Impaired 3,5,3′-triiodothyronine (T3) production in diabetic patients

Pittman, Constance S.; Suda, Abhay K.; Chambers, Joseph B.; Ray, Gautam

doi:10.1016/0026-0495(79)90103-3

Cited by 61 publications

(29 citation statements)

References 21 publications

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“…Although it is well established that DM patients have a high frequency of clinical or subclinical hypothyroidism (19,20,22), the breadth and importance of cardiac tissue thyroid dysfunction is currently unknown. To our knowledge, this is the first investigation to show that DM alone, without concomitant pathological stimuli such as hypertension or myocardial infarction may lead to cardiac tissue hypothyroidism (see Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…DM patients have a higher frequency of clinical and subclinical hypothyroidism than non-DM individuals (19)(20)(21), which is a likely contributor to increased cardiovascular risk and poor outcomes in this population (22). DM and hypothyroidism produce similar negative effects on cardiac function and are associated with impaired contractility (3,7,8,23), α to β myosin heavy chain (MHC) isoform shift (7,8,13,24), microvessel/blood flow abnormalities (4,13,(25)(26)(27), and dysregulation of Ca 2+ handling (23,(28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

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Low-Dose T3 Replacement Restores Depressed Cardiac T3 Levels, Preserves Coronary Microvasculature and Attenuates Cardiac Dysfunction in Experimental Diabetes Mellitus

Weltman

Ojamaa

Schlenker

et al. 2014

Mol Med

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Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female Sprague Dawley (SD) rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N = 10/group): STZ/N or STZ/N + 0.03 μg/mL T 3 ; age-matched vehicle-treated rats served as nondiabetic controls (C). After 2 months of T 3 treatment (3 months post-DM induction), left ventricular (LV) function was assessed by echocardiography and LV pressure measurements. Despite normal serum thyroid hormone (TH) levels, STZ/N treatment resulted in reductions in myocardial tissue content of THs (T 3 and T 4 : 39% and 17% reduction versus C, respectively). Tissue hypothyroidism in the DM hearts was associated with increased DIO3 deiodinase (which converts THs to inactive metabolites) altered TH transporter expression, reexpression of the fetal gene phenotype, reduced arteriolar resistance vessel density, and diminished cardiac function. Low-dose T 3 replacement largely restored cardiac tissue TH levels (T 3 and T 4 : 43% and 10% increase versus STZ/N, respectively), improved cardiac function, reversed fetal gene expression and preserved the arteriolar resistance vessel network without causing overt symptoms of hyperthyroidism. We conclude that cardiac dysfunction in chronic DM may be associated with tissue hypothyroidism despite normal serum TH levels. Low-dose T 3 replacement appears to be a safe and effective adjunct therapy to attenuate and/or reverse cardiac remodeling and dysfunction induced by experimental DM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low-Dose T3 Replacement Restores Depressed Cardiac T3 Levels, Preserves Coronary Microvasculature and Attenuates Cardiac Dysfunction in Experimental Diabetes Mellitus

Weltman

Ojamaa

Schlenker

et al. 2014

Mol Med

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“…Various studies have demonstrated the presence of hypothyroidism in diabetic pa tients and rats [Pittman et al, 1979;Dillmann, 1982;Sundaresan et al, 1984], Some investigators indicated that cardiac dysfunc tion in diabetes mellitus was mediated, in part, by thyroid hormones. For example, the decrease in the number of myocardial padrenoceptors mentioned above [Sundare san et al, 1984] and a depression of myosin ATPase activity [Dillmann, 1982] appeared to be results of diabetes-induced hypothy roidism.…”

Section: Discussionmentioning

confidence: 99%

“…Various studies have demonstrated the presence of hypothyroidism in diabetic pa tients and rats [Pittman et al, 1979;Dillmann, 1982], A depression of myosin ATPase or a decrease in the number of (3-adrenocep tors of the myocardium in diabetes mellitus is considered to result from deficiency of thy roid hormones [Dillmann, 1982;Sundaresan et al, 1984], However, the role of thyroid hormones in the changes in vascular reactiv ity in diabetes has never been examined.…”

Section: Introductionmentioning

confidence: 99%

Changes in Vascular Reactivity in Experimental Diabetic Rats: Comparison with Hypothyroid Rats

Takiguchi

Satoh²,

Hashimoto³

et al. 1988

J Vasc Res

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The responsiveness to vasoactive agents in the perfused mesenteric vascular bed of streptozocin-induced diabetic rats was examined and compared with that of propylthiouracil-induced hypothyroid rats. Diabetic rats at 4 and 8 weeks after the induction of diabetes showed a significant decrease in isoproterenol-induced vasodilatation. In addition, the contractile responses to norepinephrine and 5-hydroxytryptamine and the vasodilative response to acetylcholine were significantly decreased in 12-week-diabetic rats. The contractile response to nerve stimulation was markedly decreased at 8 and 12 weeks. On the other hand, hypothyroid rats showed a decreased response to isoproterenol, but they did not show any change in the response to nerve stimulation. A decrease in plasma thyroid hormone levels in diabetic rats at any time period was similar in extent to that in hypothyroid rats. The data indicate that the progressive changes in vascular reactivity in diabetic rats may be divided into two stages. In the early stage, the altered reactivity of vasculature is likely to be mediated by hypothyroidism, whereas in the later stage, it is induced by other factors, e.g. hyperglycemia and hypoinsulinemia. Adrenergic neuropathy is not caused by hypothyroidism.

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“…5 -7 Collectively, the data suggest that pressure loadinduced left ventricular hypertrophy increases the susceptibility of the myocardium to diabetes-related derangements. 1 " 7 Hypothyroidism, or a "low thyroid state," is often reported as a secondary metabolic disorder of diabetes, 8 and insulin replacement therapy has been shown to restore normal thyroid status in diabetic rats. 9 Hypothyroidism and diabetes have a number of similar effects on cardiac metabolism and function.…”

mentioning

confidence: 99%

Insulin, thyroid hormone, and heart function of diabetic spontaneously hypertensive rat.

Davidoff

Rodgers

1990

Hypertension

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Diabetes impairs cardiac performance more extensively in hypertensive rats than it does in nonhypertensive strains. A "low thyroid state" may contribute to the adverse cardiovascular effects of diabetes in spontaneously hypertensive rats (SHR). We tested this hypothesis by comparing the effects of thyroid hormone with those of insulin treatment on cardiac performance of diabetic SHR. Diabetes was induced with streptozotocin (45 mg/kg). Subsets of diabetic rats were treated with either insulin (10-20 units/kg/day) or triiodothyronine (8-10 /ig/kg/day). Heart rate and systolic arterial pressure were obtained at weekly intervals. After 8 weeks, cardiac function was assessed using an isolated working heart preparation. Diabetes reduced arterial pressure and heart rate in vivo and markedly depressed cardiac performance under volume and pressure loading conditions ex vivo, confirming previous observations. As 4 Chemically induced diabetes in hypertensive rats has a more profound effect on cardiac function than it does in normotensive models. -7Collectively, the data suggest that pressure loadinduced left ventricular hypertrophy increases the susceptibility of the myocardium to diabetes-related derangements.

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Impaired 3,5,3′-triiodothyronine (T3) production in diabetic patients

Cited by 61 publications

References 21 publications

Low-Dose T3 Replacement Restores Depressed Cardiac T3 Levels, Preserves Coronary Microvasculature and Attenuates Cardiac Dysfunction in Experimental Diabetes Mellitus

Low-Dose T3 Replacement Restores Depressed Cardiac T3 Levels, Preserves Coronary Microvasculature and Attenuates Cardiac Dysfunction in Experimental Diabetes Mellitus

Changes in Vascular Reactivity in Experimental Diabetic Rats: Comparison with Hypothyroid Rats

Insulin, thyroid hormone, and heart function of diabetic spontaneously hypertensive rat.

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