title: Impact of a mild decrease in fasting plasma glucose on β-cell function in healthy subjects and patients with type 2 diabetes.
abstract: Restoring euglycaemia for weeks or months improves insulin secretion in patients with type 2 diabetes (T2D). We tested whether mild decrements in fasting glucose (FPG) acutely affect β-cell function and insulin sensitivity. Thirteen normotolerant (NGT) and 10 T2D patients volunteered in pairs. In an isoglycemic test (Iso), after 100 min of stabilization, an incremental glucose infusion over 3 h was applied to raise plasma glucose to >22 mmol/l, followed by an arginine challenge; in a subisoglycemic test (Sub), a glucose infusion matching the plasma glucose time course of Iso was preceded by an insulin infusion period (100 min) aimed at maintaining a mild FPG reduction while avoiding hypoglycaemia. β-Cell function was assessed by mathematical modeling, whereas the acute insulin response (AIR) to arginine was determined from C-peptide levels. In the Sub, FPG was lowered by 17% in NGT and 31% in T2D patients. On the glucose ramp, total insulin release was lower in Sub than in Iso in both groups [from 106 (43) to 75 (39) nmol/m(-2) in NGT and from 71 (63) to 64 (41) nmol/m(-2) in T2D, P = 0.001]. In the Sub, β-cell glucose sensitivity was significantly (P = 0.008) reduced in NGT [from 50 (31) to 43 (21) pmol·min(-1)·m(-2)·mM(-1)] but not in T2D [19 (20) to 20 (20) pmol·min(-1)·m(-2)·mM(-1)]. Likewise, AIR was lowered in NGT [8.9 (4.6) to 7.1 (4.4) nmol/l, P = 0.048] but not in T2D [4.7 (3.3) to 5.3 (3.2) nmol/l]. Insulin sensitivity improved in NGT but only marginally in T2D. Prestimulatory glucose levels acutely influence both β-cell function and insulin sensitivity differentially in nondiabetic and type 2 diabetic individuals.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; martaseghieri@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Seghieri
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;
authors.forename: Eleni
authors.initials: E
authors.lastname: Rebelos
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;
authors.forename: Brenno D
authors.initials: BD
authors.lastname: Astiarraga
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;
authors.forename: Simona
authors.initials: S
authors.lastname: Baldi
authors.affiliation: National Research Council (CNR) Institute of Neuroscience,Padua, Italy; and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015536:Down-Regulation; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: arginine-stimulated acute insulin response; fasting plasma glucose; insulin sensitivity; β-cell function; β-cell mass