lipids and diabetes

1. DECIPHERING THE LIPID PROFILE REPORT IN DIABETES!
WHERE & WHEN TO STRESS

2. INTRODUCTION
 Diabetes (T2DM) and cardiovascular complications pose significant global public health challenges.
 Individuals with T2DM face a two- to four-fold increased risk of coronary artery disease (CAD), the leading
cause of death in this population.
 Dyslipidemia and hypertension, modifiable risk factors, contribute to more than 87% of disability in low-
and middle-income countries.
 Prediabetes, an intermediate state between normoglycemia and T2DM, is associated with an elevated risk
of cardiovascular disease.
 "Diabetic dyslipidemia" in T2DM patients is characterized by high total cholesterol (T-Chol), high
triglycerides (Tg), low high-density lipoprotein cholesterol (HDL-C), and increased levels of small dense
LDL particles.
 Lipid abnormalities vary across ethnic groups, economic levels, and access to healthcare.
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"Diabetic dyslipidemia" in T2DM patients is characterized by high total cholesterol (T-Chol), high triglycerides (Tg), low high-density lipoprotein cholesterol (HDL-C), and
increased levels of small dense LDL particles.

3. INTRODUCTION
 Abnormal levels of lipid parameters reflect the risk of T2DM, as indicated by a recent meta-analysis.
 South Asians, at lower BMI levels, develop diabetes compared to Caucasians, partly explained by
differences in body fat distribution and higher risk of visceral adiposity.
 Specific waist circumference (WC) cutoffs are recommended for South Asians by WHO and IDF due to
differences in diabetes prevalence at similar BMI levels.
 Bangladeshis exhibit the highest prevalence of CAD risk factors among South Asian populations,
contributing to earlier development of T2DM and cardiovascular complications compared to western
countries.
 In Bangladesh, CAD, stroke, and T2DM account for significant percentages of deaths, emphasizing the
urgent need for comprehensive preventive strategies.
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"Diabetic dyslipidemia" in T2DM patients is characterized by high total cholesterol (T-Chol), high triglycerides (Tg), low high-density lipoprotein cholesterol (HDL-C), and
increased levels of small dense LDL particles.

4. DIABETES CORRELATION WITH DYSLIPIDAEMIA
 Main Aim of Diabetes Management:
 Prevent atherosclerotic cardiovascular diseases (ASCVD) and microvascular complications in patients
with type 2 diabetes.
 ASCVD is a major cause of diabetes-related morbidity and mortality, leading to increased healthcare
costs.
 Association with Dyslipidemia:
 Dyslipidemia often coexists with diabetes and is a significant risk factor for ASCVD, along with
smoking, hypertension, and chronic kidney disease.
 Dyslipidemia is involved in the progression of diabetic kidney disease and diabetic retinopathy.
 Atherogenic Lipid Profiles in Diabetes:
 Patients with diabetes exhibit atherogenic lipid profiles, including elevated LDL-C levels, decreased
HDL-C levels, and hypertriglyceridemia.
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Ide S, Maezawa Y, Yokote K. Updates on dyslipidemia in patients with diabetes. Journal of Diabetes Investigation. 2023 Jun 22.

5. DIABETES CORRELATION WITH DYSLIPIDAEMIA
 Role of LDL-C in ASCVD:
 High LDL-C level is a strong risk factor for ASCVD in patients with and without diabetes.
 Cholesterol-lowering therapy using statins has shown to reduce the relative risk of primary and
secondary ASCVD events.
 Residual Risk Factors:
 Despite statin therapy, there is a residual risk, including hypertriglyceridemia, low HDL-C levels, and
small dense LDL particles.
 TG/HDL-C Ratio as a Parameter:
 The TG/HDL-C ratio is suggested as a parameter for assessing atherogenic dyslipidemia.
 Elevated TG/HDL-C ratio correlates with an increased risk of major ASCVD events.
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Ide S, Maezawa Y, Yokote K. Updates on dyslipidemia in patients with diabetes. Journal of Diabetes Investigation. 2023 Jun 22.

6. DIABETES CORRELATION WITH DYSLIPIDAEMIA
 Exploration of Other Therapies:
 Studies on fibrates, pemafibrate, and omega-3 fatty acids show mixed results in reducing CV events.
 TG-lowering therapy's effect on CV risk is controversial, and the reduction in ASCVD events may be
limited when LDL-C levels are tightly controlled.
 Impact of Glucose-Lowering Medications:
 Sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists
(GLP-1 RAs) have beneficial effects on lipid profiles.
 These medications show positive effects on endothelial function and may reduce the incidence of
non-alcoholic fatty liver disease (NAFLD).
 Pleiotropic Effects of GLP-1 RAs:
 GLP-1 RAs and tirzepatide have pleiotropic effects, including reduction in TG levels, increase in HDL-C
levels, and positive impact on NAFLD.
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Ide S, Maezawa Y, Yokote K. Updates on dyslipidemia in patients with diabetes. Journal of Diabetes Investigation. 2023 Jun 22.

7. DIABETES CORRELATION WITH DYSLIPIDAEMIA
 Management According to Guidelines:
 Dyslipidemia is managed in daily clinical settings following guidelines established in the USA, Europe, and Japan.
 Guidelines differ in lipid management goals and therapeutic recommendations, with more intensive LDL-C target levels
recommended in some regions.
 Consideration of Other Lipid Parameters:
 After achieving target LDL-C levels, guidelines recommend considering other lipid parameters such as TG and HDL-C
levels.
 Individualized Approaches:
 Different regions have different guidelines, with the Japan Atherosclerosis Society guidelines lacking medication selection
recommendations due to limited evidence in Asian populations.
 Post-Treatment Considerations:
 Lifestyle therapy and optimization of glycemic control are recommended in patients with high TG and low HDL-C levels
even after achieving target LDL-C levels.
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Ide S, Maezawa Y, Yokote K. Updates on dyslipidemia in patients with diabetes. Journal of Diabetes Investigation. 2023 Jun 22.

8. LIPID MANAGEMENT TARGETS IN DIABETES
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Ide S, Maezawa Y, Yokote K. Updates on dyslipidemia in patients with diabetes. Journal of Diabetes Investigation. 2023 Jun 22.

9. PATIENTS WITH DIABETES SHOULD BE CLASSIFIED AS HAVING HIGH
CV RISK
 ASCVD Risk in Diabetes:
 Adults with diabetes face a fourfold higher risk of atherosclerotic cardiovascular disease (ASCVD)
compared to non-diabetic adults.
 The cardiovascular risk increases with worsening glycemic control.
 All-Cause Mortality and CVD in Diabetes:
 Diabetes is associated with a 75% increase in all-cause mortality in adults, with cardiovascular disease
(CVD) contributing significantly to excess mortality.
 European Society of Cardiology Recommendations (ESC 2021):
 ESC 2021 suggests classifying patients with type 2 diabetes (DMT2) as having moderate CV risk under
specific conditions (well-controlled diabetes, recent onset, no target organ damage, and no
additional ASCVD risk factors).
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10. PATIENTS WITH DIABETES SHOULD BE CLASSIFIED AS HAVING HIGH
CV RISK
 Challenges in Clinical Practice:
 Clinical observation reveals that DMT2 patients often exhibit other risk factors and/or subclinical
organ damage, challenging the accuracy of ASCVD risk assessment.
 Underestimation of ASCVD Risk:
 The ASCVD risk in DMT2 patients is often underestimated and undertreated, as the observed patients
rarely meet the criteria set by ESC 2021.
 Early Presence of Vascular Changes:
 Macro- and microvascular changes are present in a significant proportion of patients at the time of
diabetes diagnosis.
 Prediabetes is associated with increased risks of all-cause mortality, CVDs, coronary heart disease,
and stroke.
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11. PATIENTS WITH DIABETES SHOULD BE CLASSIFIED AS HAVING HIGH
CV RISK
 Coexistence of CV Risk Factors at Diagnosis:
 At DMT2 diagnosis, other CV risk factors coexist, including abdominal obesity, dyslipidemia, arterial hypertension,
and metabolic syndrome.
 Complexity of ESC 2021 Guidelines:
 The 2021 ESC prevention guidelines are considered too complex for practitioners, potentially leading to
inappropriate treatment of some diabetic patients.
 Suggested Change in Risk Stratification Approach:
 Authors propose a change in the risk stratification approach among diabetic patients, recommending an
immediate classification into high, very high, or extreme CV risk based on the guidelines of the Polish Lipid
Association (PoLA) and other major Polish scientific societies from 2021.
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12. ACCORDING TO THE POLISH LIPID ASSOCIATION 2021
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Cardiovascular risk categories in patients with diabetes mellitus according to the
Polish Lipid Association 2021

13. GOALS AND RULES OF LIPID-LOWERING TREATMENT IN PATIENTS
WITH DIABETES AND DYSLIPIDEMIA
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Recommendations by Polish
Lipid Association 2021 on
treatment of lipid disorders in
patients with diabetes

14. LIPID DISORDER MANAGEMENT
Lipid Disorder Management Principles:
 Follow the principle: "the lower, the better" for lipid disorders in diabetic patients.
 Strive for "the earlier, the better" and maintain it as long as possible for optimal cardiovascular risk
reduction.
 Paradigm II: The Earlier, The Better:
 Increased LDL-C is associated with a significant increase in ASCVD risk.
 For every additional 1 mmol/l of LDL-C, there is a 16% increase in risk, and in subjects aged 20–49, a
47% increase is observed.
 Moderate dyslipidemia in young adults increases the risk of coronary artery disease by 67% over 15
years.
 Atherogenic effect of LDL-C depends on both concentration and duration of exposure.
 Very high and extremely high-risk patients may require upfront combination therapy for immediate
and intensive lipid lowering.
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15. LIPID DISORDER MANAGEMENT
 Paradigm III: The Longer, The Better:
 Statin discontinuation increases the risk of major CV events by approximately 30%, according to a
study involving 67,418 long-term statin users.
 Better adherence to statin therapy is associated with a significantly better prognosis and a lower risk
of CV events.
 Good adherers have a 25% lower risk of any CV event or death, lower incidence of acute coronary
syndrome, and acute cerebrovascular events.
 Patients with best adherence to statin therapy show a reduction in risk of ischemic heart disease by
18%, CVD by 47%, cerebrovascular disease by 26%, and death by 49%.
 Stopping statin use leads to a significant increase in the risk of any CV event, coronary event, and
cerebrovascular event.
 Patients adherent to LDL-C target for at least 5 years expect at least a 25% ASCVD risk reduction,
and lifetime adherence (40 years or longer) leads to a 55% ASCVD risk reduction.
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16. OPTIMIZATION OF LIPID-LOWERING TREATMENT IN PATIENTS WITH
DIABETES AND DYSLIPIDEMIA
 The main rules to remember to be effective with lipid lowering therapy (LLT) are:
 Correctly assess the ASCVD risk of the diabetic patient
 Determine the baseline LDL-C level to be able to calculate the expected absolute LDL-C reduction
needed for your patient to reach their target
 Explore the full lipid and lipoprotein profile to tailor the therapy to the specific dyslipidemia.
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17. EFFECTIVE REDUCTION OF TRIGLYCERIDE RICH LIPOPROTEINS
Personalized recommendations
of management in patients
with diabetes and dyslipidemia
to reduce the risk associated
with atherogenic dyslipidemia
and improve (do not worsen)
glucometabolic status
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18. CONCLUSION
 Optimizing LLT in Diabetes:
 Recommendations focus on high-risk patients with diabetes.
 ASCVD risk is often underestimated and undertreated.
 LDL-C Goal Achievement Challenges:
 Less than 30% of type II diabetes patients reach LDL-C targets, irrespective of CVD risk.
 Guidance prioritizes addressing the significant unmet need of LDL-C goal achievement.
 Focus on LDL-C, Exclusion of Other Biomarkers:
 Emphasis on achieving LDL-C targets; non-HDL-C, remnants, and ApoB are briefly mentioned but not
discussed.
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19. CONCLUSION
 Need for Additional Outcome Data Acknowledged:
 Some recommendations lack sufficient outcome data, requiring further evidence.
 Novel compounds and therapies are anticipated to enhance therapeutic paradigms.
 Patient Examination for CV Risk Stratification:
 Patients with diabetes should undergo a careful examination for CV risk stratification.
 Early LDL-C Target Achievement:
 Strongly recommend achieving LDL-C targets early for high-risk diabetic patients to maximize
cardiovascular disease prevention.
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20. THANK YOU