Pregnancy outcome in immigrant women with gestational diabetes mellitus.

Recent studies show adverse outcomes of pregnancy among immigrant women from countries with high diabetes rates. We compared maternal and fetal outcomes in immigrant and Italian women with gestational diabetes mellitus (GDM) followed up at our center. Maternal characteristics considered were age, pre-pregnancy body mass index (BMI), HbA1c, frequency of insulin treatment, timing and mode of delivery, and hypertensive disorders; and, for fetal outcome, infants large or small for gestational age, and fetal complications. Pre-pregnancy BMI and HbA1c were higher in immigrant GDM women than in Italians, and more of them were on insulin. No differences in maternal outcome emerged between the two groups. More large for gestational age (LGA) babies were born to immigrant women than to Italians, but no other differences emerged. Apart from newborn LGA, maternal and fetal outcomes were comparable in our immigrant and Italian GDM women. Immigrant GDM women have favourable outcomes if given access to health care and language and cultural barriers are removed.

Multivariate analysis of matrix-assisted laser desorption/ionization mass spectrometric data related to glycoxidation products of human globins in nephropathic patients.

To clarify the possible pathogenetic role of oxidation products originated from the glycation of proteins, human globins from nephropathic patients have been studied by matrix-assisted laser desorption/ionization mass spectrometry (MALDI), revealing not only unglycated and monoglycated globins, but also a series of different species. For the last ones, structural assignments were tentatively done on the basis of observed masses and expectations for the Maillard reaction pattern. Consequently, they must be considered only propositive, and the discussion which will follow must be considered in this view. In our opinion this approach does not seem to compromise the intended diagnostic use of the data because distinctions are valid even if the assignments are uncertain. We studied nine healthy subjects and 19 nephropathic patients and processed the data obtained from the MALDI spectra using a multivariate analysis. Our results showed that multivariate analytical techniques enable differential aspects of the profile of molecular species to be identified in the blood of end stage nephropathic patients. A correct grouping can be achieved by principal component analysis (PCA) and the results suggest that several products involved in carbonyl stress exist in nephropathic patients. These compounds may have a relevant role as specific markers of the pathological state.

Off-line liquid chromatography-MALDI by with various matrices and tandem mass spectrometry for analysis of glycated human serum albumin tryptic peptides.

Advanced glycation end-product (AGE)/peptides, arising from in vivo digestion of glycated proteins, are biologically important compounds, due to their reactivity against circulating and tissue proteins. For information on their possible structure, in vitro glycation of HSA and its further enzymatic digestion were performed. The resulting digestion product mixture was analysed directly by MALDI MS with various matrices [2,5-dihydroxy benzoic acid (DHB) and alpha-cyano-4-hydroxy cinnamic acid (CHCA)]. Alternatively, offline microbore LC prior to MALDI analysis was used, and showed that 63% of the free amino groups prone to glycation are modified, indicating the contemporary presence of unglycated peptides. This result proves that, regardless of the high glucose concentration employed for HSA incubation, glycation does not go to completion. Further studies showed that the collisionally activated decomposition of singly charged glycated peptides leads to specific fragmentation pathways, all related to the condensed glucose molecule. These unique product ions can be used as effective markers to establish the presence of a glucose molecule within a peptide ion.

The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic-based survey.

OBJECTIVE: We aimed at assessing the degree of association and the predictive power of the metabolic syndrome with regard to clinically detectable complications in patients with diabetes. RESEARCH DESIGN AND METHODS: Metascreen is a cross-sectional survey of metabolic syndrome and clinically detected diabetes complications performed in 8,497 patients (7,859 with type 2 diabetes and 638 with type 1 diabetes) randomly chosen in 176 diabetes outpatient clinics throughout Italy. The metabolic syndrome was defined according to either the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) or the International Diabetes Federation (IDF) diagnostic criteria. Multivariate analyses of the association(s) between either AHA/NHLBI or IDF metabolic syndrome and clinical complications were performed. Receiver-operator characteristic (ROC) curves were constructed to compare the predictive power of the two sets of diagnostic criteria of the metabolic syndrome. RESULTS: Either definition of the metabolic syndrome was an independent statistical indicator of the presence of nephropathy and neuropathy (P < 0.02-0.01) in type 1 diabetes and of all complications (P < 0.0001), including cardiovascular disease and retinopathy, in type 2 diabetes. For each complication, the ROC curves based on either AHA/NHLBI or IDF metabolic syndrome were similar to each other and to the ROC curves constructed with all continuous traits compounding the metabolic syndrome. CONCLUSIONS: The metabolic syndrome, defined according to AHA/NHLBI or IDF diagnostic criteria, is an independent clinical indicator and may be involved in the pathogenesis of both macro- and microvascular complications of diabetes.

Polymorphisms of insulin receptor substrate 1 and beta3-adrenergic receptor genes in gestational diabetes and normal pregnancy.

Gestational diabetes mellitus (GDM) is considered an important risk factor for the development of type 2 diabetes mellitus. We studied possible relations between GDM and both insulin receptor substrate 1 (IRS-1) (Gly972Arg) and beta3-adrenergic receptor (ADRB3 Trp64Arg, beta3-AR) gene mutations, considered potential modifying factors in the etiology of type 2 diabetes mellitus. We evaluated the 2 gene mutations in late gestation in 627 pregnant women, all studied using the glucose challenge test, followed (in positive tests) by the oral glucose tolerance test (100 g, Carpenter and Coustan [J Obstet Gynecol. 1982;144:768-773] criteria) We diagnosed 309 women with GDM, 41 with gestational impaired glucose tolerance and 277 normal pregnant women. Age, family history of diabetes, prepregnancy body mass index, weight gain during pregnancy, plasma glucose levels, hemoglobin A1c, islet autoantibody levels, and insulin treatment during pregnancy were all evaluated. All pregnant women were genotyped for IRS-1 (Gly972Arg) and beta3-AR (ADRB3 Trp64Arg) polymorphisms. The frequency of IRS-1 gene polymorphism was significantly higher in women with GDM than in women with a normal glucose tolerance (NGT) (P = .039), and there was a significant trend (P = .032) in the increasing frequency of mutant allele Arg from NGT > gestational impaired glucose tolerance > GDM. The search for beta3-AR gene polymorphism showed no significant differences between women with GDM and women with NGT. The X-Arg genotype of IRS-1 was significantly associated with a positive family history of diabetes in NGT (P = .006) and neared significance in GDM (P = .057). Moreover, we found that NGT carriers of both polymorphisms had a higher prepregnancy body mass index than carriers of the IRS-1 variant alone (P = .0034), the beta3-AR variant alone (P = .039), or neither (P = .048), suggesting a possible synergistic effect of the 2 gene polymorphisms. These results suggest that the IRS-1 genetic polymorphism is involved in the occurrence of gestational diabetes, as well as type 2 diabetes mellitus.

Comprehensive analysis of glycated human serum albumin tryptic peptides by off-line liquid chromatography followed by MALDI analysis on a time-of-flight/curved field reflectron tandem mass spectrometer.

Glycated peptides arising from in vivo digestion of glycated proteins, usually called advanced glycation end (AGE) product peptides, are biologically relevant compounds due to their reactivity towards circulating and tissue proteins. To investigate their structures, in vitro glycation of human serum albumin (HSA) has been performed and followed by enzymatic digestion. Using different MALDI based approaches the digestion products obtained have been compared with those arising from enzymatic digestion of the protein. Results obtained using 2,5-dihydroxybenzoic acid (DHB) indicate this as the most effective matrix, leading to an increase in the coverage of the glycated protein. Off-line microbore liquid chromatography prior to MALDI analysis reveals that 63% of the free amino groups amenable to glycation are modified. In addition, the same approach shows the co-presence of underivatised peptides. This indicates that, regardless of the high glucose concentration employed for HSA incubation, glycation does not go to completion. Tandem mass spectrometric data suggest that the collision induced dissociation of singly charged glycated peptides leads to specific fragmentation pathways related to the condensed glucose molecule. The specific neutral losses derived from the activated glycated peptides can be used as signature for establishing the occurrence of glycation processes.

Autoantibodies against oxidized LDLs and atherosclerosis in type 2 diabetes.

OBJECTIVE: The aim of our study was to examine, in type 2 diabetic patients, the relationship between autoantibodies against oxidatively modified LDL (oxLDL Ab) and two indexes of atherosclerosis, intimal-medial thickness of the common carotid artery (CCA-IMT), which reflects early atherosclerosis, and the ankle-brachial index (ABI), which reflects advanced atherosclerosis. RESEARCH DESIGN AND METHODS: Thirty newly diagnosed type 2 diabetic patients, 30 type 2 diabetic patients with long duration of disease, and 56 control subjects were studied. To detect oxLDL Ab, the ImmunoLisa Anti-oxLDL Antibody ELISA was used. ABI was estimated at rest by strain-gauge plethysmography. Carotid B-mode imaging was performed on a high-resolution imaging system (ATL HDI 5000). RESULTS: In patients with long duration of disease, IgG oxLDL Ab were significantly higher and ABI significantly lower compared with the other two groups. We found a correlation between IgG oxLDL Ab and CCA-IMT in all diabetic patients. A significant inverse correlation between IgG oxLDL Ab and ABI only in patients with long duration of disease was seen, demonstrating a close relationship between these autoantibodies and advanced atherosclerosis. CONCLUSIONS: IgG OxLDL Ab may be markers of the advanced phase of the atherosclerotic process and the response of the immunological system to the oxLDL, which are present within atherosclerotic lesions.

Importance of measuring products of non-enzymatic glycation of proteins.

Non-enzymatic glycation products are a complex and heterogeneous group of compounds which accumulate in plasma and tissues in diabetes and renal failure. There is emerging evidence that these compounds may play a role in the pathogenesis of chronic complications associated with diabetes and renal failure. So measurement of the products of non-enzymatic glycation has a twofold meaning: on one hand, measurement of early glycation products can estimate the extent of exposure to glucose and the subject's previous metabolic control; on the other hand, measurement of intermediate and late products of the glycation reaction is a precious instrument in verifying the relationship between glycation products and tissue modifications. This review summarizes current knowledge about the diagnostic utility of measuring non-enzymatic glycation products.

Glyco-oxidation in diabetes and related diseases.

BACKGROUND: Recent evidence has shown that hyperglycemia is able to cause increased production of superoxide on the mitochondrial transport chain, and that this is the key event which activates some events such as increased AGE formation, increased hexosamine and polyol flux, and activation of PKC, all believed to be important for the development of the chronic complications of diabetes, aging and uremia. In this context, non-enzymatic protein glyco-oxidation leads to the formation of a series of products whose intra- and extra-cellular accumulation is of key importance in the pathogenesis of these chronic diseases. METHODS: Various spectrometric approaches, such as matrix-assisted laser desorption ionisation (MALDI), and liquid chromatography-electrospray ionisation (ESI) were used. RESULTS AND CONCLUSIONS: The latest mass spectrometric approaches have shown their power in proteomics, and we report here some applications of this technique in the study of in vitro and in vivo non-enzymatic protein glyco-oxidation.

Peripheral artery disease in type 2 diabetes: the role of fibrinolysis.

The aim of the present study is to verify the relationship between peripheral artery disease (PAD) and some coagulation/fibrinolysis parameters in type 2 diabetic patients. Sixty-three type 2 diabetic patients, without PAD, were studied at baseline and after 4 years. Assessments included tissue-Plasminogen Activator (t-PA), Plasminogen Activator Inhibitor-1 antigen (PAI-1 Ag), Plasminogen Activator Inhibitor-1 activity (PAI-1 Act), Plasminogen (Pl), Fibrin peptide A (FPA), Fibrinogen (Fr), and the ankle/brachial pressure index (ABI). We observed a significant difference between diabetic patients and controls as regards tPA (11.8 +/- 5.4 vs. 6.6 +/- 3.0 ng/ml; p <0.05) and PAI-1 Act (17.8 +/- 9.2 vs. 11.7 +/- 6.6 ng/dl; p <0.005). After 4 years 13 diabetic patients became vasculopathic and, at baseline, had significantly lower tPA (8.9 +/- 4.8 vs. 12.5 +/- 5.3; p <0.011), and higher PAI-1 Ag (50.8 +/- 22.2 vs. 32 +/- 22.2; p <0.006), and PAI-1 Act values (24.1 +/- 9.5 vs. 16.1 +/- 8.4; p <0.014), compared with 50 diabetic patients who did not develop PAD after 4 years. These data show that the physiological equilibrium which exists between t-PA and PAI-1 moves towards higher levels in our diabetic patients compared with controls, at baseline, whereas diabetic patients who developed PAD showed a shift towards an antifibrinolytic pathway with diminished t-PA, increased PAI-1 Ag and PAI-1 Act and consequently procoagulant activity. Our study suggests that hypofibrinolysis may be involved in the future onset of PAD in type 2 diabetic patients.

Enzymatic digestion and mass spectrometry in the study of advanced glycation end products/peptides.

An extensive study was carried out on HSA and non-enzymatically glycated HSA by enzymatic digestion with trypsin and endoproteinase Lys-C, with the aim of identifying specific glycated peptides deriving from enzymatic digestion of glycated HSA. They may be considered, in pectore, as advanced glycation end products/peptides. These compounds, important at a systemic level in diabetic and nephropathic subjects, are produced by enzymatic digestion of in vivo glycated proteins: They are related to the pathological state of patients and have been invoked as responsible for tissue modifications. The digested mixtures obtained by the two enzymes were analyzed by MALDI/MS and LC/ESI/MSn, and clear cut differences were found. First of all, the digestion products of glycated HSA are generally less abundant than those observed in the case of unglycated HSA, accounting for the lower proclivity of the former to enzymatic digestion. MS/MS experiments on doubly charged ions, comparisons with a protein database, and molecular modeling to identify the lysine NH2 groups most exposed to glycation, identified some glycated peptides in digestion mixtures obtained from both types of enzymatic digestion. Residues 233K, 276K, 378K, 545K, and 525K seem to be privileged glycation sites, in agreement with the fractional solvent accessible surface values calculated by molecular modeling.

Accurate mass measurements by Fourier transform mass spectrometry in the study of advanced glycation end products/peptides.

The Maillard reaction occurring between sugars and amino groups is important in living systems. When amino groups belonging to protein chains are involved, the Maillard reaction has been invoked as responsible for protein cross-linking and the production of 'toxic' compounds. The reaction leads to the production of a heterogeneous group of substances, usually called advanced glycation end products (AGEs). Classical analytical approaches, such as spectroscopic (ultraviolet, fluorescence) and mass spectrometric (matrix-assisted laser desorption/ionization, liquid chromatography/electrospray ionization mass spectrometry) methods, have shown that the digestion mixture is highly complex. However, there are clear differences between the digestion mixtures of glycated and unglycated human serum albumin (HSA). In the former case, possible glycated peptides belonging to the AGE peptide class may be identified. Tandem mass spectrometric experiments on selected species seemed to be promising as regards structural information, but it was thought of interest to undertake the present investigation, based on liquid chromatography/electrospray ionization Fourier transform mass spectrometry, in order to obtain definitive results on their elemental composition. Using this approach, about 20 glycated peptides were detected and their possible structures were postulated by examining the known sequence of HSA.

Effect of protein leaking BK-F PMMA-based hemodialysis on plasma pentosidine levels.

BACKGROUND: Advanced glycation end-products (AGEs) are now considered to contribute to the middle molecule toxicity of uremia and, because they are not cleared by conventional low-flux hemodialysis, alternative strategies are needed to improve their removal. METHODS: In a prospective cross-over trial involving 18 adult chronic hemodialysis subjects, we evaluated the intradialytic removal and the long-term effect on predialysis levels of Protein-bound (PBPe) and Free (FPe) pentosidine by high-pore, protein-leaking BK-F Polymethylmethacrylate-based hemodialysis (BK-F-HD), by comparing it to hemodialysis using low-flux dialyzers (LF-HD). RESULTS: A single BK-F-HD session removed more PBPe, but not FPe, than LF-HD. Long-term BK-F-HD was associated with a significant decrease in pre-dialysis PBPe, FPe, and albumin (17.7 +/- 20.8, 25.3 +/- 17.3 and 8.0 +/- 3.3%, p<0.01) and no change in body mass index and protein catabolic rate, compared to LF-HD. Multiple stepwise regression analysis identified C-reactive Protein (CRP) (standardized beta coefficient=-0.629), pre-dialysis levels in LF-HD (beta=0.452) and dialysis vintage (beta=0.428) as significant determinants of BK-F-induced changes in predialysis PBPe, and predialysis FPe and PBPe levels in LF-HD as significant determinants of BK-F-induced changes in predialysis FPe (beta=0.720 and 0.286, respectively). CONCLUSIONS: Our study shows that long-term standard diffusive hemodialysis with BK-F membrane reduces predialysis PBPe and FPe levels by comparison with LF-HD, largely due to a greater intradialytic clearance of PBPe. Serum albumin is also reduced without any associated changes in nutritional status markers. The study also suggests that the effect of BK-F-HD in lowering PBPe levels is modulated by the body burden of pentosidine and is blunted or even lost in the presence of elevated CRP levels.

Advanced glycation end-products/peptides: a preliminary investigation by LC and LC/MS.

An investigation on AGE-peptides, originating by proteolysis of in vitro glycated proteins, was carried out by LC methods with different detection applied to the mixture produced by proteinase K digestion of in vitro glycated human serum albumin (HSA). Classical approaches, like spectroscopic (UV, fluorescence) and mass spectrometric methods (MALDI, LC/ESI/MS), show that the digestion mixture is highly complex. However, there are clearcut differences between the digestion mixtures of glycated and unglycated HSA, in the former case allowing identification of possible glycated peptides belonging to the AGE-peptide class. MS/ MS experiments on selected species seem to be promising as regards structural information.

Role of endogenous secretory RAGE (esRAGE) in defending against plaque formation induced by oxidative stress in type 2 diabetic patients.

OBJECTIVES: This study was conducted to examine the relationship between endogenous secretory receptors for advanced glycation end products (esRAGE) and oxidative stress in type 2 diabetic patients (T2DM) with/without advanced macro-angiopathy. METHODS: Sixty-one T2DM were assessed for glycemic control, lipid profile, AGEs, carboxymethyl-lysine (CML), soluble receptor for advanced glycation end products (sRAGE), esRAGE and vitamin E levels, and underwent echo-color-Doppler of the abdominal aorta and aorto-iliac tree, carotid and lower limb arteries to check for evidence of plaques. RESULTS: AGEs and CML levels were significantly higher in T2DM with plaques than in those without (P = 0.0156 and P = 0.007, respectively) despite a comparable metabolic control and history of disease. EsRAGE and vitamin E levels were lower in T2DM with than in those without plaques (P < 0.0001), while no differences were observed as regards sRAGE levels. Considering all T2DM, univariate regression analysis showed a positive correlation between esRAGE and vitamin E (r = 0.456, P < 0.001), and a negative correlation between esRAGE and AGEs (r = -0.284, P < 0.05). After dividing patients by the presence/absence of plaques, esRAGE only correlated directly with vitamin E (r = 0.563, P < 0.01) and CML (r = 0.479, P < 0.05) in patients without plaques. CONCLUSIONS: This is the first study to establish a relationship between esRAGE and oxidative stress and/or antioxidant power, suggesting that esRAGE upregulation might be part of the cell's antioxidative defenses against plaque forming as a result of oxidative stress in the T2DM phenotype (cases with a more efficient esRAGE production being better protected).

Subclinical diastolic dysfunction in type 2 diabetic patients with and without carotid atherosclerosis: relationship with glyco-oxidation, lipid-oxidation and antioxidant status.

OBJECTIVES: The aim of this study was to evaluate subclinical diastolic dysfunction in type 2 diabetic patients and its relationship with glyco-oxidation, lipo-oxidation and antioxidant capacity in the presence or absence of carotid plaques. BACKGROUND: Subclinical diastolic dysfunction is the early stage of diabetic cardiomyopathy, the pathogenic mechanisms of which are still little known. In particular, few data are available on the role of glyco-oxidation, lipo-oxidation and antioxidant status, factors known to be involved in the atherosclerotic process. METHODS: We assessed myocardial systolic and diastolic functions in 57 consecutive asymptomatic type 2 diabetic patients (24 patients with no carotid plaques; 33 with plaques) and 27 healthy volunteers using transthoracic echocardiography. Glyco-oxidation and lipo-oxidation parameters and antioxidant status were also evaluated in fasting venous blood samples. RESULTS: Systolic function was similar between diabetic patients and controls, while most of the diastolic parameters (A, e', E/A, E/e') differed significantly between diabetics and controls, being worse in the former. Among the diastolic parameters, only the peak late diastolic velocity A differed significantly between the two groups of diabetic patients with no carotid plaques and with plaques (0.72 ± 0.16 m/s vs 0.84 ± 0.25 m/s, p<0.05). The diastolic parameters A and E/e' related to glycemic control, glyco-oxidation and antioxidant capacity, and to LDL size and density. CONCLUSIONS: Glyco-oxidation and antioxidant status, combined with the presence of small, dense LDL correlate with subclinical diastolic dysfunction in type 2 diabetic patients. Atherosclerotic lesions are associated with an altered atrial function.

The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM).

Glucose variability has recently been investigated in diabetic patients in several studies, but most of them considered only a few variability indicators and did not systematically correlate them with patients' HbA1c levels and other important characteristics. In thus study, the correlations between HbA1c levels and metabolic control (average glucose, AG), glucose variability (SD, CONGA, MAGE, MODD, BG ROC), hyperglycemia (HBGI), hypoglycemia (LBGI) and postprandial (AUC PP) indices were investigated in patients with type 1 and type 2 diabetes. The study involved 68 patients divided into 3 groups as follows: 35 patients had type 1 diabetes (group 1); 17 had type 2 diabetes and were taking multiple daily injections (MDI) of insulin (group 2); and 16 patients had type 2 diabetes treated with OHA and/or basal insulin (group 3). The indicators were obtained over at least 48 h using a continuous glucose monitoring (CGM) system. HbA1c levels were measured at the baseline and after CGM. HbA1c correlated significantly with AG (r = 0.74), AUC PP (r = 0.69) and HBGI (r = 0.74), but only in type 1 diabetic patients. Patients with longstanding disease and type 1 diabetes had a greater glucose variability, irrespective of their HbA1c levels. Insulin therapy with MDI correlated strongly with HbA1c, but not with glucose variability. HbA1c levels identify states of sustained hyperglycemia and seem to be unaffected by hypoglycemic episodes or short-lived glucose spikes, consequently revealing shortcomings as a "gold standard" indicator of metabolic control. Glucose variability indicators describe the glucose profile of type 1 diabetic patients and identify any worsening glycemic control (typical of longstanding diabetes) more accurately than HbA1c tests.

Pregnancy complicated by diabetes: what is the best level of HbA1c for conception?

To reduce the congenital malformations that occur in pregnancies complicated by diabetes, it is essential to achieve and maintain a good metabolic control before conception. In this context, measuring HbA1c is considered as the gold standard for monitoring metabolic control in diabetes and various different HbA1c levels have been recommended as optimal in the preconception period for diabetic women planning a pregnancy. An analysis of key studies published on this issue until now clearly shows that HbA1c levels correlate closely with the occurrence of congenital malformations and other neonatal complications characteristic of pregnant diabetic women. HbA1c is therefore one of the key markers to use in monitoring metabolic control, and the most reasonable approach would seem to be to use a standardized measurement method and aim for HbA1c levels resembling normal values as closely as possible, with a view to preventing episodes of hypoglycemia.

Pregnancy outcome in morbidly obese women before and after laparoscopic gastric banding.

BACKGROUND: Increasing numbers of pregnancies are seen in obese women treated surgically with laparoscopic adjustable gastric banding (LAGB). We compared their maternal and fetal outcomes with obese women without LAGB and normal-weight controls. METHODS: Sixty-nine obese women with LAGB (83 pregnancies) were compared with 120 obese women without LAGB and 858 controls. RESULTS: By comparison with normal controls, post-LAGB pregnancies had higher rates of gestational hypertension (9.6% vs 2.4%, p < 0.05), preeclampsia/eclampsia (12.0% vs 2.3%, p < 0.001), abortion (10.8% vs 0.3%, p < 0.001), cesarean section (45.9% vs 28.2%, p < 0.01), preterm delivery (17.6% vs 3.6%, p < 0.001), and babies needing neonatal intensive care (20.3% vs 9.0%, p < 0.01). Compared with the no-LAGB obese group, the post-LAGB pregnancies had lower rates of gestational hypertension (9.6% vs 23.5%, p < 0.05), preeclampsia/eclampsia (12.0% vs 20.8%, p < 0.05), and cesarean section (45.9% vs 65.8%, p < 0.01). The post-LAGB obese women gained less weight during the pregnancy (6.6 +/- 7.9 vs 14.8 +/- 10.1 kg, p < 0.001) and experienced less gestational hypertension (14.8% vs 33%), preeclampsia/eclampsia (7.4% vs 14.8%), and macrosomia (4.2% vs 16%) than in pregnancies before LAGB. No significant differences in maternal and fetal outcomes emerged between post-LAGB pregnant women who lost versus those who gained weight during pregnancy. Compared with those no longer morbidly obese, women still morbidly obese after LAGB had a lower weight gain (2.8 +/- 11.8 vs 8.6 +/- 9.5 kg, p < 0.05) and a higher gestational hypertension rate (29.4% vs 8.9%, p < 0.05). CONCLUSION: The risks of negative maternal and fetal outcomes for obese women can be reduced by LAGB if the women are closely followed up.

Management of gestational diabetes mellitus.

The incidence of gestational diabetes mellitus (GDM) is on the increase and, if not diagnosed, managed and treated adequately, can have unfavorable maternal and fetal outcomes. Several studies have shown that glycemic values considered as adequate in the past when monitoring GDM failed to contain these adverse outcomes and randomized trials are needed to ascertain whether these targets should be lowered. Dietary restrictions remain the mainstay of GDM management and suitable physical exercise can help too. The use of rapid-acting insulin analogues (lispro and aspart) are novel treatments for improving metabolic control by reducing postprandial glycemia, while long-acting insulin analogues need to be evaluated by further studies for safety in clinical use before they can be prescribed. Numerous studies have found glyburide and metformin safe in women with GDM but more randomized controlled trials are needed, with a long-term follow-up of mother and child, to confirm these results.