Early phase insulin secretion is increased in subjects with normal fasting glucose and metabolic syndrome: a premature feature of beta-cell dysfunction

Abstract 

Background and Aims

Metabolic syndrome (MS) has been mainly related to insulin resistance, but the role of changes in insulin secretion has not been thoroughly investigated.

Methods and Results

Using an oral glucose tolerance test (OGTT) we studied beta-cell function and insulin sensitivity in subjects with normal fasting glucose with and without MS, and their relationship to fatty liver which was evaluated by abdominal-ultrasonography. In MS early phase insulin secretion, as measured by insulinogenic index (IG₃₀), was increased (p<0.05) independently from insulin sensitivity. Furthermore IG₃₀ was progressively higher as the number of factors needed for the diagnosis of MS increased (p<0.01). Insulin and C-peptide AUC were also increased (p<0.01 and p<0.05, respectively) but, in contrast to IG_30, these differences disappeared when ISI was used as a covariate. After OGTT, 51% of the subjects with MS had altered post-load glucose tolerance compared to 24.9% without MS (p<0.01). In both groups, the altered glucose tolerance was associated with a similar IG₃₀ reduction. In normo-tolerant subjects with MS the IG₃₀ was higher (+54.1%, p<0.01), and this elevation occurred irrespective of ISI; however, the beta-cell compensatory capacity for insulin resistance (disposition index) was impaired (p<0.001). Fatty liver was more frequent (p<0.001) and more severe (p<0.01) in MS, and it was significantly related to total AUC-insulin (p<0.001), independently from ISI.

Conclusion

These findings indicate that the prevalence of altered tolerance is more frequent in subjects with normal fasting glucose and MS. The hyperinsulinemia might not only be an adaptive response to insulin resistance, but a primary defect of beta-cell function contributing to glucose intolerance.

keywords: Metabolic syndrome, Hyperinsulinemia, Insulin secretion, Early phase Insulin secretion