Thyroid Research and Practice

: 2019  |  Volume : 16  |  Issue : 1  |  Page : 1--2

Glucose metabolism Type 2 diabetes mellitus and the thyroid-so near and yet…

Krishna G Seshadri 
 Editor in Chief TRP, Chennai Diabetes and Endocrine Clinic, Chennai, Tamil Nadu, India

Correspondence Address:
Dr. Krishna G Seshadri
Chennai Diabetes and Endocrine Clinic, Chennai, Tamil Nadu

How to cite this article:
Seshadri KG. Glucose metabolism Type 2 diabetes mellitus and the thyroid-so near and yet….Thyroid Res Pract 2019;16:1-2

How to cite this URL:
Seshadri KG. Glucose metabolism Type 2 diabetes mellitus and the thyroid-so near and yet…. Thyroid Res Pract [serial online] 2019 [cited 2021 May 16 ];16:1-2
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Full Text

Alterations in glucose homeostasis are common in both hypothyroidism and thyrotoxicosis.

Increased hepatic glucose output and upregulated glycogenolysis are responsible for worsening hyperglycemia in thyrotoxicosis. Thyrotoxicosis is accompanied by elevated glucose turnover, increased intestinal glucose absorption, elevated hepatic glucose output, increased free fatty acid concentrations, increased fasting and/or postprandial insulin and proinsulin levels, and increased peripheral glucose transport accompanied by glucose utilization.[1] Increased hepatic lipolysis and beta-oxidation are observed[2] with increased susceptibility to ketosis. Inflammatory mediators may also contribute to decreased insulin sensitivity.[3] In addition, excess thyroid hormone may exert effect though noradrenergic action in adipocytes.[4] Insulin resistance is also a feature of hypothyroidism.[5] Reduced glucose-stimulated insulin transport is a feature probably reflecting altered GLUT2 translocation. In hypothyroidism, there is a discernible reduction in GLUT5 (but not GLUT4) expression in skeletal muscle.[6] Metformin which has salutary effects on insulin resistance also reduces thyroid-stimulating hormone levels in hypothyroid and euthyroid patients.

Thyroid hormones may contribute to the pathogenesis of insulin resistance in type 2 diabetes mellitus (T2DM) even in the absence of thyrotoxicosis[7] or hypothyroidism acute thyroid hormone withdrawal in athyreotic patients results in insulin resistance.[8] It has been, thus, speculated that insulin resistance is the link between T2DM and thyroid dysfunction (TD).

A number of glucose transport proteins are influenced by thyroid hormones. For instance, skeletal muscle GLUT4 action is mediated by T3.[9] T3 binding to the thyroid hormone receptors TR alpha 1 is responsible for modulating the expression of genes involved in glucose metabolism.[10] The deiodinases are responsible for tissue availability of T3. A polymorphism of deiodinase type 2 (DIO2) gene, Thr92Ala confers an increased risk of T2DM.[11] Reduced T3 generation consequent to altered DIO2 expression may increase insulin resistance.

A clear clinical association between T1DM and TD is apparent with consequent recommendations for screening in clinical practice. The relationship between T2DM and TD has been tenuous. Given that both conditions are common it is unclear if their occurrence is together or related. A higher percent of TD has been reported in patients with T2DM ranging between 12% and 16%.[1] In addition, an association between hypothyroidism (subclinical and overt) have been noted. In studies from India, the prevalence has generally mirrored these global numbers, but some studies have reported upto 24%. In this issue of the journal, Hussain et al. attempt to determine the occurrence of TD in T2DM in a reasonable cohort of patients from Odisha (please add the citation from this issue). 21% of patients had TD. As expected, the largest contributor was clinical and subclinical hypothyroidism. Interesting is the fair contribution of various levels of thyrotoxicosis (up to 20%).

Targeted screening for TD in T2DM has and will continue to remain controversial. Guidelines by societies seem to express a desire for screening or case finding but stop short of recommendations-justifiably so. For the clinician, the measurement of thyroid function in T2DM must be individualized - a low threshold for testing is probably warranted, especially when clinical features are present such as unexplained inadequacies in glucose control or weight loss. The impact of TD on the comorbidities and complications of diabetes such as chronic kidney disease dyslipidemia, and cardiovascular disease warrant consideration. For instance, a higher prevalence of subclinical hypothyroidism in patients with proliferative diabetic retinopathy has been reported.[12] The ongoing development of thyroid analogs which are metabolically active will further enhance our understanding of the intricate links between thyroid and glucose metabolism. Larger pooled cohorts are required to answer the screening question. Until then, old fashioned clinical judgment must prevail.


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