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.