title: Meal-induced 24-hour profile of circulating glycated insulin in type 2 diabetic subjects measured by a novel radioimmunoassay.
abstract: Increasing evidence supports a role for glycated insulin in the insulin-resistant state of type 2 diabetes. We measured 24-hour profiles of plasma glycated insulin, using a novel radioimmunoassay (RIA), to evaluate the effects of meal stimulation and intermittent fasting on circulating concentrations of plasma glycated insulin in type 2 diabetes. Patients (n = 6; hemoglobin A(1c) [HbA(1c)], 7.2% +/- 0.6%; fasting plasma glucose, 7.4 +/- 0.7 mmol/L; body mass index [BMI], 35.7 +/- 3.5 kg/m(2); age, 56.3 +/- 4.4 years) were admitted for 24 hours and received a standardized meal regimen. Half-hourly venous samples were taken for plasma glycated insulin, glucose, insulin, and C-peptide concentrations between 8 am and midnight and 2-hourly overnight. The mean plasma glycated insulin concentration over 24 hours was 27.8 +/- 1.2 pmol/L with a mean ratio of insulin:glycated insulin of 11:1. Circulating glucose, insulin, C-peptide, and glycated insulin followed a basal and meal-related pattern with most prominent increments following breakfast, lunch, and evening meal, respectively. The mean concentrations of glycated insulin during the morning, afternoon, evening, and night-time periods were 24.4 +/- 2.5, 28.7 +/- 2.3, 31.1 +/- 2.1, and 26.2 +/- 1.5 pmol/L, respectively, giving significantly higher molar ratios of insulin:glycated insulin of 18.0:1, 14.2:1, and 12.7:1 compared with 7.0:1 at night (P <.01 to P <.001). These data demonstrate that glycated insulin circulates at relatively high concentrations in type 2 diabetes with a diurnal pattern of basal and meal-stimulated release. A higher proportion of glycated insulin circulates at night suggestive of differences in metabolic clearance compared with native insulin.
authors.affiliation: Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, Ireland; and the School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland.
authors.forename: John R
authors.initials: JR
authors.lastname: Lindsay
authors.forename: Aine M
authors.initials: AM
authors.lastname: McKillop
authors.forename: Mark H
authors.initials: MH
authors.lastname: Mooney
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Bell
authors.forename: Finbarr P M
authors.initials: FP
authors.lastname: O'harte
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004032:Diet; D004435:Eating / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006031:Glycosylation; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology; D011863:Radioimmunoassay
chemical_list: D001786:Blood Glucose; D007328:Insulin