A study found that current ADA recommendations achieved appropriate glycemic levels, with tighter glucose control showing no significant advantage.
Gestational diabetes can predispose offspring to obesity and type 2 diabetes, but the mechanism connecting the development of these diseases in the offspring is unknown. A new study was designed to try to test if intrauterine exposure to hyperglycemia was associated with metabolic disease in offspring. The thought behind this theory is that diabetes in utero alters the adipoinsular axis, or the endocrine loop that links the brain to the pancreas and can either stimulate leptin release in the adipose tissue or insulin uptake. This axis controls eating behavior and energy balance.
Adipokines help regulate energy metabolism. Specifically, leptin and adiponectin are key regulators of appetite, satiety, energy expenditure, insulin sensitivity, fat distribution, and endothelial function. It has been found that low adiponectin levels were found in people who have insulin resistant type 2 diabetes. Leptin and adiponectin are also associated with fetal growth and predictors of weight gain in early life. Another adipokine of interest is angio-like protein 4 (ANGPTL4). It’s blood circulation level was inversely correlated with body weight.
A change in the expression of adipokines can perhaps serve as an indicator of metabolic disease development in fetal tissue. The following study compared changes in newborn gene expression level in groups of mothers with different glucose level targets. Mothers were randomized into two groups: group 1 with a target fasting blood glucose of <5.1 mmol/L and postprandial of <7.0 mmol./L. or group 2 with target fasting of <5.3 mmol/L and postprandial <7.8 mmol/dL. Participants included 41 women with gestational diabetes. Target glucose levels were achieved through monitoring diet, but if levels exceeded target, insulin was initiated.
After delivery, cord blood samples were collected. Samples were analyzed for c-peptide, leptin, adiponectin, and ANGPTL4. Statistical analysis was done using SPSS and differences among groups was analyzed using Mann-Whitney test, Kruskal-Wallis, or chi square test. Groups were similar at baseline and about 40% of women in group 1 were treated with insulin versus 29% in group 2. The primary outcomes was the incidence of large-for-gestational-age infants. Secondary outcomes included neonatal death and morbidity, gestational age at birth, small birth weight, hypoglycemia, and mode of birth, among others.
Results showed no statistical significance in percent of large-for-gestational-age or small-for-age newborns, rate of caesarean section, level of c-peptide, adiponectin, and ANGPTL4 in cord blood between the two groups of mothers. Leptin levels were higher in the cord blood from group 2 (mothers having difficulty managing glucose levels). The difference from the control group however did not reach statistical significance (p=0.066). Adjustment for insulin therapy, age, and prepregnancy BMI showed group 2 with higher leptin/adiponectin ratios but no difference between group 1 and the control group.
Overall, this trial showed that despite better management of glucose, there is no difference in offspring in regards to gestational size and in any of the secondary outcomes measured either. Women who had greater difficulty managing their glucose levels had higher leptin/adiponectin ratios in the cord blood. The significance on offspring is unknown. Future research can investigate long-term developments linked to cord leptin concentration.
- Better management of glucose levels shows no advantage among women who have gestational diabetes.
- Higher leptin/adiponectin ratios were higher among women with who had higher glucose levels, but further research is needed to see what effect that will have on offspring.
- Current recommendations by ADA for fasting and postprandial glucose levels are less strict than the study’s tighter glucose-controlled group and therefore, according to this trial, are within appropriate levels.
Popova, L. Vasilyeva, A. Tkachuck, et al., “A Randomised, Controlled Study of Different Glycaemic Targets during Gestational Diabetes Treatment: Effect on the Level of Adipokines in Cord Blood and ANGPTL4 Expression in Human Umbilical Vein Endothelial Cells,” International Journal of Endocrinology (2018) Article ID 6481658, 8 pages. https://doi.org/10.1155/2018/6481658.
Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy