Study of Glucose and Lipid Metabolism by Continuous Indirect Calorimetry in Graves’ Disease: Effect of an Oral Glucose Load

Abstract

Glucose and lipid metabolism were studied in 12 patients with hyperthyroid Graves' disease for 3 h during an oral glucose tolerance test (100 g) by continuous indirect calorimetry. In the postabsorptive state, glucose oxidation was not different from that in normal subjects, but lipid oxidation was significantly increased. Impaired glucose tolerance was found, but total glucose oxidation increased after the glucose load to 47.1 +/- 2.0 (+/- SEM) vs. 33.4 +/- 1.4 g/3 h in the control group (P less than 0.001). Total glucose oxidation corresponded, in hyperthyroid patients, to the highest rate obtained with progressively increasing insulin and glucose administration in normal man. Glucose storage was clearly lower in hyperthyroid patients. After treatment in 7 patients, glucose tolerance improved significantly, and the metabolic patterns almost normalized. In the 12 hyperthyroid patients and the 7 patients after treatment (n = 19), a correlation was found between total serum T3 concentration and both basal lipid oxidation and suprabasal glucose oxidation. It is concluded that the decrease in glucose tolerance in hyperthyroidism cannot be explained by an alteration in glucose oxidation, but, rather, by a defect in nonoxidative glucose uptake in the periphery.

Thyroid hormone action in metabolic regulation

“…Animal studies have revealed that hyperthyroid animals develop elevated plasma glucose and insulin levels, due to increased hepatic glucose production including increased gluconeogenesis and glycogenolysis (Raboudi et al, 1989), and decreased glucose clearance and disposal. In human patients with Grave's hyperthyroidism, glucose tolerance is impaired (Randin et al, 1985). Hyperthyroidism is also accompanied by increased glucagon levels and growth hormone secretion, which may contribute to increased glucose level and decreased glucose tolerance.…”

Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1α in rat muscle

“…Hyperthyroidism results in marked increases in glucose uptake, fatty acid oxidation, and oxidative capacity (34,42,48). The induction of PGC-1␣ has been shown in muscle cells in culture to induce synthesis of mitochondrial enzymes involved in oxidation of pyruvate and fatty acids (11,23,29).…”

Complications of Hyperthyroidism

“…Glucose uptake in peripheral tissues especially in the skeletal muscle have been found to be increased in hyperthyroisdism [426][427][428][429]. This increased uptake is mainly related with an increase in insulin-stimulated glucose oxidation rates [430][431][432][433].…”

“…This increased uptake is mainly related with an increase in insulin-stimulated glucose oxidation rates [430][431][432][433]. Furthermore, reduced glycogenogenesis and insulin-stimulated nonoxidative glucose elimination results with intracellular glucose being redirected towards glycolysis and lactate formation [428,429,434]. The release of lactate from peripheral tissues back to the liver contributes to the Cori cycle where more hepatic glucose is being produced [434][435][436].…”