Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism

Abstract

We have examined insulin action on glucose metabolism in six hypothyroid patients before and after regular thyroid hormone treatment, and in six healthy volunteers before and after transient induction of moderate hyperthyroidism. Insulin was infused under euglycaemic and eukalaemic clamps. An appropriate amino acid infusion was used to blunt insulin-induced decreases in amino acid levels. Glucose kinetics were assessed using a primed continuous infusion of [6,6-(2)H(2)]glucose. The results showed that basal plasma insulin and glucose levels (i.e. before infusion) were similar in each case. Despite similar insulin infusion rates, the plateau value of insulin was lower after thyroid treatment in both hypothyroid patients and healthy volunteers. The rate of exogenous glucose needed to maintain plasma glucose at a steady-state level was increased by thyroid hormone in hypothyroid patients (P <0.05), but not in healthy volunteers. Thyroid treatment resulted in a significant increase in basal glucose disposal in both groups (P <0.05). Insulin, in conjunction with glucose and amino acids, significantly stimulated glucose disposal (P <0.05) under all conditions. The incremental increase in glucose disposal after infusion tended to be higher following thyroid hormone treatment, but this was not statistically significant. However, the ratio of the incremental increase in glucose disposal to the increase in plasma insulin was significantly improved after thyroid hormone treatment in hypothyroid patients (P <0.05). It was also increased in healthy volunteers, but not significantly. We conclude that thyroid hormones improve the ability of insulin to stimulate glucose disposal related to insulinaemia. This phenomenon may be highly sensitive, because it was only apparent at low thyroid hormone levels.

Association Analyses of Variants in the DIO2 Gene with Early-Onset Type 2 Diabetes Mellitus in Pima Indians

“…Thyroid hormones influence insulin action in skeletal muscle and adipose tissue in part by upregulating the expression of the muscle/fat-specific glucose transporter 4 (13,14). In contrast, studies in hypothyroid conditions show a decrease in both hepatic insulin resistance (12) and insulin-mediated glucose uptake in muscles (10,12). In humans, subclinical hypothyroidism is associated with hyperinsulinemia (15).…”

“…Experimental or spontaneous forms of thyroid dysfunction are associated with impaired glucose tolerance (10). Increase in both hepatic insulin resistance (11,12) and insulin-mediated glucose uptake is observed in hyperthyroidism as compared with euthyroid conditions (11). Thyroid hormones influence insulin action in skeletal muscle and adipose tissue in part by upregulating the expression of the muscle/fat-specific glucose transporter 4 (13,14).…”

Impaired Oxidative Endoplasmic Reticulum Stress Response Caused by Deficiency of Thyroid Hormone Receptor α

“…Several reports indicated that overt hypothyroidism is associated with profound changes in insulin sensitivity and insulin secretion, and these changes are reversible, at least in part, after recovery of thyroid function (33,34). Thyroid hormone effects on glucose homeostasis and on endocrine function of the pancreas are the result of an interaction of the thyroid hormone with its receptors.…”

Serum vaspin levels in hypothyroid patients

“…Even slightly higher TSH within the normal reference range has been linked to higher body mass index (BMI), dyslipidaemia and fatal coronary artery disease. Decreased insulin sensitivity was reported in some studies (5,6) while others could not find any association (7,8). TSH is often elevated in obesity associated with disorders of lipid and glucose metabolism.…”