Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

Objective: Although clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited. Design and methods: To investigate this, we assessed the sensitivity of glucose metabolism to insulin in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR. Results: HR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC0–300 32 190G1067 and 31 497G716 mg/dl min respectively) versus EU (27 119 G1156 mg/dl min, P!0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC0–300 11 020G985 and 9565G904 mU/l min respectively) compared with EU subjects (AUC0–300 7588G743 mU/l min, P!0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81G0.3 and 2.43G0.38 respectively) compared with EU subjects (1.27 G0.16, P!0.05), while Matsuda and Belfiore indices were decreased in HR (4.21G0.41 and 0.77G0.05 respectively, P!0.001) and SHR patients (4.47G0.33 and 0.85G0.05 respectively, P!0.05 versus EU (7.76G0.87 and 1 respectively). At 100 mU/ml insulin, i) GLUT3 levels on the monocyte plasma membrane were increased in HR (468.8G7 mean fluorescence intensity (MFI)) and SHR patients (522.2G25 MFI) compared with EU subjects (407G18 MFI, P!0.01 and P!0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8G5%) versus EU subjects (61.26G10%, P!0.05). Conclusions: Insulin-stimulated glucose transport in isolated monocytes of patients with HR was decreased compared with EU subjects. Insulin resistance was comparable in patients with both HR and SHR.