Low serum 3, 5, 3′-triiodothyronine (T3) and raised 3, 3′, 5′-triidothyronine (reverse T3 or RT3) in diabetes mellitus: Normalization on improvement in hyperglycemia

Abstract

In several pathophysiologic states, i.e., cirrhosis of liver, protein calorie malnutrition, starvation, carbohydrate deprivation, etc., thyroid hormone metabolism is reported to be altered with a decrease in serum T3 and a reciprocal increase in TR3. Uncontrolled diabetes mellitus is a similar state in which glucose does not enter the cells causing cellular starvation and hyperglycemia ensues. Therefore, serum T4, T3, RT3, T3-resin uptake, TSH, and glucose were determined after an overnight fast in 94 male diabetics (aged 28 to 85 years) during a routine follow-up visit to the outpatient clinic and 24 healthy male adults (aged 24 to 81 years). Glycosylated hemoglobin concentrations were measured as well in normal subjects and 16 newly discovered diabetics. In normal subjects, no significant relationships between fasting plasma glucose and T3 and RRT3 levels were observed. In diabetics there was a significant positive (r = 0.611; p less than 0.001) correlation between glucose and RT3. Similarly, a significant negative relationship was observed between glucose and T3 (r = 0.491; p less than 0.001). T4, free T4, T3-resin uptake, and TSH were normal in diabetics. In 16 newly discovered diabetics, with fasting plasma glucose greater than 200 mg/dl, serum T3 rose (96 +/- 5 to 128 +/- 5 ng/dl) and RT3 declined (26.3 +/- 10.4 +/- 1.4 ng/dl) on improvement of hyperglycemia (fasting plasma glucose less than 140 mg/dl) after intensive therapy for 6 to 8 weeks. Glycosylated hemoglobin levels declined as well (14.6 +/- 0.9% to 9.3 +/- 0.7%). These data indicate: (1) thyroid hormone metabolism may be altered in diabetes mellitus with a fall in serum T3 and a reciprocal rise in RT3; and (2) T3 and RT3 concentrations may serve as indicators of metabolic control in diabetes mellitus.

Low Triiodothyronine and Raised Reverse Triiodothyronine Levels in Patients Over Fifty Years of Age Who Have Type II Diabetes Mellitus: Influence of Metabolic Control, Not Age

“…Patients with fasting plasma glucose concentrations below 140 mg/dl were considered to have well‐controlled diabetes (grade I), as this level is one of the criteria established by the National Diabetes Data Group for the diagnosis of diabetes mellitus 21 . The rest of the grading was performed arbitrarily as described in our previous study 15 . Serum HbA1C concentrations corresponded very closely with fasting plasma glucose concentrations in these diabetic patients and further confirmed the grades of metabolic control (Table 1).…”

“…The major metabolic pathway of thyroxine (T 4 ) in humans has been shown to be monodeiodination, which gives rise to either 3,5,3′‐triiodothyronine (T 3 ) or 3,3′,5′‐triiodothyronine (rT 3 ) 1–4 . In several disease states, T 4 metabolism is altered, leading to the lowering of serum T 3 and the reciprocal elevation of serum rT 3 concentrations 3,5–13 . This condition is often termed “low T 3 syndrome” or “euthyroid sick disease.”…”

“…Recently we have reported lower T 3 and raised rT 3 concentrations in patients who had uncontrolled diabetes mellitus 14,15 . Furthermore, normalization of serum T 3 and rT 3 levels was observed with improvement in the metabolic control of their disease as assessed by fasting plasma glucose, glycosylated hemoglobin (HbA1C), and glycosylated protein concentrations 15,16 . Several of these patients had type II or noninsulin‐dependent diabetes mellitus (NIDDM).…”

Glucagon Administration Induces Lowering of Serum T3and Rise in Reverse T3in Euthyroid Healthy Subjects

“…A reciprocal rise in serum rT 3 level has been well documented in several low T 3 states associated with hyperglucagonemia (Kabadi, Premachandra and Eisenstein 1981;Kabadi, Premachandra and Maayan 1982;Kabadi and Premachandra 1983;Wartofsky and Burman 1982). Such an increase in serum rT 3 was observed after glucagon administration in our study.…”

“…Although one study (Sato and Robbins 1981) suggested that hypoinsulinemia may be responsible for low T 3 of euthyroid sick syndrome, it may not be always true since we have documented low T 3 and raised rT 3 levels in uncontrolled diabetics of both types, IDDM as well as NIDDM (Kabadi, Premachandra and Maayan 1982;Kabadi and Premachandra 1984), and also in cirrhotic patients during decompensated state (Kabadi, Premachandra and Eisenstein 1981;Kabadi and Premachandra 1983), both disorders associated with hyperglucagonemia and insulin deficiency or hyperinsulinemia. Thus, our findings further demonstrate that the fall in serum T 3 and a simultaneous rise in serum rT 3 observed in several euthyroid sick subjects may be induced by accompanying hyperglucagonemia.…”