title: Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes.
abstract: This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (P<0.001). The AUC amylin/C-peptide ratio was similar on both days, while AUC proinsulin/C-peptide ratio was higher with GLP-1 (P=0.02). In the patients, amylin, C-peptide and proinsulin AUCs were unaltered by near-normoglycaemia per se. Proinsulin responses to GLP-1 were unchanged, but amylin and C-peptide AUCs increased (P<0.05) after insulin treatment, and AUC amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks of near-normoglycaemia, whereas GLP-1 increased amylin and C-peptide secretion and amylin/C-peptide ratio. Near-normoglycaemia reduced proinsulin/C-peptide ratio during stimulation with GLP-1, suggesting that strict glycaemic control might ameliorate some of the disturbances in beta-cell function characterizing T2DM.
authors.affiliation: Departments of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. masmar@mfi.ku.dk
authors.forename: Meena
authors.initials: M
authors.lastname: Asmar
authors.forename: Patricia V
authors.initials: PV
authors.lastname: Højberg
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Deacon
authors.forename: Kristine
authors.initials: K
authors.lastname: Hare
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D000682:Amyloid / Q000378:metabolism; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D002096:C-Peptide; D054795:Incretins; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D052216:Glucagon-Like Peptide 1; D011384:Proinsulin; D005947:Glucose