The Ratio of Serum Uric Acid to Glycosylated Haemoglobin as a Predictor of All-Mortality in Elderly Patients with Diabetic Foot Ulcers: A Longitudinal Cohort Study

Figures & data

Figure 1 Flowchart for selecting the study participants from the Foot Health Management Anonymous Database.

Table 1 Baseline Clinical Characteristics of Subjects

Clinical parameters	Low UA/HbA1c Ratio (≤39.07) (n=107)	High UA/HbA1c Ratio (>39.07) (n=65)	p-value
Age, years	62 (53, 73)	65 (56, 75)	0.138
Gender, n (%)			0.229
Female	32 (29.9)	14 (21.5)
Male	75 (70.1)	51 (78.5)
History of diabetes foot, n (%)			0.852
No	61 (57.0)	38 (58.5)
Yes	46 (43.0)	27 (41.5)
Hypertension, n (%)			0.507
No	50 (46.7)	27 (41.5)
Yes	57 (53.3)	38 (58.5)
CHD, n (%)			0.029*
No	99 (92.5)	53 (81.5)
Yes	8 (7.5)	12 (18.5)
CVD, n (%)
No	99 (92.5)	53 (81.5)	0.029*
Yes	8 (7.5)	12 (18.5)
Smoke, n (%)			0.466
No	78 (72.9)	44 (67.7)
Yes	29 (27.1)	21 (32.3)
PAD, n (%)			0.568
No	64 (59.8)	36 (55.4)
Yes	43 (40.2)	29 (44.6)
DPN, n (%)			0.557
No	22 (20.6)	11 (16.9)
Yes	85 (79.4)	54 (83.1)
Infection severity, n (%)			0.085
PEDIS 2 grade/mild	36 (32.6)	34 (52.3)
PEDIS 3 grade/moderate	46 (43.0)	19 (29.2)
PEDIS 4 grade/Severe	25 (23.4)	12 (18.5)
Duration of diabetes, years	7 (4, 11.5)	10 (5.5, 17)	0.01*
Diabetic foot ulcer duration, days	20 (9, 30)	20 (10, 60)	0.749
SBP, mmHg	140 (119, 155)	145 (130, 163.5)	0.097
DBP, mmHg	71 (63, 80)	73 (63.5, 81.5)	0.661
WBC, ×109/L	9.12 (6.79, 11.85)	8.17 (6.91, 10.59)	0.457
Hb, g/L	109 (96.5, 126.5)	113 (94.5, 128.5)	0.653
TC, mmol/L	3.88 (3.35, 4.91)	3.96 (3.27, 4.97)	0.747
TG, mmol/L	1.18 (0.87, 1.63)	1.23 (0.94, 1.76)	0.392
HDL-C, mmol/L	0.92 (0.73, 1.11)	0.92 (0.79, 1.09)	0.621
LDL-C, mmol/L	2.51 (2, 3.17)	2.5 (1.89, 3.08)	0.692
ALB, g/L	31.9 (27.9, 36.65)	35 (31.55, 38.86)	0.011*
Cr, μmol/L	80 (63.5, 106)	110 (88.5, 140)	<0.001*
UA, μmol/L	256 (206.5, 320.5)	400 (335.5, 470)	<0.001*
FBG, mmol/L	8.87 (7.3, 12.86)	7.01 (5.63, 8.85)	<0.001*
HbA1c, %	10.1 (8.6, 11.75)	7.7 (6.55, 8.6)	<0.001*
UA/HbA1c, (μmol/L)/%	25.75 (20.00, 31.84)	48.02 (42.08, 64.97)	<0.001*

Notes: Median (inter-quartile range) for continuous variables. Percentage (%) for categorical variables. * P < 0.05.

Abbreviations: CHD, coronary heart disease; CVD, cerebrovascular disease; PAD, peripheral vascular disease of diabetes; DPN, diabetes peripheral neuropathy; PEDIS, perfusion, extent, depth, infection, and sensation; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, leukocyte; Hb, haemoglobin; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ALB, serum albumin; Cr, creatinine; UA, uric acid; FBG, fasting blood glucose; HbA1c, glycosylated haemoglobin; UA/HbA1c, uric acid to glycosylated haemoglobin ratio.

Figure 2 ROC analysis for the optimal cutoff value predicting the effect of UA or UA/HbA1c ratio on all-cause mortality.

Notes: The cutoff values for UA and UA/HbA1c were 372 μmol/L and 39.07 (μmol/L)/%, respectively. The AUC of UA was 0.681 (95% CI = 0.574–0.788, P = 0.001). The sensitivity and specificity of the UA cutoff values were 55.9% and 76.8%, respectively. The AUC of UA/HbA1c ratio was 0.742 (95% CI = 0.652–0.832, P < 0.001). The sensitivity and specificity of the UA/HbA1c cut-off values were 70.6% and 70.3%, respectively. Paired comparisons of ROC curves showed that the diagnostic efficacy of the UA/HbA1c ratio was greater than UA (P = 0.013).

Abbreviations: ROC, receiver operating characteristic curve; UA, uric acid; HbA1c, glycosylated hemoglobin; AUC, area under the curve.

Table 2 Cox Regression Analysis Evaluating Risk Factors for All-Cause Mortality in Patients with DFUs

Variables	Hazard Ratio (95% confidence Interval) for All-Cause Mortality
	Model I	p-value	Model II	p-value	Model III	p-value
High UA/HbA1c ratio	5.205(2.417–11.209)	<0.001	4.99(2.135–10.91)	<0.001	4.63(2.004–10.7)	<0.001
High UA	3.759(1.883–7.506)	<0.001	3.538(1.694–6.97)	<0.001	3.2299(1.562–6.678)	0.002
High HbA1c	0.377(0.164–0.870)	0.022	0.493(0.215–1.911)	0.049	0.968(0.380–2.464)	0.946

Notes: Model-I: unadjusted. Model-II: with Model-I adjusted by age, gender. Model-III: with Model-II adjusted by CHD, CVD, Duration of diabetes, ALB and Cr.

Abbreviations: DFUs, diabetic foot ulcers; UA, uric acid; HbA1c, glycosylated haemoglobin.

Figure 3 Forest plots showing the results of stratification analyses in subgroups.

Notes: Each stratification was adjusted for all factors, including all independent variables in the regression analysis, except for the stratification factor.

Abbreviations: HR, hazard ratio; CI, confidence interval.

Figure 4 The cumulative incidence of all-cause mortality by HbA1c level.

Notes: Kaplan-Meier analysis showed a significant negative association between low HbA1c levels and the incidence rates of all-cause mortality after a follow-up of 32 months (log rank, P < 0.001); however, HbA1c was not a risk factor for all-cause mortality within a follow-up time of 32 months (log rank, P > 0.05). High-level HbA1c was defined as HbA1c level ≥ 6.5%, and low-level HbA1c was defined as HbA1c level < 6.5%.

Abbreviation: HbA1c, glycosylated hemoglobin.

Figure 5 The cumulative incidence of all-cause mortality by UA level.

Notes: Kaplan-Meier analysis showed a significant positive association between high-level UA and the incidence rates of all-cause mortality (log-rank, P < 0.001). High-level UA referred to a serum UA concentration > 372 μmol/L, and low-level UA referred to a serum UA concentration ≤ 372 μmol/L.

Abbreviation: UA, uric acid.

Figure 6 The cumulative incidence of all-cause mortality by UA/HbA1c ratio level.

Notes: Kaplan-Meier analysis showed a significant positive association between a high UA/HbA1c ratio and the incidence rates of all-cause mortality (log-rank, P < 0.001). High-level UA/HbA1c ratio was defined as UA/HbA1c ratio > 39.07 (μmol/L)/%, and low-level UA/HbA1c ratio was defined as UA/HbA1c ratio ≤ 39.07 (μmol/L)/%.

Abbreviations: UA, uric acid; HbA1c, glycosylated hemoglobin.

Table 3 Population Attributable Risk Proportion of All-Cause Mortality Associated with High UA and High UA/HbA1c Ratio

		High UA		High UA/HbA1c
Reference	Low UA		Low UA/HbA1c
All-cause mortality PAR%		19.69		33.7

Notes: Population attributable risk percentage (PAR%) was calculated following the formula: PAR% = Pe (RR-1) / [Pe (RR-1) + 1]. Pe represents the percentage of the population with a given level of UA or UA/HbA1c.

Abbreviations: UA, uric acid; HbA1c, glycosylated haemoglobin; PAR, population attributable risk.

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