title: Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with type 2 diabetes uncontrolled by oral agents.
abstract: OBJECTIVE
  Progressive β-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs.
  
  
  METHODS
  This was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90-110 mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups.
  
  
  RESULTS
  Both insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P=0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P=0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P=0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations.
  
  
  CONCLUSIONS
  In type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study.
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Sakharova
authors.forename: Ranee R
authors.initials: RR
authors.lastname: Lleva
authors.forename: James D
authors.initials: JD
authors.lastname: Dziura
authors.forename: Geralyn R
authors.initials: GR
authors.lastname: Spollett
authors.forename: Scott K
authors.initials: SK
authors.lastname: Howell
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Beisswenger
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Inzucchi
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting