DYSLIPIDEMIA IN DIABETES

MELLITUS BASED ON
CARDIOVASCULAR RISK
STRATIFICATION

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Introduction
• Type 2 diabetes is a common cause of premature coronary artery disease and
stroke.
• Conversely, the most common cause of morbidity and mortality in type 2 diabetes is
premature cardiovascular disease (CVD).
• Moreover, the risk of CVD is increased well before the onset of overt diabetes, likely
due to the existence of the metabolic syndrome, which often precedes the onset of
hyperglycemia.
• Type 1 diabetes also is characterized by an increased risk of developing clinical
CVD and death from CVD, especially in the presence of hypertension and renal
disease.
1. Emerging Risk Factors C, Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl JMed. 2011;364(9): 829–41.
2. Livingstone SJ, Levin D, Looker HC, Lindsay RS,Wild SH, Joss N, et al. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015;313(1):37–44.
3. Morimoto A, Onda Y, Nishimura R, Sano H, Utsunomiya K, Tajima N, et al., Diabetes Epidemiology Research International Mortality Study G. Cause-specific mortality trends in a nationwide
population-based cohort of childhood-onset type 1 diabetes in Japan during 35 years of follow-up: the DERI Mortality Study. Diabetologia. 2013;56(10):2171–5.
4. Miller RG, Secrest AM, Ellis D, Becker DJ, Orchard TJ. Changing impact of modifiable risk factors on the incidence of major outcomes of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes
Complications Study. Diabetes Care. 2013;36(12): 3999–4006.
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• The risk of atherosclerotic cardiovascular disease (ASCVD) in patients with diabetes
is amplified by several concurrent atherogenic factors, including abdominal obesity,
insulin resistance, nonalcoholic fatty liver disease, hypertension, low-grade
inflammation, increased oxidative stress, a procoagulant state, endothelial
dysfunction, increased arterial wall stiffness and cardiorenal perturbations.
• However, perhaps the most important proatherogenic susceptibility in type 2
diabetes results from multifaceted dyslipidemia characterized by numerous
disturbances beyond low-density lipoprotein (LDL) cholesterol, which is often
normal in diabetes.
• These disturbances include: increased triglyceride (TG) levels and remnants of TG-
rich lipoprotein particles, depressed high-density lipoprotein (HDL) cholesterol
and HDL particle numbers, increased small dense LDL particles, apolipoprotein
(Apo) B, non-HDL cholesterol and post-prandial hyperlipidemia.

1. Stone JA, Fitchett D, Grover S, Lewanczuk R, Lin P. Vascular protection in people with diabetes. Can J Diabetes 2013;37 Suppl. 1:S100e4.
2. Newman JD, Schwartzbard AZ, Weintraub HS, Goldberg IJ, Berger JS. Primary prevention of cardiovascular disease in diabetes mellitus. J Am Coll Cardiol
2017;70:883e93. 3
3. Varbo A, Nordestgaard BG. Remnant lipoproteins. Curr Opin Lipidol 2017;28: 300e7. CAL
Dyslipidemia in type 2 Diabetes
• In type 2 diabetes and the metabolic syndrome, dyslipidemia is characterized by the
presence of hypertriglyceridemia, normal to mildly elevated levels of LDL cholesterol,
with increased numbers of small dense LDL particles, and low HDL cholesterol levels, with
variable changes in HDL composition.
• The concentration of apoB, which reflects the number of atherogenic lipoprotein particles
[VLDL, remnant particles, LDL and Lp(a)], is also increased.
• Moreover, postprandial lipemia—the increase in chylomicrons and chylomicron remnants—
is also increased in these patients.
• These abnormalities can be modulated by the presence of genetic forms of dyslipidemia,
lifestyle measures such as diet and exercise, the nature and extent of hyperglycemia
management, and the presence of complications such as nephropathy.

11. BrownWV, Clark L, Falko JM, Guyton JR, Rees TJ, Schonfeld G, et al. Optimal management of lipids in diabetes and metabolic syndrome. J Clin Lipidol. 2008;2(5):335–42.
12. Gowri MS, Van der Westhuyzen DR, Bridges SR, Anderson JW. Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may be due to the
abnormal composition of HDL. Arterioscler Thromb Vasc Biol. 1999;19(9): 2226–33.
13. GarveyWT, Kwon S, Zheng D, Shaughnessy S,Wallace P, Hutto A, et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by
nuclear magnetic resonance. Diabetes. 2003;52(2):453–62. 4
14. Ginsberg HN, Illingworth DR. Postprandial dyslipidemia: an atherogenic disorder common in patients with diabetesmellitus.AmJ Cardiol. 2001;88(6A):9H–15H. CAL
 Dyslipidemia in type 1 Diabetes
• The situation is different in type 1 diabetes, in which hypertriglyceridemia is
characteristic of the untreated or poorly treated state, when HDL cholesterol levels
also can be low.
• Although HDL cholesterol levels tend to be normal or even elevated in type 1 diabetic
subjects under good glycemic control, this increased HDL cholesterol does not always
appear to provide CVD protection.
• The presence of renal complications can modulate plasma lipids and lipoproteins,
especially the presence of the nephrotic syndrome, and lead to a similar lipid profile as
seen with type 2 diabetes.

15. Ginsberg HN. Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low HDL cholesterol levels. Diabetes. 1996;45(Suppl 3):S27–30.
16. Goldberg IJ. Clinical review 124: diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab. 2001;86(3):965–71.
17. Eckel RH, Albers JJ, Cheung MC, Wahl PW, Lindgren FT, Bierman EL. High density lipoprotein composition in insulindependent diabetes mellitus. Diabetes. 1981;30:132–8.
18. Durrington PN. Serum high density lipoprotein cholesterol in diabetes mellitus: an analysis of factors which influence its concentration. Clin Chim Acta. 1980;104(1):11–23.
19. Soedamah-Muthu SS, Vergouwe Y, Costacou T, Miller RG, Zgibor J, Chaturvedi N, et al. Predicting major outcomes in type 1 diabetes: a model development and validation study.
Diabetologia. 2014;57(11):2304–14.
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20. Costacou T, Evans RW, Orchard TJ. High-density lipoprotein cholesterol in diabetes: is higher always better? J Clin Lipidol. 2011;5(5):387–94.
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Pathogenesis of diabetic dyslipidemia

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J. M. Chehade et al. Management of Dyslipidemia in Type 2 Diabetes. Drugs (2013) 73:327–339 CAL
LIPID MANAGEMENT.
STATIN TREATMENT

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Standards of Medical Care in Diabetes. Diabetes Care 2020;43(Suppl. 1):S1–S2 CAL
Primary Prevention Recommendations

1. For patients with diabetes aged 40–75 years without atherosclerotic cardiovascular

disease, use moderate-intensity statin therapy in addition to lifestyle therapy. (A)

2. For patients with diabetes aged 20–39 years with additional atherosclerotic

cardiovascular disease risk factors, it maybe reasonable to initiate statin therapy in

addition to lifestyle therapy. (C)

Standards of Medical Care in Diabetes. Diabetes Care 2020;43(Suppl. 1):S1–S2 CAL

Primary Prevention Recommendations

1. In patients with diabetes at higher risk, especially those with multiple

atherosclerotic cardiovascular disease risk factors or aged 50–70 years, it is
reasonable to use high-intensity statin therapy. (B)

2. In adults with diabetes and 10-year atherosclerotic cardiovascular disease

risk of 20% or higher, it may be reasonable to add ezetimibe to maximally
tolerated statin therapy to reduce LDL cholesterol levels by 50% or more.
(C)

Standards of Medical Care in Diabetes. Diabetes Care 2020;43(Suppl. 1):S1–S2 CAL

Secondary prevention recommendations

1. For patients of all ages with diabetes and atherosclerotic cardiovascular disease, high-intensity

statin therapy should be added to lifestyle therapy. A

2. For patients with diabetes and atherosclerotic cardiovascular disease considered very high risk

using specific criteria, if LDL cholesterol is >70 mg/dL on maximally tolerated statin dose,

consider adding additional LDL-lowering therapy (such as ezetimibe or PCSK9 inhibitor). A

Ezetimibe may be preferred due to lower cost.

Standards of Medical Care in Diabetes. Diabetes Care 2020;43(Suppl. 1):S1–S2 CAL

Secondary prevention recommendations
3. For patients who do not tolerate the intended intensity, the maximally tolerated
statin dose should be used. E

4. In adults with diabetes aged >75 years already on statin therapy, it is reasonable
to continue statin treatment. B

5. In adults with diabetes aged >75 years, it may be reasonable to initiate statin
therapy after discussion of potential benefits and risks. C

6. Statin therapy is contraindicated in pregnancy. B

Standards of Medical Care in Diabetes. Diabetes Care 2020;43(Suppl. 1):S1–S2 CAL

Treatment of Other Lipoprotein Fractions or
Targets
1. For patients with fasting triglyceride levels ≥500 mg/dL, evaluate for secondary
causes of hypertriglyceridemia and consider medical therapy to reduce the risk of
pancreatitis. C
2. In adults with moderate hypertriglyceridemia (fasting or nonfasting triglycerides
175–499 mg/dL), clinicians should address and treat lifestyle factors (obesity and
metabolic syndrome), secondary factors (diabetes, chronic liver or kidney disease
and/or nephrotic syndrome, hypothyroidism), and medications that raise
triglycerides. C
3. In patients with atherosclerotic cardiovascular disease or other cardiovascular risk
factors on a statin with controlled LDL cholesterol but elevated triglycerides (135–
499 mg/dL), the addition of icosapent ethyl can be considered to reduce
cardiovascular risk. A
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Standards of Medical Care in Diabetes. Diabetes Care 2020;43(Suppl. 1):S1–S2 CAL
Other Combination Therapy
1. Statin plus fibrate combination therapy has not been shown to
improve atherosclerotic cardiovascular disease outcomes and is
generally not recommended. A
2. Statin plus niacin combination therapy has not been shown to provide
additional cardiovascular benefit above statin therapy alone, may
increase the risk of stroke with additional side effects, and is generally
not recommended. A

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Standards of Medical Care in Diabetes. Diabetes Care 2020;43(Suppl. 1):S1–S2 CAL
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Diabetes mellitus prevalence, disaggregated by economic status, education,
occupation, age, sex and place of residence

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