Elevated Serum Uric Acid Is Associated With Gestational Diabetes Mellitus: An Observational Cohort Study

Abstract

Context

Elevated serum uric acid may be closely related to the occurrence of gestational diabetes mellitus (GDM).

Objective

We aimed to elucidate the relationship between changes in serum uric acid before 24 weeks of gestation and the risk of GDM and associated adverse pregnancy outcomes and provide clinical epidemiological evidence for the involvement of uric acid in the etiology of GDM.

Methods

We conducted a retrospective cohort study of 23 843 singleton pregnant women between February 2018 and June 2022. The exposure factor was serum uric acid before 24 weeks of gestation, primary outcome was gestational diabetes diagnosed at 24 to 28 weeks of gestation, and secondary outcomes were GDM A2 (GDM requiring pharmacotherapy), GDM combined with pre-eclampsia, preterm delivery, and large for gestational age infants. Adjusted risk ratios (RRs) were calculated using multivariate predictive marginal proportions from logistic regression models.

Results

Among 23 843 singleton pregnant women, 3204 (13.44%) were diagnosed with GDM at 24 to 28 weeks of gestation, and elevated uric acid before 24 weeks of gestation was strongly associated with the risk of GDM. Compared with uric acid <240 µmol/L, the RR for GDM was 1.43 (95% CI 1.29-1.56) when uric acid was between 240 and 300 µmol/L; when uric acid was >300 µmol/L, the RR for GDM was 1.82 (95% CI 1.55-2.15). In secondary outcomes uric acid had a similar relationship with GDM A2, preterm birth, and GDM combined with pre-eclampsia.

Conclusion

Elevated uric acid levels before 24 weeks of gestation are associated with subsequent GDM; the best time to test for uric acid is before 18 weeks of gestation. Pregnant women with low and intermediate risk for GDM development may benefit more from serum uric acid measurements before 18 weeks of gestation.

uric acid, gestational diabetes mellitus, risk ratio, cohort study

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy, with a global prevalence of about 12.9% (1, 2). Human intake of added sugars (sucrose) and high-fructose corn syrup has increased dramatically over the past 100 years, and the changing dietary structure has led to a yearly increase in the incidence of type 2 diabetes and hyperuricemia, which has become a major public health challenge (2-4). The prevalence of GDM in China is approximately 14.8% (3). GDM increases the risk of perinatal complications in mother and child, such as macrosomia, lower gestational age at delivery, the need for induction of labor or cesarean section, and is associated with increased long-term metabolic risk in women and offspring (2). Dietary structure and mechanisms of GDM occurrence, biomarkers for clinical monitoring of GDM, and variable therapeutic targets for GDM deserve further study to implement early prevention of gestational diabetes.

Uric acid salts are the end product of purine nucleotide degradation. A high-purine diet or other dietary factors that induce purine nucleotide degradation (eg, alcohol and fructose intake) increase serum uric acid concentrations (5). Hyperuricemia is closely associated with the development of diabetes and its chronic complications. Experimental evidence suggests that uric acid affects diabetes and its complications, mainly through the effects of inflammation, oxidative stress, and endothelial functional impairment (6). However, the conclusion that uric acid is a therapeutic factor in GDM lacks clinical epidemiological evidence. Current epidemiological findings are inconsistent (7-14).

Serum uric acid testing is a simple and convenient test that is a potential variable. Investigating the relationship between serum uric acid levels and gestational diabetes may help in the health management of people at high risk for gestational diabetes. To elucidate the association between elevated serum uric acid before 24 weeks of gestation and GDM diagnosed at 24 to 28 weeks of gestation, this retrospective cohort study included 24 023 singleton pregnant women; a logistic regression model predicted marginal proportions to calculate adjusted risk ratios (RRs). In addition to GDM, we also analyzed the association of serum uric acid levels with GDM A2, GDM with pre-eclampsia, preterm birth, and large for gestational age (LGA).

Materials and Methods

Design and Participants

Our study was a retrospective cohort study with a total of 23 843 singleton pregnant women from February 2018 to June 2022 at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China). Pregnant women were enrolled in our cohort when their pregnancy records were established at our institution, approximately between 10 and 12 weeks of gestation. Study exclusion criteria were as follows: twins or multiple births, established diabetes, urinary system disease, cardiovascular system disease, uric acid test time over 24 weeks of gestation, or patient had no complete maternal and infant record. The clinical data and outcomes for mothers and neonates were obtained from the Hospital Information System (HIS) and the Laboratory Information Management System. The present study conformed with the principles of the Declaration of Helsinki. Approval was obtained from the Research Ethics Committee of the Obstetrics and Gynecology Hospital of Fudan University.

Variables and Measurements

The first serum uric acid result before 24 weeks of gestation served as the exposure factor for this study. Uric acid levels were analyzed by an automatic biochemical analyzer (Hitachi 7180, WAKO) using commercially available kits. Confounding factors for adjustment include age, body mass index (BMI) (prepregnancy), parity, use of assisted reproductive technology, history of polycystic ovary syndrome (PCOS) disease, smoking, alcohol, gestational week of uric acid testing, fasting glucose, total cholesterol, creatinine, triglycerides, high-density lipoprotein, family history of diabetes, and weight gain in pregnancy. The laboratory measurements were taken at the first visit. Interassay coefficients of variation were less than 10% for all these assays. Diagnostic information for PCOS was obtained from HIS records.

Outcomes and Measurements

The primary outcome measure was GDM. GDM A1 was defined as GDM controlled by diet and exercise, and GDM A2 was defined as GDM requiring pharmacotherapy. GDM was screened at 24 to 28 weeks of gestation using the oral glucose tolerance test recommended by the International Association of Diabetes and Pregnancy Study Groups. GDM was diagnosed when 1 or more abnormal values were obtained in the 75-g oral glucose tolerance test, namely, fasting blood glucose ≥5.1 mmol/L; 1-hour blood glucose ≥10.0 mmol/L; or 2-hour blood glucose ≥8.5 mmol/L (15).

Secondary outcomes were GDM A2, LGA, preterm birth and GDM with pre-eclampsia. LGA was defined as a neonatal birth weight greater than 90% for gestational age and sex, and was determined based on the Intergrowth-21st weight standard (16). Preterm birth was defined as delivery at <37 weeks gestational age. Pre-eclampsia was diagnosed at weeks 20 to 39 of gestation using the current American College of Obstetricians and Gynecologists guidelines (17). Diagnostic criteria for pre-eclampsia were new onset of both hypertension (systolic blood pressure of 140 mmHg or higher, diastolic blood pressure of 90 mmHg or higher, or both) and proteinuria (2+ protein or greater on dipstick urinalysis, ≥ 300 mg of protein per 24-hour urine collection) after 20 weeks of gestation. The above data are all from HIS records.

Statistical Analysis

Data are presented as means (SD) for continuous variables and percentages for dichotomous variables. The quantitative effect relationship between uric acid and the occurrence of GDM was observed by smoothing splines. We calculated adjusted RRs using multivariate predictive marginal proportions from logistic regression models. Stratification was performed according to PCOS history, BMI, and age as stratification factors, and a sensitivity analysis was performed between subgroups to investigate whether the relationship between uric acid and GDM was consistent across subgroups. Age and BMI were also adjusted for within subgroups in sensitivity analyses grouped by age and BMI. Interaction tests were performed to assess RRs between the analyzed subgroups.

Software IBM SPSS (version 21.0. IBM; Armonk, NY) and the R statistical packages (R Foundation; https://www.r-project.org; version 3.4.3) were used for statistical analysis. All P values for statistics were 2-tailed, and P < .05 was regarded to be statistically significant.

Results

The main reason for loss to follow-up was that some pregnant women had obstetric examinations that were inconsistent with delivery hospitals. Among 51 254 pregnant women, 23 843 women met the inclusion and exclusion criteria (Fig. 1). In our cohort study, a total of 3204 (13.44%) pregnant women were diagnosed with GDM. Among the 3204 GDM pregnant women, there were 2722 GDM A1 pregnant women and 482 GDM A2 pregnant women.

Figure 1.

Flowchart of participants.

In the nonpregnant population, hyperuricemia is usually defined as a serum uric acid level higher than 6.0 mg/dL in women. During pregnancy, serum uric acid usually falls below 4 mg/dL (1 mg/dL = 60 µmol/L) (18, 19). In combination with the data in the literature, our study chose 240 and 300 mmol/L as cutoff values as the uric acid categorical variable. Baseline characters that may be associated with uric acid levels and the occurrence of GDM are described in detail (Table 1). The RRs and adjusted RRs of elevated uric acid for primary and secondary outcomes are presented in Table 2.

Table 1.

Baseline characteristics

Characteristic	UA < 240 µmol/L n = 18 025	240 ≤ UA < 300 µmol/L n = 4833	UA ≥ 300 µmol/L n = 985	P
Age (years)	31.07 ± 4.03	30.94 ± 4.07	31.32 ± 4.27	.015
BMI	20.95 ± 2.64	22.32 ± 3.39	24.17 ± 4.27	<.001
UA test week	10.91 ± 2.44	11.19 ± 2.67	11.04 ± 2.82	<.001
UA (µmol/L)	192.93 ± 28.60	262.02 ± 15.99	332.02 ± 33.44	<.001
ALT (U/L)	17.26 ± 14.80	19.89 ± 18.33	24.22 ± 24.36	<.001
Creatinine (µmol/L)	43.36 ± 5.59	45.44 ± 5.97	47.15 ± 6.81	<.001
Fasting blood glucose (mmol/L)	4.51 ± 0.39	4.52 ± 0.43	4.62 ± 0.62	<.001
Total cholesterol (mmol/L)	4.50 ± 0.76	4.68 ± 0.79	4.75 ± 0.80	<.001
Triglyceride (mmol/L)	1.27 ± 0.56	1.48 ± 0.72	1.71 ± 0.85	<.001
HDL (mmol/L)	1.40 ± 0.44	1.42 ± 0.43	1.41 ± 0.40	.001
Gestational age at birth (weeks)	39.32 ± 1.26	39.20 ± 1.36	39.04 ± 1.46	<.001
Birth weight (g)	3322.99 ± 428.47	3309.55 ± 451.39	3330.64 ± 485.24	.095
Cesarean section				<.001
No	11 608 (64.40)	2940 (60.83)	540 (54.82)
Yes	6417 (35.60)	1893 (39.17)	445 (45.18)
Parity				<.001
Primipara	13 736 (76.21)	3808 (78.79)	761 (77.26)
Multipara	4289 (23.79)	1025 (21.21)	224 (22.74)
Family history of diabetes				<.001
No	17 173 (95.30)	4531 (93.77)	901 (91.66)
Yes	847 (4.70)	301 (6.23)	82 (8.34)
Tobacco				<.001
No	17 632 (97.82)	4699 (97.23)	947 (96.14)
Yes	393 (2.18)	134 (2.77)	38 (3.86)
Alcohol				.803
No	17 061 (94.65)	4568 (94.52)	936 (95.03)
Yes	964 (5.35)	265 (5.48)	49 (4.97)
IVF				<.001
No	17 225 (95.56)	4539 (93.92)	912 (92.59)
Yes	800 (4.44)	294 (6.08)	73 (7.41)
PCOS				<.001
No	17 770 (98.59)	4711 (97.48)	939 (95.33)
Yes	255 (1.41)	122 (2.52)	46 (4.67)
Weight gain in pregnancy (kg)	14.21 ± 5.09	14.31 ± 5.42	14.07 ± 6.09	.348

Data are presented as mean ± SD or n (%). The test weeks for all baseline blood tests were the same as for uric acid tests.

Abbreviations: ALT, alanine aminotransferase; BMI, body mass index; HDL, high-density lipoprotein; IVF, in vitro fertilization; PCOS, polycystic ovarian syndrome; UA, uric acid.

Table 2.

Risk of primary and secondary outcomes

Outcome	No. of patients with event (event rate)	Risk ratio (95% CI)	P	Adjust risk ratio (95% CI)	P
Primary outcome
GDM (A1 + A2)
UA < 240 µmol/L (n = 18025)	2066 (11.46%)	Reference		Reference
240 ≤ UA < 300 µmol/L (n = 4833)	857 (17.73%)	1.55 (1.44-1.66)	<.001	1.43 (1.29-1.56)	<.001
UA ≥ 300 µmol/L (n = 985)	281 (28.53%)	2.49 (2.22-2.76)	<.001	1.82 (1.55-2.15)	<.001
Secondary outcomes
GDM A2
UA < 240 µmol/L (n = 18025)	278 (1.54%)	Reference		Reference
240 ≤ UA < 300 µmol/L (n = 4833)	134 (2.77%)	1.80 (1.45-2.16)	<.001	1.36 (1.04-1.75)	.009
UA ≥ 300 µmol/L (n = 985)	70 (7.11%)	4.61 (3.56-5.91)	<.001	1.89 (1.26-2.71)	.002
LGA
UA < 240 µmol/L (n = 18025)	2081 (11.55%)	Reference		Reference
240 ≤ UA<300 µmol/L (n = 4833)	593 (12.27%)	1.06 (0.97-1.16)	.0819	0.86 (0.783-0.95)	.004
UA ≥ 300 µmol/L (n = 985)	171 (17.40%)	1.51 (1.30-1.72)	.0000	0.98 (0.81-1.56)	.424
Premature delivery
UA < 240 µmol/L (n = 18025)	729 (4.04%)	Reference		Reference
240 ≤ UA < 300 µmol/L (n = 4833)	287 (5.94%)	1.47 (1.29-1.69)	<.001	1.39 (1.18-1.62)	.001
UA ≥ 300 µmol/L (n = 985)	71 (7.21%)	1.78 (1.41-2.24)		1.51 (1.12-1.95)	.007
GDM and PE
UA < 240 µmol/L (n = 18025)	130 (0.72%)	Reference		Reference
240 ≤ UA < 300 µmol/L (n = 4833)	76 (1.57%)	2.18 (1.63-2.91)	<.001	1.25 (0.88-1.70)	.109
UA ≥ 300 µmol/L (n = 985)	54 (5.48%)	7.60 (5.47-10.24)	<.001	2.13 (1.31-3.34)	.004

Adjusted for age, parity, body mass index, test week of uric acid, ALT, fasting blood glucose, total serum cholesterol, creatinine, tobacco, alcohol, PCOS, IVF, triglycerides, HDL, family history of diabetes, and weight gain in pregnancy.

Abbreviations: GDM, gestational diabetes mellitus; LGA, large for gestational age infant; PE, pre-eclampsia.

Sensitivity analyses by age and BMI found that the effect of uric acid on GDM was consistent between subgroups. However, in pregnant women without a history of PCOS, the relationship between uric acid and GDM was clearer, and in pregnant women with a history of PCOS, the relationship between uric acid and GDM was not statistically significant (Table 3). This phenomenon may be because PCOS is a systemic metabolic syndrome, often combined with insulin resistance, and therefore a history of PCOS is itself a high risk factor for GDM, and in this population, obesity, hyperglycemia, hyperlipidemia, and insulin resistance may play a dominant role in the development of GDM, while uric acid has a weaker effect on the development of GDM than BMI, hyperglycemia, hyperlipidemia, and insulin. The effect of uric acid on the development of GDM was weaker than that of BMI, glucose, lipids, and insulin resistance, and therefore was not statistically associated with the risk of GDM.

Table 3.

Subgroup analysis of GDM and uric acid

GDM	n	No. of patients with event (event rate)	Risk ratio (95% CI)	P	P value for interaction	Adjust risk ratio (95% CI)	P	P value for interaction
PCOS					.166			.291
No
UA < 240 µmol/L	17 770	1997 (11.24%)	Reference			Reference
240 ≤ UA < 300 µmol/L	4711	819 (17.38%)	1.55 (1.44-1.67)	<.001		1.45 (1.24-1.51)	<.001
UA ≥ 300 µmol/L	939	263 (28.01%)	2.49 (2.21-2.78)	<.001		1.89 (1.61-2.22)	<.001
Yes
UA < 240 µmol/L	255	69 (27.06%)	Reference			Reference
240 ≤ UA < 300 µmol/L	122	38 (31.15%)	1.15 (0.83-1.61)	.199		1.02 (0.72-1.62)	.3528
UA ≥ 300 µmol/L	46	18 (39.13%)	1.45 (0.91-2.10)	.059		1.09(0.75-2.03)	.3925
BMI					.166
<23
UA < 240 µmol/L	14 291	1366 (9.56%)	Reference			Reference		.211
240 ≤ UA < 300 µmol/L	3000	403 (13.43%)	1.41 (1.26-1.55)	<.001		1.52 (1.35-1.71)	<.001
UA ≥ 300 µmol/L	430	73 (16.98%)	1.78 (1.41-2.13)	<.001		1.79 (1.37-2.31)	<.001
≥23
UA < 240 µmol/L	3374	656 (19.44%)	Reference			Reference
240 ≤ UA < 300 µmol/L	1719	431 (25.07%)	1.29 (1.15-1.42)	<.001		1.26(1.10-1.45)	.001
UA ≥ 300 µmol/L	535	203 (37.94%)	1.95 (1.70-2.20)	<.001		1.68 (1.38-2.04)	<.001
Age					.663			.889
<35
UA < 240 µmol/L	14 969	1492 (9.97%)	Reference			Reference
240 ≤ UA < 300 µmol/L	4072	641 (15.74%)	1.58 (1.45-1.72)	<.001		1.42 (1.26-1.57)	<.001
UA ≥ 300 µmol/L	794	207 (26.07%)	2.62 (2.28-2.98)	<.001		1.77 (1.45-2.15)	<.001
≥35
UA < 240 µmol/L	3055	573 (18.76%)	Reference			Reference
240 ≤ UA < 300 µmol/L	760	216 (28.42%)	1.52 (1.31-1.73)	<.001		1.41 (1.18-1.68)	<.001
UA ≥ 300 µmol/L	191	74 (38.74%)	2.07 (1.66-2.51)	<.001		1.84 (1.33-2.49)	<.001

Adjusted for age, parity, body mass index, test week of uric acid, alanine aminotransferase, fasting blood glucose, total serum cholesterol, creatinine, tobacco, alcohol, PCOS, IVF, triglycerides, HDL, family history of diabetes and weight gain in pregnancy.

The dose–response relationship between uric acid and the risk of GDM is shown by curve fitting, and the results showed that the incidence of GDM increased significantly with increasing serum uric acid concentration. Hierarchical fitting curves are shown at different gestational weeks for uric acid detection (before 8 weeks, 8-12 weeks, 12-18 weeks, 18-24 weeks) and different age groups (under 35 years, over 35 years); different BMI elevated uric acid (BMI <23, BMI ≥23) was associated with an increased risk of GDM (Fig 2A-2C). Figure 2A shows that uric acid levels before 8 weeks, 8 to 12 weeks, and 12 to 18 weeks were consistent with a trend in the risk of subsequent GDM, while uric acid at 18 to 24 weeks was associated with a decreased risk of subsequent GDM. We therefore consider uric acid levels before 18 weeks of gestation to be an appropriate time for testing.

Figure 2.

The dose–response relationship between serum uric acid and the risk of gestational diabetes mellitus.

To explore whether adding uric acid to traditional risk factors improves GDM prediction, we performed a comparison of the area under the receiver operating characteristic curve of the prediction model in pregnant women with different risks. Low risk is defined as triglycerides <1.7 mmol/L, BMI <23, and fasting plasma glucose <5.1 mmol/L. Moderate risk is defined as triglycerides ≥1.7 mmol/L, or BMI ≥ 23, or fasting plasma glucose ≥5.1 mmol/L. High-risk is defined as triglycerides ≥1.7 mmol/L, BMI ≥23, and fasting plasma glucose ≥5.1 mmol/L. Model 1 was (a + b + c + d), Model 2 was (b + c + d): a, uric acid; b, BMI; c, fasting plasma glucose; d, triglycerides. The results showed that adding uric acid to traditional risk factors could improve the prediction of GDM and GDM requiring pharmacotherapy in low-risk and medium-risk pregnant women (Table 4). In high-risk groups, obesity, hyperglycemia, and hyperlipidemia may play a leading role in the development of GDM. Uric acid had a weaker impact on the development of GDM than BMI, glucose, and blood lipids. Therefore, uric acid detection cannot generate additional benefits in high-risk pregnant women.

Table 4.

Prediction of GDM and GDM requiring pharmacotherapy by uric acid in different subgroups

Predictor	GDM AUC			GDM requiring pharmacotherapy AUC
	Low risk	Moderate risk	High risk	Low risk	Moderate risk	High risk
Model 1	0.6131	0.7442	0.7801	0.6613	0.8133	0.7008
Model 2	0.6039	0.7373	0.7729	0.6460	0.8078	0.6981
P value	.0115	<.0001	.4378	.0359	.0417	.6385

Model 1 was (a + b + c + d), Model 2 was (b + c + d): a, uric acid; b, BMI; c, fasting plasma glucose; d, triglycerides.

Low risk is defined as triglycerides <1.7 mmol/L, BMI < 23, and fasting plasma glucose <5.1 mmol/L. Moderate risk is defined as triglycerides ≥1.7 mmol/L, or BMI ≥23, or fasting plasma glucose ≥5.1 mmol/L. High risk is defined as triglycerides ≥1.7 mmol/L, BMI ≥23 and fasting plasma glucose ≥5.1 mmol/L.

Discussion

Main Results

Our retrospective large cohort analyzed the relationship between serum uric acid before 24 weeks of gestation and the occurrence of GDM. We found that elevated serum uric acid before 24 weeks of gestation was significantly associated with GDM, GDM requiring pharmacotherapy, preterm delivery, and GDM combined with pre-eclampsia. Subgroup analysis showed that elevated uric acid levels were a risk factor for the development of GDM in a population of pregnant women of all ages and BMI. Our study suggests that elevated uric acid before 24 weeks of gestation is associated with subsequent GDM; the best time to test for uric acid is before 18 weeks of gestation. Pregnant women with low and intermediate risk for GDM development may benefit more from serum uric acid measurements; a uric acid test in these 2 types of pregnant women can provide early warning for the subsequent GDM or GDM requiring pharmacotherapy.

Comparison With Findings of Previous Studies

There is no consensus on the exact relationship between uric acid and GDM in previous studies. Controversy mainly lies in the fact that different studies have found that the gestational age of uric acid detection and maternal age have an impact on the relationship between uric acid and GDM. Although elevated serum uric acid levels have been reported as a risk factor for gestational diabetes (7-10), when considering the demographic baseline characteristics of pregnant women, the results of different studies differed, with 1 study proposing that only elevated serum uric acid levels at 13 to 18 weeks of gestation were associated with a significantly increased risk of GDM, and stratified analysis showed that the association between serum uric acid and GDM was stronger in pregnant women aged 35 years or older (11). Another study proposed a 55.7% increased risk of GDM in the highest quartile of uric acid levels at 16 to 18 weeks of gestation compared with those in the lowest quartile; similar results were found only in pregnant women less than or equal to 35 years of age, but not in those >35 years of age (12). In contrast to our findings, a small study did not show any difference in serum uric acid levels between GDM and non-GDM women before 14 weeks of gestation (13). Another study noted no difference in blood uric acid between 24 and 28 weeks of gestation between GDM (56 cases) and controls (56 cases) (14).

These inconsistent results may be due to sample size, testing gestational weeks, confounding factors, and dietary differences in different regions. Our study was a large retrospective cohort study of 24 023 subjects; to avoid biased results due to a small sample size, our study fully adjusted for various confounders related to uric acid and GDM to avoid an exaggerated uric acid effect. Different from previous studies, our study showed a similar relationship between uric acid and GDM at different ages, different time of uric acid detection, and different BMI.

Interpretations

Diet may have influenced the uric acid levels. Uric acid levels can be lowered by reducing excessive intake of fructose and purine-containing products (20, 21). Fructose intake causes the degradation of adenosine monophosphate to inosine monophosphate and stimulates uric acid production (22), supporting that serum uric acid may be a sign of an unhealthy diet, which constitutes excess fructose/sucrose and/or purines. An unhealthy diet does itself predispose to GDM in pregnant women with predisposing factors for GDM. Therefore, the uric acid level may not be a causative factor of GDM, but it is related to GDM development and is a marker of GDM development.

Serum uric acid measurement can guide doctors to manage GDM in pregnant women with medium and low risk. Serum uric acid in these specific subgroups may guide the requirement of pharmacotherapy or just diet therapy.

Strength and Limitations

Our study is a large cohort study, and our data provide clinicians with additional evidence that high levels of serum uric acid, independent of other identified risk factors, can lead to an increased risk of developing GDM. Given that GDM has become a growing public health challenge worldwide, it is important to detect serum uric acid levels early in pregnancy. In subgroup analyses at different ages, BMI, and gestational weeks of testing, the results were statistically significant with no evidence of heterogeneity, and the significant association between serum uric acid and the development of GDM was not affected by stratification factors. However, when a history of PCOS is taken into account, it appears that high uric acid has an independent effect on the occurrence of GDM only in pregnant women without PCOS. The existence of an effect of a history of PCOS on the occurrence of uric acid and GDM is the first to be found in the current study. Although some studies have used the z-score of uric acid as a risk indicator, the clinical utility is low, due to the need to calculate the z-score of uric acid. In fact, the use of a single serum uric acid threshold is more clinically attractive. The process of measuring uric acid is simple and inexpensive and is a potential variable.

Our study also has some limitations. First, retrospective studies are imperfect, and some unmeasured indicators cannot be corrected. Absence of data on other potentially confounding factors that may influence GDM development, such as inactivity, having prediabetes prior to pregnancy, excessive weight gain during pregnancy, GDM history in previous pregnancies, etc., may complicate the interpretation of the results presented in this study. Second, our study is a single-center study of pregnant women in Shanghai, China; a multicenter study is needed in the future.

Perspectives

Our study elucidates the relationship between serum uric acid, a low-cost, simple, and readily available biomarker, and GDM in an attempt to better understand the residual factors that influence the development of diabetes. Serum uric acid is a simple and easy to perform laboratory test and a potential variable. Screening for serum uric acid concentration may be considered as a screening strategy for early detection of GDM to improve unhealthy lifestyles and high-purine and -fructose diets. Pregnant women with low and intermediate risk for GDM development may benefit more (compared with high-risk patients) from serum uric acid measurements before 18 weeks of gestation.

Our findings support the prediction of gestational diabetes in early pregnancy and thus contribute to its proper management to prevent maternal and fetal morbidity and mortality.

Financial Support

This study was supported by the National Key Research and Development Program (2021YFC2701600, 2021YFC2701601, 2021YFC2701602). National Natural Science Foundation of China (no. 81902131) and Shanghai “Rising Stars of Medical Talents” Youth Development Program (SHWRS(2020)_087).

Author Contributions

C.Yu. analyzed the data, drafted the manuscript and contributed to study design. C.Yi. and X.L. revised the article and contributed to study design. All authors reviewed the manuscript, edited it for intellectual content, and gave final approval for this version to be published.

Disclosures

The authors have nothing to disclose.

Data Availability

All data sets analyzed during the present study are not publicly available but are available from the corresponding author on reasonable request.

Abbreviations

 
• BMI

  body mass index

 
• GDM

  gestational diabetes mellitus

 
• HIS

  Hospital Information System

 
• LGA

  large for gestational age

 
• PCOS

  polycystic ovary syndrome

 
• RR

  risk ratio