The Effect of Exercise on Metabolic Responses, Inflammatory and Anti-inflammatory Factors in Women with Gestational Diabetes

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and is defined as glucose intolerance or high blood sugar (hyperglycemia), with the onset or first diagnosis during pregnancy. The prevalence of gestational diabetes varies from 1 to 20% and is increasing worldwide as maternal obesity and type 2 diabetes increase (1). Gestational diabetes increases the risk of short-term complications such as preeclampsia, cesarean delivery, macrosomia, hypoglycemia in infants, or hospitalization in neonatal intensive care units, as well as the long-term progression of type 2 diabetes (3). Some risk factors that predispose women to gestational diabetes include overweight and obesity, polycystic ovary syndrome (PCOS), pre-diabetes, gestational diabetes in a previous pregnancy, a family history of type 2 diabetes, maternal age and vitamin D deficiency (4).Blood glucose control is a vital factor in counteracting the side effects associated with GDM (5). Peripheral insulin resistance has been shown to help increase GDM-related blood glucose (6). In women with GDM, peripheral insulin sensitivity decreases and beta-cell dysfunction cannot meet the increased insulin needs during pregnancy and thus increase blood glucose (7).Metabolic disorders in GDM may be due to excessive accumulation of adipose tissue due to chronic low-grade inflammation associated with macrophage infiltration and secretion of many inflammatory cytokines. GDM is associated with an imbalance of various inflammatory processes that occur during pregnancy. Cytokines including interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and Tumour necrosis factor α (TNF-α) as well as other inflammatory markers such as C-reactive protein (CRP) increase in the female bloodstream of Obese pregnant women and women with GDM. These cytokines are biologically active compounds that participate as mediators in many metabolic pathways and affect the use of energy substrate in the fetus and offspring (8).Gestational diabetes control is based on two different approaches: interventions aimed at promoting healthy lifestyles, such as changes in diet or exercise, and anti-diabetic drug therapy (11). However, it is not clear about the characteristics of the type of exercise needed to better manage gestational diabetes. Findings from clinical and epidemiological studies do not show any maternal or fetal side effects on women with mild to moderate exercise. In fact, pregnant women are now advised to exercise regularly in the absence of medical or delivery complications (12). In the present study, some of the most important pathophysiological aspects of gestational diabetes are investigated and discuss how exercise can bring about some physiological adaptations of GDM. Metabolic changes and the role of inflammatory and anti-inflammatory factors in gestational diabetes are examined and attempts are made to elucidate the mechanisms by which exercise can be useful as an adjunctive therapy in improving metabolic conditions and reducing inflammation during gestational diabetes. In view of the above, the present study intends to investigate the effect of exercise activities on metabolic responses and inflammatory and anti-inflammatory factors in women with gestational diabetes. The aim of this study was to review the effect of exercise on metabolic responses,
inflammatory and anti-inflammatory factors in women with gestational diabetes (GDM).

Search performed for studies on the response of metabolic, inflammatory and anti-inflammatory factors to exercise in gestational diabetes in the reputable databases Springer, Hindawi, PubMed, Google Scholar, Scopus, SID and ISC using the keyword Exercise Training, Metabolic factors (glucose, insulin, glycosylated hemoglobin and insulin sensitivity), inflammatory factors (interleukin-1 beta, tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and reactive protein C (CRP)) and Anti-inflammatory factors (interleukin-10 (IL-10) were performed. 20 studies of metabolic responses and inflammatory-anti-inflammatory to exercise in women with GDM were reviewed.

In studies on metabolic factors, the benefits of exercise were observed to improve glycemic control, optimize fasting glucose and insulin concentrations, reduce glycosylated hemoglobin levels and improve insulin sensitivity in women with GDM. Also, decreased levels of inflammatory markers have been reported in women with GDM.

Evidence from randomized controlled trials shows that exercise as a supplement to standard care significantly improves postprandial control for glycemia and lowers fasting blood glucose for women with GDM (85-88). It was also found that people who exercise are prescribed less insulin (86, 89), so exercise is as effective as insulin in maintaining normal glycemia and can be helpful in meeting the need for insulin therapy. These results are clinically important because they show the potential of exercise to help lower acute blood glucose levels to normal. Glycosylated hemoglobin levels also measure long-term glycemic control (2 to 3 months), and exercise appears to improve HbA1c in the long term (87, 88). There is an acceptable physiological explanation for supporting exercise as a therapeutic supplement to improve glycemic control in women with GDM. Insulin administration does not reduce insulin resistance. In contrast, exercise increases insulin by stimulating glucose uptake into muscle by activating intracellular glucose transporters and increasing the use of intracellular fatty acids (50). Also, the amount of glucose consumed is affected by the duration and intensity of exercise. The more intense the exercise, the stronger the effect of lowering blood sugar (92). On the other hand, women with GDM show a greater inflammatory response. If inflammation promotes these adverse pregnancy outcomes, exercise may protect against the anti-inflammatory effect. Regular exercise has been shown to reduce some of the complications and risks of gestational diabetes, the protective effect of exercise in pregnant women is partly due to the reduction of inflammation (93). Exercise stimulates glucose in insulin-independent skeletal muscle.Therefore, less insulin is needed to maintain glycemia, and this appears to be mediated by muscle-derived cytokines. Both mechanisms could explain the lower first-phase insulin response seen in more active women. Inflammatory cytokines may play aprotective role on the glucose / insulin axis (39), extending this role to overweight and obese pregnant women. Pregnant women are more likely to have a more pronounced proinflammatory condition due to weight, BMI, and metabolic characteristics, which may affect their response to exercise. In general, it seems that changing the exercise version in the experiments prevents identifying the optimal type of exercise to improve metabolic conditions and reduce inflammation in women with GDM. In general, it can be concluded that aerobic and resistance or combined exercise are similarly effective in improving blood glucose control and reducing inflammation in women with GDM, provided they are similar in terms of exercise characteristics. Future studies should evaluate the effects of exercise combined with other interventions (diet) versus control (standard care-recommendation) on metabolic responses and inflammatory and anti-inflammatory factors in women with GDM, separate studies determine the effect of each intervention, and the type and severity of prescribed exercise should be considered. It seems that regular participation in exercise training can improve metabolic conditions and reduce inflammation in women with GDM. However, more studies are needed to investigate the effect of exercise, especially on inflammatory and anti-inflammatory factors in women with GDM.