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Elevated Plasma Levels of Soluble Receptors of TNF- and Their Association with Smoking and Microvascular Complications in Young Adults with Type 1 Diabetes

Division of Endocrinology and Metabolic Diseases (G.Z., M.M., G.T.), Division of Clinical Chemistry (G.F.), University of Verona Medical School, Verona; and Diabetes Unit (L.Z., G.F., G.T.), Sacro Cuore Hospital of Negrar, Verona, Italy 37024

Address all correspondence and requests for reprints to: Giovanni Targher, M.D., Servizio di Diabetologia, Ospedale Sacro Cuore, via Sempreboni, 5, 37024 Negrar (VR), Italy. E-mail: targher{at}sacrocuore.it; or Giacomo Zoppini, M.D., Division of

Abstract

The purposes of this study were 1) to compare soluble tumor necrosis factor- receptors, which are thought to reflect the degree of TNF- activation, in nondiabetic subjects and type 1 diabetic patients, and 2) to evaluate the effects of smoking and microvascular complications on soluble tumor necrosis factor- receptor levels in type 1 diabetic individuals. Plasma soluble tumor necrosis factor- receptor levels (R1 and R2) were measured in 50 young type 1 diabetic patients without clinical macroangiopathy and in a matched group of 20 healthy volunteers. When diabetic patients were grouped according to smoking and microvascular complication status, the groups of patients had similar values of age, sex, body mass index, blood pressure, lipids, creatinine, and glycometabolic control. Nevertheless, soluble tumor necrosis factor- receptor-R1 levels but not R2 levels, were markedly elevated (P < 0.05 or less) in complicated vs. uncomplicated (2.40 ± 0.3 vs. 1.80 ± 0.1 ng/ml) patients and in smokers vs. nonsmokers (2.66 ± 0.4 vs. 1.76 ± 0.1 ng/ml). In a two-factor ANOVA, both smoking (P < 0.01) and microvascular complications (P < 0.05) were independent predictors of soluble tumor necrosis factor- receptor-R1. Soluble tumor necrosis factor- receptor levels of diabetic patients who did not smoke or without complications were similar to those of healthy controls. In conclusion, smoking and microvascular complications seem to exert an additive and deleterious impact on TNF- activation, as reflected by levels of soluble tumor necrosis factor- receptors, in young adults with type 1 diabetes.

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