Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online April 27, 2007
Diabetes Care 30:1789-1794, 2007
DOI: 10.2337/dc06-2585
© 2007 by the American Diabetes Association
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc06-2585v1
30/7/1789    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schindhelm, R. K.
Right arrow Articles by Teerlink, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schindhelm, R. K.
Right arrow Articles by Teerlink, T.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Pathophysiology/Complications
Original Article

Fasting and Postprandial Glycoxidative and Lipoxidative Stress Are Increased in Women With Type 2 Diabetes

Roger K. Schindhelm, BSC, MD1, Marjan Alssema, MSC2, Peter G. Scheffer, PHD3, Michaela Diamant, MD, PHD1, Jacqueline M. Dekker, PHD2, Rob Barto3, Giel Nijpels, MD, PHD2,4, Piet J. Kostense, PHD2,5, Robert J. Heine, MD, PHD1,2, Casper G. Schalkwijk, PHD6 and Tom Teerlink, PHD3

1 Department of Endocrinology, Vrije University (VU) Medical Center, Amsterdam, the Netherlands
2 Institute for Research in Extramural Medicine, VU Medical Center, Amsterdam, the Netherlands
3 Department of Clinical Chemistry, VU Medical Center, Amsterdam, the Netherlands
4 Department of General Practice, VU Medical Center, Amsterdam, the Netherlands
5 Department of Clinical Epidemiology and Biostatistics, VU Medical Center, Amsterdam, the Netherlands
6 Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, the Netherlands

Address correspondence and reprint requests to T. Teerlink, PhD, VU University Medical Center, Clinical Chemistry, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. E-mail: t.teerlink{at}vumc.nl


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
OBJECTIVE— We studied acute changes in markers of glycoxidative and lipoxidative stress, including oxidized LDL, N{varepsilon}-(carboxyethyl)-lysine (CEL), N{varepsilon}-(carboxymethyl)-lysine (CML), and 3-deoxyglucosone (3DG), following two consecutive meals.

RESEARCH DESIGN AND METHODS— Postmenopausal women (27 with normal glucose metabolism [NGM], 26 with type 2 diabetes) received two consecutive fat-rich meals and two consecutive carbohydrate-rich meals on two occasions. Glucose and triglyceride concentrations were measured at baseline and 1, 2, 4, 6, and 8 h following breakfast; lunch was given at 4 h. Oxidized LDL–to–LDL cholesterol ratio, CEL, CML, and 3DG were measured at baseline and at 8 h.

RESULTS— Fasting oxidized LDL–to–LDL cholesterol ratio, 3DG, and CML were higher in women with type 2 diabetes compared with women with NGM and were comparable to the postprandial values at 8 h in NGM. Postprandial rises in the oxidized LDL–to–LDL cholesterol ratio and 3DG were similar in both groups. However, the oxidized LDL–to–LDL cholesterol ratio increased more after the fat-rich meals, whereas CML and 3DG increased more after the carbohydrate-rich meals. After the fat-rich meals, the increase in the oxidized LDL–to–LDL cholesterol ratio correlated with postprandial triglycerides, whereas the increase in 3DG was correlated with postprandial glucose.

CONCLUSIONS— The acute changes in markers of glycoxidative and lipoxidative stress in both type 2 diabetes and NGM suggest that postabsorptive oxidative stress may partly underlie the association of postprandial derangements and cardiovascular risk.

Abbreviations: 3DG, 3-deoxyglucosone • AGE, advanced glycation end product • CAD, coronary artery disease • CEL, N{varepsilon}-(carboxyethyl)-lysine • CML, N{varepsilon}-(carboxymethyl)-lysine • CVD, cardiovascular disease • iAUC, incremental area under the curve • NGM, normal glucose metabolism


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
Patients with type 2 diabetes have an increased risk of cardiovascular disease (CVD) (1), which can only partly be explained by classical CVD risk factors such as hypertension, high LDL cholesterol, low HDL cholesterol, and smoking (2). In postmenopausal women compared with men, the relative risk of CVD conferred by type 2 diabetes is even higher (3). Zilversmit (4) postulated in 1979 that disturbances in postprandial metabolism may contribute to the excess risk of CVD due to postprandial elevations of glucose and triglyceride-enriched lipoproteins (5,6).

Oxidative stress is regarded as a common pathway by which many of the classical CVD risk factors and postprandial dysmetabolism may initiate and promote atherosclerosis (7). Indeed, elevated levels of oxidized LDL are associated with an increased risk for CVD (8). Prolonged exposure to a high-fat diet has been shown to result in an increase in plasma levels of oxidized LDL (9). Another mechanism that might link postprandial dysmetabolism and the risk of CVD in patients with type 2 diabetes includes the formation of advanced glycation end products (AGEs), which are related to micro- and macrovascular complications (10). Two of the most studied AGEs, N{varepsilon}-(carboxyethyl)lysine (CEL) and N{varepsilon}-(carboxymethyl)lysine (CML), can be formed on proteins by both glycoxidation and lipid peroxidation pathways. {alpha}-Dicarbonyl compounds such as 3-deoxyglucosone (3DG), glyoxal, and methylglyoxal are reactive intermediates in the formation of AGEs (11). 3DG is a relatively stable intermediate, whereas glyoxal and methylglyoxal convert readily into CML and CEL, respectively. Because the latter are stable compounds, their quantification may yield more relevant information than quantification of their reactive dicarbonyl precursors.

Data on acute meal-induced changes in oxidized LDL, 3DG, and CML and CEL are limited. To date, one study in healthy young men demonstrated an increase in the oxidized LDL–to–LDL cholesterol ratio after two consecutive fat-rich mixed meals (12), and one study in patients with coronary artery disease (CAD) found that postprandial oxidized LDL was associated with the severity and extent of CAD (13).

In the present study, 26 women with type 2 diabetes and 27 women with normal glucose metabolism (NGM) received two consecutive (breakfast and lunch) fat-rich or carbohydrate-rich meals to study meal-related changes in oxidative stress (oxidized LDL), AGE compounds (CML and CEL), and a reactive AGE precursor (3DG). In addition to the effects of meal composition and the presence of diabetes, we also studied associations between postprandial changes of these markers and changes in glucose and triglycerides.


   RESEARCH DESIGN AND METHODS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
The present study was a substudy of a cross-sectional study to assess the effect and relative contributions of two consecutive fat-rich and carbohydrate-rich meals on markers of CVD risk in women with NGM (fasting glucose <6.1 mmol/l and 2-h postload glucose <7.8 mmol/l) (n = 76) and type 2 diabetes (n = 79). Women with type 2 diabetes (n = 522), recruited from the registry of the Diabetes Care System in Hoorn, the Netherlands, and women who were randomly selected from the municipal registry of Hoorn (n = 541), aged 50–65 years at the beginning of the study, were invited to participate in the study. Of these 1,063 women, 431 were complete nonresponders, 258 were not willing to participate, and 220 did not meet the inclusion criteria. Inclusion criteria were as follows: postmenopausal status, nonsmoking, no untreated endocrine disorder other than type 2 diabetes, no use of short-acting insulin analogs, no use of peroxisome proliferator–activated receptor {alpha} and {gamma} agonists, no use of oral corticosteroids, no use of hormone replacement therapy, no statin use (for NGM subjects only), A1C <9.0%, fasting cholesterol <8.0 mmol/l, fasting triglycerides <4.0 mmol/l, systolic blood pressure <190 mmHg, and no liver impairment or renal impairment. For the present study, a subsample of 26 women with type 2 diabetes (no use of statins or insulin analogs) and 27 women with NGM, matched for age, were studied. All participants gave written informed consent, and the study protocol was approved by the ethics committee of the Vrije University Medical Center in Amsterdam, the Netherlands. The study consisted of a screening visit and two visits for the test meals. On the screening visit, fasting blood samples were drawn after a 12-h overnight fast. Blood pressure was measured thrice with an oscillometric blood pressure measuring device (Colin Press-Mate BP-8800; Colin, Komaki-City, Japan) after a 15-min supine rest. Weight and height were measured in participants wearing only light clothing. Smoking and alcohol consumption were assessed by a questionnaire (14).

Test meals
Postprandial meal responses were examined following two standardized consecutive test meals (breakfast and lunch). On 1 day, both meals were high in fat content, and, on the other occasion, both meals were high in carbohydrate content. The test meal occasions were performed in random order. The fat-rich meals consisted of two croissants, 10 g butter, 40 g high-fat cheese, and 300 ml high-fat milk (3,349 kJ; 50 g fat; and 56 g carbohydrates). The carbohydrate-rich meals consisted of two slices of bread, 25 g marmalade, 30 g cooked chicken breast, 50 g ginger bread, and 300 ml drinking yogurt fortified with 45 g soluble carbohydrates (3,261 kJ; 4 g fat; and 162 g carbohydrates). Both meals were eaten within 10 min. Apart from the test meals and water (ad libitum), participants were not allowed to eat.

Laboratory analysis
Plasma glucose and serum total cholesterol, HDL cholesterol, and triglycerides were measured by enzymatic colorimetric assays (Roche, Mannheim, Germany). Fasting and postprandial LDL cholesterol was calculated according to the Friedewald formula if triglycerides were <4.5 mmol/l (15). A1C was measured with cation-exchange chromatography (Menarini Diagnostics, Florence, Italy).

Oxidized LDL was measured in EDTA plasma in duplicate with a competitive enzyme-linked immunoabsorbant assay kit (Mercodia, Uppsala, Sweden) with interassay and intra-assay coefficients of variation (CVs) of 7.8 and 4.8%, respectively. Because a fairly strong correlation between oxidized LDL and LDL cholesterol is a consistent finding in several studies (16,17), we expressed oxidized LDL as a ratio per LDL cholesterol (oxidized LDL–to–LDL cholesterol ratio), as proposed by Holvoet et al. (18).

3DG was measured with a newly developed liquid chromatography tandem mass spectrometry method after precolumn derivatization, according to a published procedure (19). In brief, 0.5 ml whole blood was mixed with 1.0 ml of 1.2 mol/l perchloric acid and immediately stored at –80°C until assayed. After thawing, the samples were centrifuged (5 min at 20,000g), and 80 µl of the supernatant was mixed with 100 µl of the internal standard solution (1 µmol/l 2,3-pentanedione dissolved in ethanol). After the addition of 20 µl of the derivatization reagent (10 mmol/l 2,4-dinitrophenylhydrazine dissolved in 1.2 mol/l perchloric acid), the samples were incubated for 16 h at room temperature. Chromatographic separation was performed on a Xterra MS C18 column (4.6 x 50 mm, 3.5-µm particle size) (Waters, Milford, MA) using a linear gradient from 40 to 95% acetonitrile in water over 9 min at a flow rate of 1 ml/min. Mass transitions of 521.1-> 431.0 and 521.1->182.1 for 3DG and 459.1->182.1 for the internal standard were monitored in negative ion mode. Intra-assay and interassay CVs for 3DG were 8 and 12%, respectively. Two subjects with NGM had missing 3DG samples because of missing blood samples. In a pilot study applying the same study protocol, we assessed the time-course of 3DG in nine type 2 diabetic subjects and eight NGM subjects and measured 3DG with a high-performance liquid chromatography method with fluorescence detection, as previously described (20). The highest 3DG concentration was observed at 8 h after the first meal (21).

Unbound CML and CEL were measured in EDTA plasma by high-performance liquid chromatography with stable isotope dilution tandem mass spectrometric detection using a procedure developed for the analysis of protein-bound CML and CEL (22), with a modified sample preparation procedure. Briefly, after centrifugation of the plasma samples (5 min at 20,000g), 50 µl of the supernatant was mixed with 150 µl of a combined internal standard solution (containing deuterated CML and CEL), and proteins were removed by centrifugation (20 min at 15,000g) in a 10-kDa cutoff ultrafiltration device (Vivaspin 500 PES; Vivascience, Hannover, Germany). A 90-µl aliquot of the ultrafiltrate was mixed with 10 µl of a 50 mmol/l nonafluoropentanoic acid solution, and 25 µl of this mixture was subjected to liquid chromatography tandem mass spectrometry analysis, as described before (22). Intra-assay and interassay CVs for CML were 3 and 4%, respectively, and for CEL, 5 and 9%, respectively.

To assess the cumulative effect of both consecutive meals, we measured oxidized LDL, 3DG, CML, and CEL at baseline and at 8 h.

Statistical analyses
Analyses were performed with SPSS for Windows version 11.01 (SPSS, Chicago, IL). Data are presented as means ± SD, and, in case of a skewed distribution, as median (interquartile range). Data were ln-transformed before testing, in case of a skewed distribution. Differences between women with NGM and type 2 diabetes were tested with Student's t test for continuous variables and {chi}2 test for dichotomous variables. Differences between meals were tested with paired-samples t tests. Postprandial changes in glucose and triglycerides were calculated as incremental areas under the curve (iAUCs) by the trapezoid method. Correlations between postprandial responses were calculated by Spearman's correlation coefficients. We considered two-sided P < 0.05 to indicate statistical significance.


   RESULTS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
The clinical and biochemical characteristics of the participants at the screening visit are presented in Table 1. Figure 1 illustrates the 8-h time courses of triglycerides and glucose after two consecutive fat-rich and two consecutive carbohydrate-rich meals. At both meal visits, fasting triglyceride and glucose levels were higher in women with type 2 diabetes compared with the women with NGM (both P < 0.001). The iAUC for triglycerides was higher following the fat-rich meals than after the carbohydrate-rich meals in both women with type 2 diabetes and NGM (both P < 0.001) but was similar in both groups. Following the carbohydrate-rich meals, the iAUC for glucose was higher in women with type 2 diabetes compared with NGM (P < 0.001), whereas this difference was borderline significant after the fat-rich meals (P = 0.06).


View this table:
[in this window]
[in a new window]

  		Table 1— Clinical and biochemical characteristics of the study population at the screening visit

 

Figure 1
View larger version (14K):
[in this window]
[in a new window]

  		Figure 1— Time course of triglycerides and glucose concentrations (means ± SD) following two consecutive fat-rich or carbohydrate-rich meals in women with NGM ({circ}) and type 2 diabetes (•).

 
LDL cholesterol significantly decreased from baseline to 8 h in both groups and after both meal types (from 3.6 ± 0.8 to 3.2 ± 0.7 mmol/l and 3.7 ± 0.8 to 3.3 ± 0.7 mmol/l for fat-rich and carbohydrate-rich meals, respectively, in NGM; 3.3 ± 0.7 to 2.9 ± 0.7 mmol/l and 3.3 ± 0.7 to 3.0 ± 0.7 mmol/l, respectively, in type 2 diabetes; all P < 0.001).

Glycoxidative and lipoxidative stress markers
The oxidized LDL–to–LDL cholesterol ratio, 3DG, CML, and CEL values in women with NGM and type 2 diabetes at baseline and at 8 h are listed in Table 2. Baseline oxidized LDL–to–LDL cholesterol ratio, 3DG, and CML were significantly higher in type 2 diabetes compared with NGM. The increase of the oxidized LDL–to–LDL cholesterol ratio during the fat-rich meals was higher than the increase during the carbohydrate-rich meals (17 ± 10 vs. 10 ± 7% in NGM and 15 ± 13 vs. 7 ± 9% in type 2 diabetes, both P < 0.05). Of interest, the fasting values of the oxidized LDL–to–LDL cholesterol ratio, 3DG, and CML in women with type 2 diabetes were similar to the postprandial values at 8 h in women with NGM (all P > 0.1).


View this table:
[in this window]
[in a new window]

  		Table 2— Fasting and postprandial (8-h) levels of oxidized LDL–to–LDL cholesterol ratio, 3DG, CML, and CEL in women with NGM compared with women with type 2 diabetes

 
The baseline oxidized LDL–to–LDL cholesterol ratio was correlated with fasting triglycerides in women with type 2 diabetes (r = 0.39, P < 0.05) but not in women with NGM. After the fat-rich meals, changes in the oxidized LDL–to–LDL cholesterol ratio correlated with changes in triglycerides, either expressed as triglyceride iAUC (r = 0.32, P < 0.05) (Fig. 2A) or as the increase over baseline at 8 h (r = 0.50, P < 0.001).


Figure 2
View larger version (9K):
[in this window]
[in a new window]

  		Figure 2— Relations between postprandial changes of the oxidized LDL–to–LDL cholesterol ratio and 8-h iAUC for plasma triglycerides (A) and between changes of 3DG and 8-h iAUC for glucose (B) after two consecutive fat-rich meals in women with NGM ({circ}) and type 2 diabetes (•). Strengths of the associations are indicated by Spearman's correlation coefficients.

 
The mean increase of 3DG after the carbohydrate-rich meals was higher than after the fat-rich meals (29 ± 21 vs. 13 ± 24%, P < 0.05 in NGM and 36 ± 17 vs. 15 ± 20%, P < 0.001 in type 2 diabetes). Fasting plasma glucose concentration was correlated with baseline 3DG in women with type 2 diabetes (r = 0.50, P < 0.01) but not in women with NGM. Postprandial changes in 3DG correlated with the glucose iAUC after the fat-rich meals (r = 0.37, P < 0.01) (Fig. 2B) but not with the glucose iAUC after the carbohydrate-rich meals. The changes of CML and CEL neither correlated with the triglycerides iAUC nor with the glucose iAUC, irrespective of meal composition.


   CONCLUSIONS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
In the present cross-sectional study in postmenopausal women with NGM and type 2 diabetes, we studied the postprandial changes of the oxidized LDL–to–LCL cholesterol ratio, 3DG, CML, and CEL following two consecutive fat-rich or carbohydrate-rich meals. The main findings are that the fasting values of the oxidized LDL–to–LDL cholesterol ratio, 3DG, and CML are higher in women with type 2 diabetes compared with women with NGM. In women with type 2 diabetes, the fasting values of the oxidized LDL–to–LDL cholesterol ratio, 3DG, and CML were similar to the postprandial values at 8 h in women with NGM. Overall, the postprandial rises of the oxidized LDL–to–LDL cholesterol ratio and 3DG were of similar magnitude in type 2 diabetes and NGM. The oxidized LDL–to–LDL cholesterol ratio showed a greater increase after the fat-rich meals, whereas CML and 3DG increased more after the carbohydrate-rich meals. The increase in the oxidized LDL–to–LDL cholesterol ratio was correlated with the rise in postprandial triglycerides, whereas the increase in 3DG was correlated with the postprandial rise of glucose.

There is increasing evidence that postprandial glucose and triglycerides may play an important role in macro- and microvascular complications (23). However, their relative contributions and the mechanisms leading to the increased CVD risk are not yet fully understood (5). Prospective studies have shown that postprandial or postload glucose levels are more strongly associated with increased CVD than fasting glucose (24,25). Oxidative stress is hypothesized to be an important pathway linking postprandial glucose and triglyceride responses to CVD (26,27). Indeed, in a recent study, it was found that postprandial oxidized LDL was a determinant of the extent of coronary atherosclerosis in patients with CAD (13). A limitation of most previous studies is that responses after a single meal were studied, which might not reflect the "real-life" burden of the postprandial state, possibly leading to an underestimation of the associations between postprandial responses and CVD risk. A recent study from our group that applied two consecutive meals (breakfast and lunch) in healthy young men demonstrated that even slightly increased levels of triglycerides and glucose were associated with endothelial dysfunction and increased markers of oxidative stress, including oxidized LDL (12). We concluded that these findings might be relevant for insulin-resistant subjects and type 2 diabetic individuals who have a more pronounced (exaggerated and prolonged) postprandial elevation of glucose and triglycerides, possibly leading to more oxidative stress. Our present findings support this conjecture, as we found that baseline oxidized LDL was higher in type 2 diabetes than in NGM, with a greater increase of oxidized LDL after the fat-rich meals compared with the carbohydrate-rich meals. Interestingly, although the fasting oxidized LDL–to–LDL cholesterol ratio was higher in the type 2 diabetic group, we found no difference in the postprandial increase in the oxidized LDL–to–LDL cholesterol ratio between NGM and type 2 diabetes.

There are multiple sources and mechanisms in the formation of AGEs in vivo, involving both oxidative and nonoxidative reactions of reducing carbohydrates and other metabolic intermediates with amino acid residues (28). The AGE precursor 3DG, which is increased in patients with diabetes (29), is formed by nonoxidative modifications of Amadori adducts and from fructose-3-phosphate (30). In line with these observations, we found that 3DG increased more after the carbohydrate-rich meals than after the fat-rich meals. In addition, postprandial changes in 3DG were significantly correlated to changes in glucose but, surprisingly, only after the fat-rich meals. This suggests involvement of additional oxidative mechanisms in its formation. In patients with type 1 diabetes, Beisswenger et al. (31) observed an increase in 3DG within 2 h, whereas in our pilot study in patients with type 2 diabetes we did not observe a rise in 3DG after the first meal (21).

Some studies have shown that total serum CML is higher in type 2 diabetes than in healthy individuals (32,33), although in other studies, no difference was observed (22). We chose not to measure total CML and CEL but rather the unbound forms of these compounds that are continuously released during degradation of intracellular proteins with a rapid turnover. Because oxidative stress not only enhances formation of protein-bound CML and CEL but also triggers proteasomal degradation of damaged proteins (34,35), the unbound fraction of CML and CEL may better reflect formation of AGEs by oxidative stress. We observed that CML was affected by both meal types. However, possibly due to a relatively large biological variation, as reflected by differences in the baseline CML and CEL values at the two meal visits, these changes were less consistent than for oxidized LDL and 3DG. Future studies should assess whether changes in the protein-bound forms of CML and CEL are more informative.

The major precursor of CML is glyoxal, and oxidative stress seems to enhance the formation of glyoxal from glucose (36), which is consistent with our finding of a greater increase in CML after the carbohydrate-rich meals compared with the fat-rich meals.

This study has few limitations. First, both groups were not matched for BMI, lipids, blood pressure, and alcohol intake, all of which may have independent effects on the parameters measured. However, we chose not to match for these variables to avoid selection of relatively healthy type 2 diabetic patients. Second, our study was performed in elderly postmenopausal women, and the changes observed might be different in younger women as well as in men.

In summary, we found significant elevations of postprandial oxidized LDL–to–LDL cholesterol ratios, 3DG, and CML in postmenopausal women with type 2 diabetes and NGM. Because postprandial increases in {alpha}-dicarbonyls and associated AGEs are related to cellular damage, therapies aimed at reducing postprandial glycemia and triglyceridemia may contribute to the reduction in micro- and macrovascular complications.


   Acknowledgments
 
This study was supported by Novartis Switzerland and a grant from Dutch Diabetes Research Foundation (no. 2001.00.052).

We thank Danielle van Assema for her assistance in organization and Rick Vermue for his excellent technical assistance.


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 27 April 2007. DOI: 10.2337/dc06-2585.

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 December 21, 2006. Accepted for publication April 18, 2007.


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

  1. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229–234, 1998[Abstract/Free Full Text]
  2. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR: Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS). BMJ 23:316:823–828, 1998
  3. Becker A, Bos G, de Vegt F, Kostense PJ, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD: Cardiovascular events in type 2 diabetes: comparison with nondiabetic individuals without and with prior cardiovascular disease: 10-year follow-up of the Hoorn Study. Eur Heart J 24:1406–1413, 2003[Abstract/Free Full Text]
  4. Zilversmit DB: Atherogenesis: a postprandial phenomenon. Circulation 60:473–485, 1979[Abstract/Free Full Text]
  5. Heine RJ, Dekker JM: Beyond postprandial hyperglycaemia: metabolic factors associated with cardiovascular disease. Diabetologia 45:461–475, 2002[Medline]
  6. Tushuizen ME, Diamant M, Heine RJ: Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes. Postgrad Med J 81:1–6, 2005[Abstract/Free Full Text]
  7. Haidara MA, Yassin HZ, Rateb M, Ammar H, Zorkani MA: Role of oxidative stress in development of cardiovascular complications in diabetes mellitus. Curr Vasc Pharmacol 4:215–227, 2006[Medline]
  8. Meisinger C, Baumert J, Khuseyinova N, Loewel H, Koenig W: Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation 112:651–657, 2005[Abstract/Free Full Text]
  9. Silaste ML, Rantala M, Alfthan G, Aro A, Witztum JL, Kesaniemi YA, Horkko S: Changes in dietary fat intake alter plasma levels of oxidized low-density lipoprotein and lipoprotein(a). Arterioscler Thromb Vasc Biol 24:498–503, 2004[Abstract/Free Full Text]
  10. Kilhovd BK, Berg TJ, Birkeland KI, Thorsby P, Hanssen KF: Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease. Diabetes Care 22:1543–1548, 1999[Abstract/Free Full Text]
  11. Baynes JW, Thorpe SR: Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 28:1708–1716, 2000[Medline]
  12. Tushuizen ME, Nieuwland R, Scheffer PG, Sturk A, Heine RJ, Diamant M: Two consecutive high-fat meals affect endothelial-dependent vasodilation, oxidative stress and cellular microparticles in healthy men. J Thromb Haemost 4:1003–1010, 2006[Medline]
  13. Graner M, Kahri J, Nakano T, Sarna SJ, Nieminen MS, Syvanne M, Taskinen MR: Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery disease. Eur J Clin Invest 36:764–770, 2006[Medline]
  14. Mooy JM, Grootenhuis PA, de Vries H, Valkenburg HA, Bouter LM, Kostense PJ, Heine RJ: Prevalence and determinants of glucose intolerance in a Dutch caucasian population: the Hoorn Study. Diabetes Care 18:1270–1273, 1995[Abstract]
  15. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502, 1972[Abstract]
  16. Wu T, Willett WC, Rifai N, Shai I, Manson JE, Rimm EB: Is plasma oxidized low-density lipoprotein, measured with the widely used antibody 4E6, an independent predictor of coronary heart disease among U.S. men and women? J Am Coll Cardiol 48:973–979, 2006[Abstract/Free Full Text]
  17. Hoogeveen RC, Ballantyne CM, Bang H, Heiss G, Duncan BB, Folsom AR, Pankow JS: Circulating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Diabetologia 50:36–42, 2007[Medline]
  18. Holvoet P, Kritchevsky SB, Tracy RP, Mertens A, Rubin SM, Butler J, Goodpaster B, Harris TB: The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort. Diabetes 53:1068–1073, 2004[Abstract/Free Full Text]
  19. Zwiener C, Glauner T, Frimmel FH: Method optimization for the determination of carbonyl compounds in disinfected water by DNPH derivatization and LC-ESI-MS-MS. Anal Bioanal Chem 372:615–621, 2002[Medline]
  20. Schalkwijk CG, Posthuma N, ten Brink HJ, ter Wee PM, Teerlink T: Induction of 1,2-dicarbonyl compounds, intermediates in the formation of advanced glycation end-products, during heat-sterilization of glucose-based peritoneal dialysis fluids. Perit Dial Int 19:325–333, 1999[Abstract/Free Full Text]
  21. Schindhelm RK, Alssema M, Heine RJ, Barto R, Nijpels G, Dekker JM, Diamant M, Teerlink T, Schalkwijk CG: Carbohydrate, but not fat-rich meals cause a rise in plasma 3-deoxyglucosone concentration in females with type 2 diabetes mellitus. (Abstract). Diabetes 54 (Suppl. 1):A163, 2005
  22. Teerlink T, Barto R, ten Brink HJ, Schalkwijk CG: Measurement of nepsilon(carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine in human plasma protein by stable-isotope-dilution tandem mass spectrometry. Clin Chem 50:1222–1228, 2004[Abstract/Free Full Text]
  23. Ceriello A: The post-prandial state and cardiovascular disease: relevance to diabetes mellitus. Diabetes Metab Res Rev 16:125–132, 2000[Medline]
  24. de Vegt F, Dekker JM, Ruhe HG, Stehouwer CD, Nijpels G, Bouter LM, Heine RJ: Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia 42:926–931, 1999[Medline]
  25. The DECODE Study Group, the European Diabetes Epidemiology Group: Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria: Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe. Lancet 354:617–621, 1999[Medline]
  26. Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E: Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106:1211–1218, 2002[Abstract/Free Full Text]
  27. Anderson RA, Evans ML, Ellis GR, Graham J, Morris K, Jackson SK, Lewis MJ, Rees A, Frenneaux MP: The relationships between post-prandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes. Atherosclerosis 154:475–483, 2001[Medline]
  28. Baynes JW, Thorpe SR: Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9, 1999[Abstract]
  29. Hamada Y, Nakamura J, Fujisawa H, Yago H, Nakashima E, Koh N, Hotta N: Effects of glycemic control on plasma 3-deoxyglucosone levels in NIDDM patients. Diabetes Care 20:1466–1469, 1997[Abstract]
  30. Thornalley PJ, Langborg A, Minhas HS: Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J 344:109–116, 1999[Medline]
  31. Beisswenger PJ, Howell SK, O'Dell RM, Wood ME, Touchette AD, Szwergold BS: {alpha}-Dicarbonyls increase in the postprandial period and reflect the degree of hyperglycemia. Diabetes Care 24:726–732, 2001[Abstract/Free Full Text]
  32. Schleicher ED, Wagner E, Nerlich AG: Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest 99:457–468, 1997[Medline]
  33. Wautier MP, Massin P, Guillausseau PJ, Huijberts M, Levy B, Boulanger E, Laloi-Michelin M, Wautier JL: N(carboxymethyl)lysine as a biomarker for microvascular complications in type 2 diabetic patients. Diabetes Metab 29:44–52, 2003[Medline]
  34. Shringarpure R, Grune T, Mehlhase J, Davies KJ: Ubiquitin conjugation is not required for the degradation of oxidized proteins by proteasome. J Biol Chem 278:311–318, 2003[Abstract/Free Full Text]
  35. Mehlhase J, Grune T: Proteolytic response to oxidative stress in mammalian cells. Biol Chem 383:559–567, 2002[Medline]
  36. Nagai R, Unno Y, Hayashi MC, Masuda S, Hayase F, Kinae N, Horiuchi S: Peroxynitrite induces formation of N(epsilon)-(carboxymethyl) lysine by the cleavage of Amadori product and generation of glucosone and glyoxal from glucose: novel pathways for protein modification by peroxynitrite. Diabetes 51:2833–2839, 2002[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc06-2585v1
30/7/1789    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schindhelm, R. K.
Right arrow Articles by Teerlink, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schindhelm, R. K.
Right arrow Articles by Teerlink, T.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum