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Inflammation markers are modulated by responses to diets differing in postprandial insulin responses in individuals with the metabolic syndrome^1,2,3

¹ From the Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, Finland (PK, MK, LP, HM, MU, and KP); the Institute of Medicine, Internal Medicine, Kuopio University Hospital, Finland (DEL and LN); the Institute of Biomedicine, Department of Physiology, University of Kuopio, Finland (DEL and MA); and VTT, Espoo, Finland (KP)

² Supported by Tekes–the Finnish Funding Agency for Technology and Innovation #70094/02, the Sigrid Juselius Foundation, the Jenny and Antti Wihuri Foundation, the Yrjö Jahnsson Foundation, and ABS Graduate School.

³ Address reprint requests and correspondence to P Kallio, Department of Clinical Nutrition, Food and Health Research Centre, University of Kuopio, PO Box 1627 70211 Kuopio, Finland. E-mail: petteri.kallio{at}uku.fi.

	ABSTRACT

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Background: Inflammation may be a mechanism by which high postprandial insulin and glucose responses increase the risk of type 2 diabetes mellitus.

Objective: We hypothesized that dietary carbohydrates characterized by different postprandial insulin responses may differentially modify cytokine concentrations in plasma and gene expression in subcutaneous adipose tissue.

Design: Individuals (n = 47) with the metabolic syndrome were randomly assigned to a 12-wk diet with oat and wheat bread and potato (high postprandial insulin response) or rye bread and pasta (low postprandial insulin response). Postprandial glucose and insulin responses to the oat and wheat bread meal and to the rye bread meal were determined in 19 individuals before intervention.

Results: During the 12-wk diet, the change in the gene expression of interleukin (IL)-10 receptor and tumor necrosis factor- in subcutaneous adipose tissue differed between the groups (P = 0.002 and P = 0.083, respectively). Moreover, the change in fasting plasma concentrations of IL-1β and IL-6 differed between the groups (P = 0.020 and P = 0.055, respectively). In the postprandial challenge, the insulin response to the rye bread meal was lower than that to the oat and wheat bread meal (P < 0.001), whereas there were no differences in the mean blood glucose response. In contrast, plasma glucose concentrations decreased more below fasting concentrations 2.5–3 h after the oat and wheat bread meal than after the rye bread meal. A late postprandial rebound of free fatty acids was detected after the oat and wheat bread meal (P = 0.048).

Conclusions: Long-term intake of cereal foods with differing postprandial insulin responses may be a factor that modulates the inflammatory status in individuals with the metabolic syndrome.

Key Words: Gene-nutrient interactions • adipose tissue • inflammation • cytokines • postprandial response

	INTRODUCTION

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In some epidemiologic studies, diets with a high glycemic index and low in whole grains have been associated with an increased risk of type 2 diabetes (T2DM) (1-3). On the other hand, diets with a low glycemic index and load or high in whole grains have been associated with decreased concentrations of inflammation markers (4). Low-grade inflammation has been implicated in obesity and in the development of comorbidities, such as the metabolic syndrome, T2DM, and cardiovascular disease (5-7). Whole-grain diets with a low glycemic index probably decrease the risk of T2DM through improved insulin resistance and β cell function (8), but modulation of inflammation may be another mechanism (9).

Repeated postprandial hyperinsulinemia and early postprandial hyperglycemia may cause insulin resistance, β cell dysfunction, and inflammation (9, 10). Moreover, an exaggerated postprandial insulin response may cause transient late postprandial hypoglycemia, activating the glucocorticoid axis and eliciting secretion of counter-regulatory stress hormones. We have shown that rye bread generates a lower postprandial insulin response than does wheat bread, even though the initial postprandial glucose response remains unchanged (11). This is not due to the higher fiber content of rye bread, but may be due to the bread structure (12). In our previous 8- to 12-wk dietary intervention trials, high-fiber rye bread (13) and rye bread and pasta (14) increased early insulin secretion, possibly indicating improvement in β cell function. Moreover, in microarray analyses we previously showed that long-term carbohydrate modification with oat and wheat bread and potato can modulate the expression of genes in several pathways responding to metabolic stress in the subcutaneous adipose tissue of subjects with the metabolic syndrome (15).

The mechanisms by which the oat and wheat bread and potato diet can induce metabolic stress and immune activation are unclear. Hypothetically, repeated mild, late postprandial hypoglycemia induced by carbohydrates with a high glycemic or insulinemic index could activate counter-regulatory stress hormones such as cortisol and catecholamines, which restore fasting glucose concentrations and increase nonesterified fatty acid concentrations (10). We have also shown that the ingestion of wheat bread results in initial hyperinsulinemia and a subsequent transient drop in glycemia below fasting concentrations, which was not seen after the consumption of rye bread (12, 16).

In the present study, we sought to clarify whether the long-term consumption of cereal products with different postprandial insulin responses can modulate inflammation markers in subjects with the metabolic syndrome. Induction of metabolic stress was also studied by determining the postprandial responses of insulin, glucose, catecholamines, and nonesterified fatty acids to rye bread and to oat and wheat bread meals.

	SUBJECTS AND METHODS

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Subjects
Forty-seven overweight or obese men and women with the metabolic syndrome, as defined by the National Cholesterol Education Program (17), were recruited to participate in the 12-wk dietary intervention (Table 1). The study population was described in detail earlier (15). Moreover, 19 subjects (9 women and 10 men) with the metabolic syndrome [body mass index (in kg/m²): 31.9 ± 0.7; fasting plasma glucose: 6.3 ± 0.1 mmol/L; and waist circumference: 109 ± 2.1 cm] were recruited to participate in a postprandial challenge before the long-term intervention. The subjects gave written informed consent before participating in the study. The Ethics Committee of the University of Kuopio and Kuopio University Hospital approved the study. The study was carried out according to the Declaration of Helsinki.

Table 2

Postprandial challenge
The subjects (n = 19) were served 2 separate test meals consisting of either oat and wheat breads or rye breads to be used in the intervention in random order on 2 separate study visits. The test meals contained 50 g carbohydrate available from the test breads, 40 g cucumber, and 3 dL of a noncaloric orange drink (sweetened with sweetening agent). For the oat and wheat bread portion, the bread constituted half of the available carbohydrates (25 g) in the test portion. The remaining half was composed of equal portions (6.25 g) of the other 4 breads. For the rye bread portion, the endosperm rye bread constituted half of the available carbohydrates (25 g) in the test bread portion. The remaining half was composed of equal portions of the other 4 breads. Blood samples were drawn through the catheter before and 15, 30, 45, 60, 90 120, 150, and 180 min after the beginning of eating. Serum insulin, plasma glucose, and free fatty acids were analyzed at every time point. Samples for the measurement of plasma catecholamine (adrenaline, noradrenaline) were taken at time points 0, 60, 120, and 180 min.

Biochemical measurements
Serum insulin was analyzed by using the chemiluminescent immunoassay (ACS 180 Plus Automated Chemiluminescence System; Bayer Diagnostics, Tarrytown, NY). Plasma glucose was analyzed by using the glucose dehydrogenase photometric method (Merck Diagnostica, Darmstadt, Germany) and KonePro Clinical Chemistry Analyser (Thermo Clinical Labsystems, Konelab, Finland). Plasma free fatty acids were determined by an enzymatic method from Wako Chemicals GmbH (Neuss, Germany). To analyze catecholamines, plasma samples were collected in 10-mL plastic tubes in ice containing EGTA and reduced glutathione as a preservative. Samples were centrifuged immediately, and plasma was stored frozen at –70 °C until analyzed. For the analyses, Chromsystems #5000 reagent kit for HPLC analysis of catecholamines in plasma (Chromsystems Instruments and Chemicals GmbH, Munich, Germany) was used according to the manufacturer's instructions. Intraassay variation for noradrenaline was 4.1–6.7% and for adrenaline was 3.5–8.5%. Interassay variation for noradrenaline was 7.1–7.2% and for adrenaline was 7.6–10.1%. Plasma cytokines—ie, tumor necrosis factor- (TNF-), interleukin (IL)-1β, IL-6, and IL-10 were measured by using high-sensitivity enzyme-linked immunosorbent assay kits (R&D Systems, Minneapolis, MN).

Adipose tissue biopsy, RNA extraction, and real-time polymerase chain reaction
Adipose tissue was collected with the needle biopsy technique from the superficial abdominal subcutaneous adipose tissue lateral to the umbilicus under local anesthesia (10 mg/mL lidocaine; Orion Pharma, Espoo, Finland). Biopsy samples were collected after the subjects had fasted for 12 h. Samples for RNA extraction were washed immediately twice with Gibco phosphate-buffered saline (Invitrogen, Carlsbad, CA) and stored in RNAlater (Ambion, Austin, TX) at 4 °C. Total RNA obtained before and after the intervention from the adipose tissue of each subject was extracted initially with Trizol (Invitrogen) followed by further purification with the RNeasy Mini-Kit (Qiagen, Valencia, CA). Real-time quantitative polymerase chain reaction (RT-PCR) was performed by using TaqMan chemistry (Applied Biosystems, Foster City, CA). The selection process for the endogenous control and other details of the procedure were described earlier (15).

Statistical analyses
The data were analyzed with SPSS 14.0 for WINDOWS (SPPS Inc, Chicago, IL) and GraphPad Prism 4.0 for WINDOWS (GraphPad Software, San Diego, CA). Data are expressed as means ± SEMs unless indicated otherwise. Data with skewed distributions were transformed logarithmically. Data are represented in untransformed form. Postprandial challenge in terms of insulin, glucose, and free fatty acid responses was analyzed with multivariate analysis of variance. The differences between the test meals at individual time points were analyzed only if there was an overall significance by analysis of variance. Differences in catecholamine concentrations were determined with Wilcoxon's nonparametric paired test (oat and wheat bread versus rye bread). Both mRNA expression data from RT-PCR and plasma cytokine concentrations from long-term diet intervention were analyzed with a general linear model for repeated measures corrected with the baseline variable.

	RESULTS

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mRNA expression of subcutaneous adipose tissue during the 12-wk diet intervention
We detected a significant difference in IL-10 receptor (IL-10R) mRNA expression between the groups (Table 3). The oat and wheat bread and potato diet up-regulated the mRNA expression of IL-10R 1.4-fold (P < 0.001, within group change), whereas with rye bread and pasta diet expression was suppressed (P = 0.002, between-group change). There was a trend for a difference (P = 0.083) in TNF- mRNA expression between the groups. Closer observation showed a time effect of the results (P = 0.009); therefore, we also conducted a within-group analysis of TNF- expression. We found a significant 1.24-fold up-regulation of TNF- gene expression after the oat and wheat bread and potato diet intervention (P = 0.024) compared with baseline.

View this table: [in this window] [in a new window]   TABLE 3. mRNA expression of interleukin-10 receptor , interleukin-10, tumor necrosis factor-, and interleukin-1β in subcutaneous adipose tissue at the beginning (0 wk) and at the end (12 wk) of the intervention1

Table 4

Figure 1

View larger version (16K): [in this window] [in a new window]   FIGURE 1.. Mean (±SEM) serum insulin and plasma glucose concentrations in response to the consumption of rye bread () and oat and wheat bread () in subjects with the metabolic syndrome (n = 19). Glucose: multivariate ANOVA (P < 0.001); insulin: multivariate ANOVA (P = 0.002). *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

Figure 3

View larger version (16K): [in this window] [in a new window]   FIGURE 2.. Mean (±SEM) plasma free fatty acid concentrations in response to the consumption of rye bread and oat and wheat bread in subjects with the metabolic syndrome (n = 19). Multivariate ANOVA for overall significance (P = 0.048). **P < 0.01.

View larger version (14K): [in this window] [in a new window]   FIGURE 3.. Mean (±SEM) plasma adrenaline and noradrenaline concentrations in response to the consumption of rye bread () and oat and wheat bread () in subjects with the metabolic syndrome (n = 19). Wilcoxon's nonparametric paired t test for the difference between consequent time points. *P < 0.05 for comparison between 2 time points after the oat and wheat bread challenge.

	DISCUSSION

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In the oat and wheat bread and potato group, circulating concentrations of IL-1β and IL-6 tended to increase, whereas in the rye-pasta group they tended to decrease. The difference between groups in the change in cytokine concentrations was of at least borderline significance. In abdominal subcutaneous adipose tissue, gene expression of TNF- and IL-10 receptor increased in the oat and wheat bread and potato group, but mRNA levels did not change or tended to decrease in the rye-pasta group. Although no change in hs-CRP concentrations were noted, the findings indicated differential modulation of adipose gene expression of cytokines and their serum concentrations by the high-carbohydrate diet with oat and wheat bread and potato compared with the diet with rye bread and pasta.

IL-1β and IL-6 are proinflammatory cytokines and markers of inflammation. IL-6 stimulates the secretion of major proinflammatory cytokines such as IL-1. In turn, IL-1β and TNF-, which are also secreted from adipose tissue, induce IL-6 secretion. These proinflammatory cytokines are up-regulated in obesity (18) and likely play an important role in the pahthophysiological processes underlying the metabolic syndrome, T2DM, and cardiovascular disease.

Overall, the oat and wheat bread and potato diet seemed to exacerbate inflammation, whereas the rye bread and pasta diet tended to be noninflammatory. These findings are also consistent with those of our previous report based on microarray studies, in which we found activation of pathways related to the IL pathway and inflammation mediated by chemokine and cytokine signaling pathways after the oat and wheat bread and potato diet (15). Up-regulation of IL-10 receptor in the oat and wheat bread and potato group can be interpreted as an antiinflammatory response, perhaps in compensation for the changes in proinflammatory cytokines. IL-6 has also been shown to up-regulate IL-10 expression (19).

Our study is the first longer-term dietary intervention to suggest that carbohydrate modification may influence the protein or mRNA expression of inflammatory markers in both serum and adipose tissue. The dietary fiber content has been found to modulate plasma concentrations of adiponectin and IL-18 (20). In the present study, the fiber content of the diets did not differ greatly (14, 15), and adjustment for the differences in fiber intake did not affect the results. Short-term and dramatic weight loss can decrease the gene expression of certain cytokines in adipose tissue (21). In the present study, however, no changes in body weight occurred.

Previous studies indicate that short-term acute hyperglycemia combined with hyperinsulinemia may increase circulating concentrations of radical oxygen species and proinflammatory cytokines (22, 23). Postprandial hyperglycemia seems to induce inflammatory responses by activating the nuclear transcription factor B pathway in circulating mononuclear cells (24, 25), although the magnitude of the postprandial glucose and insulin responses may not be the primary factor influencing the degree of the inflammatory response (26). Whereas insulin resistance is associated with and probably in part caused by inflammation, insulin itself has acute antiinflammatory properties (9). Because the postprandial insulin responses were higher and glucose responses were similar in the oat and wheat bread and potato group, postprandial glucose and insulin responses were unlikely to directly explain the generally proinflammatory changes seen in that group. The inflammatory changes seen after the oat and wheat bread and potato diet could nonetheless exacerbate insulin resistance and increase the risk of T2DM over time (9). Hypothetically, increased early postprandial hyperinsulinemia and late mild postprandial hypoglycemia also can affect inflammation (10).

Oat and wheat breads produced markedly higher postprandial insulin responses than did rye bread for up to 2 h, independently of fiber content. The differences in insulin responses are in line with the findings of our previous studies, in which rye and white wheat breads were used (16). Interestingly, we detected no significant differences in early postprandial glucose responses during a 3-h postprandial challenge. Thus, the lower insulin response to rye bread did not seem to be due to a higher circulating concentration of glucose or to a slower absorption rate. The lower postprandial insulin secretion that was observed after rye bread consumption may have been due to bread structure (13). The fiber content did not account for the lower postprandial insulin response to rye bread, because the postprandial insulin response to low-fiber rye bread was as low as that of high-fiber rye bread (12). It is unlikely that differences in intake of protein, saturated fat, carbohydrate, and fiber in the rye bread and pasta or oat and wheat bread and potato groups differentially affected early insulin secretion in the long-term intervention (14, 16). Differences in macronutrient intakes, other than carbohydrate, are also unlikely to explain the difference in insulin responses (11). The higher insulin response observed during the first hour may explain lower glucose concentrations in the oat and wheat bread and potato group during the later postprandial phase, decreasing below fasting concentrations.

The decrease in plasma glucose below fasting concentrations was also mirrored by an increase in nonesterified fatty acids during the third hour of the postprandial challenge, which reflects increased mobilization from adipose tissue. Because the increase in nonesterified fatty acids peaks between 4 and 6 h after a carbohydrate or mixed meal, a longer follow-up would be necessary to confirm a different effect of the carbohydrate modification on late postprandial effects of glycemia and nonesterified fatty acid mobilization. The longer postprandial suppression of free fatty acids after the rye bread could be explained with insulin and glucose responses.

The present findings imply that a markedly high postprandial insulin response may result in metabolic processes similar to those seen after ingestion of a meal with a high glycemic index. In the late postprandial period after a high-glycemic-index meal, stimulation of lipolysis and a late rebound in nonesterified fatty acids occurs as blood glucose decrease below fasting concentrations (10). Sustained increases in serum free fatty acid concentrations can cause insulin resistance (27). Moreover, increased concentration of TNF- and IL-6 are associated with insulin resistance (28, 29). There were no differences between rye bread and pasta or oat and wheat bread and potato diets in glucose tolerance or fasting insulin concentrations during the intervention. Over a longer period, however, the changes seen in the oat and wheat bread and potato group could predispose to worsening insulin resistance and glucose intolerance.

Plasma adrenalin concentrations decreased sharply with increases in plasma glucose and insulin concentrations in the early postprandial period, but increased during the mid- to late postprandial period after the oat and wheat bread meal. The increase in plasma adrenaline may be in response to the rapid decline in the concentrations of glucose, presumably to prevent developing hypoglycemia (30).

Modification of carbohydrate intake by replacing cereal products with rye bread and pasta, which are characterized by a low postprandial insulin response, and oat and wheat bread and potato, which are characterized by a high postprandial insulin response, differentially modulate the mRNA expression of inflammatory markers in both adipose tissue and circulating concentrations of serum in men and women with the metabolic syndrome, even in the absence of weight loss. The proinflammatory changes occurring with high oat and wheat bread and potato intakes may increase the risk of T2DM and cardiovascular disease in the long term.

	ACKNOWLEDGMENTS

 
We thank the staff of VTT Biotechnology for the development of the study breads and the staff of the Department of Clinical Nutrition, University of Kuopio, for their valuable contributions in carrying out the present study. We especially acknowledge Kari Savolainen for analyzing the catecholamines.

The authors' responsibilities were as follows—MK, DEL, LN, HM, and KP: contributed to the design of the study; PK: carried out the practical aspects of the study, including RNA isolation and RT-PCR; PK and MK: conducted the statistical analysis; MA: performed the cytokine analyses; PK, MK, and DEL: wrote the first draft of the manuscript; and MU, LP, MA, and LN: provided critical revision of the manuscript drafts. All authors participated in the writing of the final manuscript. None of the authors had any conflicts of interest.

	REFERENCES

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Ludwig DS. Clinical update: the low-glycaemic-index diet. Lancet 2007;369:890–2.[Medline]
2. Qi L, van Dam RM, Liu S, Franz M, Mantzoros C, Hu FB. Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation in diabetic women. Diabetes Care 2006;29:207–11.[Abstract/Free Full Text]
3. Lindstrom J, Peltonen M, Eriksson JG, et al. High-fibre, low-fat diet predicts long-term weight loss and decreased type 2 diabetes risk: the Finnish Diabetes Prevention Study. Diabetologia 2006;49:912–20.[Medline]
4. Qi L, Hu FB. Dietary glycemic load, whole grains, and systemic inflammation in diabetes: the epidemiological evidence. Curr Opin Lipidol 2007;18:3–8.[Medline]
5. Pradhan AD, Ridker PM. Do atherosclerosis and type 2 diabetes share a common inflammatory basis? Eur Heart J 2002;23:831–4.[Free Full Text]
6. Laaksonen DE, Niskanen L, Nyyssonen K, et al. C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 2004;47:1403–10.[Medline]
7. Laaksonen DE, Niskanen L, Nyyssonen K, Punnonen K, Tuomainen TP, Salonen JT. C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study. Eur Heart J 2005;26:1783–9.[Abstract/Free Full Text]
8. Hu FB, van Dam RM, Liu S. Diet and risk of Type II diabetes: the role of types of fat and carbohydrate. Diabetologia 2001;44:805–17.[Medline]
9. Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005;111:1448–54.[Free Full Text]
10. Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 2002;287:2414–23.[Abstract/Free Full Text]
11. Leinonen K, Liukkonen K, Poutanen K, Uusitupa M, Mykkanen H. Rye bread decreases postprandial insulin response but does not alter glucose response in healthy Finnish subjects. Eur J Clin Nutr 1999;53:262–7.[Medline]
12. Juntunen KS, Laaksonen DE, Autio K, Niskanen L, et al. Structural differences between rye and wheat breads but not total fiber content may explain the lower postprandial insulin response to rye bread. Am J Clin Nutr 2003;78:957–64.[Abstract/Free Full Text]
13. Juntunen KS, Laaksonen DE, Poutanen KS -, Niskanen LK, Mykkanen HM. High-fiber rye bread and insulin secretion and sensitivity in healthy postmenopausal women. Am J Clin Nutr 2003;77:385–91.[Abstract/Free Full Text]
14. Laaksonen DE, Toppinen LK, Juntunen KS, et al. Dietary carbohydrate modification enhances insulin secretion in persons with the metabolic syndrome. Am J Clin Nutr 2005;82:1218–27.[Abstract/Free Full Text]
15. Kallio P, Kolehmainen M, Laaksonen DE, et al. Dietary carbohydrate modification induces alterations in gene expression in abdominal subcutaneous adipose tissue in persons with the metabolic syndrome: the FUNGENUT Study. Am J Clin Nutr 2007;85:1417–27.[Abstract/Free Full Text]
16. Juntunen KS, Niskanen LK, Liukkonen KH, Poutanen KS, Holst JJ, Mykkanen HM. Postprandial glucose, insulin, and incretin responses to grain products in healthy subjects. Am J Clin Nutr 2002;75:254–62.[Abstract/Free Full Text]
17. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486–97.[Free Full Text]
18. Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract 2005;69:29–35.[Medline]
19. Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans Am J Physiol Endocrinol Metab 2003;285:E433–7.[Abstract/Free Full Text]
20. Esposito K, Nappo F, Giugliano F, et al. Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus. Am J Clin Nutr 2003;78:1135–40.[Abstract/Free Full Text]
21. Clement K, Viguerie N, Poitou C, et al. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J 2004;18:1657–69.[Abstract/Free Full Text]
22. Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab 2000;85:2970–3.[Abstract/Free Full Text]
23. Esposito K, Nappo F, Marfella R, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002;106:2067–72.[Abstract/Free Full Text]
24. Aljada A, Mohanty P, Ghanim H, et al. Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Am J Clin Nutr 2004;79:682–90.[Abstract/Free Full Text]
25. Aljada A, Ghanim H, Mohanty P, Syed T, Bandyopadhyay A, Dandona P. Glucose intake induces an increase in activator protein 1 and early growth response 1 binding activities, in the expression of tissue factor and matrix metalloproteinase in mononuclear cells, and in plasma tissue factor and matrix metalloproteinase concentrations. Am J Clin Nutr 2004;80:51–7.[Abstract/Free Full Text]
26. Motton DD, Keim NL, Tenorio FA, Horn WF, Rutledge JC. Postprandial monocyte activation in response to meals with high and low glycemic loads in overweight women. Am J Clin Nutr 2007;85:60–5.[Abstract/Free Full Text]
27. Frayn KN. Adipose tissue and the insulin resistance syndrome. Proc Nutr Soc 2001;60:375–80.[Medline]
28. Ruderman NB, Keller C, Richard AM, et al. Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 2006;55(suppl 2):S48–54.[Abstract/Free Full Text]
29. Krogh-Madsen R, Moller K, Dela F, Kronborg G, Jauffred S, Pedersen BK. Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans Am J Physiol Endocrinol Metab 2004;286:E766–72.[Abstract/Free Full Text]
30. Tse TF, Clutter WE, Shah SD, Cryer PE. Mechanisms of postprandial glucose counterregulation in man. J Clin Invest 1983;72:278–86.[Medline]

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