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Assessment of beta-cell function during the oral glucose tolerance test by a minimal model of insulin secretion. 2001

A Cretti, and M Lehtovirta, and E Bonora, and B Brunato, and M G Zenti, and F Tosi, and M Caputo, and B Caruso, and L C Groop, and M Muggeo, and R C Bonadonna
University of Verona School of Medicine, Verona, Italy.

OBJECTIVE To characterise the performance of beta-cell during a standard oral glucose tolerance test (OGTT). METHODS Fifty-six subjects were studied. A minimal analogic model of beta-cell secretion during the OGTT was applied to all OGTTs (see below). The amount of insulin secreted over 120' in response to oral glucose (OGTT-ISR; Insulin Units 120'-1 m-2 BSA) and an index of beta-cell secretory 'force' (beta-Index; pmol.min-2.m-2 BSA) were computed with the aid of the model. In protocol A, 10 healthy subjects underwent two repeat 75 g OGTT with frequent (every 10'-15') blood sampling for glucose and C-peptide to test the reproducibility of OGTT-ISR and beta-Index with a complete or a reduced data set. In protocol B, 7 healthy subjects underwent three OGTTs (50, 100 or 150 g), to test the stability of the beta-Index under different glucose loads. In protocol C, 29 subjects (15 with normal glucose tolerance, 7 with impaired glucose tolerance and 7 with newly diagnosed type 2 diabetes) underwent two repeat 75 g OGTT with reduced (every 30' for 120') blood sampling to compare the reproducibility and the discriminant ratio (DR) of OGTT-ISR and beta-index with the insulinogenic index (IG-Index: Delta Insulin 30' - Basal/Delta Glucose 30' - Basal). In protocol D, 20 subjects (14 with normal glucose tolerance, 5 with impaired glucose tolerance and 1 with newly-diagnosed type 2 diabetes) underwent a 75 g OGTT and an intravenous glucose tolerance test (IVGTT) on separate days to explore the relationships between acute (0'-10') insulin response (AIR) during the IVGTT and beta-index and OGTT-ISR during the OGTT. RESULTS In all protocols, the minimal analogic model of C-peptide secretion achieved a reasonable fit of the experimental data. In protocol A, a good reproducibility of both beta-index and OGTT-ISR was observed with both complete and reduced (every 30') data sets. In protocol B, increasing the oral glucose load caused progressive increases in OGTT-ISR (from 2.63 +/- 0.70 to 5.11 +/- 0.91 Units.120'-1.m-2 BSA; P < 0.01), but the beta-index stayed the same (4.14 +/- 0.35 vs. 4.29 +/- 0.30 vs. 4.30 +/- 0.33 pmol.min-2.m-2 BSA). In protocol C, both OGTT-ISR and beta-index had lower day-to-day CVs (17.6 +/- 2.2 and 12.4 +/- 2.4%, respectively) and higher DRs (2.57 and 1.74, respectively) than the IG-index (CV: 35.5 +/- 6.3%; DR: 0.934). OGTT-ISR was positively correlated to BMI (P < 0.03), whereas beta-index was inversely related to both fasting and 2 h plasma glucose (P < 0.01 for both). In protocol D, beta-index, but not OGTT-ISR, was significantly correlated to AIR (r = 0.542, P < 0.02). CONCLUSIONS Analogically modelling beta-cell function during the OGTT provides a simple, useful tool for the physiological assessment of beta-cell function.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D003924 Diabetes Mellitus, Type 2 A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY. Diabetes Mellitus, Adult-Onset,Diabetes Mellitus, Ketosis-Resistant,Diabetes Mellitus, Maturity-Onset,Diabetes Mellitus, Non-Insulin-Dependent,Diabetes Mellitus, Slow-Onset,Diabetes Mellitus, Stable,MODY,Maturity-Onset Diabetes Mellitus,NIDDM,Diabetes Mellitus, Non Insulin Dependent,Diabetes Mellitus, Noninsulin Dependent,Diabetes Mellitus, Noninsulin-Dependent,Diabetes Mellitus, Type II,Maturity-Onset Diabetes,Noninsulin-Dependent Diabetes Mellitus,Type 2 Diabetes,Type 2 Diabetes Mellitus,Adult-Onset Diabetes Mellitus,Diabetes Mellitus, Adult Onset,Diabetes Mellitus, Ketosis Resistant,Diabetes Mellitus, Maturity Onset,Diabetes Mellitus, Slow Onset,Diabetes, Maturity-Onset,Diabetes, Type 2,Ketosis-Resistant Diabetes Mellitus,Maturity Onset Diabetes,Maturity Onset Diabetes Mellitus,Non-Insulin-Dependent Diabetes Mellitus,Noninsulin Dependent Diabetes Mellitus,Slow-Onset Diabetes Mellitus,Stable Diabetes Mellitus
D005240 Feasibility Studies Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. Feasibility Study,Studies, Feasibility,Study, Feasibility

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