Increased Insulin Action and Clearance in Hyperthyroid Newly Diagnosed IDDM Patient: Restoration to Normal With Antithyroid Treatment

In a patient with hyperthyroidism and newly diagnosed insulin-dependent diabetes mellitus (IDDM), insulin action and clearance were studied before the initiation of antithyroid treatment and at 3-mo intervals for 1 yr thereafter. The sequential euglycemic clamp technique (5 mM) was used with insulin infusion rates of 0.5, 1.0, 2.0, and 5.0 mil · kg⁻¹ · min⁻¹ in four steps of 2 h. The data were compared with nine control subjects and nine newly diagnosed euthyroid IDDM patients treated with insulin for 0.5 mo. Insulin sensitivity was increased in the patients (ED₅₀ 40 vs. 52 mU/L, range 43–70, in controls and 70 mU/L, range 59–120, in IDDM subjects). Insulin responsiveness was markedly elevated; the steady-state glucose infusion rate (SSGIR) of step 4 was 104 vs. 64 μmol · kg⁻¹ · min⁻¹ (range 50–79) in controls and 61 junol · kg⁻¹ · min⁻¹ (range 47–69) in IDDM subjects. Insulin clearance was elevated in all steps (1-3, 20–23 vs. 9–15 ml · kg⁻¹ · min⁻¹; 4, 18 vs. 6–12 ml · kg⁻¹ · min⁻¹ in control and IDDM subjects). Parallel to the normalization of thyroid metabolism, insulin action (ED50 60 mU/L, SSGIR in step 4, 51 μmol · kg⁻¹ · min⁻¹) and insulin clearance (steps 1–3, 11–14 ml · kg⁻¹ · min⁻¹; step 4, 7 ml · kg⁻¹ · min⁻¹) returned to the normal range in 6 mo. Both remained within the normal range until 12 mo. In the patient with newly diagnosed IDDM, the initial marked increases of insulin action and clearance were due to coexistent hyperthyroidism. With the amelioration of the hyperthyroid state, both processes became normal. The parallelism between insulin action and clearance suggests a functional relationship.