Insulin and Proinsulin Dynamics Progressively Deteriorate From Within the Normal Range Toward Impaired Glucose Tolerance

CONTEXT: Slight elevations in plasma glucose (PG) manifest in advance of diabetes onset, but abnormalities in immunoreactive insulin (IRI), proinsulin (Pro), and adiponectin dynamics during this stage remain poorly understood. OBJECTIVE: The objective of this work is to investigate whether IRI and Pro dynamics become abnormal as glucose tolerance deteriorates from within the normal range toward impaired glucose tolerance (IGT), as well as the relationship between PG, and these dynamics and serum adiponectin levels. DESIGN: A cross-sectional study was designed. SETTING: This study took place at Jichi Medical University in Japan. PARTICIPANTS AND MEASUREMENTS: PG, IRI, and Pro levels were determined in 1311 young Japanese individuals (age < 40 years) with normal or IGT before and at 30, 60, and 120 minutes during a 75-g oral glucose tolerance test. Participants were assigned to 4 groups according to glucose tolerance, and then background factors, adiponectin levels, insulin sensitivity (SI), and insulin secretion (β) indexes were determined. RESULTS: PG levels as well as IRI and Pro levels 60 and 120 minutes after glucose-loading increased incrementally with deteriorating glucose tolerance. All measures of β and the SI measure index of insulin sensitivity (ISI)-Matsuda decreased incrementally. Serum adiponectin levels were not significantly different among the glucose tolerance groups, but were independently and negatively correlated with fasting glucose. CONCLUSIONS: Early β decreased and postloading Pro levels became excessive in a progressive manner as glucose tolerance deteriorated from within the normal range toward IGT.