Fas/Fas-Ligand pathway is impaired in patients with type 2 diabetes. Influence of hypertension and insulin resistance

Objectives: In type 2 diabetic patients with no cardiac history or symptoms, 1) to evaluate whether the soluble forms of Fas (sFas) and Fas-ligand (sFasL), involved in apoptosis, may be markers of silent coronary disease or related to hypertension or microangiopathic complications; 2) to examine the effect of short-term glycemic control on sFas and sFasL. Methods: (1) sFas and sFasL were measured with the ELISA method in 44 asymptomatic diabetic patients, 33 with hypertension, and with a normal myocardial scintigraphy (n = 14), with silent myocardial ischemia (SMI) and without (n = 15) or with (n = 15) significant coronary stenoses; and in 14 controls; (2) sFas and sFasL were measured in 15 poorly controlled diabetic patients before and after 7 days of CSII treatment. Results: (1) sFas and sFasL differed in the four groups of patients (p = 0.003 each). sFas was significantly higher in the patients with SMI without (p = 0.035) and with coronary stenoses (p = 0.002) than in the control group. sFasL was lower in the three groups of diabetic patients (p < 0.05 each) than in control group. In the diabetic population, sFas correlated positively with hypertension (p = 0.021), and sFasL negatively with hypertension (p = 0.027) and HOMA index in the non-insulin treated patients (p = 0.049); (2) sFas did not differ before or after CSII, and there was a marginal decrease in sFasL. Conclusion: Fas-mediated apoptosis is involved in type 2 diabetes and might be associated with hypertension and/or its vascular consequences. sFasL might be affected by insulin resistance. sFas and sFasL are not effective markers of SMI.