3.1. Clinical characteristics of study participants in three groups
The study cohort included 254 type 2 diabetic participants with early-stage DKD consisting of high SUA group and normal SUA group, and 85 control participants as control group. The clinical characteristics of all study participants are listed in Table 1. The participants in three groups were similar in gender, age, systolic blood pressure (SBP), and diastolic blood pressure (DBP) (P > 0.05 for all). A significant trend was observed for BMI, TC, HDL-C, LDL-C, TG, FBG, HbA1c, FINS, HOMA-IR, CR, eGFR, UACR, FT3, FT4, TSH and SUA in three groups (P < 0.01 for all). High SUA group had the significantly increased levels of BMI, TG, FBG, HbA1c, HOMA-IR, CR, FT3 and FT4, and the significantly decreased level of eGFR compared with normal SUA group and control group (P < 0.017 for all). The levels of BMI, TG, FBG, HbA1c and HOMA-IR were significantly elevated in normal SUA group than those in control group (P < 0.017 for all), and no significant difference was detected in CR, eGFR, FT3 and FT4 between normal SUA group and control group (P > 0.017 for all). Both high SUA group and normal SUA group exhibited the significantly higher levels of TC, LDL-C, FINS and UACR, and the significantly lower level of HDL-C than control group (P < 0.017 for all), and there was no significant difference in these parameters between high SUA group and normal SUA group (P > 0.017 for all). Furthermore, compared with normal SUA group and control group, high SUA group was with a higher SUA level (Fig. 1) and a lower TSH level (Fig. 2) (P < 0.017 for both). However, no significant difference was observed in SUA and TSH between normal SUA group and control group (P > 0.017 for both). The decreased TSH in high SUA group might indicate the possible association between thyroid function and uric acid metabolism in type 2 diabetic participants with early-stage DKD.
Table 1
Clinical characteristics of study participants in three groups
Parameters | High SUA group (n = 126) | Normal SUA group (n = 128) | Control group (n = 85) | P |
Gender (M/F) | 82/44 | 72/56 | 52/33 | 0.353 |
Age (years) | 51.86 ± 10.68 | 53.89 ± 11.13 | 51.35 ± 10.77 | 0.177 |
BMI (kg/m2) | 26.99 ± 5.33‡† | 25.09 ± 3.83† | 23.58 ± 3.05 | < 0.001 |
SBP (mmHg) | 117.98 ± 9.63 | 118.32 ± 8.28 | 118.28 ± 11.82 | 0.956 |
DBP (mmHg) | 68.83 ± 8.75 | 67.86 ± 7.38 | 68.55 ± 7.84 | 0.618 |
TC (mmol/L) | 4.90 ± 1.30† | 4.72 ± 1.33† | 4.33 ± 0.61 | 0.003 |
HDL-C (mmol/L) | 1.03 ± 0.25† | 1.11 ± 0.31† | 1.54 ± 0.33 | < 0.001 |
LDL-C (mmol/L) | 2.78 ± 0.87† | 2.70 ± 1.07† | 2.39 ± 0.46 | 0.006 |
TG (mmol/L) | 2.20 (1.54, 3.01)‡† | 1.55 (1.05, 2.33)† | 0.78(0.62,1.12) | < 0.001 |
FBG (mmol/L) | 9.30 ± 2.41‡† | 7.92 ± 2.57† | 5.02 ± 0.34 | < 0.001 |
HbA1c (%) | 9.06 ± 2.07‡† | 8.45 ± 1.90† | 5.57 ± 0.39 | < 0.001 |
FINS (mIU/L) | 15.40(10.98,20.03)† | 14.70(9.23,18.20)† | 8.70(5.37,12.40) | < 0.001 |
HOMA-IR | 5.51 (4.66, 7.53)‡† | 4.67 (3.06, 6.46) † | 1.99 (1.26, 2.76) | < 0.001 |
CR (µmol/L) | 73.22 ± 21.66‡† | 59.95 ± 14.85 | 61.97 ± 11.29 | < 0.001 |
eGFR (mL/min/1.73 m2) | 111.06 ± 34.75‡† | 134.84 ± 35.83 | 128.70 ± 30.71 | < 0.001 |
UACR (mg/g) | 37.98(33.88,90.02)† | 37.76(33.23,52.48)† | 3.45 (1.79, 5.29) | < 0.001 |
FT3 (pg/ml) | 3.63 ± 0.50‡† | 3.46 ± 0.41 | 3.47 ± 0.37 | 0.004 |
FT4 (ng/dl) | 1.34 ± 0.20‡† | 1.25 ± 0.16 | 1.23 ± 0.14 | < 0.001 |
TSH (µIU/ml) | 1.54 (1.10, 2.25) ‡† | 2.03 (1.29, 3.05) | 2.03 (1.33, 2.95) | < 0.001 |
SUA (µmol/L) | 420.30 ± 65.31‡† | 280.09 ± 65.04 | 274.64 ± 67.60 | < 0.001 |
3.2. Correlation between clinical parameters and thyroid hormones and SUA in type 2 diabetic participants with early-stage DKD
Then, the Pearson’s or Spearman’s analyses were performed to assess the underlying association between thyroid function and uric acid metabolism in 254 type 2 diabetic participants with early-stage DKD including individuals in high SUA group and normal SUA group. The results showed that SUA was positively correlated with BMI (r = 0.351, P < 0.001), TG (r = 0.386, P < 0.001), FBG (r = 0.200, P = 0.001), FINS (r = 0.257, P < 0.001), HOMA-IR (r = 0.406, P < 0.001), CR (r = 0.593, P < 0.001), UACR (r = 0.252, P < 0.001), FT3 (r = 0.220, P < 0.001) and FT4 (r = 0.355, P < 0.001), and was negatively associated with HDL-C (r = -0.293, P < 0.001) and eGFR (r = -0.491, P < 0.001) in type 2 diabetic participants with early-stage DKD (Table 2). Moreover, SUA was negatively correlated with TSH (r = -0.346, 95% confidence interval: -0.457 to -0.211, P < 0.001) in type 2 diabetic participants with early-stage DKD (Fig. 3). These findings suggested that decreased TSH was associated with elevated SUA in type 2 diabetic participants with early-stage DKD.
Table 2
Correlation between clinical parameters and SUA in type 2 diabetic patients with early-stage DKD (n = 254)
Parameters | r | P |
Age (years) | -0.113 | 0.072 |
BMI (kg/m2) | 0.351 | < 0.001 |
SBP (mmHg) | 0.108 | 0.087 |
DBP (mmHg) | 0.071 | 0.257 |
TC (mmol/L) | 0.025 | 0.687 |
HDL-C(mmol/L) | -0.293 | < 0.001 |
LDL-C (mmol/L) | 0.003 | 0.967 |
TG (mmol/L) | 0.386 | < 0.001 |
FBG (mmol/L) | 0.200 | 0.001 |
HbA1c (%) | 0.053 | 0.398 |
FINS (mIU/L) | 0.257 | < 0.001 |
HOMA-IR | 0.406 | < 0.001 |
CR (µmol/L) | 0.593 | < 0.001 |
eGFR (mL/min/1.73 m2) | -0.491 | < 0.001 |
UACR (mg/g) | 0.252 | < 0.001 |
FT3 (pg/ml) | 0.220 | < 0.001 |
FT4 (ng/dl) | 0.355 | < 0.001 |
TSH (µIU/ml) | -0.346 | < 0.001 |
3.3. Multiple regression analysis of clinical parameters and thyroid hormones correlated with SUA in type 2 diabetic participants with early-stage DKD
Furthermore, to explore the role of thyroid function in uric acid metabolism, the multiple stepwise regression analysis was performed to determine which parameters were independently correlated with SUA in type 2 diabetic participants with early-stage DKD. The results showed that after adjusting for the confounders, the increased CR (β = 2.049, P < 0.001), TG (β = 10.068, P < 0.001), UACR (β = 0.262, P = 0.001), FBG (β = 5.280, P = 0.003) and FINS (β = 1.440, P = 0.034), and the decreased TSH (β = -24.906, P < 0.001) were independently related to higher SUA in type 2 diabetic participants with early-stage DKD (Table 3). The model had an adjusted R-squared value of 0.574 (F = 57.792 and P < 0.001).
Table 3
Multiple regression of parameters associated with SUA in type 2 diabetic patients with early-stage DKD
Parameters | β | SE | 95% CI | Standardized β | P |
Constant | 150.129 | 26.107 | 98.709 ~ 201.550 | | < 0.001 |
CR (mIU/L) | 2.049 | 0.257 | 1.543 ~ 2.555 | 0.415 | < 0.001 |
TSH (µIU/ml) | -24.906 | 3.733 | -32.258 ~ -17.553 | -0.286 | < 0.001 |
TG (mmol/L) | 10.068 | 1.774 | 6.574 ~ 13.562 | 0.244 | < 0.001 |
UACR (mg/g) | 0.262 | 0.076 | 0.113 ~ 0.411 | 0.182 | 0.001 |
FBG (mmol/L) | 5.280 | 1.735 | 1.862 ~ 8.698 | 0.143 | 0.003 |
FINS (mIU/L) | 1.440 | 0.675 | 0.111 ~ 2.769 | 0.111 | 0.034 |
3.4. Logistic regression analysis of clinical parameters and thyroid hormones associated with hyperuricemia in type 2 diabetic patients with early-stage DKD
Subsequently, to further clarify the role of TSH in uric acid metabolism, the logistic regression analysis of the associations between the anthropometric parameters and the thyroid hormones and hyperuricemia in type 2 diabetic patients with early-stage DKD was analyzed, and the adjusted results were shown in Table 4. TG, CR, FBG and TSH were independently associated with hyperuricemia in type 2 diabetic patients with early-stage DKD. Elevated SUA was positively associated with TG [odds ratio (OR) = 0.799, P < 0.006], CR (OR = 0.936, P < 0.001), and FBG (OR = 0.822, P = 0.002). Notably, decreased TSH with an OR of 1.654 (P = 0.002, 95% confidence interval: 1.218 to 2.247) was associated with hyperuricemia in type 2 diabetic patients with early-stage DKD.
Table 4
Logistic regression of parameters associated with hyperuricemia in type 2 diabetic patients with early-stage DKD
| β | SE | OR | 95% CI | P |
TG (mmol/L) | -0.224 | 0.082 | 0.799 | 0.680 ~ 0.938 | 0.006 |
CR (µmol/L) | -0.066 | 0.014 | 0.936 | 0.911 ~ 0.961 | < 0.001 |
FBG (mmol/L) | -0.196 | 0.063 | 0.822 | 0.727 ~ 0.931 | 0.002 |
TSH (µIU/ml) | 0.503 | 0.156 | 1.654 | 1.218 ~ 2.247 | 0.002 |