Effect of alpha-lipoic acid supplementation on the lipid profile and lipid ratios in women with gestational diabetes mellitus: A clinical trial study

Abstract Background Evidence suggests that Oxidative stress has been shown to plays an important role in gestational diabetes mellitus (GDM) etiology. On the other hand, women with GDM are at an increased risk for complications such as endothelial dysfunction and cardiovascular diseases. Objective To investigate the effects of alpha-lipoic acid (ALA) on the maternal circulating values of lipid profile and lipid ratios in women with GDM. Materials and Methods Sixty women with GDM were participated in the present study. The ALA group (n = 30) received ALA (100 mg/day) and the placebo group (n = 30) received cellulose acetate (100 mg/day) for eight wk. The maternal circulating values of hemoglobin A1C, triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglyceride-glucose (TyG) index, atherogenic index of plasma (AIP), non-HDL-C, and lipid ratios were assessed before and after the intervention. P-value < 0.05 was considered as statistically significant. Results The values of TyG index (p < 0.001), TG (p = 0.006), TG/HDL-C (p = 0.003), and AIP (p = 0.005) decreased significantly in the ALA group after the intervention. Conclusion Maternal circulating values of TyG index, TG, TG/HDL, AIP decreased after eight wk of ALA supplementation in women with GDM.


Introduction
Gestational diabetes mellitus (GDM) is a condition that is initiated or diagnosed for the first time in pregnancy, which is defined as glucose intolerance. This type of diabetes increases insulin resistance in body. Mothers suffering from GDM are at a high risk for type 2 diabetes in future.
Clinical studies have shown that oxidative stress plays a role in the pathophysiology of numerous diseases (1). Normal pregnancy is regarded as a condition associated with increased oxidative stress. However, despite the increasing oxidative stress, there is a balance between antioxidants and oxidants in normal pregnancy. Bodies of evidence suggest that oxidative stress plays an important role in pregnancy complications such as GDM, preeclampsia, and hydatidiform mole (2,3). Alpha-lipoic acid (ALA) ( Short-term treatment with ALA in patients with type 2 diabetes mellitus (T2DM) has been suggested to improve lipid profile by improving oxidative stress and inflammatory responses (6). A systematic review has shown that supplementation with ALA can improve lipid profile except HDL-C in patients with metabolic diseases (7).
A review study has suggested that ALA not only has no side effects but also has protective effects against embryopathy, fetal mortality, and placental ultrastructural changes due to diabetes during pregnancy (8). Women with a history of GDM are at an increased risk for complications such as endothelial dysfunction and cardiovascular diseases (9).
It has been shown that lipid profile controlling during GDM can prevent impairment of the feto-placental endothelial function (10  were selected using the convenience sampling method. Of them, 10 were excluded based on the inclusion criteria. Thus, 60 of them were enrolled in the current study ( Figure 1).

Randomization
Participants were divided into ALA and placebo groups using simple randomization method by the random number

Ethical consideration
The current study was approval by the Ethics

Statistical analysis
Qualitative data were evaluated using the

Results
In this study, data of the participants in two groups (n = 30/each) were analyzed.
No significant differences were observed in the demographic and biochemical data of the two groups at the baseline (Tables I   and II). In addition, no significant changes were observed in the weight, systolic blood pressure, and BMI in each group following the intervention.
Intragroup and intergroup comparisons of the variables are given in Tables III and IV At the end of the trial, serum levels of ALA were increased in the ALA group (1.10 ± 0.10 vs 4.51 ± 0.24 µg/ml, p < 0.001), while no changes were observed in the placebo group (1.14 ± 0.07 vs 1.12 ± 0.07 µg/ml, p = 0.134).
Results of the ANCOVA test were significant

Discussion
The current study showed that the maternal circulating values of TyG index, TG, TG/HDL-C, and AIP decreased after an eight-week supplementation with ALA in womenwith GDM.
ALA supplementation at a dosage of 100 mg/day in women with GDM showed no significant changes in weight, systolic blood pressure, and BMI in both groups.
De Cicco and colleagues (19) found that the combination therapy with ALA and myoinositol significantly reduces BMI in women with polycystic ovary syndrome. Noori and colleagues (20) found that consumption of 800 mg of ALA in diabetic nephropathy significantly decreases systolic blood pressure in the supplement group compared with the placebo group.
Orally consumed ALA is absorbed almost entirely from intestine (21 (15,26). AIP value has been shown to be a good biomarker for the risk of atherosclerosis and cardiovascular diseases. In addition, the calculation of AIP, especially when lipid profile is in normal range, has been proposed, which can show more useful data than traditional lipid analysis about patient's situation (14,27). Results from the ANCOVA did not point to a statistically significant difference for TG/TC. Therefore, reduced TG/TC values may not be attributed to the intervention effects. An increase in the TG/HDL-C ratio was reported in GDM compared with healthy pregnancy (28). The TC/HDL-C, LDL-C/HDL-C, and TG/HDL ratios showed significant positive correlations with HOMA-IR. Therefore, these ratios could be used as simple alternative markers for assessing insulin resistance during pregnancy and predicting women at a high risk for GDM (29). It has been shown that ALA can increase A major limitation of the present study was the lack of a healthy control group to allow the comparison of the results obtained from the participants with them.

Conclusion
The results of the current study in women with GDM showed a significant decrease in the maternal circulating values of TyG index, TG, TG/HDL, AIP, and TBARS in the ALA group compared to the placebo group at the end of the intervention. More studies are required to evaluate the potential effects of ALA on the reduction of birth defects in women suffering from GDM.