The Correlation between Thyroid Hormone Levels and the Kidney Disease Progression Risk in Patients with Type 2 Diabetes

Figures & data

Figure 1 The KDIGO risk categories.

Notes: Green, low risk; yellow, moderate risk; orange, high risk; red, very high risk.

Abbreviations: ACR, albumin/creatinine ratio; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes.

Table 1 The Clinical Characteristics of Study Subjects with or without DKD

Variables	Patients without DKD (n=264)	Patients with DKD (n=188)	P value
Sex (n, female/male)	121/143	92/96	0.515
Age (years)	65.09 ± 11.62	63.15 ± 11.91	<0.001
BMI (kg/m^2)	24.58 (22.48, 26.59)	24.90 (22.63, 27.62)	0.063
FBG (mmol/L)	8.20 (6.60, 11.08)	8.52 (6.40, 11.18)	0.763
HbA1c (%)	8.5 (6.8, 10.7)	8.8 (7.1, 10.7)	0.328
BUN (mmol/L)	5.10 (4.20, 5.97)	6.00 (4.67, 8.18)	<0.001
SCr (µmol/L)	64 (54, 76)	81 (60, 112)	<0.001
UA (µmol/L)	275 (228, 334)	318 (256, 391)	<0.001
TG (mmol/L)	1.34 (1.02, 2.19)	1.53 (1.04, 2.30)	0.280
TC (mmol/L)	4.45 (3.84, 5.31)	4.40 (3.66, 5.15)	0.280
HDL-C (mmol/L)	1.22 (1.06, 1.43)	1.20 (1.00, 1.41)	0.166
LDL-C (mmol/L)	2.63 (2.13, 3.33)	2.54 (1.96, 3.14)	0.048
eGFR (mL/min/1.73m^2)	107.28 ± 39.47	84.21 ± 48.98	<0.001
ACR (mg/g)	12.48 (8.53, 18.30)	128.40 (49.17, 444.75)	<0.001
FT3 (pmol/L)	4.52 (4.13, 4.84)	4.15 (3.72, 4.66)	<0.001
FT4 (pmol/L)	16.82 (15.42, 18.34)	16.52 (14.73, 18.04)	0.038
TSH (mIU/L)	2.03 (1.34, 2.97)	2.46 (1.42, 3.86)	0.013

Notes: Data are presented as mean ± standard deviations or medians (25th, 75th percentile) or numbers. DKD was defined as eGFR <60 mL/min/1.73 m² and/or ACR ≥30 mg/g.

Abbreviations: DKD, diabetic kidney disease; BMI, body mass index; FBG, fasting blood glucose; HbA1c, glycated hemoglobin; BUN, blood urea nitrogen; SCr, serum creatinine; UA, uric acid; TG, triglycerides; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; FT₃, free triiodothyronine; FT₄, free thyroxine; TSH, thyroid-stimulating hormone.

Figure 2 The prevalence of thyroid dysfunction in subjects with or without DKD.

Notes: A, B, C and D represent the prevalence of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, and subclinical hypothyroidism respectively.

Table 2 Thyroid Hormone Levels in Different ACR, eGFR and KDIGO Risk Categories

Categories (n, %)		FT3 (pmol/L)	FT4 (pmol/L)	TSH (mIU/L)
ACR	Normal albuminuria (267, 59.1%)	4.51 (4.12, 4.83)	16.76 (15.43, 18.32)	2.06 (1.35, 3.01)
	Microalbuminuria (120, 26.5%)	4.18 (3.75, 4.66)	16.61 (14.80, 18.32)	2.45 (1.42, 3.76)
	Massive albuminuria (65, 14.4%)	4.10 (3.55, 4.68)	16.52 (14.19, 17.74)	2.44 (1.39, 3.96)
	P value	<0.001	0.062	0.094
eGFR (mL/min/1.73m^2)	≥90 (332, 73.4%)	4.49 (4.11, 4.83)	16.72 (15.27, 18.34)	2.16 (1.42, 3.29)
	60–89 (78, 17.3%)	4.23 (3.75, 4.62)	16.72 (15.52, 18.23)	1.86 (1.28, 3.35)
	45–59 (22, 4.9%)	3.82 (3.70, 4.03)	16.18 (14.01, 18.60)	3.18 (1.73, 4.83)
	30–44 (10, 2.2%)	3.55 (3.15, 5.26)	16.29 (11.44, 16.73)	1.32 (0.98, 3.11)
	<30 (10, 2.2%)	3.34 (2.75, 4.12)	14.42 (13.07, 16.32)	2.14 (1.18, 4.27)
	P value	<0.001	0.011	0.088
KDIGO categories	Low risk (264, 58.4%)	4.52 (4.13, 4.84)	16.82 (15.54, 18.34)	2.03 (1.34, 2.97)
	Moderate risk (109, 24.1%)	4.22 (3.78, 4.71)	16.52 (15.14, 18.12)	2.44 (1.46, 3.50)
	High or very high risk (79, 17.5%)	3.97 (3.56, 4.55)	16.52 (13.92, 17.93)	2.58 (1.38, 4.41)
	P value	<0.001	0.05	0.045

Note: Data are presented as numbers (proportions) or medians (25th, 75th percentile).

Table 3 Correlation Between Thyroid Hormones and Parameters of Renal Function

Parameters		r value	P value
FT3 with	SCr	−0.168	<0.001
	eGFR	0.325	<0.001
	ACR	−0.267	<0.001
FT4 with	SCr	−0.107	0.023
	eGFR	0.165	<0.001
	ACR	−0.109	0.021
TSH with	SCr	0.043	0.359
	eGFR	−0.128	0.006
	ACR	0.104	0.027

Table 4 Logistic Regression Analysis of Thyroid Hormones and the Risk of Having Diabetic Nephropathy

Variable	Β	SE	Wald X^2	OR (95% CI)	P value
FT3	−0.55	0.16	11.58	0.58 (0.42–0.79)	0.001
FT4	−0.03	0.03	1.16	0.97 (0.92–1.02)	0.281
TSH	0.02	0.02	2.11	1.02 (0.99–1.05)	0.147

Note: All models were adjusted for sex, age, FBG, HbA1c, TC, TG, HDL-C and LDL-C.

Table 5 Logistic Regression Analysis of Thyroid Hormones and the Risk of Diabetic Nephropathy Progression

Variable	Moderate KDIGO Risk		High or Very High KDIGO Risk
	OR (95% CI)	P value	OR (95% CI)	P value
FT3	0.65 (0.45–0.93)	0.020	0.50 (0.33–0.74)	0.001
FT4	0.98 (0.92–1.04)	0.476	0.96 (0.89–1.04)	0.332
TSH	1.02 (0.99–1.06)	0.119	1.02 (0.98–1.05)	0.333

Notes: The low KDIGO risk group was classified as the reference group. All models were adjusted for sex, age, FBG, HbA1c, TC, TG, HDL-C and LDL-C.

Table 6 Subgroup Analysis of FT₃ and Risk of DKD Progression Stratified by Male and Female

Subgroup	Ranges of FT3 (pmol/L)	Moderate KDIGO Risk		High or Very High KDIGO Risk
		OR (95% CI)	P value	OR (95% CI)	P value
Male	>4.78	1.0	–	1.0	–
	4.31–4.78	1.10 (0.45–2.64)	0.838	0.62 (0.24–1.61)	0.325
	≤4.30	1.93 (0.74–5.04)	0.181	3.66 (1.54–8.71)	0.003
Female	>4.44	1.0	–	1.0	–
	4.00–4.44	1.36 (0.60–3.04)	0.461	1.49 (0.32–7.01)	0.614
	≤3.99	2.37 (1.02–5.51)	0.044	7.23 (1.72–30.34)	0.007

Notes: The levels of FT₃ were divided into tri-sectional quantiles. The low KDIGO risk group and the highest tertile of FT₃ were classified as the reference groups of dependent variable and independent variable, respectively. All models were adjusted for age, FBG, HbA1c, TC, TG, HDL-C, and LDL-C.