Dr. Ron’s Research Review – February 4, 2015

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This week’s research review focuses on rT3 and diabetes.

A study found that patients with diabetes mellitus (fasting plasma glucose greater than 200 mg/dl) had low serum T3 and raised reverse T3 (T3) that normalized on improvement of their hyperglycemia (FPG < 140 mg/dl) after intensive therapy for 6 to 8 weeks. (Kabadi et al., 1982)

A second study included 220 type II diabetics age 40-85 years. Serum T4, free T4, T3 resin uptake, and TSH in diabetic patients were not significantly altered compared with 37 young normal control subjects, irrespective of age or the grade of metabolic control. Serum T3 levels declined and rT3 levels rose in the diabetic patients with worsening of the metabolic control. However, with comparable metabolic control, the levels were not significantly different from the younger patients. (Kabadi and Premachandra, 1984)

A recent study published in Hormone and Metabolic Research found that T3/rT3-ratio is associated with insulin resistance (HOMA) independent of TSH. This was a cross sectional study group with 22 pairs that were matched with a cohort of 353 euthyroid subjects with normal glucose metabolism who did not take any medication. 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). (Ruhla, Arafat et al. 2011)

Dr. Ron


 

Articles

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
            (Kabadi et al., 1982) Download
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
            (Kabadi and Premachandra, 1984) Download
Several studies have demonstrated that the uncontrolled diabetic state in both type I as well as type II diabetes mellitus is characterized by altered thyroid hormone metabolism, which results in the lowering of serum triiodothyronine (T3) levels and a reciprocal elevation of T3 (rT3) levels. Because the majority of type II diabetics are over 50 years of age and because numerous previous reports have implicated aging as a cause of low T3 and high rT3 levels, we studied 220 type II diabetics from 40-85 years of age to assess the influence of aging and metabolic control on thyroid hormone levels. Serum thyroxine (T4) free T4, T3 resin uptake, and thyroid-stimulating hormone (TSH) measurements in diabetic patients were not significantly altered compared with 37 young normal control subjects, irrespective of age or the grade of metabolic control. Serum T3 levels declined and rT3 levels rose in the diabetic patients with worsening of the metabolic control. However, with comparable metabolic control, the levels were not significantly different from the younger patients. Therefore, low T3 and high rT3 levels observed in patients of any age who have type II diabetes mellitus may be exclusively caused by deranged metabolic control of their disease.

T3/rT3-ratio is associated with insulin resistance independent of TSH
            (Ruhla et al., 2011) Download
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.

 


References

Kabadi, U. M., B. N. Premachandra, and M. Maayan (1982), ‘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’, Acta Diabetol Lat, 19 (3), 233-42. PubMedID: 7148329
Kabadi, U. M. and B. N. Premachandra (1984), ‘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’, J Am Geriatr Soc, 32 (5), 375-79. PubMedID: 6715765
Ruhla, S., et al. (2011), ‘T3/rT3-ratio is associated with insulin resistance independent of TSH’, Horm Metab Res, 43 (2), 130-34. PubMedID: 21104580