Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH)

Abstract

To evaluate beta-cell function and insulin sensitivity in subjects with overt (OH) and subclinical hypothyroidism (SH) before and after T4 replacement therapy. Disturbances in glucose metabolism have been observed in hypothyroid states. However, the clinical significance and potential reversibility of these alterations by T4 replacement therapy remain to be elucidated especially in patients with SH. Parameters of glucose metabolism have been investigated in subjects with OH (n = 12) and SH (n = 11). Insulin sensitivity has been assessed by the euglycaemic-hyperinsulinaemic clamp technique and beta-cell function by mathematical modelling of data derived from an oral glucose tolerance test. Fasting and dynamic glycaemia as assessed by the AUC(Glucose) remained unaltered following substitution therapy (P > 0.05). Insulin sensitivity significantly improved only in subjects with OH (P < 0.05). Fasting insulin and proinsulin concentrations increased proportionally in both groups (P < 0.05) with the proinsulin : insulin ratio remaining unchanged (P > 0.05). Total insulin secretion was higher in OH before initiation of therapy (P < 0.05). In both groups, dynamic parameters including total insulin secretion, hepatic insulin extraction and the adaptation index were significantly attenuated (P < 0.05) after restoration of thyroid function, whereas the disposition index and the basal insulin secretion rate remained unaltered (P > 0.05). In summary, SH and OH are characterized by attenuated basal plasma insulin levels and increased glucose-induced insulin secretion. T4 replacement therapy partially ameliorates the insulin secretion profile and reduces the demand on pancreatic beta-cells after glucose challenge to an extent that exceeds any effect attributable to the improvement in insulin sensitivity.