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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (3): 427-433. doi: 10.19723/j.issn.1671-167X.2022.03.006

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Effects of gestational weight on the association between serum high sensitivity C reaction protein and gestational diabetes mellitus among twin gestations: A cohort study

Yang-yang CHEN1,Yu-bo ZHOU2,3,Jing YANG4,Yu-meng HUA1,Peng-bo YUAN4,Ai-ping LIU1,*(),Yuan WEI4,*()   

  1. 1. Department of Social Medicine and Health Education, Peking University School of Public Health, Beijing 100191, China
    2. Institute of Reproductive and Child Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
    3. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China
    4. Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
  • Received:2022-01-27 Online:2022-06-18 Published:2022-06-14
  • Contact: Ai-ping LIU,Yuan WEI E-mail:apingliu@163.com;weiyuanbysy@163.com
  • Supported by:
    the National Key Research and Development Program of China(2016YFC1000401);the National Key Research and Development Program of China(2016YFC1000408)

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Abstract:

Objective: To investigate the association between serum high sensitivity C-reaction protein (hsCRP) in early pregnancy and gestational diabetes mellitus (GDM) among twin pregnant women, and to explore the effects of the pre-pregnant body mass index (BMI) and gestational weight gain (GWG) status on such association. Methods: Twin pregnant women with pre-pregnant BMI greater than or equal to 18.5 kg/m2 were recruited at Department of Obstetrics and Gynecology of Peking University Third Hospital from March 2017 to December 2020. Serum samples collected in early pregnancy were analyzed for hsCRP using particle-enhanced immunoturbidimetric method. In the following visits, the information about GWG and GDM were prospectively collected in every trimester. The association effect between hsCRP tertiles and GDM were estimated using Logistic regression, and further converted into risk ratio (RR). Cochran-Mantel-Haenszel test and mediation analysis were used to explore the effects of BMI and GWG status on the association. Results: Among the included 570 twin pregnant women, 31.6% deve-loped GDM, 26.1% were pre-pregnant overweight or obesity, and 49.5% with GWG out of referenced range. After adjustment for confounding factors, risk of developing GDM in twin gestations with the middle tertile and highest tertile of serum hsCRP in early pregnancy were 1.42 fold (95%CI: 1.02-1.89) and 1.54 fold (95%CI: 1.12-2.02), respectively, compared with the lowest tertile of serum hsCRP, and there existed significantly linear trend (P=0.022). Findings from mediation analysis illustrated that pre-pregnant BMI had partial mediating effect on the association, and BMI accounted for 23.84% (P < 0.001) of the increasing GDM risks with elevated hsCRP. Joint analysis with hsCRP and GWG found that those who were with GWG out of referenced range accompanied with the higher hsCRP tertiles (>1.21 mg/L) had significantly 2.31 fold increased risk according to those who were with GWG in the referenced range accompanied with the lowest hsCRP tertile (≤1.21 mg/L, P < 0.01). Conclusion: Elevated hsCRP in early pregnancy significantly increased GDM risk among twin pregnant women. The hsCRP-GDM association was dependent on GWG status, and pre-pregnant BMI had partial mediating effect on such association. It is suggested that twin pregnant women should consider systemic inflammation and gestational weight at the same time to reduce GDM risk.

Key words: Twin pregnancy, C-reactive protein, Diabetes, gestational, Body mass index

CLC Number: 

  • R714.256

Table 1

Characteristics of twin pregnant women among hsCRP tertiles"

Items Total (n=570) T1 (n=178) T2 (n=191) T3 (n=201) P
hsCRP/(mg/L), M (P25, P75) 1.94 (0.93, 4.21) 0.61 (0.64, 0.92) 1.86 (1.59, 2.33) 5.28 (3.99, 7.24)
Maternal age/years, M (P25, P75) 33 (31, 36) 32 (31, 36) 33 (31, 36) 34 (31, 36)
Nationality, n (%) 0.333
  Han 526 (92.3) 166 (93.3) 179 (93.7) 181 (90.0)
  Minority 44 (7.7) 12 (6.7) 12 (6.3) 20 (10.0)
Educational level, n (%) < 0.001
  High school and below 54 (9.5) 11 (6.2) 12 (6.3) 31 (15.4)ac, bc
  Bachelor 319 (56.0) 91 (51.1) 106 (55.5) 122 (60.7)
  Master and above 197 (34.6) 76 (42.7) 73 (38.2) 48 (23.9)
Couple income per year (10 000 yuan), n (%) 0.128
   < 12 141 (24.7) 36 (20.2) 42 (22.0) 63 (31.3)
  ≥12 103 (18.1) 35 (19.7) 32 (16.8) 36 (17.9)
  ≥20 139 (24.4) 46 (25.8) 45 (23.6) 48 (23.9)
  ≥30 187 (32.8) 61 (34.3) 72 (37.7) 54 (26.9)
Smoking (or passively), n (%) 0.483
  No 467 (81.9) 146 (82.0) 161 (84.3) 160 (79.6)
  Yes 103 (18.1) 32 (18.0) 30 (15.7) 41 (20.4)
Alcohol, n (%) 0.423
  No 516 (90.5) 158 (88.8) 177 (92.7) 181 (90.0)
  Yes 54 (9.5) 20 (11.2) 14 (7.3) 20 (10.0)
Pre-pregnant BMI, n (%) < 0.001
  Normal 421 (73.9) 154 (86.5) 150 (78.5) 117 (58.2)ac, bc
  Overweight or obesity 149 (26.1) 24 (13.5) 41 (21.5) 84 (41.8)
Parity, n (%) 0.954
  0 484 (84.9) 152 (85.4) 161 (84.3) 171 (85.1)
  1- 86 (15.1) 26 (14.6) 30 (15.7) 30 (14.9)
Aspirin use, n (%) 0.516
  No 441 (77.4) 134 (75.3) 153 (80.1) 154 (76.6)
  Yes 129 (22.6) 44 (24.7) 38 (19.9) 47 (23.4)
Conception mode, n (%) 0.052
  Nature 161 (28.3) 59 (33.3) 57 (29.8) 45 (22.4)
  Assisted reproductive technology 408 (71.7) 118 (66.7) 134 (70.2) 156 (77.6)
Chorionic, n (%) 0.870
  Dichorionic 398 (75.2) 121 (73.8) 140 (76.1) 137 (75.7)
  Monochorionic 131 (24.8) 43 (26.2) 44 (23.9) 44 (24.3)
Gestational weeks at blood drawing, M (P25, P75) 9 (8, 10) 8 (7, 10) 9 (8, 10) 9 (8, 10)ac
Gestational weight gain, n (%) 0.256
  In the range 228 (40.0) 73 (41.0) 80 (41.8) 75 (37.3)
  Above the range 282 (49.5) 91 (51.1) 94 (49.2) 97 (48.3)
  Below the range 60 (10.5) 14 (7.9) 17 (8.9) 29 (14.4)
GDM, n (%) 0.017
  No 390 (68.4) 136 (76.4) 127 (66.5) 127 (63.2)ac
  Yes 180 (31.6) 42 (23.6) 64 (33.5) 74 (36.8)

Table 2

Associations between serum hsCRP tertiles and GDM"

Model Unadjusted Adjusted
T1 T2 T3 Ptrend T1 T2 T3 Ptrend
Model 1 Ref. 1.42 (1.02, 1.88)* 1.56 (1.15, 2.03)** 0.015 Ref. 1.42 (1.02, 1.89)** 1.54 (1.12, 2.02)** 0.022
Model 2 Ref. 1.38 (0.99, 1.84) 1.41 (1.02, 1.88)* 0.081 Ref. 1.38 (0.99, 1.85) 1.40 (1.00, 1.89) 0.089
Model 3 Ref. 1.44 (1.04, 1.91)* 1.58 (1.17, 2.06)** 0.012 Ref. 1.43 (1.03, 1.91)* 1.55 (1.13, 2.04)** 0.021

Table 3

Correlation on hsCRP tertiles and GDM among BMI or gestational weight gain status"

hsCRP tertiles BMI Gestational weight gain status
Normal Overweight or obesity In the range Above the range Below the range
n GDM, n (%) n GDM, n (%) n GDM, n (%) n GDM, n (%) n GDM, n (%)
Total 421 117 (27.79) 149 63 (42.28) 228 56 (24.56) 282 107 (37.94) 60 17 (28.33)
T1 154 35 (22.73) 24 7 (29.17) 73 13 (17.81) 91 27 (29.67) 14 2 (14.29)
T2 150 46 (30.67) 41 18 (43.90) 80 20 (25.00) 94 39 (41.49) 17 5 (29.41)
T3 117 36 (37.34) 84 38 (45.24) 75 23 (30.67) 97 41 (42.27) 29 10 (34.48)
PCMH=0.087 PCMH=0.014

Table 4

Mediation of BMI or gestational weight gain on the association between hsCRP and GDM"

Items Mediation of BMI on the association Mediation of gestational weight gain on the association
T1 vs. T2 T2 vs. T3 T1 vs. T3 T1 vs. T2 T2 vs. T3 T1 vs. T3
Total effect 0.099*
(0.003, 0.190)		 0.028
(-0.074, 0.120)		 0.127***
(0.039, 0.210)		 0.100
(-0.011, 0.180)		 0.029
(-0.068, 0.100)		 0.129***
(0.037, 0.210)
Mediated effect 0.009*
(0.001, 0.020)		 0.024*
(0.010, 0.050)		 0.030***
(0.004, 0.050)		 0.001
(-0.007, 0.010)		 0.006
(-0.001, 0.020)		 0.006
(-0.001, 0.020)
Direct effect 0.091
(-0.004, 0.190)		 0.005
(-0.103, 0.100)		 0.097*
(0.017, 0.180)		 0.099
(-0.010, 0.180)		 0.023
(-0.076, 0.100)		 0.122***
(0.032, 0.200)
Proportion of mediation 8.59%
(-0.002, 1.460)		 83.80%
(-4.980, 7.810)		 23.84%***
(0.049, 0.660)		 0.76%
(-0.085, 0.160)		 20.54%
(-1.124, 1.850)		 4.77%
(-0.016, 0.190)

Figure 1

Mediation of BMI on the association between hsCRP and GDM hsCRP T3 accounted for 23.84% (P < 0.001) of the increasing GDM risks with elevated hsCRP in comparison to hsCRP T1. * P < 0.001. GDM, gestational diabetes mellitus; BMI, body mass index; hsCRP, high sensitivity C-reaction protein; T1, tertile 1; T3, tertile 3."

Table 5

Joint association effect of hsCRP and gestational weight gain on GDM"

hsCRP & gestational weight gain n Unadjusted Adjusted
T1 & in the range 73 Reference Reference
T1 & above the range 91 1.67 (0.95, 2.68) 1.66 (0.93, 2.68)
T1 & below the range 14 0.80 (0.13, 2.34) 0.78 (0.13, 2.29)
T2 & in the range 80 1.40 (0.75, 2.40) 1.39 (0.73, 2.38)
T2 & above the range 94 2.33 (1.46, 3.38)*** 2.31 (1.44, 3.36)**
T2 & below the range 17 1.65 (0.59, 3.23) 1.66 (0.59, 3.24)
T3 & in the range 75 1.72 (0.96, 2.78) 1.68 (0.93, 2.74)
T3 & above the range 97 2.37 (1.50, 3.42)*** 2.31 (1.44, 3.37)**
T3 & below the range 29 1.94 (0.92, 3.27) 1.90 (0.89, 3.24)
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