Studies of insulin resistance in patients with clinical and subclinical hypothyroidism.

Objective: Although clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO).

Design And Methods: To investigate this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO.

Results: All three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97+/-0.22) and SHO (1.99+/-0.13) versus EU (1.27+/-0.16, P<0.05), while Matsuda index was decreased in HO (3.89+/-0.36) and SHO (4.26+/-0.48) versus EU (7.76+/-0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 microU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215+/-19 mean fluorescence intensity, MFI) and SHO (218+/-24 MFI) versus EU (270+/-25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481+/-30 MFI) and SHO (462+/-19 MFI) were decreased versus EU (571+/-15 MFI, P=0.04 and 0.004 respectively).

Conclusions: In patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.