- Baseline characteristics
Detailed baseline demographic and clinical characteristics of included subjects were presented in Table 1. The two groups were age- and sex-matched. The mean (±SD) age of the patients with T2DM was 54.85 (± 14.1) years old, ranging from 18 to 90 years. Male patients constituted the majority (n = 221, 65.0%). The mean (±SD) BMI of the patients was 24.6 (± 3.8) kg/m2. About 30% of the study population had a family history of diabetes. Social history of smoking was reported by 28.5% of the patients. Mean (±SD) HbA1c level was 11.9 (± 2.5) %. Levels of FT3, FT4 and TSH were significantly lower in patients with T2DM (FT3 3.53 ± 0.81 pmol/L, FT4 14.54 ± 2.78, TSH 1.66 ± 1.80 μIU/ml) as compared to controls (FT3 5.07 ± 0.68 pmol/L, FT4 17.16 ± 3.07, TSH 2.49 ± 2.13 μIU/ml) (P < 0.001). TD was found in 72 (21.2%) patients with T2DM and 5 (4.3%) in nondiabetic subjects (P < 0.001). To avoid the impact of acute condition on thyroid function, we exclude the patients with DK or DKA. Levels of thyroid hormones (FT3 3.71 ± 0.69 pmol/L, FT4 14.63 ± 2.63, TSH 1.59 ± 1.44 μIU/ml) remained to be lower and the prevalence of TD (n = 31, 13.0%) remained to be higher in patients with diabetes than in controls (P < 0.001).
Table 1 Demographic and clinical characteristics of subjects.
Characteristic
|
Newly diagnosed T2DM
|
Non-T2DM
|
P
|
n = 340
|
n = 120
|
|
Demographic data
|
Age, years
|
54.9 ± 14.1
|
54.1 ± 10.2
|
0.532
|
Male, n (%)
|
221 (65.0)
|
74 (61.7)
|
0.513
|
Hypertension, n (%)
|
124 (36.5)
|
15 (12.5)
|
< 0.001*
|
Clinical parameters
|
BMI, kg/m2
|
24.6 ± 3.8
|
24.4 ± 2.8
|
0.501
|
Systolic BP, mmHg
|
134 ± 19
|
130 ± 22
|
0.073
|
Diastolic BP, mmHg
|
85 ± 12
|
83 ± 15
|
0.073
|
HbA1c, %
|
11.9 ± 2.5
|
5.8 ± 0.7
|
< 0.001*
|
FPG, mmol/L
|
13.3 ± 5.0
|
5.0 ± 0.7
|
< 0.001*
|
eGFR, ml/min/1.73m2
|
91.4 ± 26.0
|
90.0 ± 17.4
|
0.519
|
TG, mmol/L
|
2.65 ± 3.86
|
1.73 ± 1.24
|
< 0.001*
|
TC, mmol/L
|
5.26 ± 1.49
|
4.89 ± 0.90
|
< 0.001*
|
LDL-C, mmol/L
|
3.40 ± 1.10
|
3.15 ± 0.91
|
0.015*
|
HDL-C, mmol/L
|
1.02 ± 0.29
|
1.22 ± 0.29
|
< 0.001*
|
Uric acid, μmol/L
|
344 ± 205
|
379 ± 95
|
0.074
|
Thyroid function
|
|
|
|
FT3, pmol/L
|
3.53 ± 0.81
|
5.07 ± 0.68
|
< 0.001*
|
FT4, pmol/L
|
14.54 ± 2.78
|
17.16 ± 3.07
|
< 0.001*
|
FT3/FT4 ratio
|
0.30 ± 0.06
|
0.25 ± 0.06
|
< 0.001*
|
TSH, μIU/ml
|
1.66 ± 1.80
|
2.49 ± 2.13
|
< 0.001*
|
Thyroid dysfunction, n (%)
|
72 (21.2)
|
5 (4.2)
|
< 0.001*
|
Continuous data are expressed as means ± standard deviation, categorical data as n (%). BMI, body mass index; BP, blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; FT3, free triiodothyronine; FT4, free thyroxine; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein cholesterol; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TG, triglycerides; TSH, thyroid stimulating hormone; *P-value < 0.05.
- Analyses of associated factors of thyroid status
Among the categories of thyroid disorders, low T3 syndrome (n = 50, 14.7%) was the most common form, followed by subclinical hyperthyroidism (n = 14, 4.1%), hypothyroidism (n = 6, 1.8%) and subclinical hypothyroidism (n = 2, 0.6%). Distribution of thyroid status and the corresponding thyroid hormone levels were shown in Table 2. Higher prevalence of TD was found in patients over 60 years old (n = 32, 27.4%) than in younger patients (n = 40, 17.2%) (P = 0.044). We found a lower level of FT3 (3.21 ± 0.74 pmol/L) in patients with diabetic ketosis (DK) or diabetic ketoacidosis (DKA) than patients without DK or DKA (3.71 ± 0.69 pmol/L)(P < 0.001). Moreover, the level of FT3 further decreased with the deterioration of DK (2.60 ± 1.23 pmol/L) (P = 0.005). The level of FT4 (12.54 ± 3.64 pmol/L) was also significantly lower in patients with DKA (P = 0.004). But no difference was shown between patients with DK (14.75 ± 2.80 pmol/L) and patients without DK (14.63 ± 2.63 pmol/L) in FT4 level. Lower level of FT3 (3.12 ± 0.86 pmol/L) was also found in patients with DN (P < 0.001), accompanied with lower levels of FT4 and TSH, compared with patients with normoalbuminuria. The levels of FT3 and FT4 were lower in patients over 60 years old (FT3 3.32 ± 0.77 pmol/L, FT4 14.08 ± 2.80 pmol/L) than in patients with younger age (FT3 3.64 ± 0.81 pmol/L, FT4 14.78 ± 2.74 pmol/L) (P < 0.001, P = 0.027, respectively). Pearson correlation analysis revealed negative factors of FT3 level including DK or DKA, DN, age and HbA1c. Positive correlated factors of FT3 level included eGFR, diastolic blood pressure (DBP), fasting C-peptide, 2-h C-peptide, fasting insulin, 2-h insulin and HOMA-IR. DK or DKA and age remained to be negative correlated factors of FT4. DK or DKA, DN and HbA1c remained to be negative correlated factors of FT3/FT4 ratio. None of the metabolic or demographic parameters was strongly associated with TSH level (Table 3).
Table 2 Distribution of thyroid status in patients with newly diagnosed T2DM
Thyroid status
|
N (%)
|
FT3, pmol/L
|
P1
|
FT4, pmol/L
|
P2
|
TSH, μIU/ml
|
P3
|
Positive thyroid antibodies
|
P4
|
Total
|
340 (100)
|
3.52 (0.81)
|
-
|
14.54 (2.78)
|
-
|
1.66 (1.80)
|
-
|
28 (8.5)
|
-
|
Euthyroid
|
268 (78.8)
|
3.78 (0.64)
|
-
|
14.77 (2.64)
|
-
|
1.61 (1.00)
|
-
|
16 (6.6)
|
-
|
Low T3 syndrome
|
50 (14.7)
|
2.32 (0.47)
|
< 0.001*
|
13.46 (2.92)
|
0.002*
|
1.04 (0.68)
|
< 0.001*
|
5 (10.4)
|
0.444
|
Subclinical hyperthyroidism
|
14 (4.1)
|
3.34 (0.52)
|
0.011*
|
15.12 (2.88)
|
0.625
|
0.27 (0.10)
|
< 0.001*
|
4 (30.8)
|
0.005*
|
Hypothyroidism
|
6 (1.8)
|
2.72 (0.70)
|
0.013*
|
11.80 (4.10)
|
0.007*
|
11.15 (6.26)
|
0.013*
|
3 (50.0)
|
0.001*
|
Subclinical hypothyroidism
|
2 (0.6)
|
3.32 (0.42)
|
0.305
|
14.77 (4.55)
|
1.000
|
5.08 (0.71)
|
< 0.001*
|
0 (0.0)
|
1.000
|
FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone; P, group with thyroid dysfunction versus group in euthyroid status; P1, comparison of FT3 level; P2, comparison of FT4 level; P3, comparison of TSH level; P4, comparison of proportion of positive thyroid antibodies; *P-value < 0.05.
Table 3 Correlation between thyroid hormones and demographic and metabolic parameters
Variables
|
FT3
|
FT4
|
FT3/FT4 ratio
|
TSH
|
r
|
P
|
r
|
P
|
r
|
P
|
r
|
P
|
Age
|
-0.168
|
0.002*
|
-0.141
|
0.009*
|
-0.101
|
0.063
|
0.063
|
0.247
|
BMI
|
0.079
|
0.159
|
0.002
|
0.971
|
0.073
|
0.195
|
0.080
|
0.156
|
DK or DKA
|
-0.388
|
< 0.001*
|
-0.113
|
0.038*
|
-0.348
|
< 0.001*
|
0.092
|
0.089
|
Diabetic nephropathy
|
-0.302
|
< 0.001*
|
-0.072
|
0.187
|
-0.272
|
< 0.001*
|
-0.057
|
0.299
|
Urinary total protein (mg/24h)
|
-0.292
|
< 0.001*
|
-0.192
|
0.001*
|
-0.168
|
0.004*
|
0.027
|
0.644
|
Albumin excretion rate (mg/24h)
|
-0.263
|
< 0.001*
|
-0.191
|
0.004*
|
-0.130
|
0.054
|
0.094
|
0.165
|
eGFR
|
0.150
|
0.006*
|
0.179
|
0.001*
|
0.044
|
0.417
|
-0.046
|
0.396
|
Diabetic peripheral neuropathy
|
0.009
|
0.873
|
0.126
|
0.020*
|
-0.068
|
0.212
|
0.031
|
0.564
|
HbA1c
|
-0.224
|
< 0.001*
|
0.111
|
0.041*
|
-0.273
|
< 0.001*
|
0.016
|
0.765
|
FPG
|
0.030
|
0.586
|
0.173
|
0.001*
|
-0.042
|
0.442
|
-0.019
|
0.733
|
LDL-C
|
0.065
|
0.230
|
-0.001
|
0.985
|
0.113
|
0.039*
|
-0.070
|
0.199
|
HDL-C
|
0.065
|
0.230
|
0.020
|
0.710
|
0.042
|
0.439
|
-0.006
|
0.909
|
Triglyceride
|
-0.060
|
0.270
|
-0.117
|
0.031*
|
0.033
|
0.547
|
0.012
|
0.827
|
Total cholesterol
|
0.002
|
0.968
|
-0.067
|
0.218
|
0.090
|
0.097
|
-0.075
|
0.169
|
Fasting C-Peptide
|
0.241
|
< 0.001*
|
0.017
|
0.764
|
0.195
|
0.001*
|
0.065
|
0.262
|
2-h C-Peptide
|
0.372
|
< 0.001*
|
0.025
|
0.670
|
0.347
|
< 0.001*
|
0.041
|
0.490
|
Fasting insulin
|
0.173
|
0.020*
|
-0.139
|
0.062
|
0.282
|
< 0.001*
|
0.010
|
0.892
|
2-h insulin
|
0.167
|
0.020*
|
-0.194
|
0.011*
|
0.337
|
< 0.001*
|
-0.002
|
0.976
|
HOMA-IR
|
0.178
|
0.002*
|
0.070
|
0.225
|
0.112
|
0.053
|
0.105
|
0.071
|
HOMA-β
|
0.042
|
0.470
|
-0.080
|
0.168
|
0.051
|
0.381
|
0.071
|
0.905
|
Systolic BP
|
0.043
|
0.434
|
-0.067
|
0.216
|
0.035
|
0.521
|
-0.045
|
0.413
|
Diastolic BP
|
0.176
|
0.001*
|
0.069
|
0.203
|
0.096
|
0.077
|
-0.088
|
0.105
|
BMI, body mass index; BP, blood pressure; DK, diabetic ketosis; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; FPG, free plasma glucose; FT3, free triiodothyronine; FT4, free thyroxine; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; HOMA-β, homeostasis model assessment of β cell function; LDL-C, low-density lipoprotein cholesterol; TSH, thyroid stimulating hormone; *P-vale < 0.05.
- Analyses of associated factors of DN
Comparisons between patients with DN and patients with normoalbuminuria was shown in Additional file 1. FT3 level (3.07 ± 0.89 vs 3.67 ± 0.72, P < 0.001) and FT3/FT4 ratio (0.26 ± 0.05 vs 0.22 ± 0.06, P < 0.001) was significantly lower in patients with DN . Furthermore, there was a decline of FT3 level with progressing albuminuria. FT3 level was inversely correlated with the level of urinary total protein (mg/24h) and the presence of DN (Table 3, Figure 1). After adjusting various confounding factors, multivariate analysis indicated low FT3 level as a strong independent risk factor (OR = 0.364, P < 0.001) for DN. (Table 4).
Table 4 Multivariate analysis of associated factors of diabetic nephropathy in patients with newly diagnosed T2DM
Variable
|
OR
|
β
|
Wald χ2
|
P
|
Age
|
1.011
|
0.011
|
0.525
|
0.469
|
Hypertension
|
1.212
|
0.193
|
0.607
|
0.607
|
BMI
|
1.095
|
0.092
|
3.825
|
0.049*
|
HOMA-IR
|
1.021
|
0.021
|
7.286
|
0.007*
|
HOMA-β
|
1.001
|
0.001
|
1.862
|
0.172
|
DK or DKA
|
2.043
|
0.715
|
4.082
|
0.043*
|
eGFR
|
1.000
|
0.000
|
0.001
|
0.980
|
FT3
|
0.364
|
-1.011
|
11.856
|
0.001*
|
FT4
|
1.102
|
0.097
|
2.279
|
0.131
|
BMI, body mass index; DK, diabetic ketosis; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; FT3, free triiodothyronine; FT4, free thyroxine; HOMA-β, homeostasis model assessment of β cell function; HOMA-IR, homeostasis model assessment of insulin resistance; *P-value < 0.05.