title: Associations of glucose control with insulin sensitivity and pancreatic beta-cell responsiveness in newly presenting type 2 diabetes.
abstract: We examined the ability of indices of insulin sensitivity and pancreatic beta-cell responsiveness to explain interindividual variability of clinical measures of glucose control in newly presenting type 2 diabetes. Subjects with newly presenting type 2 diabetes (n = 65; 53 males and 12 females; age, 54 +/- 1 yr; body mass index, 30.5 +/- 0.7 kg/m(2); mean +/- SE) underwent an insulin-modified iv glucose tolerance test to determine minimal model-derived insulin sensitivity (S(I)), glucose effectiveness, first-phase insulin secretion, and disposition index. Subjects also underwent a standard meal tolerance test (MTT) to measure fasting/basal (M(0)) and postprandial (M(I)) pancreatic beta-cell responsiveness. Stepwise linear regression used these indices to explain interindividual variability of fasting and postprandial plasma glucose and insulin concentrations and glycated hemoglobin (HbA(1C)). All measures of pancreatic beta-cell responsiveness (M(0), M(I), and first-phase insulin secretion) were negatively correlated with fasting plasma glucose (P < 0.01) and positively correlated with fasting plasma insulin (FPI) and insulin responses to MTT (P < 0.05). S(I) demonstrated negative correlation with FPI (P < 0.001) but failed to correlate with any glucose variable. M(I) followed by disposition index (composite index of insulin sensitivity and pancreatic beta-cell responsiveness) were most informative in explaining interindividual variability. It was possible to explain 70-80% interindividual variability of fasting plasma glucose, FPI, HbA(1C), and insulin responses to MTT, and only 25-40% interindividual variability of postprandial glucose. In conclusion, postprandial insulin deficiency is the most powerful explanatory factor of deteriorating glucose control in newly presenting type 2 diabetes. Indices of insulin sensitivity and pancreatic beta-cell responsiveness explain fasting glucose and HbA(1C) well but fail to explain postprandial glucose.
authors.affiliation: Metabolic Modelling Group, Centre for Measurement and Information in Medicine, City University, London, EC1V OHB, United Kingdom.
authors.forename: Ahmed I
authors.initials: AI
authors.lastname: Albarrak
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Luzio
authors.forename: Ludovic J
authors.initials: LJ
authors.lastname: Chassin
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Playle
authors.forename: David R
authors.initials: DR
authors.lastname: Owens
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin