Association Between Sensitivity to Thyroid Hormone Indices and Diabetic Retinopathy in Euthyroid Patients with Type 2 Diabetes Mellitus

Figures & data

Table 1 Clinical and Laboratory Characteristics of the Study Participants

DR	NDR	DR	P-value
N	262	160
Age (years)	52.55 ± 11.82	55.66 ± 9.02	0.005
BMI (kg/m^2)	26.45 ± 3.50	25.52 ±3.59	0.009
Duration of diabetes (years)	5.00 (1.00–10.00)	10.00 (5.00–15.00)	<0.001
HbA1c (%)	8.70 ± 1.99	8.84 ±1.85	0.451
FT3 (pmol/L)	4.59 ± 0.70	4.48 ± 0.66	0.109
FT4 (pmol/L)	17.39 ± 2.54	16.73 ± 2.18	0.006
TSH (uIU/mL)	2.01 ± 0.91	2.11 ± 0.99	0.327
TSHI	2.92 ± 0.59	2.87 ± 0.53	0.386
TT4RI	34.68 ± 16.08	34.63 ± 15.81	0.975
TFQI	−0.01 (−0.31–0.26)	−0.05 (−0.24–0.16)	0.184
TC (mmol/L)	4.85 ± 1.30	4.81 ± 1.19	0.732
TG (mmol/L)	1.77 (1.15–2.83)	1.59 (1.00–2.73)	0.428
LDL-C (mmol/L)	2.68 ± 0.85	2.70 ± 0.86	0.777
HDL-C (mmol/L)	1.02 ± 0.28	1.05 ± 0.27	0.219
Sex, n (%)			0.043
Male	170 (64.89)	88 (55.00)
Female	92 (35.11)	72 (45.00)
Smoking, n (%)			0.901
No	180 (68.70)	109 (68.12)
Yes	82 (31.30)	51 (31.87)
Drinking, n (%)			0.826
No	189 (72.14)	117 (73.12)
Yes	73 (27.86)	43 (26.88)
Hypertension, n (%)			0.303
No	138 (52.67)	76 (47.50)
Yes	124 (47.33)	84 (52.50)

Notes: Data are expressed as mean ± standard deviation, median (quartile 25, quartile 75) or numbers (%).

Abbreviations: BMI, body mass index; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HbA1c, glycated hemoglobin; FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone; TSHI, TSH Index; TT4RI, TSH T4 resistance index; TFQI, Thyroid Feedback Quantile-based Index; DR, diabetic retinopathy. P value < 0.05 was considered significant.

Figure 1 The association between sensitivity to thyroid hormone indices and the prevalence of DR in euthyroid patients with T2DM in unadjusted (A–C) and adjusted models (D–F). (A) TSHI and DR; (B) TT4RI and DR; (C) TFQI and DR. (D) TSHI and DR; (E) TT4RI and DR; (F) TFQI and DR. The solid and dashed lines represent the estimated values and their corresponding 95% confidence interval. The adjustment factors included Sex, Age, BMI, Duration of diabetes, HbA1c, HDL-C, FT3, and FT4.

Table 2 Threshold Effect Analysis of Sensitivity to Thyroid Hormone Indices on DR Using the Two-Piecewise Linear Regression Model

Incident DR	Crude (OR, 95% CI, P)	Adjusted (OR, 95% CI, P)
Exposure TSHI
Fitting model by standard linear regression	0.86 (0.61, 1.21) 0.39	1.20 (0.79, 1.83) 0.40
Fitting model by two-piecewise linear regression
Inflection point of thyroid hormone Index	3.28	3.54
< Inflection point	1.22 (0.77, 1.92) 0.40	1.45 (0.91, 2.31) 0.12
> Inflection point	0.17 (0.04, 0.73) 0.02	0.06 (0.00, 1.64) 0.10
Log likelihood ratio	0.017	0.008
Exposure TT4RI
Fitting model by standard linear regression	1.00 (0.99, 1.01) 0.98	1.01 (0.99, 1.02) 0.47
Fitting model by two-piecewise linear regression
Inflection point of thyroid hormone Index	11.69	11.67
< Inflection point	1.25 (0.89, 1.75) 0.19	1.34 (0.95, 1.89) 0.10
> Inflection point	1.00 (0.98, 1.01) 0.66	1.00 (0.99, 1.02) 0.88
Log likelihood ratio	0.155	0.092
Exposure TFQI
Fitting model by standard linear regression	0.70 (0.42, 1.18) 0.18	1.41 (0.69, 2.91) 0.35
Fitting model by two-piecewise linear regression
Inflection point of thyroid hormone Index	0.18	0.23
< Inflection point	1.34 (0.62, 2.90) 0.45	3.19 (1.24, 8.17) 0.02
> Inflection point	0.13 (0.02, 0.66) 0.01	0.11 (0.01, 0.93) 0.04
Log likelihood ratio	0.022	<0.001

Notes: Crude model was adjust for: None Adjusted model was adjust for: Sex; Age; BMI; Duration of diabetes; HbA1c; HDL-C; FT3; FT4. P value < 0.05 was considered significant.

Abbreviations: OR Odds ratios, CI Confidence, Ref Reference; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; HbA1c, glycated hemoglobin; FT3, free triiodothyronine; FT4, free thyroxine; TSHI, TSH Index; TT4RI, TSH T4 resistance index; TFQI, Thyroid Feedback Quantile-based Index; DR, diabetic retinopathy.

Table 3 Threshold Effect Analysis of Sensitivity to Thyroid Hormone Indices on DR Using the Two-Piecewise Linear Regression Model with Sex Differences

Sex	Male (OR, 95% CI, P)	Female (OR, 95% CI, P)	Total (OR, 95% CI, P)
Exposure TSHI
Fitting model by standard linear regression			P-interaction: <0.001
	0.96 (0.54, 1.70) 0.88	1.69 (0.85, 3.35) 0.13	1.20 (0.79, 1.83) 0.39
Fitting model by two-piecewise linear regression			P-interaction: 0.017
Inflection point of thyroid hormone Index	3.28	2.05	3.54
< Inflection point	1.31 (0.66, 2.60) 0.43	11.61 (0.23, 582.05) 0.22	1.45 (0.91, 2.31) 0.12
> Inflection point	0.05 (0.00, 1.09) 0.06	1.32 (0.59, 2.95) 0.49	0.06 (0.00, 1.64) 0.09
Log likelihood ratio	0.022	0.197	0.008
Exposure TT4RI
Fitting model by standard linear regression			P-interaction: 0.012
	1.00 (0.98, 1.02) 0.87	1.02 (0.99, 1.04) 0.13	1.01 (0.99, 1.02) 0.47
Fitting model by two-piecewise linear regression			P-interaction: 0.106
Inflection point of thyroid hormone Index	55.95	14.29	11.67
< Inflection point	1.00 (0.98, 1.02) 0.99	1.18 (0.84, 1.65) 0.34	1.34 (0.95, 1.89) 0.09
> Inflection point	0.96 (0.85, 1.10) 0.58	1.01 (0.99, 1.04) 0.28	1.00 (0.99, 1.02) 0.88
Log likelihood ratio	0.004	0.30	0.092
Exposure TFQI
Fitting model by standard linear regression			P-interaction: <0.001
	1.14 (0.41, 3.17) 0.79	2.33 (0.76, 7.18) 0.14	1.41 (0.69, 2.91) 0.35
Fitting model by two-piecewise linear regression			P-interaction: 0.012
Inflection point of thyroid hormone Index	0.09	0.26	0.23
< Inflection point	4.10 (0.97, 17.31) 0.05	3.75 (0.91, 15.49) 0.07	3.19 (1.24, 8.17) 0.02
> Inflection point	0.06 (0.00, 0.73) 0.03	0.39 (0.01, 11.42) 0.58	0.11 (0.01, 0.93) 0.04
Log likelihood ratio	0.003	0.263	<0.001

Notes: Crude model was adjust for: None, Adjusted model was adjust for: Sex; Age; BMI; Duration of diabetes; HbA1c; HDL-C; FT3; FT4, P value < 0.05 was considered significant.

Abbreviations: OR Odds ratios, CI Confidence, Ref Reference; BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; HbA1c, glycated hemoglobin; FT3, free triiodothyronine; FT4, free thyroxine; TSHI, TSH Index; TT4RI, TSH T4 resistance index; TFQI, Thyroid Feedback Quantile-based Index; DR, diabetic retinopathy.

Figure 2 The association between sensitivity to thyroid hormone indices and the prevalence of DR in euthyroid patients with T2DM are stratified by gender. (A) TSHI and DR; (B) TT4RI and DR; (C) TFQI and DR. Age, BMI, Duration of diabetes, HbA1c, HDL-C, FT3, and FT4 were adjusted.