Gestational diabetes and pre-pregnancy overweight: possible factors involved in newborn macrosomia.

AIM: Good glycemic control in gestational diabetes mellitus (GDM) seems not to be enough to prevent macrosomia (large-for-gestational-age newborns). In GDM pregnancies we studied the effects of glycemic control (as glycosylated hemoglobin [HbA1c]), pre-pregnancy body mass index (PP-BMI) and gestational weight gain per week (GWG-W) on the frequency of macrosomia. METHODS: We studied 251 GDM pregnancies, divided into two groups: PP-BMI<25.0kg/m(2) (the non-overweight group; n=125), and PP-BMI≥25.0kg/m(2) (the overweight group; n=126). A newborn weight Z-score>1.28 was considered large-for-gestational-age. Statistical analysis was carried out using the Student's t-test and χ(2) -test, receiver-operator characteristic curves and linear and binary logistic regressions. RESULTS: Prevalence of macrosomia was 14.9% among GDM (n=202/251, 88.4%) with good glycemic control (mean HbA1c<6.0%), and 28.1% in those with mean HbA1c≥6.0% (n=49/251, P<0.025). Macrosomia rates were 10.4% in the non-overweight group and 24.6% in the overweight group (P=0.00308), notwithstanding both having similar mean HbA1c (5.48±0.065 and 5.65±0.079%, P=0.269), and similar GWG-W (0.292±0.017 and 0.240±0.021kg/week, P=0.077). Binary logistic regressions showed that PP-BMI (P=0.012) and mean HbA1c (P=0.048), but not GWG-W (P=0.477), explained macrosomia. CONCLUSIONS: Good glycemic control in GDM patients was not enough to reduce macrosomia to acceptable limits (<10% of newborns). PP-BMI and mean HbA1c (but not GWG-W) were significant predictors of macrosomia. Thus, without ceasing in our efforts to improve glycemic control during GDM pregnancies, patients with overweight/obesity need to be treated prior to becoming pregnant.

[Role of peripheral serotonin in the insulin secretion and glucose homeostasis]. / Papel de la serotonina periférica en la secreción de insulina y la homeostasis de la glucosa.

The most studied roles of serotonin (5-hydroxytryptamine, 5HT) have been related to its action in the Central Nervous System (CNS). However, most of 5HT is produced outside the CNS, mainly in the enterochromaffin cells of the gut. Additionally, other tissues such as the endocrine pancreas, particularly ß-cells, have its own serotonin system able to synthesize, secrete and respond to extracellular 5HT through cell surface receptors subtypes that have been grouped in 7 families (HTR1-7). Interestingly, 5HT is stored in granules and released together with insulin from ß-cells and its biological significance is likely a combination of intra and extracellular actions. The expression of enzymes involved in 5HT synthesis and their receptors varied markedly in ß-pancreatic cells during pregnancy, in parallel with an increase in their insulin secretion potential (probably through the action of Htr3a) and an increase in ß-cell mass (through the action of Htr2b and Htr1d). In addition, it has been suggested that gut-derived 5HT may promote hepatic gluconeogenesis during prolonged fasting through Htr2b receptor. Taken together, these findings suggest that peripheral 5HT plays an important role in the regulation of glucose homeostasis through the differential expression and activation of 5-HT membrane receptors on the surface of hepatocytes, adipocytes and pancreatic ß-cells.

La función más conocida de la serotonina (5-Hidroxitriptamina, 5HT) se refiere a su acción en el Sistema Nervioso Central (SNC). Sin embargo, la mayoría de la 5HT corporal se genera periféricamente, principalmente en las células enterocromafines del intestino. Se ha descrito que la célula -pancreática posee un sistema serotoninérgico propio que le permite sintetizar, almacenar, secretar y responder a la 5HT extracelular a través de sus receptores, de los que se conocen numerosos subtipos agrupados en 7 familias (Htr1-7). Interesantemente, la 5HT se libera conjuntamente con la insulina y sólo recientemente se ha descifrado parte de su significado biológico, que incluiría una compleja combinación de efectos intra y extracelulares que eventualmente podrían jugar un papel en la regulación de la secreción de esta hormona. De forma fisiológica, la expresión de las enzimas involucradas en la síntesis de 5HT y de sus receptores se modifica marcadamente en células durante la gestación, en coincidencia con un incremento en el potencial secretor de insulina (vía la acción del receptor ionotrópico Htr3a) y un aumento en la masa de células (vía la acción de receptores Htr1d y Htr2b). En otros tejidos, se ha sugerido que la 5HT procedente del intestino promueve la gluconeogénesis hepática y la lipólisis en adipocitos durante el ayuno, por medio de su acción sobre el receptor Htr2b. En conjunto, estos hallazgos sugieren que la 5HT periférica podría tener un rol importante en la homeostasis de la glucosa por medio de la expresión y activación diferencial de receptores de superficie en células clave, tales como hepatocitos, adipocitos y células -pancreáticas.