Aims: The aim of this study was to evaluate the relative importance of insulin sensitivity (SI), and the first (1st ISEC) and second phase insulin secretion (2nd ISEC) in the development of type 2 diabetes (T2D) in Chinese subjects. Methods: A total of 96 subjects, including 19 with normal fasting glucose, 21 with pre-diabetes, and 56 with T2D were enrolled. Subjects underwent a modified low dose graded glucose infusion (M-LDGGI; a simplified version of Polonsky's method) and frequently sampled intravenous glucose tolerance test. The results were interpreted as the slope of the changes of plasma insulin against the glucose levels. By observing the respective percentage reduction, the deterioration rate of each parameter was compared. Results: As fasting plasma glucose (FPG) levels increased, SI decreased mildly and non-significantly, while the 1st and 2nd ISECs decreased more dramatically and significantly. More importantly, the decrease of the 1st ISEC from baseline was greater than that of the 2nd ISEC. Conclusions: Since the 1st ISEC decreased the most with increasing FPG levels, it is concluded that the 1st ISEC is the key trigger of T2D development. On the contrary, the 2nd ISEC remained more stable across increasing FPG levels. This latter finding may explain the effectiveness of insulin secretagogues during the early stage of T2D. The results of this study can be helpful in the development of interventions aimed at stopping the progression and/or treating T2D in Chinese populations.
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