.1111/pedi.13409Search in Google Scholar PubMed

132 National Center of Gerontology, Chinese Society of Geriatrics, Diabetes Professional Committee of Chinese Aging Well Association. [Guideline for the management of diabetes mellitus in the elderly in China (2024 edition)]. Chin J Diabetes Mellit2024;16:147-189.Search in Google Scholar

133 Gencer B, Marston NA, Im K, Cannon CP, Sever P, Keech A, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet 2020;396:1637-1643.10.1016/S0140-6736(20)32332-1Search in Google Scholar PubMed PubMed Central

134 Ouchi Y, Sasaki J, Arai H, Yokote K, Harada K, Katayama Y, et al. Ezetimibe lipid-lowering trial on prevention of atherosclerotic cardiovascular disease in 75 or older (EWTOPIA 75): a randomized, controlled trial. Circulation 2019;140:992-1003.10.1161/CIRCULATIONAHA.118.039415Search in Google Scholar PubMed

135 Saran R, Robinson B, Abbott KC, Bragg-Gresham J, Chen X, Gipson D, et al. US renal data system 2019 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 2020;75:A6-A7.10.1053/j.ajkd.2019.09.003Search in Google Scholar PubMed

136 Barylski M, Nikfar S, Mikhailidis DP, Toth PP, Salari P, Ray KK, et al. Statins decrease all-cause mortality only in CKD patients not requiring dialysis therapy—a meta-analysis of 11 randomized controlled trials involving 21,295 participants. Pharmacol Res 2013;72:35-44.10.1016/j.phrs.2013.03.007Search in Google Scholar PubMed

137 Group SC. Study of Heart and Renal Protection (SHARP):randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9438 patients with chronic kidney disease. Am Heart J 2010;160:785-79410.1016/j.ahj.2010.08.012Search in Google Scholar PubMed

138 Charytan DM, Sabatine MS, Pedersen TR, Im K, Park JG, Pineda AL, et al. Efficacy and safety of evolocumab in chronic kidney disease in the FOURIER trial. J Am Coll Cardiol 2019;73:2961-2970.10.1016/j.jacc.2019.03.513Search in Google Scholar PubMed

139 Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011;377:2181-2192.10.1016/j.ymed.2011.08.055Search in Google Scholar

140 Wanner C, Krane V, März W, Olschewski M, Mann JFE, Ruf G, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238-248.10.1056/NEJMoa043545Search in Google Scholar PubMed

141 Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395-1407.10.1056/NEJMoa0810177Search in Google Scholar PubMed

142 Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol 2019;71:793-801.10.1016/j.jhep.2019.06.021Search in Google Scholar PubMed

143 Bazick J, Donithan M, Neuschwander-Tetri BA, Kleiner D, Brunt EM, Wilson L, et al. Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: guidelines for referral in NAFLD. Diabetes Care 2015;38:1347-1355.10.2337/dc14-1239Search in Google Scholar PubMed PubMed Central

144 Doycheva I, Zhang T, Amjad W, Thuluvath PJ. Diabetes and hepatocellular carcinoma: incidence trends and impact of liver disease etiology. J Clin Exp Hepatol 2020;10:296-303.10.1016/j.jceh.2019.11.004Search in Google Scholar PubMed PubMed Central

145 Duell PB, Welty FK, Miller M, Chait A, Hammond G, Ahmad Z, et al. Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American heart association. Arterioscler Thromb Vasc Biol 2022;42:e168-e185.10.1161/ATV.0000000000000153Search in Google Scholar PubMed

146 Adams LA, Harmsen S, St Sauver JL, Charatcharoenwitthaya P, Enders FB, Therneau T, et al. Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study. Am J Gastroenterol 2010;105:1567-1573.10.1038/ajg.2010.18Search in Google Scholar PubMed PubMed Central

147 Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005;54:3541-3546.10.2337/diabetes.54.12.3541Search in Google Scholar PubMed

148 Wild SH, Walker JJ, Morling JR, McAllister DA, Colhoun HM, Farran B, et al. Cardiovascular disease, cancer, and mortality among people with type 2 diabetes and alcoholic or nonalcoholic fatty liver disease hospital admission. Diabetes Care 2018;41:341-347.10.2337/dc17-1590Search in Google Scholar PubMed

149 Zhou YY, Zhou XD, Wu SJ, Hu XQ, Tang B, Poucke SV, et al. Synergistic increase in cardiovascular risk in diabetes mellitus with nonalcoholic fatty liver disease: a meta-analysis. Eur J Gastroenterol Hepatol 2018;30:631-636.10.1097/MEG.0000000000001075Search in Google Scholar PubMed

150 Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL 2nd, Goldstein LB, et al. Statin safety and associated adverse events: a scientific statement from the American heart association. Arterioscler Thromb Vasc Biol.2019;39:e38-e81.10.1161/ATV.0000000000000081Search in Google Scholar PubMed

151 Liberis A, Petousis S, Tsikouras P. Lipid disorders in pregnancy. Curr Pharm Des 2021;27:3804-3807.10.2174/1381612827666210421103245Search in Google Scholar PubMed

152 Banach M. Where are the recommendations on healthy lifestyle and cardiovascular disease prevention for pregnant women? J Am Heart Assoc 2020;9:e016052.10.1161/JAHA.120.016052Search in Google Scholar PubMed PubMed Central

153 Döbert M, Varouxaki AN, Mu AC, Syngelaki A, Ciobanu A, Akolekar R, et al. Pravastatin versus placebo in pregnancies at high risk of term preeclampsia. Circulation 2021;144:670-679.10.1161/CIRCULATIONAHA.121.053963Search in Google Scholar PubMed

154 Costantine MM, West H, Wisner KL, Caritis S, Clark S, Venkataramanan R, et al. A randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia. Am J Obstet Gynecol 2021;225:666.e1-666.e15.10.1016/j.ajog.2021.05.018Search in Google Scholar PubMed PubMed Central

155 Vahedian-Azimi A, Makvandi S, Banach M, Reiner Ž, Sahebkar A. Fetal toxicity associated with statins: a systematic review and meta-analysis. Atherosclerosis 2021;327:59-67.10.1016/j.atherosclerosis.2021.05.006Search in Google Scholar PubMed

156 Vahedian-Azimi A, Bianconi V, Makvandi S, Banach M, Mohammadi SM, Pirro M, et al. A systematic review and meta-analysis on the effects of statins on pregnancy outcomes. Atherosclerosis 2021;336:1-11.10.1016/j.atherosclerosis.2021.09.010Search in Google Scholar PubMed

157 Edwards AP, Hekel BE. Appraisal of disability attitudes and curriculum of nursing students: a literature review. Int J Nurs Educ Scholarsh 2021;18:20210029.10.1515/ijnes-2021-0029Search in Google Scholar PubMed

158 Multidisciplinary Expert Consensus Working Group on the Clinical Management of Hypertriglyceridemia. [Multidisciplinary Expert Consensus on the Clinical Management of Hypertriglyceridemia]. Chin Circ J2023;38:621-633.Search in Google Scholar
Published Online: 2024-10-01

© 2024 Yang Xiao, Bilian Yu, Chen Chao, Shuai Wang, Die Hu, Chao Wu, Yonghong Luo, Lingxiang Xie, Chenyu Li, Daoquan Peng, Zhiguang Zhou; Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, National Society of Cardiometabolic Medicine, published by De Gruyter on behalf of Scholar Media Publishing

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Articles in the same Issue

  1. Guideline and Consensus
  2. Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition)
  3. Review Article
  4. Role of viral hepatitis in pregnancy and its triggering mechanism
  5. Original Article
  6. Machine learning-based phenogroups and prediction model in patients with functional gastrointestinal disorders to reveal distinct disease subsets associated with gas production
  7. Recognition of differently expressed genes and DNA methylation markers in patients with Lupus nephritis
  8. PRP improves the outcomes of autologous skin graft transplantation on the esophagus by promoting angiogenesis and inhibiting fibrosis and inflammation
  9. Identification of functional heterogeneity of immune cells and tubular-immune cellular interplay action in diabetic kidney disease
  10. Actin-related protein 2/3 complex subunit 1B promotes ovarian cancer progression by regulating the AKT/PI3K/mTOR signaling pathway
  11. Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes
  12. Inhibition of heterogeneous nuclear ribonucleoproteins A1 and oxidative stress reduces glycolysis via pyruvate kinase M2 in chronic thromboembolic pulmonary hypertension
https://doi.org/10.2478/jtim-2024-0014
Keywords for this article
diabetes mellitus; type 1; type 2; dyslipidemia; atherosclerotic cardiovascular disease
Creative Commons
BY-NC-ND 4.0

Articles in the same Issue

  1. Guideline and Consensus
  2. Chinese expert consensus on blood lipid management in patients with diabetes (2024 edition)
  3. Review Article
  4. Role of viral hepatitis in pregnancy and its triggering mechanism
  5. Original Article
  6. Machine learning-based phenogroups and prediction model in patients with functional gastrointestinal disorders to reveal distinct disease subsets associated with gas production
  7. Recognition of differently expressed genes and DNA methylation markers in patients with Lupus nephritis
  8. PRP improves the outcomes of autologous skin graft transplantation on the esophagus by promoting angiogenesis and inhibiting fibrosis and inflammation
  9. Identification of functional heterogeneity of immune cells and tubular-immune cellular interplay action in diabetic kidney disease
  10. Actin-related protein 2/3 complex subunit 1B promotes ovarian cancer progression by regulating the AKT/PI3K/mTOR signaling pathway
  11. Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes
  12. Inhibition of heterogeneous nuclear ribonucleoproteins A1 and oxidative stress reduces glycolysis via pyruvate kinase M2 in chronic thromboembolic pulmonary hypertension
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