THE COMPARISON OF THE SECOND PHASE INSULIN SECRETION DERIVED FROM ORAL GLUCOSE TOLERANCE TEST AND LOW DOSE GRADED GLUCOSE INFUSION TEST

Background: the pathogeneses of type 2 diabetes (T2DM) are impaired insulin action and secretion, including the second phase insulin secretion (SPIS). However, SPIS is difcult to be measured. The study aimed to validate the SPIS derived from the simpler oral glucose tolerance test (OGTT) against the SPIS derived from the more complicated gold standard test, i.e. low dose graded glucose infusion test (LDGGI). Methods: Fourteen participants (3 with normal glucose tolerance, 8 with pre-diabetes and 3 with T2DM) were enrolled. They received both a standard LDGGI and an OGTT. The mathematical method which is called deconvolution was applied in both tests. The slope of the insulin secretion rate (ISR) against glucose levels during the LDGGI was obtained and regarded as the gold standard (SPIS-L). At the same time, the SPIS calculated from OGTT with minimal model was also obtained (SPIS-O). Results: Pearson correlation was used to assess the correlation between SPIS-L and SPIS-O. There was a signicant correlation between SPIS-L and SPIS-O (r = 0.843, p = 0.000). At the same time, a good agreement between the SPIS-L and SPIS-O was also found from the Bland-Altman plot. Conclusion: SPIS-O is highly correlated with the gold standard, i.e., the SPIS-L. Since it is easier to be performed, future researches focusing on SPIS by using OGTT might be expedited.

Long-term stability of low insulin responses to glucose in non-diabetic subjects

We investigated the stability of the insulin response to glucose in healthy subjects by making retrospective comparisons of insulin responses after two 60 min glucose infusion tests performed many years apart. The subjects (N =49) were divided into two lower and two higher quartiles as assessed by the incremental 0–10 min insulin area during the initial glucose infusion test. Ages were initially 32.3±2.8 years in lower quartiles and 26.6±1.1 in higher quartiles and body mass indexes 21.6±0.6 kg/m2 and 21.8±0.5, respectively. The interval between the first and second glucose infusion tests was 8.1±2.8 years for lower quartiles and 10.4±1.3 for higher quartiles. In lower quartiles, the 0–10 min insulin area at first testing was 157.1±15.9 mU/l × 10 min and at follow-up 202.2±26.6 (+ 29%, NS). In higher quartiles, the insulin area decreased from 654.8±70.6 mU/l × 10 min at first testing to 489.8±53.6 at follow-up (−25%, p<0.05). The 0–60 min glucose area did not change significantly between glucose infusion tests in lower quartiles (+ 5%), but did increase by 12% (p<0.005) in higher quartiles. Only one subject of the lowest quartile at first testing changed to higher quartiles at follow-up. Predictable "regression toward the mean" at follow-up was moderate, hence the individual insulin response to glucose was relatively stable with time. This finding is compatible with the hypothesis that genetic factors are of major importance for the insulin response to glucose.

Oral glucose tolerance test and insulin sensitivity in low insulin responders

Oral and iv glucose tolerance, insulin response to iv and oral glucose load as well as insulin sensitivity were evaluated in 58 'low insulin responders'. They were selected from a group of 226 healthy subjects with normal fasting blood glucose and normal iv glucose tolerance test on the basis of a low insulin response during a standardized glucose infusion test (GIT). The insulin response to GIT was analysed by parameter identification in a mathematical model (parameter KI). Insulin sensitivity was also measured by computer analysis of GIT (parameter KG) and, in a limited group of subjects, by a somatostatin infusion test. Thirty-three low insulin responders had normal OGTT, whereas 5 demonstrated borderline-1, 16 borderline-2, and 4 decreased OGTT. The first group of subjects demonstrated normal or enhanced insulin sensitivity. Borderline and decreased OGTT, in most instances, was accompanied by decreased insulin sensitivity, implying that a subgroup of low insulin responders exhibited signs of both impaired insulin response to glucose and insulin resistance. Since these defects characterize manifest type-2 diabetes, these subjects possibly may run a high risk to develop this type of diabetes. On the other hand, low insulin response in combination with increased insulin sensitivity may reflect adaptation of the secretory capacity of B-cells to the need of insulin.