title: Chronic reduction of fasting glycemia with insulin glargine improves first- and second-phase insulin secretion in patients with type 2 diabetes.
abstract: OBJECTIVE
  Insulin secretion is often diminished in hyperglycemic patients with type 2 diabetes. We examined whether chronic basal insulin treatment with insulin glargine improves glucose-induced insulin secretion.
  
  
  METHODS
  Fourteen patients with type 2 diabetes on metformin monotherapy received an add-on therapy with insulin glargine over 8 weeks. Intravenous glucose tolerance tests (IVGTTs) were performed before and after the intervention, with and without previous adjustment of fasting glucose levels using a 3-h intravenous insulin infusion.
  
  
  RESULTS
  Fasting glycemia was lowered from 179.6 ± 7.5 to 117.6 ± 6.5 mg/dL (P < 0.001), and HbA(1c) levels declined from 8.4 ± 0.5 to 7.1 ± 0.2% (P = 0.0046). The final insulin dose was 59.3 ± 10.2 IU. Acute normalization of fasting glycemia by intravenous insulin reduced C-peptide levels during the IVGTT (P < 0.0001). In contrast, insulin and C-peptide responses to intravenous glucose administration were significantly greater after the glargine treatment period (P < 0.0001, respectively). Both first- and second-phase insulin secretion increased significantly after the glargine treatment period (P < 0.05, respectively). These improvements in insulin secretion were observed during both the experiments with and without acute adjustment of fasting glycemia.
  
  
  CONCLUSIONS
  Chronic supplementation of long-acting basal insulin improves glucose-induced insulin secretion in hyperglycemic patients with type 2 diabetes, whereas acute exogenous insulin administration reduces the β-cell response to glucose administration. These data provide a rationale for basal insulin treatment regiments to improve postprandial endogenous insulin secretion in hyperglycemic patients with type 2 diabetes.
authors.affiliation: Department of Medicine I, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pennartz
authors.forename: Nina
authors.initials: N
authors.lastname: Schenker
authors.forename: Björn A
authors.initials: BA
authors.lastname: Menge
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Schmidt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000069036:Insulin Glargine; D000078790:Insulin Secretion; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine