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, AUC(0-300) 32 190 +/- 1067 and 31 497 +/- 716 mg/dl min respectively) versus EU (27 119 +/- 1156 mg/dl min, P<0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC(0-300) 11 020 +/- 985 and 9565 +/- 904 mU/l min respectively) compared with EU subjects (AUC(0-300) 7588 +/- 743 mU/l min, P<0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81 +/- 0.3 and 2.43 +/- 0.38 respectively) compared with EU subjects (1.27 +/- 0.16, P<0.05), while Matsuda and Belfiore indices were decreased in HR (4.21 +/- 0.41 and 0.77 +/- 0.05 respectively, P<0.001) and SHR patients (4.47 +/- 0.33 and 0.85 +/- 0.05 respectively, P<0.05 versus EU (7.76 +/- 0.87 and 1 respectively). At 100 mu U/ml insulin, i) GLUT3 levels on monocyte plasma membrane were increased in HR (468.8 +/- 7 mean fluorescence intensity (MFI)) and SHR patients (522.2 +/- 25 MFI) compared with EU subjects (407 +/- 18 MFI, P<0.01 and P<0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8 +/- 5%) versus EU subjects (61.26 +/- 10%, 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.