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Cited by 205Diabetes, Cardiovascular Risks, and LipoproteinsLipoproteins and Cardiovascular HealthLipid metabolism and disorders

Lipoprotein abnormalities and their consequences for patients with type 2 diabetes

Krentz, Andrew J·2003·Diabetes Obesity and Metabolism
DOI 10.1046/j.1462-8902.2003.0310.x
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Abstract

Dyslipidaemia is common in patients with Type 2 diabetes and is held to be responsible for considerable CVD-related morbidity and mortality. Patients with Type 2 diabetes are at high risk from complications associated with atherosclerosis and should therefore receive preventive interventions. At the level of the adipocyte, impaired insulin action leads to increased rates of intracellular hydrolysis of triglycerides with the release of NEFA. The rise in NEFA provides substrate for the liver that, in the presence of impaired insulin action and relative insulin deficiency, is associated with complex alterations in plasma lipids: * Plasma VLDL levels are raised. (i). Increased VLDL levels are associated with post-prandial hyperlipidaemia that is compounded by impaired LPL activity. The latter may be independently associated with CAD. (ii). Remnant particles can deliver more cholesterol to macrophages than LDL-C particles. Thrombogenic alterations in the coagulation system also ensue from hypertriglyceridaemia. * Plasma HDL-C levels are reduced. (i). The reduction in cardioprotective HDL-C means a reduction of cholesterol efflux from the tissues--the first step in reverse cholesterol transport to the liver from peripheral tissues. (ii). The antioxidant and antiatherogenic activities of HDL-C are reduced when circulating levels are low. * LDL-C particles become small and dense. Small, dense LDL-C particles are held to be more atherogenic than their larger, buoyant counterparts because they (a) are more liable to oxidation and (b) may more readily adhere to and subsequently invade the arterial wall. The atherogenicity of LDL-C may also be enhanced by nonenzymatic glycation. Metabolic and lipid abnormalities can often be improved with lifestyle changes, including dietary modification, weight loss, smoking cessation and increased exercise. Although attainment of better glycaemic control may improve diabetic dyslipidaemia, pharmacological intervention is usually required. Several large-scale clinical trials, including 4S and more recently HPS, have clearly demonstrated the benefits of statins in reducing cardiovascular events. By virtue of their high absolute risk of CVD, many patients with Type 2 diabetes may achieve a greater risk reduction than their non-diabetic counterparts. For example, in 4S there was a 43% reduction in total mortality risk among patients with diabetes compared with 29% for non-diabetics and a reduced risk of MI by 55% vs. 32% for diabetic and non-diabetics, respectively. In the diabetic subgroup in HPS, there were reductions of approximately 25-30% in the risk of first major vascular events. More recently, the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was halted early because of a significant reduction in cardiovascular events compared with placebo. Surprisingly an analysis of subgroups failed to show significance among the diabetic population, although the sample size, shortened follow-up period and higher drop-in statin use among diabetics on placebo may have affected results. The Collaborative Atorvastatin Diabetes Study (CARDS), involving 2800 patients with Type 2 diabetes, was halted 2 years early in June 2003 because patients allocated atorvastatin had significant reductions in MI, stroke and surgical procedures compared with those receiving placebo. The UKPDS demonstrated that the appearance and progression of certain microvascular complications of Type 2 diabetes could be reduced by treatment directed at hyperglycaemia and hypertension. In addition, correction of dyslipidaemia in patients with diabetes is important in reducing the high toll from macrovascular disease. The subjects in the HPS had similar lipid profiles to the participants in UKPDS, suggesting that additional benefit would accrue from a therapeutic assault on the main cardiovascular risk factors simultaneously. We now have firm evidence that appropriate use of statins in patients with Type 2 diabetes can significantly reduce cardiovascular morbidity and mortality.

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  • Because elevated plasma glucose, lipids, and lipid oxidation have been associated with coronary artery disease, these data suggest the potential role of edible berries in ameliorating these risk factors.

    “Since elevated plasma glucose, lipids, and lipid oxidation have been associated with coronary artery disease (CAD),52,53 these data suggest the potential role of edible berries in ameliorating these risk factors.”

    From Berries: emerging impact on cardiovascular health (2010) · cites this paper as [52]

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Authors
Krentz, A. J.
Affiliations
Southampton General Hospital (GB)
Corresponding author
Krentz, Andrew J
ORCID
Krentz, Andrew J
Venue
Diabetes Obesity and Metabolism
Publisher
Wiley
Published
2003-10-22
Volume
5
Issue
s1
Pages
S19-27
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1046/j.1462-8902.2003.0310.x
OpenAlex
W2117545273
Cited by
205
References
56
Citations by year
2025: 3 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 9 · 2016: 12 · 2015: 10 · 2014: 21 · 2013: 10 · 2012: 14
FWCI
1.66
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
type 2 diabetes, dyslipidemia, cardiovascular disease, atherosclerosis, hypertriglyceridemia, small dense LDL, HDL cholesterol, remnant lipoproteins, lipoprotein lipase, VLDL, glycation, statins, lifestyle modification, reverse cholesterol transport, coronary artery disease, thrombosis
MeSH terms
Coronary Artery Disease, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Humans, Hyperlipidemias, Insulin Resistance, Cholesterol, HDL, Cholesterol, LDL, Risk Factors, Hypertriglyceridemia, Randomized Controlled Trials as Topic

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