title: The switch from sulfonylurea to preprandial short- acting insulin analog substitution has an immediate and comprehensive beta-cell protective effect in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Supplementary insulin therapy provides assistance to meal-time insulin secretion in patients with type 2 diabetes and may have protective effects on beta-cell function.
  
  
  METHODS
  This study explored the immediate effect of supplementary insulin therapy on beta- cell function in patients with glimepiride monotherapy (five women, 15 men; 61.8 +/- 6.4 years old; body mass index, 31.1 +/- 4.4 kg/m(2); hemoglobin A1c, 7.0 +/- 1.3%). After 1 week of continued glimiperide therapy, the patients were randomized either to continue with their oral treatment or to switch to a fixed-dose supplementary insulin therapy (8 U of insulin aspart subcutaneously before each meal) for another week. Oral glucose tolerance tests (OGTTs) after drug uptake were performed at days 7 and 14, with measurement of glucose, insulin, C-peptide, intact and total proinsulin, glucagon, lactate, free fatty acids, and adiponectin.
  
  
  RESULTS
  Significant reductions from baseline were seen in the supplementary insulin therapy group for the fasting values of insulin (from 13.1 +/- 5.1 microU/mL to 10.6 +/- 5.2 microU/mL, P < 0.01), intact proinsulin (from 18.3 +/- 11.2 pmol/L to 10.3 +/- 4.6 pmol/L, P micro 0.05), total proinsulin (from 43.3 +/- 22.7 pmol/L to 29.7 +/- 14.5 pmol/L, P < 0.01), split proinsulin (from 24.9 +/- 13.8 pmol/L to 19.4 +/- 10.8 pmol/L, P micro 0.01), and the degree of beta-cell dysfunction (P < 0.05). Also, lower values for intact and total proinsulin and split proinsulin in the OGTT were observed in this group during the OGTT at the end point, while no changes at all occurred in the glimepiride group.
  
  
  CONCLUSIONS
  A fixed low-dose preprandial insulin aspart therapy resulted in an overall beta-cell protection with an improved fasting beta-cell secretion profile already within 1 week. Our study indicates that supplementary insulin therapy might be a reasonable alternative to bedtime basal insulin injections for initiation of insulin therapy in patients with type 2 diabetes.
authors.affiliation: IKFE, Institute for Clinical Research and Development, Mainz, Germany. AndreasP@ikfe.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
authors.forename: Babette
authors.initials: B
authors.lastname: Lorra
authors.forename: Michel R
authors.initials: MR
authors.lastname: Abdollahnia
authors.forename: Peter H
authors.initials: PH
authors.lastname: Kann
authors.forename: Dominik
authors.initials: D
authors.lastname: Mathieu
authors.forename: Christine
authors.initials: C
authors.lastname: Pehnert
authors.forename: Christina
authors.initials: C
authors.lastname: Oligschleger
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005949:Glucose Oxidase; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061267:Insulin Aspart; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005949:Glucose Oxidase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D011384:Proinsulin; D013453:Sulfonylurea Compounds; C057619:glimepiride