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. 2008 Jun 22:7:20.
doi: 10.1186/1475-2840-7-20.

Intensification of oxidative stress and inflammation in type 2 diabetes despite antihyperglycemic treatment

Raymond Farah  1 , Revital Shurtz-Swirski, Olga Lapin
Affiliations

Intensification of oxidative stress and inflammation in type 2 diabetes despite antihyperglycemic treatment

Raymond Farah et al. Cardiovasc Diabetol. .

Abstract

Introduction: The metabolic deregulation associated with diabetes mellitus (DM) causes secondary pathophysiologic changes in multiple organ systems. Endothelial injury is induced by oxidative stress (OS) and inflammation. We have previously shown that DM type 2 patients are exposed to increased OS and inflammation contributed in part by primed peripheral polymorphonuclear leukocytes (PMNLs).

Aims: To characterize the effect of oral medication on PMNL priming, on PMNL-related and on systemic inflammation, in correlation to changed diabetes parameters in patient with newly diagnosed type 2 DM.

Methods: PMNLs were separated from DM patient's prior and following treatment with either metformin (Glucophage), or Thiazolidinedione (rosiglitazone) and from healthy control subjects (HC). Rate of superoxide release from phorbol ester-stimulated PMNLs and CD11b on PMNLs assessed PMNL priming. White blood cells (WBC) and PMNL counts and apoptosis reflected PMNL-related inflammation. CRP, fibrinogen, transferrin and albumin blood levels reflected systemic inflammation.

Results: Both metformin and rosiglitazone treatments reduced significantly the high levels of glucose and HbA1c, and slightly improved lipid profile during 2 months. PMNL priming parameters, higher compared to HC, increased after 2 months of metformin treatment. Rosiglitazone treatment decreased PMNL priming. ALP, higher in DM, significantly decreased following 2 months of both treatments. Systemic inflammation markers (fibrinogen, CRP), higher in DM, decreased following both treatments. Transferrin and albumin were similar to HC. PMNL-related inflammation markers were higher in DM; however, only PMNL apoptosis decreased after both treatments. Monocyte counts, higher in DM compared to HC, decreased following both treatments. Serum insulin levels, higher in DM compared to HC, decreased following both treatments. PMNL-related priming and inflammation parameters positively correlated with HbA1c.

Conclusion: The present research adds new facet in evaluating anti-hyperglycemic treatment in type 2 DM patients. Despite sufficient glycemic control using both treatments, some PMNL-related parameters deteriorated. Thus, anti hyperglycemic treatment should be favored due to its combined anti-PMNL priming and anti-inflammatory effect, in addition to its anti-hyperglycemic characteristics, according to the correlation among these parameters. Such combined treatment may reduce morbidity and mortality common in DM patients.

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Figures

Figure 1
Figure 1
PMNL priming parameters, namely, rate of superoxide release (a) and PMNL CD11b levels (b), before and following 1 and 2 months of either metformin (blank) or combined Roziglytazone (dotted) treatment. Data are mean ± SEM. aP < 0.05, vs. HC subjects; b P < 0.05, vs. untreated DM patients.
Figure 2
Figure 2
Correlation between the rates of superoxide release from separated PMA-stimulated PMNLs and either blood HbA1c (A) or blood glucose levels (B). Data refers to values from DM patients and HC subjects.
Figure 3
Figure 3
Correlation between blood HbA1c levels and either (A) WBC or PMNL (B) counts. Data refers to values from DM patients and HC subjects.
See this image and copyright information in PMC

References

    1. Stern MP. The effect of glycemic control on the incidence of macrovascular complications of type 2 diabetes. Arch Fam Med. 1998;7:155–162. doi: 10.1001/archfami.7.2.155. - DOI - PubMed
    1. Medical management of type 2 diabetes. 4. Vol. 10. American Diabetes Association; 1998. p. 108.
    1. Vogel RA. Coronary risk factor, endothelial function, and aatherosclerosis: a review. Clin Cardiol. 1997;20:426–432. - PMC - PubMed
    1. Laakso M, Lehto S. Epidemiology of macrovascular disease in diabetes. Diabetes Rev. 1997;5:294–295.
    1. Stehouwer CD, Labmert J, Donker AJ, van Hinsbergh VW. Endothelial dysfunction and pathogenesis of diabetic angipathy. Cardiovasc Res. 1997;34:55–68. doi: 10.1016/S0008-6363(96)00272-6. - DOI - PubMed

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