title: Effects of insulin and oral anti-diabetic agents on glucose metabolism, vascular dysfunction and skeletal muscle inflammation in type 2 diabetic subjects.
abstract: BACKGROUND
  To test potential differences between the actions of anti-diabetic medications, we examined the effects of oral hypoglycaemic agents versus glargine-apidra insulin therapy in T2DM.
  
  
  METHODS
  T2DM subjects were randomized to either oral hypoglycaemic agents (pioglitazone, metformin and glipizide, n = 9) or insulin therapy (n = 12) for 6 months. Carotid intimal media thickness, vascular reactivity (flow-mediated vasodilatation; percent change in brachial artery basal diameter post-ischaemia) and sublingual nitrate were measured with ultrasonography. Euglycemic hyperinsulinemic (80 mU/m(2) ) clamp with [3]-3H-glucose and muscle biopsies were performed.
  
  
  RESULTS
  Fasting plasma glucose (~257 to ~124 mg/dL, oral hypoglycaemic agents and ~256 to ~142 mg/dL, IT) and HbA(1c) (~10.3 to ~6.4%, OHA and ~10.7 to ~7.1%, IT) improved comparably. Endogenous glucose production (~2.1 to ~1.7 mg/kg/min, oral hypoglycaemic agents and ~2.3 to ~2.0 mg/kg/min, insulin therapy) and endogenous glucose production suppression by insulin (~0.4 to ~0.3 mg/kg min, oral hypoglycaemic agents and ~0.5 to ~0.7 mg/kg min, insulin therapy) were different. Total glucose disposal × 100 increased in the oral hypoglycaemic agents group (~5.2 to ~8.1; p = 0.03), but not in insulin therapy (~6.0 to ~5.4 mg/kg/min/µU/mL × 100). OHA reduced CIMT (~0.080 to ~0.068 cm; p < 0.05), whereas insulin therapy did not (~0.075 to ~0.072 cm). After sublingual nitrate, brachial artery basal diameter increased in the OHA group (~8.7 to ~18.2%), but not in insulin therapy (~11.2 to ~15.0%; p < 0.02). Except for plasma adiponectin (~7 to ~15, oral hypoglycaemic agents versus ~6 to ~10, IT), changes in inflammatory markers in the circulation and in muscle (IκBα, super-oxidase dismutase 2, monocyte-chemo-attractant protein 1, p-ERK and JNK) were equivalent.
  
  
  CONCLUSIONS
  Oral hypoglycaemic agents and insulin therapy treated patients achieved adequate glycemic control and the effects on circulating and muscle inflammatory biomarkers were similar, but only oral hypoglycaemic agents improved insulin sensitivity, vascular function and carotid intimal media thickness. These findings in a small sample suggest that the use of oral hypoglycaemic agents provides additional benefits to patients with T2DM.
authors.affiliation: Diabetes Division, Texas Diabetes Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Joya-Galeana
authors.forename: M
authors.initials: M
authors.lastname: Fernandez
authors.forename: A
authors.initials: A
authors.lastname: Cervera
authors.forename: S
authors.initials: S
authors.lastname: Reyna
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: C
authors.initials: C
authors.lastname: Triplitt
authors.forename: N
authors.initials: N
authors.lastname: Musi
authors.forename: R A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: E
authors.initials: E
authors.lastname: Cersosimo
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004338:Drug Combinations; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000069036:Insulin Glargine; D007333:Insulin Resistance; D049528:Insulin, Long-Acting; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D017058:Mexican Americans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009220:Myositis / Q000150:complications / Q000188:drug therapy*; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C479079:insulin glulisine