Published Online
on June 16, 2003

A more recent version of this article appeared on July 1, 2003

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Submitted on December 19, 2002
Revised on April 3, 2003
Accepted on April 4, 2003

Enhanced Lipid Peroxidation and Platelet Activation in the Early Phase of Type 1 Diabetes Mellitus. Role of Interleukin-6 and Disease Duration

Giovanni Davì MD^*, Francesco Chiarelli MD, Francesca Santilli MD, Mariapina Pomilio MD, Sergio Vigneri MD, Angela Falco MD, Stefania Basili MD, Giovanni Ciabattoni MD, and Carlo Patrono MD

From the Center of Excellence on Aging and Departments of Medicine and Aging and Drug Sciences (G.D., F.C., F.S., M.P., A.F., G.C.), University of Chieti G. D'Annunzio Schools of Medicine and Pharmacy, Chieti, Italy; Department of Medicine (S.V.), University of Palermo, Palermo, Italy; and University of Rome La Sapienza (S.B., C.P.), Rome, Italy.

^* To whom correspondence should be addressed. E-mail: gdavi{at}unich.it.

Background--To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F₂ (8-iso-PGF₂) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A₂ biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F₂-isoprostane formation in this setting.

Methods and Results--A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM (6 weeks, group A), matched for age and gender with 23 patients with stable disease (>1 year, group B). Urinary 8-iso-PGF₂ and 11-dehydro-TXB₂ were measured in all patients and in age- and gender-matched controls. Circulating interleukin-6 (IL-6), tumor necrosis factor-, and C-reactive protein were also determined as markers of the inflammatory response. Fifteen of the 23 children in group A were reexamined after 12 months. Compared with either controls or group B, diabetic children in group A showed significantly higher levels of 8-iso-PGF₂, 11-dehydro-TXB₂, IL-6, tumor necrosis factor-, and C-reactive protein. Statistically significant correlations between IL-6 and both 8-iso-PGF₂ (r=0.63, P<0.001) and 11-dehydro-TXB₂ (r=0.51, P<0.01) were observed. The 15 patients reexamined after 1 year showed a significant reduction in lipid peroxidation and platelet activation (P<0.02 and P<0.001, respectively), consistent with reduced levels of IL-6 and tumor necrosis factor-.

Conclusions--These results demonstrate that enhanced lipid peroxidation and platelet activation represent early events in T1DM that are possibly related to an acute inflammatory response. These noninvasive indexes may help in further examining T1DM pathophysiology and monitoring pharmacological interventions to interfere with disease development and progression.

Key words: diabetes mellitus • inflammation • platelets

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