title: Diabetes treatments have differential effects on nontraditional cardiovascular risk factors.
abstract: OBJECTIVE
  The aim of this study was to determine the effect of basal insulin, alone or with a sensitizer, or a combination of oral agents on nontraditional risk factors for cardiovascular disease (CVD).
  
  
  METHODS
  We randomized 57 patients with T2DM to either (1) continuous subcutaneous basal Lispro insulin at a single rate using an insulin pump (basal insulin) or (2) basal insulin and oral pioglitazone 30 mg daily (basal insulin +Pio) or (3) a sulfonylurea and metformin (SU+M). We measured glycosylated hemoglobin (HbA1c), plasma high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor-1 (PAI-1), 8-epi-prostaglandin F2 alpha (PGF2alpha), serum lipoprotein (a) [Lp (a)], and lipoprotein profile at baseline and after 20 weeks of treatment.
  
  
  RESULTS
  HbA1c decreased by >or=2% (P<.001) and to comparable levels (P=NS) in all groups. Despite improved glycemia, hsCRP did not change in any group, whereas plasma PAI-1 fell with basal insulin +Pio (P<.02) and SU+M (P<.01). PGF2alpha declined with basal insulin (P<.02) and SU+M (P<.001). High-density lipoprotein cholesterol (HDL-C) increased only with basal insulin +Pio (18.2%, P<.05). Lp (a) increased with basal insulin therapy alone (P<.01). Data were pooled from all groups to determine the overall effect of glycemic control-there was a significant (P<.001) decline in HbA1c, PAI-1, and PGF2alpha and an increase in HDL-C (P<.001). There was no correlation between HbA1c reduction and changes in these parameters.
  
  
  CONCLUSIONS
  We conclude that excellent glycemic control per se does not impact nontraditional risk factors for CVD equally, but various diabetes medications have different effects on these risk factors. These findings may have implications for making appropriate therapeutic choices for patients with Type 2 diabetes, although larger studies with more appropriate treatment comparisons may be necessary.
authors.affiliation: Tulane University Health Sciences Center, New Orleans, LA 70112, USA. vfonseca@tulane.edu
authors.forename: Vivian A
authors.initials: VA
authors.lastname: Fonseca
authors.forename: Pierre
authors.initials: P
authors.lastname: Theuma
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.forename: Cindy A
authors.initials: CA
authors.lastname: Leissinger
authors.forename: Sanda
authors.initials: S
authors.lastname: Clejan
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015237:Dinoprost / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives; D061268:Insulin Lispro; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012044:Regression Analysis; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000008:administration & dosage
chemical_list: D002097:C-Reactive Protein; D015237:Dinoprost; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D008074:Lipoproteins; D008687:Metformin; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones