The aetiology of type 2 diabetes is not yet completely understood. Although low physical activity and hyperalimentation are lifestyle factors associated with an increased risk of the disease, type 2 diabetes has been claimed to be a manifestation of an inflammatory response.60-62 A recent study examined prospectively the effects of the classical pro-inflammatory cytokines IL-1P, IL-6, and TNF-a on the development of type 2 diabetes. Data suggest that the pattern of circulating inflammatory cytokines modifies the risk for type 2 diabetes. In particular, a combined elevation of IL-1 P and IL-6 independently increases the risk of type 2 diabetes. These data strongly support the hypothesis that a subclinical inflammmatory reaction plays a role in the pathogenesis of type 2 diabetes.63
Several mechanisms may be implied in the involvement of inflammatory cytokines in the pathogenesis of the disease. For instance, both IL-6 and IL-1 P act on the liver to produce the characteristic dyslipidemia of the metabolic syndrome, with increased very low-density lipo-proteins high-density lipoproteins.62 Carriers of the G SNP at -174 at 5-upstream of IL-6, characterized by high IL-6 plasma levels, appear to be prone to develop lipid abnormalities and have a worse glucose handling capacity, a higher blood glycosylated hemoglobin, a higher fasting insulin levels, and an higher insulin sensitivity.64'65
Accordingly, in the Leiden 85-Plus Study66 it has been demonstrated that low production of IL-10 by stimulated peripheral blood cells, associates with the metabolic syndrome and type 2 diabetes. It was found that individuals with raised blood glucose tended to have a low capacity to produce IL-10. A similar association was shown between high plasma triglyceride concentrations and low production capacity of IL-10. Even if this study does not consider the possibility that the elevation of blood glucose concentration itself could have a direct effect upon cellular IL-10 production, it seems to confirm the role of inflammation in the aetiology of type 2 diabetes.
A partial confirmation of the role that low production of IL-10 may play in metabolic diabetes was recently offered by immunogenetic studies on association of interleukin-10 (IL-10) gene promoter region polymorphisms and adult onset of type 1 diabetes.67 The frequency of the ATA haplotype at -1082G/A, -819C/T, and -592C/A SNP was increased in adult-onset patients. Even if the pathogeneses of the two disease are very different, considering that up to 75% of IL-10 production capacity in humans derives from genetic factors,10 the possibility that IL-10 polymorphisms may play a role in genetic predisposition or protection against type 2 diabetes seems to be a conceivable hypothesis.
On the other hand, a confirmation on the role of low IL-10 in type 2 diabetes pathogenesis came from animal models. Experimental studies using gene-targeted mice68 provide direct evidence that IL-10 offers some protection against endothelial dysfunction during diabetes and that this effect is mediated by inhibition of increases in reactive oxygen species in blood vessels. It was also demonstrated that endogenous IL-10 is an important counterbalance to mechanisms that produce endothelial dysfunction during diabetes68 and that mucosal administration of IL-10 enhances oral tolerance in diabetes.68,69
Was this article helpful?