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RSSDI consensus recommendations for dyslipidemia management in diabetes mellitus

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Abstract

Diabetic dyslipidemia is characterised by low HDL-C and high triglyceride levels. Unlike the Caucasian population, though LDL-C levels are not very high, there is a preponderance of more atherogenic small, dense LDL particles among Indians. Furthermore, apo B levels are elevated. This, unique ‘atherogenic dyslipidemia’, is frequently encountered in South Asians with diabetes. People with type 2 diabetes are considered to be at high risk for vascular events. Hence, irrespective of other risk factors such as age, male gender, hypertension, family history, smoking, obesity, and polycystic ovary syndrome in women, they must be screened for dyslipidemia. Other major ASCVD risk factors include family history of hyperlipidemia, low levels of HDL-C, hypertriglyceridemia, and increased levels of total serum cholesterol level, non-HDL-C, LDL-C, apo B, Lp(a), triglyceride-rich remnants, and small, dense LDL-C. In patients with diabetes, dyslipidemia should be assessed at diagnosis and annually thereafter. In patients with type 1 diabetes, screening for dyslipidemia should be initiated from the age of 12 years. Periodical screening for dyslipidemia is recommended in overweight or obese children with a family history of type 2 diabetes, or those from a predisposed race/ethnicity like Asian, American Indian, etc. Both fasting and non-fasting lipid profiles are important for managing Indian patients with dyslipidemia. For routine screening, a fasting lipid profile is not mandatory; the decision to acquire fasting or non-fasting lipid values must be individually tailored. Apolipoprotein B level is considered an enhanced estimate of an individual’s exposure to atherosclerotic lipoproteins, and may be predominantly valuable for assessment of risk in individuals where LDL-C measurement underestimates this burden (those with diabetes mellitus, high triglycerides, obesity, or low LDL-C). The QRISK3 assessment tool algorithm calculates an individual’s risk of developing a heart attack or stroke over 10 years, and takes into account ethnicity as a risk factor. Considering the possible genetic influence of Indian ethnicity on CVD, the QRISK3 score exemplifies as the current most accurate CVD screening tool available for the Indian population.

Stratification of ASCVD risk in Indian diabetic patients:

High risk: diabetes with 0–1 other major ASCVD risk factors and no evidence of target organ damage.

Very high risk: diabetes with ≥2 other major ASCVD risk factors or evidence of target organ damage.

High-risk patients necessitate management comparable to that for secondary prevention of CVD. The most important step in defining treatment goals for dyslipidemia in diabetic patients is an extensive assessment of their cardiovascular risk, with LDL-C as the primary target, and non HDL-C, HDL-C, and apo B as secondary targets. A comprehensive strategy is essential in the management of dyslipidemia so as to regulate lipid levels and tackle related metabolic deviations and modifiable risk factors.

Essential considerations to improve lipid profile and glycemic control, and reduce CVD risk:

• Accomplish healthy weight and aerobic activity level,

• Implement an energy-restricted, well-balanced diet,

• No or at most moderate alcohol consumption, and

• Smoking (or any other tobacco use) cessation.

Medical nutrition therapy plays a central part in diabetes management; every individual with diabetes must be actively engaged in self-management, education, and treatment planning with their healthcare team, together with the collective development of an individualised eating plan. Statins are beneficial as a primary or secondary prevention strategy, to reduce the risk of cardiovascular events, in patients with ASCVD or multiple cardiovascular risk factors especially in those with diabetes. Unless contraindicated, first-line cholesterol-lowering therapy includes the use of moderate- to high-intensity statin. Ezetimibe, when combined with statins, provides additive and complementary therapeutic lipid effects, resulting in considerable reductions in LDL-C and significant achievement of target cholesterol levels. It also permits the use of lower dosage of statins without compromising efficacy, reducing the odds of dose-dependent statin adverse effects. Bempedoic acid seems to provide a safe and effective oral therapeutic option for lipid lowering in patients intolerant to statins. PCSK9 inhibitor therapy, in diabetes, induces analogous relative reductions in cardiovascular risk, and is recommended to further reduce LDL-C in patients aged 40–79 years with LDL-C ≥190 mg/dL, with ASCVD risk factors, or other significant additional-high risk markers (including diabetes) and LDL-C ≥100 mg/dL or non-HDL-C ≥130 mg/dL on maximally tolerated statin therapy and/or ezetimibe. Fenofibrate has shown to reduce CVD in diabetic patients with elevated triglycerides and low HDL-C levels. Saroglitazar has well-documented positive effects in the management of diabetic dyslipidemia; not only does it improve lipid parameters (triglycerides, apo B, non-HDL-C), it has a significant impact on glycemic parameters (HbA1c and fasting blood glucose) in dyslipidemic patients. It, hence, appears as a novel therapy for decreasing cardiovascular risk in patients with type 2 diabetes. Omega-3 fatty acids offer additional benefits when administered as an add-on to statins, and could be attributed to the lowering of detrimental chronic inflammatory markers in people with diabetes and high-risk cardiovascular patients. Icosapent ethyl may provide additional risk reduction benefit, beyond a statin, in individuals with ASCVD or diabetes and multiple risk factors and triglyceride ≥150 mg/dL. Considering the evidence in patients with diabetic dyslipidemia combined with the experience and consensus of the experts, we recommend a step-wise approach for the management for diabetic dyslipidemia in the Indian population (Table 7).

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Acknowledgment

We acknowledge the assistance provided by consultant medical writers, Dr. Aafreen Saiyed and Dr. Suraj Ghag, in the preparation of these Guidelines.

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Saboo, B., Agarwal, S., Makkar, B.M. et al. RSSDI consensus recommendations for dyslipidemia management in diabetes mellitus. Int J Diabetes Dev Ctries 42, 3–28 (2022). https://doi.org/10.1007/s13410-022-01063-6

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