title: Meal-induced increases in C-reactive protein, interleukin-6 and tumour necrosis factor α are attenuated by prandial + basal insulin in patients with Type 2 diabetes.
abstract: OBJECTIVE
  To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes.
  
  
  METHODS
  This test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks.
  
  
  RESULTS
  Post-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve.
  
  
  CONCLUSIONS
  Controlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high-sensitivity C-reactive protein, interleukin-6 and tumour necrosis factor α compared with basal insulin. The rise in post-meal glucose, but not triglycerides, significantly correlated with the rise in post-meal inflammatory and glycative biomarkers.
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Dartmouth Medical School and Dartmouth-Hitchcock Medical Center, Hanover, NH, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Beisswenger
authors.forename: W V
authors.initials: WV
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Ceriello
authors.forename: N A
authors.initials: NA
authors.lastname: Le
authors.forename: R B
authors.initials: RB
authors.lastname: Goldberg
authors.forename: J P
authors.initials: JP
authors.lastname: Cooke
authors.forename: D C
authors.initials: DC
authors.lastname: Robbins
authors.forename: S
authors.initials: S
authors.lastname: Sarwat
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.forename: C A
authors.initials: CA
authors.lastname: Jones
authors.forename: M H
authors.initials: MH
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014481:United States
chemical_list: D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha