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Published online February 15, 2007
Diabetes Care 30:1289-1291, 2007
DOI: 10.2337/dc06-1948
© 2007 by the American Diabetes Association
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Pathophysiology/Complications
Brief Report

Preß1-HDL Concentration Is a Predictor of Carotid Atherosclerosis in Type 2 Diabetic Patients

Satoshi Hirayama, MD1, Takashi Miida, MD2, Osamu Miyazaki, PHD3 and Yoshifusa Aizawa, MD1

1 Division of Endocrinology and Metabolism, Niigata University, Niigata, Japan
2 Division of Clinical Preventive Medicine, Niigata University, Niigata, Japan
3 Daiichi Pure Chemicals, Ibaraki, Japan

Address correspondence and reprint requests to Takashi Miida, Division of Clinical Preventive Medicine, Niigata University, Asahimachi 1-757, Niigata, 951-8510, Japan. E-mail: miida{at}med.niigata-u.ac.jp

Abbreviations: CAD, cardiovascular disease • LCAT, lecithin-cholesterol acyltransferase • max IMT, greatest intima-media thickness


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
Pre-ß1-HDL is a minor HDL subfraction that stimulates cholesterol efflux from cell membranes (1,2). However, the fasting preß1-HDL concentration is elevated in patients with coronary artery disease (CAD), hyperlipidemia, and obesity and in hemodialysis patients (3–7). We examined whether the preß1-HDL concentration is elevated in type 2 diabetic patients and whether elevated preß1-HDL concentration is a predictor of carotid atherosclerosis.


   RESEARCH DESIGN AND METHODS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
We measured the preß1-HDL concentration in 30 patients with type 2 diabetes (mean ± SD age 58.5 ± 12.3 years, 13 men and 17 women) and in 30 age- and sex-matched healthy control subjects. We excluded patients receiving hypolipidemic agents and those with renal dysfunction. The diabetic group had a long duration of disease (9.9 ± 8.6 years), high A1C levels (10.4 ± 2.0%), and high BMI (26.1 ± 6.5 kg/m2). The preß1-HDL in frozen plasma, pretreated with sucrose solution for stabilization, was measured using an immunoassay (8). In the diabetic group, we evaluated the severity of carotid atherosclerosis using ultrasonography with a 7.5-MHz probe. The greatest intima-media thickness (max IMT) and plaque score were determined as previously reported (9).


   RESULTS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
The diabetic group had higher triglyceride concentrations than the control subjects (166.9 ± 138.4 vs. 90.9 ± 28.6 mg/dl, P < 0.01), while the two groups did not differ significantly in total cholesterol (215.1 ± 49.9 vs. 201.0 ± 20.9 mg/dl), LDL cholesterol (135.9 ± 37.1 vs. 125.3 ± 17.9 mg/dl), or HDL cholesterol (55.5 ± 18.7 vs. 58.3 ± 16.6 mg/dl) concentrations. Although the diabetic group had lower apoliopoprotein (apo)AI (the only protein component of preß1-HDL) levels than the control subjects (124.6 ± 20.8 vs. 137.8 ± 27.1 mg/dl, P < 0.05), the former had higher absolute and relative preß1-HDL concentrations than the latter (24.5 ± 6.0 vs. 20.3 ± 5.7 mg/l apoAI, respectively, P < 0.01; 1.99 ± 0.51 vs. 1.49 ± 0.36% apoAI, P < 0.001). In the diabetic group, the absolute preß1-HDL concentration was not correlated with HDL cholesterol or apoAI, while the relative preß1-HDL concentration was negatively correlated with HDL cholesterol and apoAI (r = –0.49, P < 0.01; r = –0.43, P < 0.05). In comparisons using nonsmokers only, the diabetic group (n = 18) had greater absolute and relative preß1-HDL concentrations than control subjects (n = 28) (24.3 ± 6.7 vs. 20.0 ± 5.7 mg/l apoAI, respectively, P < 0.05; 1.86 ± 0.58 vs. 1.46 ± 0.36% apoAI, P < 0.05).

B-mode ultrasound imaging revealed that carotid atherosclerosis was more severe in the diabetic group than in the control subjects. The mean max IMT in the diabetic group was nearly twice that in the control subjects (1.20 ± 0.70 vs. 0.64 ± 0.12 mm, P < 0.001). A higher max IMT, defined as >1.0 mm or at least one carotid plaque, was detected in 80% of the diabetic patients.

In the diabetic group, the max IMT had significant correlations with the absolute and relative preß1-HDL (Fig. 1) and LDL cholesterol concentrations (r = 0.373, P = 0.043). The plaque score had positive correlations with age (r = 0.540, P = 0.002), duration of diabetes (r = 0.472, P = 0.008), and both the absolute and relative preß1-HDL concentrations (Fig. 1). Stepwise multiple regression analysis was performed using the max IMT or plaque score as the dependent variable, and preß1-HDL (model 1, absolute concentration; model 2, relative concentration) together with other risk factors (age, sex, duration of diabetes, triglycerides, LDL cholesterol, A1C, systolic blood pressure, and Brinkman index [cigarettes per day multiplied by years smoked]) as the independent variables. The preß1-HDL concentration was selected as an independent risk factor for the max IMT (model 1, R = 0.382, P = 0.037, B = 0.382, F = 4.776; model 2, R = 0.563, P = 0.006, B = 0.454, F = 7.024) and plaque score (model 1, R = 0.630, P = 0.001, B = 0.473, F = 7.773; model 2, R = 0.681, P = 0.0002, B = 0.493, F = 8.668 [R, multiple correlation coefficient; B, partial correlation coefficient]). Of the other variables, LDL cholesterol was also selected for the max IMT and the duration of diabetes and age for plaque score.


Figure 1
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  		Figure 1— Positive correlation between the preß1-HDL concentration and the indexes of carotid atherosclerosis defined as the max IMT and plaque score (PS) in type 2 diabetic patients. The preß1-HDL concentration is expressed as absolute (•) or relative ({circ}) concentrations. In the diabetic group (n = 30), the max IMT and plaque score had significant positive correlations with both the absolute and relative preß1-HDL concentrations.

 

   CONCLUSIONS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
Our results indicate that the preß1-HDL concentration is elevated in the diabetic group and that a high preß1-HDL concentration is a predictor of carotid atherosclerosis. Many prospective studies have reported positive correlations between the severity of carotid atherosclerosis and cardiovascular risks in general populations and diabetic patients (9,10). Accelerated atherosclerosis in diabetic patients may be explained by insulin resistance, chronic inflammation, hyperglycemia, and dyslipidemia (11,12).

Interestingly, the absolute preß1-HDL concentration was associated with carotid atherosclerosis but not with glycemic control or other HDL markers. In the group combining hypertriglyceridemics and normolipidemics, the absolute preß1-HDL concentration did not significantly correlate with either HDL cholesterol or apoAI levels (5). Furthermore, patients with CAD or hemodialysis patients (high-risk patients for CAD) had an elevated preß1-HDL concentration despite low HDL cholesterol or apoAI (3,4,7). These data correspond well with our study.

An increased preß1-HDL concentration in atherosclerotic disorders may result either from the impaired maturation of preß1-HDL into {alpha}-HDL (3,6,7,13) or from enhanced production of preß1-HDL (5,14). Previously, we found that low lecithin-cholesterol acyltransferase (LCAT) activity was closely related to a high preß1-HDL concentration (3,7). In diabetic patients, the relationship between LCAT activity and atherosclerosis was inconsistent (15,16). In healthy Japanese control subjects, the most important determinant of the preß1-HDL concentration was not the LCAT mass but the rate of LCAT-dependent conversion of preß1-HDL into {alpha}-HDL (17). Therefore, we need to determine the LCAT-dependent conversion rate of preß1-HDL in diabetic patients in a future study.

Another possible explanation for the high preß1-HDL concentration in diabetic patients is the enhanced production of preß1-HDL from {alpha}-HDL. The rates of preß1-HDL synthesis and recycling of {alpha}-HDL to preß1-HDL were elevated in diabetic patients (14). The PLTP (phospholipid transfer protein) activity enhances preß1-HDL synthesis and is positively associated with carotid atherosclerosis in type 2 diabetes (18,19). As measuring PLTP activity is quite difficult, it might be more useful to measure the preß1-HDL concentration when evaluating carotid atherosclerosis.

In conclusion, the preß1-HDL concentration is elevated in type 2 diabetic patients, and an elevated preß1-HDL concentration is a predictor of carotid atherosclerosis. A prospective study would confirm the clinical significance of preß1-HDL in type 2 diabetic patients.


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 15 February 2007. DOI: 10.2337/dc06-1948.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

Received for publication September 19, 2006. Accepted for publication February 6, 2007.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 

  1. Castro GR, Fielding CJ: Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein. Biochemistry 27:25–29, 1988[Medline]
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  3. Miida T, Nakamura Y, Inano K, Matsuto T, Yamaguchi T, Tsuda T, Okada M: Pre beta 1-high-density lipoprotein increases in coronary artery disease. Clin Chem 42:1992–1995, 1996[Abstract/Free Full Text]
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  5. Miida T, Sakai K, Ozaki K, Nakamura Y, Yamaguchi T, Tsuda T, Kashiwa T, Murakami T, Inano K, Okada M: Bezafibrate increases preß1-HDL at the expense of HDL2b in hypertriglyceridemia. Arterioscler Thromb Vasc Biol 20:2428–2433, 2000[Abstract/Free Full Text]
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  8. Miida T, Miyazaki O, Nakamura Y, Hirayama S, Hanyu O, Fukamachi I, Okada M: Analytical performance of a sandwich enzyme immunoassay for preß1-HDL in stabilized plasma. J Lipid Res 44:645–650, 2003[Abstract/Free Full Text]
  9. Handa N, Matsumoto M, Maeda H, Hougaku H, Kamada T: Ischemic stroke events and carotid atherosclerosis: results of the Osaka Follow-up Study for Ultrasonographic Assessment of Carotid Atherosclerosis (the OSACA Study). Stroke 26:1781–1786, 1995[Abstract/Free Full Text]
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This Article
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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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