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 (1.97G0.22) and SHO (1.99G0.13) versus EU (1.27G0.16, P!0.05), while Matsuda index was decreased in HO (3.89G0.36) and SHO (4.26G0.48) versus EU (7.76G0.87, P!0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 mU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215G19 mean fluorescence intensity, MFI) and SHO (218G24 MFI) versus EU (270G25 MFI, PZ0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481G30 MFI) and SHO (462G19 MFI) were decreased versus EU (571G15 MFI, PZ0.04 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.
Activation of WBC leads to increased expression of GLUT1, GLUT3 and GLUT4 isoforms on their plasma membrane; this process was further augmented by insulin. During infection, these mechanisms may help to redistribute glucose as a potential source of energy away from peripheral tissues and direct it towards cells that mediate the immune response and are therefore crucial to survival.
In hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.
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