Revisiting link between abnormal uric acid levels and gestational diabetes: A systematic review

As of right now, there is no widely accepted method for
preventing or treating GDM. The only treatments available are insulin therapy
and lifestyle modifications, both of which have limited effectiveness because
insulin resistance is a prevalent manifestation in GDM patients. Regularly
consumed medications, like metformin and glyburide, have revealed agreeable
results, there have been concerns about the long-established influence of these
drugs on pregnant women and their children. An untimely recognition of GDM is
mandatory to keep down unfavourable after-effect for mother-newborn duo.

UA is the end-product of purine metabolism, which decreases
by 25–35% in the early stages of pregnancy before increasing towards normal
values near term in a healthy pregnancy. Multiple studies have demonstrated
that high amounts of uric acid are harmful to metabolic health because they
impede insulin signalling, which leads to insulin resistance. In light of this,
hyperuricemia has been suggested as a part of the metabolic syndrome linked to
insulin resistance.

Moreover, there may be a link between UA levels and
resistance to insulin in expectant women with prenatal hypertension. Compared
to women without the illness, women with gestational diabetes have greater
amounts of uric acid throughout the early phases of pregnancy. Despite a great
deal of study being done in this area, the occurrence of GDM hasn’t been
invariably linked to UA levels throughout pregnancy. The possible impact of
elevated UA levels on the potential of GDM is a topic of debate. Thus, so as to
successfully handle this medical condition among this high-risk population, an
in-depth knowledge of this problem is required. To verify whether elevated
levels of UA throughout pregnancy can raise the chance of subsequently
developing GDM, independent of already recognised risk factors, authors Jankar
et al set out to conduct a systematic review.

The articles have been chosen from the databases PubMed, Embase
and Scopus. They discussed all applicable publications that explored the
interrelation between serum UA and GDM, accompanying the formerly recorded
articles. Other articles independent of this field are refrained from. This
systematic review exhibited a bond between GDM and serum UA levels.

120 articles were chosen using the structured literature
search. 30 duplicate papers were removed, while 38 articles were left out due to
titles and abstracts, 9 studies were found using pertinent references, 24 articles
were eliminated on the grounds of inclusion criteria, and nineteen articles
that satisfied both exclusion and inclusion criteria were chosen. 9
observational studies, 8 cohort studies, 1 descriptive case series study, and 1
case-control study were incorporated in the literature review.

A major factor in GDM is insulin resistance. Numerous
investigations have revealed that the ingenious molecule uric acid plays a role
in insulin resistance. In addition to interfering with insulin function; uric
acid also has a propensity to cause inflammation and oxidative stress. The
delicate equilibrium in the body can be severely disrupted by these two
troublemakers, which can result in the development of gestational diabetes. Uric
acid also has an impact on those priceless pancreatic beta cells that make
insulin. These cells may be harmed by uric acid, which could reduce their
ability to produce enough insulin to regulate blood sugar levels.

Increased renal excretion and the uricosuric impact of
elevated oestrogen levels during pregnancy lead to decreased serum UA levels. Pregnancy
causes a 25% drop in blood concentration from 6 to 12 mL/min to 12 to 20 mL/min
due to the faster clearance of UA. The changes in renal processing have been
associated with variations in blood uric acid levels during pregnancy. Raised
serum UA levels are linked with a number of unfavourable pregnancy outcomes. It
may result in cardiovascular illness, renal dysfunction, and oxidative
stress—conditions that are frequently seen in severe preeclampsia. A number of
theories have been put forth to explain how hyperuricemia affects the course of
pregnancy.

The results of this study demonstrated that perinatal
discomfort is more common in children born to mothers who have hyperuricemia. If
neglected, glucose intolerance which is initially identified during pregnancy,
can have negative effects on both the mother and the foetus. GDM usually
appears in the latter half of the second or third trimester of pregnancy and
lastsIt is already known that hyperuricemia independently predisposes people to
diabetes mellitus, cardiovascular morbidityand metabolic syndrome. Non-pregnant
females experiencing hyperuricemia without symptoms experience increased
insulin resistance due to release of inflammatory cytokines and oxidative
stress, this eventually causes blood glucose levels to rise. Similarly, it
raises the incidence of GDM and is a major risk factor for insulin resistance
during pregnancy. Elevated UA is linked to pregnancy related insulin
resistance. Therefore, the main emphasis of this review was on the role that
hyperuricemia plays in pregnant women’s development of GDM until delivery.

The development and mechanism of insulin resistance
resulting from hyperuricemia are identical in non-pregnant and pregnant
females. An increased incidence of insulin resistance and GDM is associated
with hyperuricemia. This is typically caused by the activation of oxidative
changes in adipose tissues through the production of UA by adipocytes, the
suppression of nitric oxide release by endothelial cells, and the facilitating
involvement of inflammatory cytokines. Additional research is required to
firmly demonstrate a link between hyperuricemia and GDM. In addition, we must
determine the pathophysiologic mechanisms that underlie this connection and the
part that various predisposing variables play in the progression to GDM when
conjunction with increased UA levels. It may be possible to expedite early
diagnosis and screening with more research. By treating gestational diabetes
early on, both the mother and the foetus can be spared the possibility of
adverse effects.

Source: Jankar et al. / Indian Journal of Obstetrics and
Gynecology Research 2024;11(3):315–324;

https://doi.org/10.18231/j.ijogr.2024.061