ABSTRACT
<p><b>BACKGROUND</b>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 macroangiopathy, and whether intensive multifactorial intervention could prevent or at least postpone the occurrence of macroangiopathy.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antihypertensive Agents , Pharmacology , Therapeutic Uses , Blood Glucose , Metabolism , C-Reactive Protein , Metabolism , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Diabetic Angiopathies , Hypoglycemic Agents , Pharmacology , Therapeutic Uses , Hypolipidemic Agents , Pharmacology , Therapeutic Uses , Multivariate Analysis , Serum Amyloid A Protein , Metabolism , Triglycerides , Blood , Tunica MediaABSTRACT
<p><b>OBJECTIVE</b>To construct a single plasmid vector mediating doxycycline-inducible recombined human insulin gene expression in myotube cell line.</p><p><b>METHODS</b>An expression cassette of rtTAnls driven by promoter of human cytomegalovirus and a furin-cuttable recombined human insulin expression cassette driven by a reverse poly-tetO DNA motif were cloned into a single plasmid vector (prTR-tetO-mINS). The prTR-tetO-mINS and pLNCX were co-transfected into a myotube cell line (C2C12) and pLNCX vector were used as a control. After selection with G418, the transfected cells were induced with doxycycline at concentrations of 0, 2, and 10 microg/mL. RT-PCR was used to determine expression levels of recombinant insulin mRNA at the 5th day. Insulin production in cell cultures medium (at different incubation time) and cell extracts (at the 7th day) were analyzed with human pro/insulin RIA kits.</p><p><b>RESULTS</b>Immune reactive insulin (IRI) level in cell medium was found increased at 24 hours of doxycycline incubation, and still increased at the 5th day. After withdrawn of doxycycline, IRI decreased sharply and was at baseline three days later. IRI and human insulin mRNA levels were positively related to different levels of doxycycline. A 25-fold increase in IRI was found against background expression at the 7th day.</p><p><b>CONCLUSION</b>Human insulin expression can be successfully regulated by doxycycline and the background was very low. This single tet-on insulin expression system may provide a new approach to a controlled insulin gene therapy in skeletal muscle.</p>