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Background A five-year follow-up study of intensive multifactorial intervention was undertaken to assess the changes of circulating serum amyloid A(SAA)levels and the incidence of atherosclerosis(AS)in patients with short-duration type 2 diabetes mellitus(T2DM)without maoroangiopathy,and whether intensive multifactorial intervention could prevent or at least postpone the occurence of macroangiopathy.Methods Among 150 patients with short-duration T2DM,75 were assigned to receive conventional outpatient treatment (conventional group)and the others underwent intensive multifactorial integrated therapy targeting hyperglycemia,hypertension,dyslipidemia and received aspirin simultaneously(intensive group).Results Plasma SAA levels were higher in diabetic patients than those in healthy control subjects,and decreased obviously after intensive multifactorial intervention.The levels of SAA were positively correlated with body mass index(BMI),waist hip ratio(WHR),triglyceride(TG),high sensitive C-reactive protein(hs-CRP)and common carotid intima-media thickness(CC-IMT).The standard-reaching rates of glycemia,blood pressure and lipidemia were significantly higher in intensive group than those of conventional group.The incidence of macroangiopathy decreased by 58.96% in intensive group compared with conventional group.Conclusions Intensive multifactorial intervention may significantly reduce the SAA levels and prevent the occurrence of AS in short-duration patients with T2DM.SAA might be one of the risk factors of T2DM combined with AS.