Avicenna Journal of Clinical Medicine

Volume 33, Issue 2

Original Article

The Risk of Metabolic Syndrome in Women with a History of Gestational Diabetes: A Population-Based Study

Marzieh Saei Ghare Naz1 , Maryam Mousavi1, Vida Ghasemi2, Soudabe Motamed3, Fereidoun Azizi4, Fahimeh Ramezani Tehrani1*

  1. Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. Department of Midwifery, Asadabad School of Medical Sciences, Asadabad, Iran
  3. Department of Public Health, Asadabad School of Medical Sciences, Asadabad, Iran
  4. Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

BRIEF TEXT

Background and Objective

Gestational diabetes mellitus is defined as impaired glucose tolerance that is first detected in the second or third trimester of pregnancy [1]. A meta-analysis estimated the global prevalence of gestational diabetes at 14%, while the prevalence in the Middle East region is 27.6% [2]. …. [3]. Gestational diabetes mellitus is associated with an increased risk of adverse short- and long-term outcomes for the mother and fetus [4, 5]. ….[4, 6]. …. [7]. One of the most important complications that is more likely to occur in women with a history of gestational diabetes is metabolic syndrome [8, 9]. Gestational diabetes can be a strong predictor for the development of any of the components of metabolic syndrome [10]. ….. [9, 11]. …. [12, 13]. … [12]. On the other hand, some recent evidence suggests that women with a history of gestational diabetes may continue to adopt a healthier lifestyle in life due to awareness of their metabolic disorder, which may reduce their risk of chronic disease-related mortality in the long term [14]. This study aimed to evaluate the risk of metabolic syndrome in women with a history of gestational diabetes in the population of participants of the Tehran Lipid and Glucose Study (TLGS).

Materials and Methods

This cross-sectional study was based on the TLGS cohort [15]. For the present study, data from the seventh phase of the study were used. Information on pregnancy complications was collected using self-report and then confirmed by medical records [16, 17] .The level of physical activity was evaluated using a modifiable activity questionnaire [18]. Anthropometric measurements were based on the standard protocol of TLGS. To assess blood pressure after 15 minutes of rest, it was measured twice in a sitting position using a standard mercury sphygmomanometer. The average values of these measurements were used in the analysis. Venous blood samples were taken after 12 to 14 hours of overnight fasting. Diabetes was defined as a fasting glucose level of ≥126 mg/dL, or a two-hour postprandial blood glucose level of ≥200 mg/dL, or the use of antidiabetic drugs prior to the time of this study [19]. Metabolic syndrome were defined as the presence of all three of the following five risk factors according to the interim joint statement [20]: 1) abdominal obesity: waist circumference ≥ 90 cm [21]; 2) high fasting blood glucose ≥ 100 mg/dL or antidiabetic drug therapy, 3) high fasting triglyceride (TG) ≥ 150 mg/dL or drug therapy; 4) low fasting high-density lipoprotein cholesterol (HDL-C) < 50 mg/dL or drug therapy; and [5] hypertension, defined as systolic blood pressure (SBP) ≥130 mmHg, diastolic blood pressure (DBP) ≥85 mmHg, or treatment with antihypertensive drugs. This study was carried out after obtaining the code of ethics (IR.SBMU.ENDOCRINE.REC.1405.031) from Shahid Beheshti Institute of Endocrine Sciences and Metabolism of Medical Sciences, Tehran, Iran.

Results

In this cross-sectional study, 375 women without a history of GDM and 119 with a history of GDM were studied. In women without a history of GDM, body mass index (BMI) (P = 0.002), systolic blood pressure (P < 0.001), diastolic blood pressure (P = 0.004), and number of deliveries (P < 0.001) were higher than in those with a history of GDM (Table 1). The prevalence of metabolic syndrome was 36.1% in the group with a history of GDM and 42.3% in the group without a history (P = 0.23) (Table 1). After adjusting for age and BMI, history of GDM was significantly positively associated with fasting blood sugar (FBS) (β = 25.37, P >.001), triglycerides (β = 46.41, P = 0.009), and waist circumference (WC) (β = 4.54, P < 0.001) (Table 2). After controlling for additional confounders (smoking, physical activity, number of deliveries, diabetes mellitus), this association remained significant only for FBS (β = 11.74, P = 0.003) and WC (β = 4.01, P < 0.001) (Table 2). No significant association was observed with the other components of metabolic syndrome (P > 0.05) (Table 2). In the logistic regression model adjusted for age and BMI, women with a history of GDM had a 3.31-fold higher chance of developing metabolic syndrome (OR = 3.31; P < 0.001) (Table 3). However, this association was not significant after controlling for additional confounders (P = 0.11) (Table 3).

Discussion

This study found a metabolic syndrome prevalence of 40.8% overall, 36.1% in women with a history of GDM, and 42.3% in those without GDM. In adjusted models, women with prior GDM had more than 3.3-fold higher odds of metabolic syndrome after controlling for age and BMI; however, after further adjustment, the odds ratio became non-significant. Nevertheless, after full adjustment, women with a GDM history had significantly higher waist circumference, fasting glucose, and triglycerides than those without GDM.

These findings align with prior evidence. A meta-analysis reported that women with previous GDM had a 2.36-fold increased risk of metabolic syndrome compared with those without (RR: 2.36) [8]. A Danish cohort of 435 post-GDM women showed a 28% incidence of metabolic syndrome, with 8% developing overt diabetes [12]. NHANES data (n = 10,251) similarly indicated elevated risks among women with prior GDM for obesity (odds ratio [OR]: 1.67), hyperlipidemia (OR: 1.28), type 2 diabetes (OR: 5.39), metabolic syndrome (OR: 1.62) [22]. Although GDM is diagnosed during pregnancy, it identifies women with an evolving cardiometabolic risk profile that may begin early in life, contributing to long-term risks of type 2 diabetes and cardiovascular disease [23, 24]. Recent UK Biobank data suggest that women with prior GDM who maintain the healthiest lifestyles do not face elevated all-cause mortality or major cardiovascular events, whereas those with poorer lifestyles do [14]. … [25, 26].

Mechanistically, GDM is linked to endothelial dysfunction, insulin resistance, oxidative stress, and epigenetic changes [27]. Reduced incretin secretion and pro-inflammatory cytokines impair insulin signaling and glucose uptake [28, 29].

Clinically, these results support systematic, long-term screening of post-GDM women for glucose, weight, and lipids, with referral to primary care or endocrinology for management.

Conclusion

The results of this study showed that a history of GDM had a significant positive association with some metabolic indices, including FBS, triglycerides, and WC.

References

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Table 1. Demographic and Metabolic Syndrome Characteristics by GDM History

VariableTotal
(n = 494)		History of GDMP value
Yes (n = 119)No (n = 375)
Age (y)52 ± 7.4841.7 ± 98.6552.5 ± 78.11< 0.001
BMI (Kg/m2)52 ± 4.7128.4 ± 9.7429.4 ± 61.640.002
SBP (mmHg)109.51 ± 14.38105.10 ± 50.68110.15 ± 85.20< 0.001
SBP (≥130 mmHg)42 (8.8)2 (1.7)40 (11.2)0.002
DBP (mmHg)73 ± 8.9572.7 ± 29.8274.9 ± 24.260.04
DBP (≥85 mmHg)47 (9.9)5 (4.2)42 (11.8)0.01
Parity2 ± 1.031 ± 78.952.10 ± 22.04< 0.001
FBS (mg/dL)94 ± 34.73101.10 ± 31.03108.16 ± 43.730.10
FBS (≥100 mg/dL)151 (31.7)44 (37)107 (30)0.15
WC (cm)94.10 ± 21.7193.11 ± 18.2394.10 ± 55.540.23
WC (≥90 cm)312 (65.5)74 (62.2)238 (66.7)0.37
TG (mg/dL)121 ± 133.66157.23 ± 42.1142.67 ± 30.790.48
TG (≥150 mg/dL)169 (35.5)41 (34.5)128 (35.9)0.78
HDL-C (mg/dL)50 ± 10.9148.11 ± 68.2450.10 ± 85.760.06
HDL-C (<50 mg/dL)237 (49.8)63 (52.9)174 (48.7)0.42
Metabolic syndrome, No. (%)Yes194 (40.8)43 (36.1)151 (42.3)0.23
No282 (52.9)76 (63.9)206 (57.7)
Smoking, No. (%)Yes14 (2.9)3 (2.5)11 (3.1)0.75
No462 (97.1)116 (97.5)346 (96.9)
Physical activity, moderate to high,
No. (%)		Yes140 (29.4)29 (24.4)111 (31.1)0.16
No336 (70.6)90 (75.6)246 (68.9)
DM, No. (%)Yes92 (19.3)30 (25.2)62 (17.4)0.06
No384 (80.7)89 (74.8)295 (82.6)

Abbreviations: GDM, gestational diabetes mellitus; BMI, Body mass index; SBP, systolic blood pressure; DBP, Diastolic blood pressure; FBS, fasting blood sugar; WC, waist circumference; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; DM, diabetes mellitus.

Table 2. Association between GDM and Cardiometabolic Indices Using Linear Regression

VariablesModel 1P valueModel 2P valueModel 3P value
β (95% CI)β (95% CI)β (95% CI)
SBP-5.35 (-8.31, -2.39)< 0.0010.88 (-2.78, 4.56)0.63-0.46 (-4.24, 3.32)0.81
DBP-1.95 (-3.80, 0.09)0.04-0.34 (-2.71, 2.01)0.77-0.41 (-2.86, 2.04)0.74
WC-1.36 (-3.60, 0.87)0.234.54 (2.89, 6.20)< 0.0014.01 (2.31, 5.72)< 0.001
FBS7.06 (-0.13, 14.26)0.05525.37 (-30.17, 33.56)< 0.00111.74 (4.03, 19.46)0.003
TG15.39 (-11.98, 42.77)0.2746.41 (11.60, 81.22)0.00932.60 (-3.19, 68.39)0.07
HDL-C-2.17 (-4.43, 0.09)0.06-2.46 (-5.30, 0.37)0.08-0.85 (-3.74, 2.04)0.56

Model 1: crude; model 2: adjusted for age and BMI (body mass index); model 3: adjusted for age and BMI, smoking, physical activity, parity, diabetes mellitus

Abbreviations: GDM, gestational diabetes mellitus; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBS, fasting blood sugar; WC, waist circumference; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; β (95% CI), beta coefficient (95% confidence interval).

Table 3. Association between GDM and Metabolic Syndrome Using Logistic Regression

VariableModel 1P valueModel 2P valueModel 3P value
OR (95% CI)OR (95% CI)OR (95% CI)
Metabolic syndrome0.77 (0.50, 1.18)0.233.31 (1.75, 6.27)< 0.0011.76 (0.87, 3.57)0.11

Abbreviations: GDM, gestational diabetes mellitus; OR (95% CI), odds ratio (95% confidence interval).

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