Evaluation of second phase insulin secretion with simple surrogates derived from the mixed meal tolerance test in patients with type 2 diabetes

The major contributors to the pathogenesis of type 2 diabetes are impaired insulin action and insulin secretion, including second phase insulin secretion (2^nd ISEC). This study aimed to compare surrogates derived from the mixed meal tolerance test (MTT) with 2^nd ISEC derived from modified low-dose graded glucose infusion (M-LDGGI) in patients with type 2 diabetes. We were subsequently able to decide which surrogate would be performed easily and accurately. Twenty type 2 diabetes patients were enrolled. They received both MTT and M-LDGGI. The standardized MTT meals were provided at 8:00 A.M. and 12:00 P.M. The M-LDGGI was a simplified version of the Polonsky method; only two 80-min stages of glucose infusion (2 and 6 mg/kg/min) were given. The slopes of the insulin to glucose curve during the test were regarded as the 2^nd ISEC. First, we used the area under the insulin curve (AUC_IN) during MTT to quantify the 2^nd ISEC. The best correlated AUC_IN was from 60-240 min. Second, the slopes between any two time points of the plasma insulin to glucose level (SLOPE_I/G) were also assessed. The time period best correlated with 2^nd ISEC was from 0-120 min (SLOPE_0-120). Finally, the insulin-to-glucose ratio (IG_r) of each time point was used to estimate the 2^nd ISEC, and the best correlation was observed at 180 min. In conclusion, estimating 2^nd ISEC surrogates derived from MTT proved to be possible. The most accurate surrogate is the SLOPE_0-120, while IG_r180 is another less precise but more convenient method.