Thyroid hormones are positively associated with insulin resistance early in the development of type 2 diabetes

Thyroid hormones have generally been found normal in diabetic patients. The question of whether variation within the euthyroid range influences insulin sensitivity in type 2 diabetes remains to be established. To investigate this, a meal was given to four groups: 17 healthy volunteers (controls), 22 first-degree relatives of type 2 diabetic subjects (relatives), 15 subjects with impaired glucose tolerance (IGT), and 24 subjects with overt type 2 diabetes (DM). Blood was drawn for 360 min for measurements of glucose and insulin. Plasma-free-T4(FT4) and plasma-free-T3(FT3) levels were measured. Fasting and postprandial insulin resistance was assessed by HOMA-IR and ISI indices, respectively. FT4 levels were found to be lower in controls (13.73 +/- A 0.48 pmol/l) than relatives, IGT, and DM (15.33 +/- A 0.52, 16.13 +/- A 0.65, and 17.7 +/- A 0.85 pmol/l, respectively, P = 0.007). FT3 levels were lower in controls (3.68 +/- A 0.09 pmol/l) than in relatives, IGT, and DM (4.35 +/- A 0.1, 4.8 +/- A 0.067, and 4.87 +/- A 0.11 pmol/l, respectively, P = 0.001). HOMA-IR was positively associated with FT4 and FT3 levels (beta-co-efficient = 1.876 +/- A 0.476, P = 0.001; and 0.406 +/- A 0.090, P = 0.001, respectively). ISI was negatively associated with FT4 and FT3 levels (beta-co-efficient = -0.051 +/- A 0.009, P = 0.001 and -0.009 +/- A 0.002, P = 0.001, respectively). In conclusion, increases of thyroid hormone levels within the normal range associate positively with insulin resistance. These data suggest that thyroid hormones may be part of the pathogenetic mechanism to explain metabolic derangement early in the development of type 2 diabetes.