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 oil 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 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 1,00 mu U/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215 +/- 9 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 MR) and SHO (462 +/- 19 MFI) were decreased versus EU (571 +/- 15 MFI. P = 0.04 and 0.004 respectively). Conclusions: In patients with 140 and SHO: i) insulin resistance was comparable: H) insulin-stimulated rates Of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters oil 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.