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Gestational Diabetes Long-term, Metabolic Conse...

We have found interesting trends in our studies on the development of diabetes after GDM in pregnancy in Denmark over the years. In our first follow-up study, performed a median of 6 years after pregnancy, in 241 women with previous diet-treated GDM between 1978 and 1985, we found that almost 18% had developed diabetes (4% type 1 diabetes and 14% type 2 diabetes) and 17% had prediabetes (defined as impaired glucose tolerance and/or impaired fasting glucose) [8]. Some 13 years later we re-invited the same women for another follow-up study [9]. At this time, after a median of 19 years, 37% of the 151 participants had diabetes (5% type 1 diabetes, 32% type 2 diabetes), while 29% had prediabetes, meaning only a third had normal glucose tolerance. Simultaneously, we investigated a cohort of 330 women who had diet-treated GDM in the period between 1987 and 1996. Among this newer cohort, followed for a median of 7 years, 41% had diabetes (4% type 1 diabetes, 37% type 2 diabetes) and 26% had prediabetes [9]. Multivariate analysis revealed that the risk of developing diabetes in the new cohort was threefold that in the old one. The main difference between the two cohorts was that the pre-pregnancy BMI was three units (kg/m2) higher in the new cohort than in the older cohort. In accordance with other studies, we found that increasing pre-pregnancy BMI, higher fasting glucose at GDM diagnosis, early gestational age at GDM diagnosis and post-partum impaired glucose tolerance were risk factors for the subsequent development of overt diabetes. More than half of the women with type 2 diabetes were diagnosed during the course of the study, and were thus unaware of the fact that they had the disease prior to participation. Furthermore, it was found that the risk of the metabolic syndrome in women with previous GDM was over three times that in the general group, even when adjusted for age and BMI [10]. Thus, our Danish data are in accordance with other studies. A review by Bellamy et al [7] reported that in women with previous GDM the risk of developing diabetes is more than seven times that in women who had a normoglycaemic pregnancy, underlining the importance of prevention or postponement of development of diabetes and cardiovascular disease in these women. It has been estimated that GDM is the best known predictor of type 2 diabetes, and that approximately one-third of women with type 2 diabetes may have had previous GDM [11]. Thus, a large potential exists for preventing or delaying the onset of type 2 diabetes in these women. Epidemiological studies indicate that women with previous GDM who are physically active or do not gain weight after pregnancy have a reduced risk of progressing to overt diabetes [12, 13]. In accordance with this, in randomised controlled trials, lifestyle intervention and medical treatment have both been shown to decrease the number who progress to diabetes by approximately 50% in women with previous GDM [14, 15].

Gestational diabetes Long-term, metabolic conse...

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Based on an OGTT, we found that exposure to intrauterine hyperglycaemia was associated with impaired insulin sensitivity and relatively impaired insulin secretion in adulthood, both of which are characteristics of type 2 diabetes [25]. Chronic inflammation has been closely associated with type 2 diabetes and the metabolic syndrome, and we set out to investigate this as well. Levels of high-sensitivity CRP, IL-6 and YKL40 were investigated in O-GDM but no abnormalities were found [26], indicating that exposure to intrauterine hyperglycaemia does not affect the level of chronic inflammation in O-GDM. Finally, no major changes in incretin and glucagon function (during OGTT) were found in the offspring, but slightly reduced levels of glucagon-like peptide 1 in the fasting state, and reduced suppression of glucagon during OGTT may contribute to the increased risk of glucose intolerance among O-GDM [27].

GDM is associated with an increased risk of pregnancy and neonatal complications including hypertensive disorders, preterm birth, fetal macrosomia, and neonatal hypoglycemia [1]. Moreover, on the long term, women with previous GDM have a higher risk of developing adverse metabolic outcomes in comparison to women without GDM; in a recent meta-analysis, the risk of developing type 2 diabetes mellitus (T2DM) was approximately 10-fold higher for women with previous GDM compared to women without GDM [5]. Additionally, women with a history of GDM are more at risk of developing prediabetes/impaired glucose regulation [6] and the metabolic syndrome (MetS) [7]. Given these increased risks of adverse metabolic outcomes for women with previous GDM, it is recommended that these women should be regularly screened after pregnancy in order to detect impairments in glucose metabolism timely and to support them to optimize metabolic health after pregnancy [8, 9].

To evaluate the role of BMI in the long-term metabolic outcomes of women with previous GDM, the present study compared the long-term risk of T2DM, prediabetes, and the MetS and examined differences in metabolic profiles years after pregnancy between women with previous GDM and a control group of women without GDM matched on date of birth, prepregnancy BMI, and parity.

Despite similar BMI and body composition, impaired metabolic outcomes were reported for women with previous GDM compared to women without GDM; one in four women developed T2DM in comparison to none in the group without GDM, and women with previous GDM had approximately a 3-fold increased risk of developing prediabetes. The increased risk of T2DM after GDM as reported in the present study is in line with the results of a recent meta-analysis [5]. However, estimates of the relative risk for T2DM after GDM vary largely within the literature. This variation is likely to be attributable to differences in ethnicity, follow-up duration, and diagnostic criteria for GDM. Given these differences, it is difficult to evaluate the effect of adjusting for obesity-induced insulin resistance when comparing populations. Previous Danish studies of T2DM after GDM either did not include a control group [34, 35] or excluded women with insulin-treated GDM [36].

Despite similar BMI, women with previous GDM are at increased risk of developing long-term adverse metabolic outcomes and have a lower insulin sensitivity and decreased beta cell function years after pregnancy compared to women without GDM; 26% of the women with previous GDM developed T2DM compared to none in a matched control group, and women with previous GDM had approximately a 3-fold higher risk of prediabetes and the MetS. The results of this study support that beta cell dysfunction and insulin resistance contribute to these conditions. Our findings suggest that next to obesity, additional factors play a role in development of adverse metabolic outcomes after GDM. Future studies are needed to examine whether interventions to minimize the risk of adverse metabolic outcomes after GDM benefit from targeting modifiable risk factors in addition to obesity.

Although the surgery mediated weight loss has a positive effect on pregnancy outcome, the procedures might be associated with adverse outcomes as well, for example micronutrient deficiencies, iron or B12 deficiency anemia, dumping syndrome, surgical complications such as internal hernias, and small for gestational age (SGA) offspring, possibly due to maternal undernutrition. Also, there is no international consensus concerning the ideal time to conception after BS. Hence, the present narrative review intents to summarize the available literature concerning the most common challenges which arise before and during pregnancy after BS, such as fertility related considerations, vitamin and nutritional deficiencies and their adequate compensation through supplementation, altered glucose metabolism and its implications for gestational diabetes screening, the symptoms and treatment of dumping syndrome, surgical complications and the impact of BS on pregnancy outcome. The impact of different bariatric procedures on pregnancy and fetal outcome will also be discussed, as well as general considerations concerning the monitoring and management of pregnancies after BS.

Whereas BS leads to the mitigation of many obesity-related pregnancy complications, such as gestational diabetes mellitus (GDM), pregnancy induced hypertension and fetal macrosomia; those procedures pose new risks which might lead to adverse outcomes for mothers and offspring, for example nutritional deficiencies, anemia, altered maternal glucose metabolism and small for gestational age children.

A Swedish national cohort study investigated the outcomes of 670 singleton pregnancies of post-surgical women and detected that pregnant women who underwent BS have a lower risk of gestational diabetes and large for gestational age (LGA) neonates, but a higher risk of SGA infants. No significant difference in the frequency of fetal malformations was found [29].

Several other studies (Table 2) found an increased risk of SGA infants born to mothers after malabsorptive or mixed bariatric surgeries [22, 52, 100, 102, 117], but not after solely restrictive procedures [52, 99]. The pathophysiology of this phenomenon requires further elucidation, but there seems to be an association between low maternal glucose levels in glucose challenge or oral glucose tolerance tests and SGA fetuses [95, 127]. An association between lower neonatal weight, glucose nadir and increased insulin release during an OGTT was most recently observed by our study group in offspring of mothers after RYGB [104]. In addition, Gascoin et al. found a significant inverse correlation between birth weight and length and maternal weight loss between surgery and pregnancy (the greater the weight loss the lower the birth weight and length). There were also low cord blood IGF1 and Leptin levels in infants from RYGB mothers, hinting to a decreased anabolism in those infants [63]. Low birth weight seems to have detrimental effects on the offspring even in adulthood. Being born SGA is considered to be a risk factor for the development of insulin resistance and type 2 diabetes, the metabolic syndrome and cardiovascular diseases [128], possibly due to fetal programming by changes in the intrauterine environment in malnourished mothers (thrifty phenotype hypothesis) [129]. Therefore, it might even be considered to prefer restrictive over malabsorptive BS techniques in young women who have a desire to bear children to avoid those complications [52]. 041b061a72


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