L Volpe

Intermediate metabolism in normal pregnancy and in gestational diabetes

Complex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow‐up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined. Copyright

Maternal triglyceride levels and newborn weight in pregnant women with normal glucose tolerance

Objective  To determine the predictive value of serum triglyceride levels (TG) for neonatal weight in pregnant women with positive diabetic screening but normal glucose tolerance.

Triglyceride metabolism in pregnancy.

During pregnancy, complex changes occur in lipid profiles. From the 12th week of gestation, phospholipids, cholesterol (total, LDL, HDL), and triglycerides (TG) increase in response to estrogen stimulation and insulin resistance. Transition to a catabolic state favors maternal tissue lipid use as energy sources, thus sparing glucose and amino acids for the fetus. In addition, maternal lipids, that is, cholesterol, are available for fetal use in building cell membranes and as precursor of bile acids and steroid hormones. It is also required for cell proliferation and development of the growing body. Free-fatty acids (FFA), oxidized in the maternal liver as ketone-bodies, represent an alternative fuel for the fetus. Maternal hypertriglyceridemia (vs. other lipids) has many positive effects such as contributing to fetal growth and development and serving as an energy depot for maternal dietary fatty acids. However, increased TG during pregnancy appears to increase risk of preeclampsia and preterm birth. Some have suggested that maternal hypertriglyceridemia has a role in increasing cardiovascular risk later in life. This chapter reviews lipid metabolism during pregnancy to elucidate its effect on fetal growth and its potential role in pregnancy-associated complications and future cardiovascular risk.

C-reactive protein and metabolic syndrome in women with previous gestational diabetes.

This study evaluates the presence of metabolic syndrome (MS) and its association with C‐reactive protein (CRP) and other cardiovascular (CV) risk factors, in a sample of women with and without previous Gestational Diabetes (pGDM).

Normal Glucose Tolerance and Gestational Diabetes Mellitus What is in between

OBJECTIVE— The aim of this article was to define the metabolic phenotype of pregnant women with one abnormal value (OAV) during an oral glucose tolerance test (OGTT) and to test whether OAV could be considered metabolically comparable to gestational diabetes mellitus (GDM) or a specific entity between GDM and normal pregnancy. RESEARCH DESIGN AND METHODS— After 100-g 3-h OGTTs, 4,053 pregnant women were classified as having GDM, OAV, or normal glucose tolerance (NGT). Those with OAV were subdivided into three subgroups: fasting hyperglycemia (one abnormal value at fasting during an OGTT), 1-h hyperglycemia (one abnormal value at 1 h during an OGTT [1h-OAV]), or 2- or 3-h hyperglycemia (one abnormal value at 2 or 3 h during an OGTT). As derived from the OGTT, we measured insulin sensitivity (insulin sensitivity index [ISI] Matsuda) and insulin secretion (homeostasis model assessment for the estimation of β-cell secretion [HOMA-B], first- and second-phase insulin secretion). The product of the first-phase index and the ISI was calculated to obtain the insulin secretion–sensitivity index (ISSI). RESULTS— GDM was diagnosed in 17.9% and OAV in 18.7% of pregnant women; women with GDM and OAV were older and had higher BMI and serum triglyceride levels than those with NGT (all P < 0.05). Women with NGT had the highest ISI followed by those with OAV (−21.7%) and GDM (−32.1%). HOMA-B results were comparable with those for OAV and GDM but significantly (P < 0.01) lower than those for NGT; first- and second-phase insulin secretion appeared progressively reduced from that in women with NGT to that in women with OAV and GDM (P < 0.01). ISSI was higher in women with NGT than in women with either OAV (−34%) or GDM (−51.7%) (P < 0.001). Among OAV subgroups, the 1h-OAV subgroup showed the lowest ISSI (P < 0.05). CONCLUSIONS— OAV and GDM are clinically indistinguishable, and both groups are different from women with NGT. Women with GDM and OAV showed impaired insulin secretion and insulin sensitivity, although these defects are more pronounced in women with GDM. Compared with other OAV subgroups, 1h-OAV could be considered a more severe condition.

Maternal Metabolic Control and Perinatal Outcome in Women With Gestational Diabetes Mellitus Treated With Lispro or Aspart Insulin Comparison with regular insulin

Gestational diabetes mellitus (GDM) is associated with increased risk of maternal and neonatal morbidity with macrosomia being the most common neonatal complication (1). The risk of macrosomia and/or disproportionate fetal growth is closely related to 1-h postprandial glucose concentration (2). Therefore, the treatment of GDM should be aimed at normalizing maternal glycemia including the early postprandial response. Insulin therapy is needed whenever strict normoglycemia cannot be achieved by medical nutritional therapy alone (3). Because of their pharmacokinetic properties, short-acting insulin analogs (Insulin Aspart [ASP] and Insulin Lispro [LIS]) could be more effective in pregnancy than human regular insulin (HI) (4). Nevertheless, data …

Early Subclinical Atherosclerosis in Women With Previous Gestational Diabetes Mellitus

To determine if women with previous gestational diabetes mellitus (pGDM), a population at high risk for type 2 diabetes and metabolic syndrome (1), have signs of subclinical atherosclerosis, we measured carotid intimal-medial thickness (IMT) and multiple cardiovascular risk factors in 28 women with and 24 without pGDM (control group) 2 years after delivery. A 75-g 2-h oral glucose tolerance test was performed for assessment of glucose tolerance, area under the glucose curve (AUCgluc), insulin sensitivity index, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, oxidized LDL (oxLDL), C-reactive protein (CRP), adiponectin, and fibrinogen. Family history, anthropometric parameters, and blood pressure were recorded. IMT was measured at four segments of …

Universal screening and intensive metabolic management of gestational diabetes: cost-effectiveness in Italy

Abstract This study retrospectively evaluated two groups of pregnant women. Group A women (n=1338) were universally screened for gestational diabetes mellitus (GDM) and GDM patients were intensively treated. In Group B (n=4035), screening was performed only in women at high risk for GDM and treatment was conventional. This study confirms the validity of a cost-effective screening program for the diagnosis of GDM and that selective screening may be an option only in a situation where healthcare resources are very scarce and/or universal screening of any kind is not feasible. Once the diagnosis of GDM has been made, metabolic management with an intensive approach is important to reduce maternal and fetal morbidity. Diagnosis of GDM and intensive treatment represent a cost for the public health system, but permit a significant monetary savings in terms of costs linked to maternal and neonatal morbidity.

Continuous subcutaneous insulin infusion and multiple dose insulin injections in Type 1 diabetic pregnant women: a case-control study

The aim of this study was to evaluate the effects of continuous subcutaneous insulin infusion (CSII) on glycemic control and pregnancy outcomes in Type 1 diabetic pregnant women. We retrospectively evaluated 42 subjects, 20 treated with CSII and 22 with multiple dose insulin injections (MDI). The two groups were comparable for age, pre-pregnancy BMI, and primiparous rate, whereas women in the CSII group showed a tendency toward a longer diabetes duration (p = 0.06). Pre-pregnancy diabetic retinopathy and/or nephropathy were present in nine women of CSII and three of MDI. In all women metabolic control improved during pregnancy, without differences between the two groups and at the end of gestation HbA1c was 6.3 ± 0.6 in CSII and 6.1 ± 1.1% in MDI. Moreover, there were no differences in weight gain, whereas insulin requirement resulted significantly (p = 0.009) lower in CSII than in MDI. We recorded only one severe hypoglycaemic episode in both groups. No cases of deteriorations of the chronic diabetic complications were observed. The delivery occurred at 36.4 ± 2.2 weeks; birth weight, the rate of large for gestational age, and the parameters of foetal morbidity were similar in both groups. In conclusions, CSII and MDI are both effective in improving maternal glucose control and have both similar pregnancy outcomes.

Gestational diabetes, inflammation, and late vascular disease.

Physiological changes of pregnancy include insulin resistance and activation of the innate immunity with an inflammatory response. The working hypothesis is that the sub-clinical inflammation associated with excessive adiposity may favor the development of gestational diabetes (GDM) and Type 2 diabetes and other metabolic abnormalities related to cardiovascular disease later in life. In this paper we review the complex interrelationship among inflammatory markers, metabolic syndrome, and endothelium dysfunction in women with GDM and discuss if women with previous GDM (pGDM) could be considered at risk for cardiovascular diseases. MEDLINE was searched for articles relating GDM and the adipokines (tumor necrosis factor-α and adiponectin) as well as the acute-phase inflammatory biomarker C-reactive protein that contribute to the development of diabetic pregnancy and vascular complications. However, to date, in pGDM women no prospective study is available, to corroborate the hypothesis that inflammatory pattern could be taken as predictor of cardiovascular disease later in life. Therefore, our paper should provide arguments to perform follow-up programs to prevent cardiovascular events in women with pGDM. Control of body weight, regular physical exercise are indeed powerful intervention tools able at improving insulin sensitivity and reduce sub-clinical inflammation, both involved in the patoghenesis of cardiovascular disease.