Invest Clin 66(2): 157 - 165, 2025 https://doi.org/10.54817/IC.v66n2a03

Corresponding author: Yan Song, Department of Surgery, The Second People’s Hospital of Beilun District, Ningbo

315809, Zhejiang Province, China. E-mail: songyansphbd@hosp-edu.cn

Correlation between thyroid hormone values

and anemia in elderly patients with diabetic

nephropathy.

Jingjing Yu1#, Keke Tang2# and Yan Song3

1Department of Endocrinology, The Second People’s Hospital of Beilun District,

Ningbo Zhejiang Province, China.

2Department of Endocrinology, The First Affiliated Hospital of Ningbo University,

Ningbo Zhejiang Province, China.

3Department of Surgery, The Second People’s Hospital of Beilun District, Ningbo,

Zhejiang Province, China.

#The two authors contributed equally to this study.

Keywords: correlation; diabetic nephropathy; elderly; anemia severity; thyroid hormone.

Abstract. We aimed to explore the correlation between thyroid hormone

levels and anemia severity in elderly diabetic nephropathy (DN) patients. Elder-

ly DN patients (140 in total) diagnosed and treated during November 2019 and

December 2023 were retrospectively recruited as a DN group, 140 patients with

uncomplicated diabetes mellitus as a simple diabetes group, and 140 healthy

subjects as a healthy group. A non-anemia group (n=63) and an anemia group

(n=77) were set up as sets of the DN group according to the hemoglobin (Hb)

level, and the anemia group was further divided into a severe group (n=48)

(Hb<60 g/L), a moderate group (n=16) (60 g/L≤Hb<90 g/L) and a mild

group (n=13) (Hb≥90 g/L). Compared to the simple diabetes group, signifi-

cantly increased levels of serum TSH and significantly decreased levels of FT4

and FT3 were found in the DN group (p<0.05). A significant increase in TSH

levels and significant decreases in FT4 and FT3 levels were detected in the

serum from the moderate group compared with those from the mild group

(p<0.05). The same trends in these levels were observed from the severe group

compared to the moderate group (p<0.05). Hb had a negative correlation with

TSH and positive correlations with FT4 and FT3 (p<0.05). High TSH and low

FT4 and FT3 may be related to anemia in elderly patients with DN, and they

have correlations with the severity of anemia.

158 Yu et al.

Investigación Clínica 66(2): 2025

Correlación entre los valores de hormonas tiroideas y anemia

en pacientes ancianos con nefropatía diabética.

Invest Clin 2025; 66 (2): 157 – 165

Palabras clave: correlación; nefropatía diabética; ancianos; gravedad de la anemia;

hormona tiroidea.

Resumen. Nuestro objetivo fue explorar la correlación entre el nivel de

hormona tiroidea y la severidad de la anemia en pacientes ancianos con nefro-

patía diabética (ND). Se reclutaron retrospectivamente 140 pacientes ancianos

con ND diagnosticados y tratados entre noviembre de 2019 y diciembre de

2023, 140 pacientes con diabetes mellitus sin nefropatía y 140 sujetos sanos

como grupo control sano. El grupo de ND se dividió en un grupo sin anemia

(n=63) y un grupo con anemia (n=77) de acuerdo con el nivel de hemoglobina

(Hb). El grupo con anemia fue subdividido en grave (n=48) (Hb<60 g/L), mo-

derada (n=16) (60 g/L-Hb<90 g/L) y leve (n=13) (Hb-90 g/L). En compara-

ción con el grupo de diabetes simple, se encontró un aumento significativo de

los niveles séricos de TSH y una disminución significativa de los niveles de FT4

y FT3 en el grupo de DN (p<0,05). Se encontró un aumento significativo del ni-

vel de TSH junto con disminuciones significativas de los niveles de FT4 y FT3 en

el suero del grupo moderado en comparación con los del grupo leve (p<0,05).

Las mismas tendencias en estos niveles se observaron en el grupo grave cuando

se compararon con el grupo moderado (p<0,05). La Hb tuvo una correlación

negativa con TSH y correlación positiva con FT4 y FT3 (p<0,05). Niveles altos

de TSH y bajos de FT4 y FT3 podrían estar relacionados con anemia y su grave-

dad en pacientes ancianos con ND.

Received: 24-01-2025 Accepted: 27-04-2025

INTRODUCTION

With the development of population ag-

ing, the incidence of diabetes mellitus and

other chronic diseases has been increasing

year by year. It is estimated that diabetes mel-

litus may affect 642 million people globally

by 2040, with an incidence rate of 8.8-10.4%

1. Being a microvascular complication of dia-

betes mellitus characterized by the highest

prevalence and severity, diabetic nephropathy

(DN) has become the leading contributor to

end-stage renal disease 2. As the disease pro-

gresses, the patient’s renal function gradually

declines, decreasing erythropoietin (EPO)

produced by the kidney, iron absorption, and

red blood cell survival time, thus significantly

increasing the incidence of anemia 3. Anemia

suggests that DN has progressed to a severe

stage, and renal failure occurs, resulting in

ineffective excretion of metabolites and tox-

ins in the body and further worsening the

condition of the disease. In addition, anemia

can lead to insufficient oxygen supply to or-

gans, aggravating complications of diabetes

mellitus, such as cardiovascular diseases and

retinopathy. Diabetic patients with chronic

anemia are at higher risk of developing car-

dio-cerebrovascular diseases, retinopathy, ne-

phropathy and neuropathy.

In addition, due to a significant de-

crease in urine protein and gradual impact

Thyroid hormone, anemia and elderly diabetic nephropathy 159

Vol. 66(2): 157 - 165, 2025

on the hypothalamic-pituitary-thyroid axis

function with the progression of the disease,

the synthesis of thyroid hormones declines

in DN patients, and thyroid dysfunction oc-

curs. Thyroid hormones may be implicated

in glomerular filtration rate (GFR) regula-

tion and blood circulation in the kidneys 4.

The rate of thyroid function abnormality in

patients with kidney disease at stage G5 is

significantly higher than that at stage G1

(39.1% vs. 8.3%), and it is considered that

the severity of kidney disease may be closely

related to thyroid function 5. Moreover, the

severity of type 2 diabetes mellitus (T2DM)

in elderly patients also correlates with blood

glucose-related indicators and thyroid hor-

mone levels. Free triiodothyronine (FT3),

free thyroxine (FT4) and other thyroid hor-

mones in mild and severe T2DM in elderly

patients are at significantly lower levels

than in healthy controls 6, suggesting that

the changes in thyroid hormone levels may

be related to the severity of T2DM in elderly

patients. However, no reports are available

yet on whether thyroid hormone level is re-

lated to the severity of anemia in elderly DN

patients.

Because of this, the level changes of

thyroid hormones in patients with different

severities of anemia were analyzed in this

study to explore the correlations of thyroid

hormones with anemia severity in elderly DN

subjects, aiming to provide a reference for

diagnosis and treatment in clinical practice.

PATIENTS AND METHODS

Subjects

One hundred and forty older adults di-

agnosed with DN and hospitalized for treat-

ment herein during November 2019 and De-

cember 2023 were retrospectively recruited

into the DN group. The following inclusion

criteria were utilized: 1) patients satisfying

the diagnosis and classification criteria for

diabetes mellitus in the Guideline for Pre-

vention and Treatment of Type 2 Diabetes

Mellitus in China (2020 Edition) 7, 2) those

who met the diagnostic and treatment cri-

teria for DN 8, 3) those with urinary albu-

min excretion rate (AER) ≥30 mg/24 h,

GFR≤60 mL/min·1.73 m2 or urinary micro-

albumin/creatinine ratio (ACR) ≥3 mg/g,

and 4) those without renal transplantation

or dialysis history. The adopted exclusion

criteria included: 1) patients who had taken

drugs that may affect urinary protein excre-

tion before participating in the study, 2)

those with no obvious hepatic and renal dys-

function previously and no severe complica-

tions of diabetes mellitus recently, 3) those

complicated with other kidney diseases, or

4) those complicated with mental illness or

cognitive dysfunction. Another 140 patients

with uncomplicated diabetes mellitus en-

tered the simple diabetes group, in addition

to 140 healthy subjects as the healthy group.

Their gender, age, and body mass index were

not significantly different from those in the

DN group.

Grouping criteria

According to the GFR, patients with

chronic DN were divided into stage 5 group

(n=11, GFR<15 mL/min·1.73 m2), stage 4

group (n=20, 15 mL/min·1.73 m2≤GFR<30

mL/min·1.73 m2), stage 3 group (n=43, 30

mL/min·1.73 m2≤GFR<60 mL/min·1.73

m2), stage 2 group (n=39, 60 mL/min·1.73

m2≤GFR<90 mL/min·1.73 m2), and stage 1

group (n=27, GFR≥90 mL/min·1.73 m2).

An anemia group (n=77) plus a non-

anemia group (n=63) were established as

subsets of the DN group according to the

hemoglobin (Hb) level. Hb ≤120 g/L in fe-

males and ≤130 g/L in males indicated ane-

mia.

The anemia group was further divided

into a severe group (n=48) (Hb<60 g/L),

a moderate group (n=16) (60 g/L≤Hb＜90

g/L) and a mild group (n=13) (Hb≥90 g/L).

Detection of thyroid hormones

All patients were enrolled to collect fast-

ing venous blood (5 mL) in the morning for

centrifugation. Then, the supernatant was

160 Yu et al.

Investigación Clínica 66(2): 2025

harvested to measure thyroid-stimulating

hormone (TSH), FT4 and FT3 using an MPI-

A electrochemiluminescence analyzer (Xi’an

Remex Analysis Instruments Co., Ltd.) in

strict accordance with the kit instructions.

TSH (Item No.: ZY-TSH-Hu), FT4 (Item No.:

ZY-fT4-Ge) and FT3 test kits (Item No.: ZY-

fT3-Ge) were purchased from Shanghai Zeye

Biotechnology Co., Ltd.

Statistical analysis

The SPSS 24.0 software for statistical

analysis was employed. The description for-

mat of ( ± SD) was utilized for the mea-

surement data distributed normally, which

were compared by the independent-sample

t-test between two groups and by the uni-

variate multi-sample mean test among mul-

tiple groups. The count data were described

by [n (%)] and subjected to the chi-square

test for comparisons. The correlations of

thyroid hormone level with anemia sever-

ity were explored by the Pearson analysis. A

difference with statistical significance was

marked with p<0.05.

RESULTS

Baseline data

Table 1 exhibits the three groups of

baseline data.

Thyroid hormone levels in DN patients

Compared to the healthy group, a sig-

nificant increase in TSH levels and signifi-

cant decreases in FT4 and FT3 levels were

detected in the serum from the simple

diabetes group (t=19.307, -6.34, -16.16;

p<0.05). In comparison with the simple dia-

betes group, significantly increased levels of

serum TSH and significantly decreased lev-

els of FT4 and FT3 were observed in the DN

group (t=17.989, -6.702, -14.076; p<0.05)

(Table 2).

Association between DN and anemia

In the DN group, anemia occurred in 77

cases, including 7, 11, 32, 16 and 11 cases in

stages 1-5, respectively. The incidence and

severity of anemia were found to rise gradu-

ally as the stage of DN increased (p<0.05)

(Table 3).

Changes in thyroid hormone levels

in patients with different severities

of anemia

The serum levels of TSH, FT4 and FT3

in the severe, moderate, mild, and non-ane-

mia groups were detected with significant

differences (p<0.05). Compared to the mild

group, the moderate group exhibited evident

elevations in serum TSH levels and marked

decreases in FT4 and FT3 levels (t=2.613,

Table 1. Baseline data.

Group n

Sex n (%) Age

(years)

 ± SD

Body mass

index (kg/m2)

 ± SD

Smoking

history

n (%)

Drinking

history

n (%)

Female Male

DN 140 77 (55) 63 (45) 52.84±8.15 23.69±2.26 81 (57.86) 87 (62.14)

Simple

diabetes

140

71 (50.71)

69 (49.29)

53.15±7.26

24.12±2.24

76 (54.29)

80 (57.14)

Healthy 140 74 (52.86) 66 (47.14) 52.77±7.49 24.08±2.32 75 (53.57) 82 (58.57)

F/χ20.516 0.10 1.53 0.597 0.769

p 0.773 0.907 0.218 0.742 0.681

DN: Diabetic nephropathy. The measurement data were compared by univariate multi-sample mean test among

multiple groups. The count data were subjected to the chi-square test for comparisons.

Thyroid hormone, anemia and elderly diabetic nephropathy 161

Vol. 66(2): 157 - 165, 2025

-1.88, -3.439; p<0.05). The TSH levels

climbed significantly, whereas the FT4 and

FT3 levels dropped significantly in the se-

rum from the severe group when compared

with the moderate group (t=3.555, -4.598,

6.366; p<0.05) (Table 4).

Correlation of thyroid hormone levels

with anemia severity

As revealed by the Pearson’s correlation

analysis, Hb had a negative correlation with

TSH, but it had a positive correlation with

FT4 and FT3 (p<0.05) (Fig. 1).

DISCUSSION

DN has the early pathological charac-

teristics of glomerular basement membrane

thickening and mesangial expansion and

the late characteristics of glomeruloscle-

rosis and renal tubule interstitial fibrosis 9.

Early diagnosis and intervention are crucial

for managing DN, particularly in elderly pa-

tients, who are often more vulnerable to its

progression due to poor diabetes manage-

ment and comorbidities. Therefore, predict-

ing disease progression and achieving timely

intervention in elderly DN patients are vital

for improving the outcomes.

A growing body of research has high-

lighted the correlation between thyroid

dysfunction and DN. Hypothyroidism, a

common thyroid disorder in patients with

T2DM, has been identified as a potentially

significant contributing factor to DN 10,11.

Thyroid hormones play a critical role in

regulating metabolic processes. These hor-

mones contribute to the development of

the body, support cardiac output, and pro-

mote myocardial contractility. Additionally,

they are involved in maintaining renal func-

tion stability 12.

Table 2. Thyroid hormone levels in diabetic nephropathy patients.

Group n TSH (μIU/mL)

 ± SD

FT4 (pmol/L)

 ± SD

FT3 (pmol/L)

 ± SD

DN 140 5.83±1.72 ab 13.75±4.01 ab 3.55±0.93 ab

Simple diabetes 140 2.85±0.94 a17.31±4.84 a5.51±1.36 a

Healthy 140 1.17±0.42 20.79±4.33 9.70±2.75

F582.14 89.34 403.37

p <0.001 <0.001 <0.001

The measurement data were compared by univariate multi-sample mean test among multiple groups. ap<0.05 vs.

healthy group, bp<0.05 vs. simple diabetes group.

Table 3. Association between diabetic nephropathy and incidence and severity of anemia.

Group n Severe

n (%)

Moderate

n (%)

Mild

n (%)

None

n (%)

Stage 5 11 9 (81.82) 1 (9.09) 1 (9.09) 0 (0)

Stage 4 20 11 (55) 4 (20) 1 (5) 4 (20)

Stage 3 43 24 (55.81) 5 (11.63) 3 (6.98) 11 (25.58)

Stage 2 39 4 (10.26) 3 (7.69) 4 (10.26) 28 (71.79)

Stage 1 27 0 (0) 3 (11.11) 4 (14.81) 20 (74.07)

χ257.405

p <0.001

The count data were subjected to the chi-square test for comparisons.

162 Yu et al.

Investigación Clínica 66(2): 2025

Hypothyroidism may exacerbate DN

through several mechanisms. One of the

most critical effects is the reduction in insu-

lin sensitivity, which leads to worsened blood

glucose control and insulin resistance. This

dysfunction is compounded by the inflam-

matory response triggered by hyperglyce-

mia, which inhibits 5’-deiodinase activity, a

key enzyme involved in converting T4 to T3.

This reduction in FT3 levels damages the re-

nal tubular function and reduces the renal

plasma flow and glomerular capillary hydro-

static pressure, further compromising renal

function 13. In addition, DN-associated hyper-

glycemia and other metabolic disturbances

can directly or indirectly affect the hypotha-

lamic-pituitary-thyroid axis, impairing thy-

roid hormone production and contributing

to worsening renal function.

In this study, DN patients had signifi-

cantly increased levels of serum TSH and

decreased levels of FT3 and FT4, indicating

that thyroid hormone dysregulation may be

an important factor in the progression of

DN. As kidney function declines, the ability

of the kidney to convert T4 to T3 through

5’-deiodinase activity is diminished. Addi-

tionally, metabolic disturbances in DN, in-

cluding selenium deficiency (a cofactor for

5’-deiodinase), further exacerbate the dys-

Table 4. Changes in thyroid hormone levels in diabetic nephropathy subjects with various

severities of anemia and no anemia.

Group n TSH (μIIU/mL)

 ± SD

FT4 (pmol/L)

 ± SD

FT3 (pmol/L)

 ± SD

Non-anemia 63 3.30±0.76 15.17±2.30 4.29±1.02

Anemia

Mild 13 6.28±1.19 a12.42±3.15 a3.07±0.86 a

Moderate 16 7.64±1.61 ab 10.37±2.61 ab 2.14±0.51 ab

Severe 48 9.41±2.03 abc 7.16±1.72 abc 1.26±0.37 abc

F168.00 117.38 141.03

p <0.001 <0.001 <0.001

The measurement data were compared by univariate multi-sample mean test among multiple groups. ap<0.05 vs.

non-anemia group, bp<0.05 vs. mild group, c<0.05 vs. moderate group.

Fig. 1. Correlation between thyroid hormones and anemia severity.

Thyroid hormone, anemia and elderly diabetic nephropathy 163

Vol. 66(2): 157 - 165, 2025

function of thyroid hormone conversion 14.

As the disease progresses, T3 levels continue

to decrease, and this reduction is correlated

with worsening renal function 15. Further-

more, serum T3 levels have been shown to

serve as an independent risk factor for DN,

with lower T3 levels associated with greater

disease severity 16,17

Another important aspect of DN pro-

gression is anemia, which frequently occurs

as a complication and significantly affects

patient outcomes 18. Anemia in DN is pri-

marily caused by reduced EPO production

as kidney function deteriorates. EPO, which

is secreted by the kidneys, plays a central

role in red blood cell production 19. As kid-

ney function declines, EPO secretion is im-

paired, leading to anemia. The incidence

of anemia in DN can reach 100% in stage 5

DN, and its severity is correlated with the de-

gree of renal dysfunction 20. Consistently, we

found in this study that the anemia severity

was closely related to the progression of DN,

with Hb levels as an important marker for

disease severity.

In addition to kidney dysfunction, thy-

roid hormone levels also influence anemia.

Disruption of thyroid hormone function may

exacerbate anemia in DN patients through

various mechanisms. Specifically, thyroid

hormone resistance can disrupt the balance

between erythropoiesis and the differentia-

tion of erythrocyte progenitor cells. Besides,

chronic anemia can lead to altered endo-

crine function and impaired EPO secretion

21. In the present study, the serum TSH levels

increased significantly, and the levels of FT4

and FT3 decreased with increasing severity

of anemia. All of these levels had significant

associations with Hb. Hence, the impaired

kidney function in DN reduces the kidney’s

ability to regulate thyroid hormones, con-

tributing to further disturbances in thyroid

function 22.

Furthermore, anemia itself may induce

a stress state, thus affecting the hypotha-

lamic-pituitary-thyroid axis function. Under

stress, more thyrotropin-releasing hormone

may be secreted from the hypothalamus to

promote the secretion of more TSH by the

pituitary gland. However, due to renal dys-

function and the loss of thyroid hormone-

binding proteins, the synthesis and secre-

tion of thyroid hormones remain impaired,

resulting in decreased levels of FT4 and FT3

23. This cycle may aggravate the anemia and

accelerate the progression of DN.

Exploring the relationship between thy-

roid hormone disruption and anemia sever-

ity in elderly DN patients provides important

insights for clinical management. By moni-

toring thyroid hormone levels besides kidney

function and anemia status, healthcare pro-

viders may be able to predict better disease

progression and tailor interventions to miti-

gate adverse outcomes. Our study contrib-

utes to this understanding by demonstrating

that thyroid hormone imbalances, particu-

larly low FT3 and FT4 levels, are closely as-

sociated with the severity of anemia in DN

patients.

Nevertheless, this study has limitations.

The duration of this study was short, the

sample size was small, and no data were col-

lected on the association between the sever-

ity of anemia and thyroid hormone levels in

patients undergoing kidney transplantation

or dialysis. Therefore, further studies are

still required.

In conclusion, high TSH and low FT4

and FT3 may be the factors related to anemia

in elderly patients with DN, and they have as-

sociations with the severity of anemia.

ACKNOWLEDGEMENTS

None.

Funding

None.

Conflict of Interest

The authors declare no conflict of inter-

est.

164 Yu et al.

Investigación Clínica 66(2): 2025

Number ORCID of authors

• Jingjing Yu (JY):

0009-0003-7126-9306

• Keke Tang (KT):

0009-0000-9354-2543

• Yan Song (YS):

0009-0006-1900-3203

Participation of the authors

All authors had participated in the de-

velopment and writing of the paper.

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