Handisurya A et al. (2008) Effects of thyroxine replacement therapy on glucose metabolism in subjects with subclinical and overt hypothyroidism. Clin Endocrinol (Oxf) [doi:10.1111/j.1365-2265.2008.03280.x]

Overtly hypothyroid patients often have profoundly impaired glucose metabolism, which is partly reversed by restoration of the euthyroid state. Handisurya and colleagues have now shown that reversal of even subclinical hypothyroidism significantly reduces glucose-stimulated insulin secretion. Interestingly, insulin secretion decreased to a greater extent than could be expected from improved insulin sensitivity alone.

The study included 23 patients with Hashimoto thyroiditis, of whom 12 had overt hypothyroidism and 11 had subclinical hypothyroidism. Assessments of β-cell function and insulin sensitivity were done before and 6 months after initiation of levothyroxine therapy.

Both groups of patients had low fasting insulin levels and increased glucose-stimulated insulin secretion at baseline. Levothyroxine therapy significantly improved insulin sensitivity only in patients with overt hypothyroidism. Patients' insulin-secretion profiles improved, but did not normalize, on levothyroxine therapy; however, these improvements resulted in reduced demand on pancreatic β cells after a glucose challenge.

Hypothyroid patients often have increased circulating levels of free fatty acids, which increase insulin resistance via attenuation of glucose uptake and oxidation. Handisurya and colleagues suggest that levothyroxine might decrease free fatty acid levels and thereby attenuate glucose-stimulated insulin secretion. Levothyroxine therapy is warranted even in individuals with subclinical hypothyroidism, especially if they have risk factors for impaired glucose metabolism, given their high likelihood of progression to overt hypothyroidism.