Diabetic complications in pregnancy: is resveratrol a solution?

Abstract

Diabetes is a metabolic disorder that, during pregnancy, may affect fetal development. Fetal outcome depends on the type of diabetes present, the concentration of blood glucose and the extent of fetal exposure to elevated or frequently fluctuating glucose concentrations. The result of some diabetic pregnancies will be embryonic developmental abnormalities, a condition referred to as diabetic embryopathy. Tight glycemic control in type 1 diabetes during pregnancy using insulin therapy together with folic acid supplementation are partially able to prevent diabetic embryopathy; however, the protection is not complete and additional interventions are needed. Resveratrol, a polyphenol found largely in the skins of red grapes, is known to have antidiabetic action and is in clinical trials for the treatment of diabetes, insulin resistance, obesity and metabolic syndrome. Studies of resveratrol in a rodent model of diabetic embryopathy reveal that it significantly improves the embryonic outcome in terms of diminishing developmental abnormalities. Improvements in maternal and embryonic outcomes observed in rodent models may arise from resveratrol’s antioxidative potential, antidiabetic action and antidyslipidemic nature. Whether resveratrol will have similar actions in human diabetic pregnancy is unknown. Here, we review the potential therapeutic use of resveratrol in diabetes and diabetic pregnancy.

Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases

“…Resveratrol has been in use since ancient times as an Indian herbal preparation termed 'Darakchasava', which is derived from fermented grapes. Remarkably, the effects described for Darakchasava more than 4500 years ago (Singh et al, 2013) are the same described for resveratrol today. Today, Darakchasava is produced by several pharmaceutical companies and contains about 1.3-6.0 mg/L resveratrol (Paul et al, 1999).…”

“…The glucuronide-and sulfate-conjugated metabolites of resveratrol peaked in plasma at 30-60 min post-administration, with a plasma half-life of 9.2 h. (Walle et al, 2004). In contrast, only small amounts of unmodified resveratrol (<5 ng/mL) were detected in plasma in a similar timeframe (Singh et al, 2013). In another study conducted on mice, rats, and humans, it was shown that within 24 h after administration of 0.03 mg/kg body weight (BW) resveratrol, nearly 50% of the resveratrol was excreted in the urine.…”

“…Concentrations of these metabolites are reported to be higher than resveratrol post-absorption and to have longer half-lives (Andres-Lacueva et al, 2009;Polycarpou et al, 2013). In fact, the majority of orally dosed resveratrol is found in urine as sulfateor glucuronic acid-conjugates (Singh et al, 2013). In particular, the proportion of glucuronide-and sulfate-metabolites are reported to change depending on the tissue and species considered (Juan et al, 2010;Azorín-Ortuño et al, 2011): glucuronide conjugates are reported to be the main metabolites in rodents, whereas primarily sulfates are found in humans (Walle, 2011); moreover, the quantity of glucuronides is higher than sulfates in rat testes and liver, but not in lung (Juan et al, 2010).…”

“…In fact, resveratrol was found to modulate embryonic oxidative stress and apoptosis in diabetic pregnancy: in particular, it reduced oxidative stress by restoring the level of reduced glutathione, total thiol, lipid peroxidation, and 4-hydroxy-2-non-enal (HNE) in diabetic dams (Singh et al, 2013).…”

Normalizing Metabolism in Diabetic Pregnancy: Is It Time to Target Lipids?

“…Resveratrol administered to the dam has been detected in fetal plasma in rodents, but no data exists in humans. A recent review examined the possibility of using resveratrol for complications of diabetic pregnancy and reports a reduction in maternal glucose, cholesterol, and triglycerides, as well as a reduction in neural tube defects, in rodent models of diabetic pregnancy (57). Human pregnancy studies have not yet been undertaken.…”