Urine Uric Acid Excretion Levels are Positively Associated with Obesity and Abdominal Obesity in Type 2 Diabetes Patients without Chronic Kidney Disease

Figures & data

Figure 1 Flowchart for inclusion of participants.

Table 1 Characteristics of the Patients According to UUAE Quartiles

Variables	Q1 (n=694)	Q2 (n=698)	Q3 (n=696)	Q4 (n=697)	p value	^#p value
UUAE (μmol/24h)	<2211	2211–2841	2842–3591	>3591	–	–
Male (n, %)	342 (49.3%)	358 (51.3%)	407 (58.5%)	467 (67.0%)	<0.001	<0.001
Age (years)	63±13	60±13	57±11	54±11	<0.001	<0.001
DD (months)*	108 (48–168)	84 (12–144)	60 (12–120)	60 (12–120)	<0.001	0.006
Hypertension (n, %)	403 (58.1%)	352 (50.4%)	346 (49.7%)	360 (51.6%)	0.007	0.004
Smoking (n, %)	161 (23.2%)	153 (21.9%)	227 (32.6%)	280 (40.2%)	<0.001	0.001
Alcohol (n, %)	78 (11.2%)	91 (13.0%)	110 (15.8%)	170 (24.4%)	<0.001	0.01
IIAs (n, %)	530 (76.4%)	505 (72.3%)	489 (70.3%)	482 (69.2%)	0.003	0.019
LLD (n, %)	181 (26.1%)	212 (30.4%)	192 (27.6%)	267 (38.3%)	<0.001	<0.001
AHAs (n, %)	369 (53.2%)	314 (45.0%)	321 (46.1%)	320 (45.9%)	0.009	0.006
Metformin (n, %)	340 (49.0%)	365 (52.3%)	401 (57.6%)	440 (63.1%)	<0.001	<0.001
SUs (n, %)	489 (70.5%)	438 (62.8%)	432 (62.1%)	430 (61.7%)	0.001	0.14
TZDs (n, %)	78 (11.2%)	80 (11.5%)	112 (16.1%)	124 (17.8%)	<0.001	<0.001
GIs (n, %)	503 (72.5%)	483 (69.2%)	469 (67.4%)	456 (65.4%)	0.03	0.954
SBP (mmHg)	133±18	132±18	130±17	130±16	0.012	0.293
DBP (mmHg)	78±9	80±9	81±10	81±10	<0.001	<0.001
WC (cm)	87±11	87±10	89±9	93±10	<0.001	<0.001
WHR	0.9±0.1	0.9±0.1	0.9±0.1	0.9±0.1	<0.001	<0.001
BMI(kg/m^2)	23.8±3.6	24.3±3.3	25.0±3.2	26.2±3.3	<0.001	<0.001
WBCC (×10^9)	6.38±1.92	6.30±1.75	6.29±1.88	6.34±1.90	0.792	0.768
FPG(mmol/l)*	7.3 (5.9–9.5)	7.4 (6.0–9.6)	7.7 (6.2–9.9)	8.3 (6.9–10.1)	<0.001	<0.001
2h PPG(mmol/l)*	13.0 (9.1–16.3)	13.3 (10.0–16.7)	13.5 (10.3–16.6)	14.1 (10.8–17.3)	<0.001	<0.001
FCP (ng/ml)*	1.39 (0.81–2.32)	1.57 (0.93–2.23)	1.69 (1.13–2.43)	1.91 (1.24–2.77)	<0.001	<0.001
2h PCP (ng/ml)*	3.02 (1.58–4.95)	3.59 (1.92–5.37)	3.79 (2.28–5.35)	4.14 (2.56–5.60)	<0.001	<0.001
HbA1C (%)	9.2±2.5	9.2±2.5	9.1±2.4	9.1±2.1	0.894	0.268
HOMA2-IR	1.46±1.15	1.47±0.94	1.59±0.87	1.84±1.07	<0.001	<0.001
TTG (mmol/l)*	1.30 (0.89–1.85)	1.42 (0.97–2.06)	1.43 (1.01–2.08)	1.72 (1.16–2.58)	<0.001	<0.001
TC (mmol/l)	4.61±1.14	4.73±1.20	4.68±1.07	4.77±1.14	0.061	0.036
HDL-C (mmol/l)	1.15±0.31	1.15±0.31	1.11±0.28	1.05±0.32	<0.001	<0.001
LDL-C (mmol/l)	2.99±0.95	3.12±0.98	3.08±0.88	3.11±0.94	0.046	0.025
ALT (U/l)*	17 (12–25)	18 (13–27)	20 (14–32)	24 (16–41)	<0.001	<0.001
AST (U/l)*	19 (16–23)	19 (16–24)	19 (15–25)	21 (16–28)	<0.001	<0.001
γ-GT (U/l)*	21 (15–31)	22 (16–35)	23 (17–35)	27 (19–45)	<0.001	<0.001
Cr (μmol/l)*	67 (55–87)	67 (55–80)	65 (56–78)	66 (55–78)	0.054	0.001
SUA (μmol/l)*	302 (249–371)	314 (255–380)	306 (255–372)	320 (267–377)	0.007	0.078
UAE (mg/24h)*	10.9 (5.8–45.9)	10.2 (6.2–25.6)	9.7 (6.4–22.6)	13.0 (7.8–33.6)	<0.001	<0.001
eGFR (mL/min/1.73 m^2)*	103 (80–128)	107 (88–130)	111 (93–133)	115 (98–137)	<0.001	0.004
CRP (mg/l)*	1.15 (0.47–3.44)	1.09 (0.5–2.72)	1.09 (0.48–2.37)	1.2 (0.53–2.90)	0.389	0.13

Notes: Values are expressed as the mean±S.D, or median with interquartile range, or percentages. P-value: The p-values were not adjusted for age and sex for the trend. ^#P-value: The ^#p-values were adjusted for age and sex for the trend. *The Mann–Whitney U-test was applied.

Abbreviations: UUAE, urine uric acid excretion; DD, duration of diabetes; IIAs, insulin or insulin analogues; LLDs, lipid-lowering drugs; AHAs, antihypertensive agents; SUs, sulfonylureas; TZDs, thiazolidinediones; GIs, glycosidase inhibitors; SBP, systolic blood pressure; DBP, diastolic blood pressure; WC, waist circumstance; WHR, waist–hip ratio; BMI, body mass index; WBCC, white blood cell count; FBG, fasting plasma glucose; 2h PPG, 2-hour postprandial plasma glucose; FCP, fasting C-peptide; 2h PCP, 2-hour postprandial C-peptide; HbA1C, glycosylated hemoglobin A1C; HOMA2-IR, the Homeostasis Model Assessment Indexes-Insulin Resistance; TTG, total triglycerides; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ALT, aspartate aminotransferase; AST, alanine aminotransferase; γ-GT, γ-Glutamyl- transferase; Cr, creatinine; SUA, serum uric acid; UAE, urinary albumin excretion; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein.

Table 2 Comparison of Characteristics Between Men and Women Subjects

Variables	Total (2785)	Men (n=1574)	Women (n=1211)	p value	^#p value
UUAE(μmol/24h)	2842 (2211–3594)	2970 (2326–3786)	2665 (2098–3323)	<0.001	<0.001
Age (years)	59±13	56±13	61±12	<0.001	–
DD (months)*	84 (24–132)	60 (12–120)	96 (36–156)	<0.001	<0.001
Hypertension (n, %)	1461 (52.5%)	764 (48.5%)	697 (52.5%)	<0.001	0.043
Smoking (n, %)	821 (29.5%)	794 (50.4%)	27 (2.2%)	<0.001	<0.001
Alcohol (n, %)	449 (16.1%)	440 (28.0%)	9 (0.7%)	<0.001	<0.001
IIAs (n, %)	2006 (72.1%)	1138 (72.4%)	868 (71.7%)	0.682	0.556
LLD (n, %)	852 (30.8%)	477 (30.5%)	375 (31.1%)	0.706	0.523
AHAs (n, %)	1324 (47.7%)	686 (43.8%)	638 (52.8%)	<0.001	0.034
Metformin (n, %)	1546 (55.8%)	851 (54.3%)	695 (57.6%)	0.081	0.011
SUs (n, %)	1789 (64.5%)	926 (59.1%)	863 (71.5%)	<0.001	<0.001
TZDs (n, %)	394 (14.2%)	209 (13.3%)	185 (15.4%)	0.135	0.085
GIs (n, %)	1911 (68.9%)	1029 (65.7%)	882 (73.1%)	<0.001	0.008
SBP (mmHg)	132±17	130±17	134±18	<0.001	<0.001
DBP (mmHg)	80±10	80±10	81±9	0.059	0.235
WC (cm)	89±10	90±10	88±10	<0.001	<0.001
WHR	0.9±0.1	0.9±0.1	0.9±0.1	<0.001	<0.001
BMI (kg/m^2)	24.8±3.5	24.8±3.4	24.8±3.6	0.944	0.809
WBCC (×10^9)	6.32±1.87	6.42±1.98	6.21±1.70	0.003	0.022
FPG(mmol/l)*	7.73 (6.21–9.77)	7.80 (6.26–9.86)	7.62 (6.13–9.66)	0.076	0.759
2h PPG(mmol/l)*	13.48 (9.97–16.79)	13.54 (9.83–16.87)	13.39 (10.12–16.64)	0.772	0.729
FCP (ng/ml)*	1.65 (1.00–2.44)	1.62 (0.94–2.40)	1.68 (1.06–2.48)	<0.001	0.006
2h PCP (ng/ml)*	3.64 (2.04–5.37)	3.47 (1.94–5.25)	3.89 (2.19–5.47)	<0.001	<0.001
HbA1C (%)	9.1±2.4	9.2±2.5	9.0±2.3	0.004	0.017
HOMA2-IR	1.59±1.03	1.56±1.02	1.62±1.03	0.168	0.026
TTG (mmol/l)*	1.45 (1.00–2.15)	1.39 (0.95–2.14)	1.52 (1.04–2.17)	0.002	<0.001
TC (mmol/l)	4.70±1.14	4.53±1.10	4.91±1.15	0.061	<0.001
HDL-C (mmol/l)	1.11±0.31	1.01±0.29	1.19±0.32	<0.001	<0.001
LDL-C (mmol/l)	3.08±0.94	2.97±0.91	3.21±0.97	<0.001	<0.001
ALT (U/l)*	19 (13–31)	20 (14–32)	18 (13–29)	<0.001	0.009
AST (U/l)*	19 (16–25)	19 (16–25)	19 (16–25	0.589	0.986
γ-GT (U/l)*	23 (17–37)	25 (17–39)	22 (16–34)	<0.001	<0.001
Cr (μmol/l)*	67 (56–80)	75 (65–87)	56 (49–66)	<0.001	<0.001
SUA (μmol/l)*	311 (256–374)	327 (273–392)	288 (240–350)	<0.001	<0.001
UAE (mg/24h)*	11.00 (6.52–28.76)	11.11 (6.46–33.98)	10.92 (6.66–26.32)	0.372	0.026
eGFR (mL/min/1.73 m^2)*	100 (84–120)	111 (93–133)	101 (84–120)	0.683	<0.001
CRP (mg/l)*	1.11 (0.49–2.79)	1.04 (0.46–2.59)	1.19 (0.56–3.03)	0.004	0.182

Notes: Values are expressed as the mean±S.D, or median with interquartile range, or percentages. P-value: The p-values were not adjusted for age for the trend. ^#P-value: The ^#p-values were adjusted for age for the trend. *The Mann–Whitney U-test was applied.

Abbreviations: UUAE, urine uric acid excretion; DD, duration of diabetes; IIAs, insulin or insulin analogues; LLDs, lipid-lowering drugs; AHAs, antihypertensive agents; SUs, sulfonylureas; TZDs, thiazolidinediones; GIs, glycosidase inhibitors; SBP, systolic blood pressure; DBP, diastolic blood pressure; WC, waist circumstance; WHR, waist–hip ratio; BMI, body mass index; WBCC, white blood cell count; FBG, Fasting plasma glucose; 2h PPG, 2-hour postprandial plasma glucose; FCP, fasting C-peptide; 2h PCP, 2-hour postprandial C-peptide; HbA1C, glycosylated hemoglobin A1C; HOMA2-IR, the Homeostasis Model Assessment Indexes-Insulin Resistance; TTG, total triglycerides; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ALT, aspartate aminotransferase; AST, alanine aminotransferase; γ-GT, γ-Glutamyl- transferase; Cr, creatinine; SUA, serum uric acid; UAE, urinary albumin excretion; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein.

Figure 2 Prevalence of obesity in T2D. (A) Comparison of the obesity prevalence between men and women with T2D after adjusting for age and DD. (B) Prevalence of abdominal obesity prevalence between men and women with T2D after adjusting for age and DD. (C) Prevalence of obesity stratified by age in T2D. (D) Prevalence of abdominal obesity stratified by age in T2D. (E) Prevalence of obesity stratified by DD in T2D. (F) Prevalence of abdominal obesity stratified by DD in T2D.

Figure 3 Comparisons of obesity prevalence and UUAE levels. (A) Comparison of the prevalence of obesity among the UUAE quartile groups after adjusting for age, sex, and DD. (B) Comparison of the prevalence of moderate-severe obesity among the UUAE quartile groups after adjusting for age, sex, and DD. (C) Comparison of the prevalence of abdominal obesity among the UUAE quartile groups after adjusting for age, sex, and DD. (D) Comparison of the prevalence of moderate-severe abdominal obesity among the UUAE quartile groups after adjusting for age, sex, and DD.

Figure 4 Comparisons of UUAE levels. (A) Comparison of UUAE levels between the patients with and without obesity after adjusting for age, sex, and DD. (B) Comparison of UUAE levels between the patients with and without moderate-severe obesity after adjusting for age, sex, and DD. (C) Comparison of UUAE levels between the patients with and without abdominal obesity after adjusting for age, sex, and DD. (D) Comparison of UUAE levels between the patients with and without moderate-severe abdominal obesity after adjusting for age, sex, and DD.

Table 3 Association of UUAE Quartiles with Obesity and Abdominal Obesity

	ORs (95% CI)				P values for Trend
	Q1	Q2	Q3	Q4
Obesity
Model 1	1	1.254 (1.011–1.557)	1.520 (1.226–1.884)	3.059 (2.459–3.806)	<0.001
Model 2	1	1.281 (1.026–1.598)	1.559 (1.248–1.946)	3.130 (2.497–3.924)	<0.001
Model 3	1	1.230 (0.978–1.545)	1.429 (1.135–1.800)	2.703 (2.136–3.421)	<0.001
Model 4	1	1.229 (0.927–1.630)	1.352 (1.016–1.800)	2.355 (1.748–3.174)	<0.001
Abdominal obesity
Model 1	1	1.138 (0.918–1.410)	1.321 (1.064–1.640)	2.256 (1.793–2.838)	<0.001
Model 2	1	1.299 (1.026–1.644)	1.741 (1.366–2.220)	3.594 (2.762–4.676)	<0.001
Model 3	1	1.236 (0.971–1.573)	1.635 (1.275–2.097)	3.118 (2.383–4.080)	<0.001
Model 4	1	1.214 (0.896–1.644)	1.578 (1.152–2.160)	2.818 (2.004–3.961)	<0.001

Notes: Model 1: unadjusted. Model 2: adjusted for age, sex, HTN, DD, smoking, and alcohol. Model 3: further adjusted for SBP, DBP, the use of LLDs, AHAs, IIAs, SUs, Metformin, GIs and TZDs. Model 4: further adjusted for WBCC, ALT, AST, γ-GT, TC, TG, HDL-C, LDL-C, Cr, eGFR, SUA, FPG, 2h PPG, UAE, CRP, HbA1C, FCP, 2h C-P, HOMA2-IR.

Abbreviations: UUAE, urine uric acid excretion; OR, odds ratio; CI, confidence interval; Q, Quartile; HTN, hypertension; DD, duration of diabetes; SBP, systolic blood pressure; DBP, diastolic blood pressure; IIAs, insulin or insulin analogues; LLDs, lipid-lowering drugs; AHAs, antihypertensive agents; SUs, sulfonylureas; TZDs, thiazolidinediones; GIs, glycosidase inhibitors; WBCC, white blood cell count; ALT, aspartate aminotransferase; AST, alanine aminotransferase; γ-GT, γ-glutamyl- transferase; TTG, total triglycerides; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Cr, creatinine; eGFR, estimated glomerular filtration rate; SUA, serum uric acid; FBG, Fasting plasma glucose; 2h PPG, 2-hour postprandial plasma glucose; UAE, urinary albumin excretion; CRP, C-reactive protein; HbA1C, glycosylated hemoglobin A1C; FCP, fasting C-peptide; 2h PCP, 2-hour postprandial C-peptide; HOMA2-IR, the Homeostasis Model Assessment Indexes-Insulin Resistance.

Table 4 Association of UUAE with Obesity and Abdominal Obesity Among CKD and Non-CKD Patients

	CKD		Non-CKD		Total
	OR (95% CI)	P values	OR (95% CI)	P values	OR (95% CI)	P values
Obesity
Model 1	1.420 (1.127–1.789)	0.003	1.555 (1.425–1.697)	<0.001	1.500 (1.386–1.624)	<0.001
Model 2	1.453 (1.150–1.836)	0.002	1.562 (1.428–1.708)	<0.001	1.523 (1.405–1.652)	<0.001
Model 3	1.296 (1.009–1.664)	0.042	1.425 (1.298–1.566)	<0.001	1.415 (1.299–1.541)	<0.001
Model 4	1.119 (0.815–1.536)	0.486	1.332 (1.184–1.499)	<0.001	1.334 (1.199–1.485)	<0.001
Abdominal obesity
Model 1	1.235 (0.972–1.570)	0.084	1.371 (1.256–1.498)	<0.001	1.335 (1.232–1.447)	<0.001
Model 2	1.490 (1.132–1.961)	0.004	1.665 (1.505–1.843)	<0.001	1.618 (1.475–1.775)	<0.001
Model 3	1.249 (0.926–1.686)	0.146	1.551 (1.397–1.722)	<0.001	1.516 (1.378–1.668)	<0.001
Model 4	1.204 (0.821–1.767)	0.342	1.429 (1.252–1.630)	<0.001	1.444 (1.280–1.628)	<0.001

Notes: Model 1: unadjusted. Model 2: adjusted for age, sex, HTN, DD, smoking, and alcohol. Model 3: further adjusted for SBP, DBP, the use of LLDs, AHAs, IIAs, SUs, Metformin, GIs and TZDs. Model 4: further adjusted for WBCC, ALT, AST, γ-GT, TC, TG, HDL-C, LDL-C, Cr, eGFR, SUA, FPG, 2h PPG, UAE, CRP, HbA1C, FCP, 2h C-P, HOMA2-IR.

Abbreviations: UUAE, urine uric acid excretion; CKD, chronic kidney disease; OR, odds ratio; CI, confidence interval; Q, quartile; HTN, hypertension; DD, duration of diabetes; SBP, systolic blood pressure; DBP, diastolic blood pressure; IIAs, insulin or insulin analogues; LLDs, lipid-lowering drugs; AHAs, antihypertensive agents; SUs, sulfonylureas; TZDs, thiazolidinediones; GIs, glycosidase inhibitors; WBCC, white blood cell count; ALT, aspartate aminotransferase; AST, alanine aminotransferase; γ-GT, γ-glutamyl- transferase; TTG, total triglycerides; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Cr, creatinine; eGFR, estimated glomerular filtration rate; SUA, serum uric acid; FBG, fasting plasma glucose; 2h PPG, 2-hour postprandial plasma glucose; UAE, urinary albumin excretion; CRP, C-reactive protein; HbA1C, glycosylated hemoglobin A1C; FCP, fasting C-peptide; 2h PCP, 2-hour postprandial C-peptide; HOMA2-IR, the Homeostasis Model Assessment Indexes-Insulin Resistance.