triiodothyronine--reverse and Insulin-Resistance

Thyroid dysfunction has been shown to be associated with insulin resistance (IR). This may involve peripheral thyroid hormone metabolism, which is assumed to be reflected by the ratio triiodothyronine/reverse triiodothyronine (T3/rT3-ratio). To explore a potential association between the T3/rT3-ratio and IR we investigated pairs which differed in IR, but were matched by sex, age, body mass index (BMI), and thyroid stimulating hormone (TSH). For this purpose, matched pair analyses were embedded into a cross sectional study group. 22 pairs were matched from either the first or the third tertile of HOMA%S of a cohort of 353 euthyroid subjects with normal glucose metabolism who did not take any medication. The T3/rT3-ratio was compared in the matched pairs. The T3/rT3-ratio was significantly increased in the insulin resistant subjects compared to their insulin sensitive partners (8.78 ± 0.47 vs. 7.33 ± 0.33, p=0.019). Furthermore the T3/rT3-ratio was lower in men compared to women (p for the within-subject effect=0.046) both in the insulin sensitive and the insulin resistant subjects. Here we show that the T3/rT3-ratio, which is supposed to reflect the tissue thyroid hormone metabolism, is significantly increased in insulin resistant subjects. This further supports a link between thyroid function and IR.

Topics: Adult; Blood Glucose; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Thyrotropin; Triiodothyronine; Triiodothyronine, Reverse

Variations in thyroid function within the normal range are associated with differences in metabolism and body composition. For instance, TSH is positively associated with body mass index (BMI). This could be due to alterations in thyroid hormone activity, or to direct effects of TSH, as the TSH receptor (TSHR) is also expressed in adipose tissue. The TSHR-Asp727Glu polymorphism is associated with lower serum TSH levels in vivo. In this study, we analysed whether serum thyroid parameters and the TSHR-Asp727Glu polymorphism were associated with glucose metabolism and insulin resistance. In addition, we analysed the Thr92Ala polymorphism in the type 2 deiodinase (D2), which was recently associated with insulin resistance.. Genotypes were determined in a population of 349 elderly men (age 77.7 +/- 3.5 years), for whom serum thyroid parameters and data on insulin resistance, such as fasting blood glucose, serum insulin and homeostasis model assessment (HOMA) values, were available.. In nondiabetic, euthyroid subjects, TSH was positively associated with leptin levels, whereas FT4 and rT3 were significantly negatively correlated with insulin and HOMA. Carriers of the TSHR-Glu727 allele had a significantly higher glucose (P = 0.01), insulin (P = 0.001), glycated haemoglobin (HbA1c) (P = 0.002), HOMA (P = 0.001) and leptin (P = 0.008). The D2-Ala(92) allele showed a trend towards higher levels of insulin (P = 0.07) and a higher HOMA (P = 0.09).. In this population of nondiabetic elderly men, serum thyroid parameters and the TSHR-Asp727Glu polymorphism were associated with relative insulin resistance. Our study suggests that genetic variation in TSHR plays a role in insulin resistance and thereby influences glucose metabolism.

Topics: Age Factors; Aged; Analysis of Variance; Biomarkers; Blood Glucose; Body Composition; Gene Frequency; Genetic Predisposition to Disease; Heterozygote; Humans; Insulin; Insulin Resistance; Leptin; Linear Models; Linkage Disequilibrium; Male; Polymorphism, Genetic; Receptors, Thyrotropin; Thyrotropin; Thyroxine; Triiodothyronine, Reverse

The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect.. Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-D-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects.. Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulin-stimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content.. Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration.

Topics: Adipose Tissue; Animals; Blood Glucose; Carnitine O-Palmitoyltransferase; Energy Metabolism; Fatty Acids, Nonesterified; Gene Expression; Glucose; Glucose Clamp Technique; Hormones, Ectopic; Hyperthyroidism; Insulin; Insulin Resistance; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Leptin; Male; Muscle, Skeletal; Propylthiouracil; Rats; Rats, Wistar; Resistin; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Triiodothyronine, Reverse

Topics: AMP-Activated Protein Kinases; Animals; Energy Metabolism; Glucose; Hypothyroidism; Insulin Resistance; Leptin; Multienzyme Complexes; Protein Serine-Threonine Kinases; Rats; Thyroid Hormones; Triiodothyronine; Triiodothyronine, Reverse