title: Glucagon-stimulated insulin secretion in patients with type 2 diabetes mellitus: support for the concept of glucose toxicity.
abstract: Parameters of blood glucose control and insulin secretion were evaluated in 114 patients with type 2 diabetes mellitus, who were no longer controlled satisfactorily by maximal doses of oral hypoglycaemic agents, and compared with those obtained in 11 healthy control subjects, 32 patients with recently-diagnosed type 2 diabetes, and 16 tablet-treated and 36 insulin-treated patients. Newly-diagnosed patients were slightly younger (60 +/- 13 yr) and had a slightly higher body mass index (29.4 +/- 6.5 kg/m2). Known duration of diabetes was 9 yr (range 1-37) in secondary failure, and 11 yr (range 1-31) in insulin-treated patients. Fasting blood glucose was the highest (13.8 +/- 2.8 mmol/l) in secondary failure and newly-diagnosed patients (12.6 +/- 3.8 mmol/l) compared to tablet-treated (8.7 +/- 3.3 mmol/l) and insulin-treated patients (9.6 +/- 3.2 mmol/l, p less than 0.05). HbA1c levels were comparably elevated. In insulin-treated patients, fasting plasma C-peptide levels were lower relative to the mutually comparable levels in the other 3 diabetic groups. Fasting plasma insulin levels did not differ between the 4 diabetic groups. C-peptide release after glucagon (C-peptide AUC) was comparable in all 4 diabetic groups, although in tablet-treated patients the ratio C-peptide AUC/fasting blood glucose was higher (p less than 0.05). We conclude that the clinical usefulness of determining residual insulin secretion in type 2 diabetic patients is limited, and that the similar reduction of insulin secretion in severely hyperglycaemic newly-diagnosed and secondary failure type 2 diabetic patients supports the concept of "glucose toxicity".
authors.affiliation: Department of Internal Medicine, University Hospital Maastricht, Netherlands.
authors.forename: B H
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.forename: P P
authors.initials: PP
authors.lastname: Menheere
authors.forename: L
authors.initials: L
authors.lastname: Nijst
authors.forename: G J
authors.initials: GJ
authors.lastname: Rondas-Colbers
authors.forename: J P
authors.initials: JP
authors.lastname: Sels
authors.forename: A C
authors.initials: AC
authors.lastname: Nieuwenhuijzen Kruseman
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005934:Glucagon; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013453:Sulfonylurea Compounds; D005934:Glucagon