Abstract
IntroductionThe 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).AimsTo 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.MethodsPMNLs 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.ResultsBoth 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.ConclusionThe 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.
Highlights
The metabolic deregulation associated with diabetes mellitus (DM) causes secondary pathophysiologic changes in multiple organ systems
polymorphonuclear leukocytes (PMNLs)-related inflammation markers were higher in DM; only PMNL apoptosis decreased after both treatments
Higher in DM compared to healthy control subjects (HC), decreased following both treatments
Summary
The metabolic deregulation associated with diabetes mellitus (DM) causes secondary pathophysiologic changes in multiple organ systems. Oxidative stress, and inflammation all play a key role and participate in the development of endothelial dysfunction [4,5,6,7]. Chronic exposure to increased levels of hydroxyl radicals in vivo likely plays a significant role in the origine of diabetes-associated endothelial dysfunction. We have previously shown that in other clinical situations known to be associated with endothelial dysfunction and accelerated atherosclerosis such as uremia, hypertension and type 2 diabetes, PMN are primed, contributing to OS and inflammation [14,15,16]. The inability of diabetic neutrophils to reduce apoptosis following LPS exposure resulted in relatively increased apoptosis This would cause decreased functional longevity of neutrophils and increased neutrophil clearance from infectious sites, possibly contributing to the increased susceptibility and severity of infections in diabetic patients [17]. In the present study we compare PMNL priming parameters in diabetic patients, treated daily with metformin for two months to those treated with rosiglitazone
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