Nino Cristiano Chilelli

Pregnancy and foetal outcome after bariatric surgery: a review of recent studies

It is well known that maternal obesity has adverse effects on the health of offspring, causing immediate and long-term morbidities. The various types of procedure coming under the heading of bariatric surgery have proved effective in preventing some maternal and foetal complications in morbidly obese pregnant women. This review aims to assess the role, the risks and the benefits of bariatric surgery for mothers and offspring. According to recent findings, pregnancy and neonatal outcomes in morbidly obese women who have undergone bariatric surgery depend to some extent on the type of surgery used. Maternal complications, nutritional defects and intestinal obstruction are more frequently reported after Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) than after laparoscopic adjustable gastric banding (LAGB) procedures, whereas caesarean section, preterm delivery and neonatal death are more commonly reported after RYGB than after LAGB. The authors of the only long-term follow-up study conducted on this subject reported that the rate of obesity in the children dropped by 52% after bariatric surgery for the mother, and the cases of severe obesity decreased by 45%. Data on pregnancy and bariatric surgery confirm that the procedure is more effective than dietary measures alone in morbidly obese women, and that pregnancy outcome is generally favorable after surgery. Some studies have indicated, nonetheless, that pregnancies after bariatric surgery are at higher risk: the women affected require special medical attention, particularly as concerns gastrointestinal symptoms and vitamin deficiencies, warranting nutritional/dietary counselling by a multidisciplinary team before, during and after pregnancy.

Genetic variability of the fructosamine 3-kinase gene in diabetic patients.

Abstract Background: Nonenzymatic glycation appears to be an important factor in the pathogenesis of diabetic complications. Fructosamine 3-kinase (FN3K), initially identified in erythrocytes, appears to be responsible for the removal of fructosamine from proteins, suggesting a protective role in nonenzymatic glycation. Recently, genetic variants in the FN3K gene have been studied in diabetic patients. The aim of our study was the molecular characterization of the FN3K gene in a representative group of Italian patients with type 1 (T1DM) and 2 (T2DM) diabetes mellitus and in a cohort of healthy controls. Methods: Seventy diabetic subjects (35 type 1 and 35 type 2) with stable glycemic control and 33 healthy control subjects were evaluated using PCR and direct sequencing of the FN3K gene. Denaturing high performance liquid chromatography (DHPLC) was used in controls for screening for the presence of the genetic variants previously found in diabetic patients. Results: Seven different genetic variants were identified, five of them already reported and two new: the p.R187X and p.Y239C mutations identified in two females affected by T2DM. No significant association was found between certain polymorphisms and diabetes conditions. Preliminary haplotype studies are also reported. With respect to genotypes, we noted that some were not present in all the investigated cohort, and some were found related to higher glycated hemoglobin compared to others, although not at a significant level, probably because of the small number of subjects investigated. Conclusions: In conclusion, this study identified two new mutations and additional variants within the FN3K gene. This is the first study on FN3K in Italy. Future work is needed to achieve a better understanding of the FN3K enzyme and its possible clinical utility in the management of diabetic patients.

Glucose Fluctuations during Gestation: An Additional Tool for Monitoring Pregnancy Complicated by Diabetes

Continuous glucose monitoring (CGM) gives a unique insight into magnitude and duration of daily glucose fluctuations. Limited data are available on glucose variability (GV) in pregnancy. We aimed to assess GV in healthy pregnant women and cases of type 1 diabetes mellitus or gestational diabetes (GDM) and its possible association with HbA1c. CGM was performed in 50 pregnant women (20 type 1, 20 GDM, and 10 healthy controls) in all three trimesters of pregnancy. We calculated mean amplitude of glycemic excursions (MAGE), standard deviation (SD), interquartile range (IQR), and continuous overlapping net glycemic action (CONGA), as parameters of GV. The high blood glycemic index (HBGI) and low blood glycemic index (LBGI) were also measured as indicators of hyperhypoglycemic risk. Women with type 1 diabetes showed higher GV, with a 2-fold higher risk of hyperglycemic spikes during the day, than healthy pregnant women or GDM ones. GDM women had only slightly higher GV parameters than healthy controls. HbA1c did not correlate with GV indicators in type 1 diabetes or GDM pregnancies. We provided new evidence of the importance of certain GV indicators in pregnant women with GDM or type 1 diabetes and recommended the use of CGM specifically in these populations.

Gestational Diabetes Mellitus and Future Cardiovascular Risk: An Update

The prevalence of gestational diabetes mellitus is increasing in parallel with the rising prevalence of type 2 diabetes and obesity around the world. Current evidence strongly suggests that women who have had gestational diabetes mellitus are at greater risk of cardiovascular disease later in life. Given the growing prevalence of gestational diabetes mellitus, it is important to identify appropriate reliable markers of cardiovascular disease and specific treatment strategies capable of containing obesity, diabetes, and metabolic syndrome in order to reduce the burden of cardiovascular disease in the women affected.

Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients

Abstract Diabetes mellitus is a global pandemic and continues to increase in numbers and significance. Several pathogenic processes are involved in the development of such disease and these mechanisms could be influenced by genetic, epigenetic and environmental factors. Non-enzymatic glycation reactions of proteins have been strongly related to pathogenesis of chronic diabetic complications. The identification of fructosamine 3-kinase (FN3K), an enzyme involved in protein deglycation, a new form of protein repair, is of great interest. FN3K phosphorylates fructosamines on the third carbon of their sugar moiety, making them unstable and causing them to detach from proteins, suggesting a protective role of this enzyme. Moreover, the variability in FN3K activity has been associated with some polymorphisms in the FN3K gene. Here we argue about genetic studies and evidence of FN3K involvement in diabetes, together with results of our analysis of the FN3K gene on a Caucasian cohort of diabetic patients. Present knowledge suggests that FN3K could act in concert with other molecular mechanisms and may impact on gene expression and activity of other enzymes involved in deglycation process.

The emerging role of telemedicine in managing glycemic control and psychobehavioral aspects of pregnancy complicated by diabetes

There is a gradual decline in concern of specialists who follow up the care of pregnant women with diabetes. In addition, due to the dwindling economic resources allocated to health services, access to specialized healthcare facilities is becoming more difficult. Telemedicine, or medicine practiced at a distance, is inserted in this context with applications differing for type of interaction (real-time or deferred, i.e., videoconferencing versus store-and-forward data transmission), type of monitoring (automatic versus requesting cooperation from the patient), and type of devices used (web connections and use of mobile phones or smartphones). Telemedicine can cope with the current lack of ability to ensure these patients frequent direct contact with their caregivers. This approach may have an impact not only on the classical maternal-fetal outcome, but also on some underestimated aspects of patients with diabetes in pregnancy, in this case their quality of life, the perception of “diabetes self-efficacy,” and the glycemic variability. In this paper, we will analyze the current evidence regarding the use of telemedicine in pregnancies complicated by diabetes, trying to highlight the main limitations of these studies and possible strategies to overcome them in order to improve the effectiveness of future clinical interventions with these medical applications.

Curcumin and Boswellia serrata Modulate the Glyco-Oxidative Status and Lipo-Oxidation in Master Athletes

Background: Chronic intensive exercise is associated with a greater induction of oxidative stress and with an excess of endogenous advanced glycation end-products (AGEs). Curcumin can reduce the accumulation of AGEs in vitro and in animal models. We examined whether supplementation with curcumin and Boswellia serrata (BSE) gum resin for 3 months could affect plasma levels of markers of oxidative stress, inflammation, and glycation in healthy master cyclists. Methods. Forty-seven healthy male athletes were randomly assigned to Group 1, consisting of 22 subjects given a Mediterranean diet (MD) alone (MD group), and Group 2 consisted of 25 subjects given a MD plus curcumin and BSE (curcumin/BSE group). Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), high-sensitivity c-reactive protein (hs-CRP), total AGE, soluble receptor for AGE (sRAGE), malondialdehyde (MDA), plasma phospholipid fatty acid (PPFA) composition, and non-esterified fatty acids (NEFA) were tested at baseline and after 12 weeks. Results: sRAGE, NEFA, and MDA decreased significantly in both groups, while only the curcumin/BSE group showed a significant decline in total AGE. Only the changes in total AGE and MDA differed significantly between the curcumin/BSE and MD groups. Conclusions. Our data suggest a positive effect of supplementation with curcumin and BSE on glycoxidation and lipid peroxidation in chronically exercising master athletes.

Effectiveness of a diet with low advanced glycation end products, in improving glycoxidation and lipid peroxidation: a long-term investigation in patients with chronic renal failure

To the Editor, Advanced glycation end products (AGEs) have a crucial role in the process of atherosclerosis, particularly in patients with chronic renal failure (CRF), which have a dual form of damage, namely an increased formation of serum AGEs and their reduced clearance [1, 2]. We previously observed that AGEs can react with the peritoneal matrix protein, giving a reason for the gradual loss of peritoneal membrane function observed in patients undergoing long-term peritoneal dialysis [3, 4]. Dietary AGEs, products of Maillard reaction in various foods, form the majority of glycation-free adducts, the greater proportion of circulating AGEs in diabetic and nondiabetic subjects, contributing to the pathogenesis of several chronic diseases [3, 5]. Low-AGE diet could reduce several markers of systemic inflammation and oxidative stress in patients with diabetes [6]. Only one trial confirmed these findings even in nondiabetic patients with CRF, while other studies did not, performing short-term observations with low-AGE diet [6]. The primary aim of this pilot study was to evaluate the effect of a long-term low-AGE diet vs a standard diet on plasma and urine markers of glycoxidation and inflammation, in a group of non-diabetic patients with CRF. Moreover, patients with CRF have higher levels of oxidized LDL (ox-LDL), a marker of lipid peroxidation, with a putative role for ox-LDL in the progression of glomerular injury [7]. Lipid peroxidation and glycoxidation demonstrated a synergetic contribution to the renal tissue damage observed in patients with CRF [8]. Secondary aim of this study was therefore to assess the effect of low-AGE diet on lipid profile and ox-LDL level, since currently there are no data in this issue.

Lower urinary tract symptoms (LUTS) in males with type 2 diabetes recently treated with SGLT2 inhibitors—overlooked and overwhelming? A retrospective case series

As outlined in the latest recommendations for patients with type 2 diabetes (DM2), sodium glucose cotransporter 2 inhibitors (SGLT2i) can be added on treatments with metformin or sulfonylurea plus metformin if glycemic goals are not met [1]. Genital and urinary infections are well-known side effects of SGLT2i, with reported odds ratios in the range of 3.21–5.23, compared with placebo [2, 3]. Lower urinary tract symptoms (LUTS) are urological complications occurring in patients with DM2—males in particular—, whereas little is known about their prevalence in patients treated with SGLT2i [4]. This association is of particular interest because a symptom such as polyuria— often reported by patients starting treatment with SGLT2i— may be the sign of a urological predisposing conditions, rather than a side effect of a new treatment. Hence this case-series on male patients who had recently started treatment with SGLT2i, to assess the prevalence of new-onset LUTS. We documented any predisposing medical conditions, such as benign prostatic hyperplasia or autonomic neuropathy, that might influence the presence of LUTS.

Role of glycemic variability in gestational diabetes mellitus (GDM): still an uphill climb

Insulin resistance tends to increase in physiological pregnancy because of the gradually rising levels of feto-placental hormones such as progesterone, cortisol, growth hormone, prolactin, and human placental lactogen. In response to this imbalance, the pancreas normally compensates with a higher insulin secretion. When this compensatory mechanism fails, glucose intolerance develops and, in pregnancy, this is called gestational diabetes mellitus (GDM) [1]. The resulting maternal hyperglycemia gives rise to a concomitant fetal hyperinsulinemia via the placenta, leading primarily to fetal macrosomia, which is the main cause of well-known complications relating to the fetus’s development (e.g., shoulder dystocia, Erb’s paralysis, hypoxia, and acidosis) and to the course of labor (e.g., perineal laceration, cesarean section) [2]. Clinical evidence has confirmed that the main goal of glycemic management in GDM is to keep the mother’s blood glucose levels as close as possible to the normal range. A number of studies have demonstrated that macrosomia correlate with glycemic control in pregnancy complicated by diabetes [3]. It has recently been suggested that glucose variability, characterized by significant glucose excursions, may overlap with HbA1c levels in determining the risk of diabetes-related complications [4]. Oscillating blood sugar levels have been shown to increase free radicals and endothelial dysfunction, which are the links between hyperglycemia and the activation of pathological pathways that lead to tissue damage [5], and it has been reported that containing these hyperglycemic spikes coincides with a reduction in some markers of oxidative stress. In pregnancy complicated by diabetes even transient periods of hyperglycemia may lead to accelerated fetal growth, resulting in macrosomic infants. These peaks are difficult to capture using common glucose monitoring methods based on six to eight glucose measurements a day, whereas continuous glucose monitoring (CGM) systems are more revealing because they enable glucose levels to be monitored constantly throughout the day [6]. Despite recent opportunities to shed further light on the subject, glucose variability is still a poorly understood factor in GDM patients, especially its link with maternal and fetal complications. In one study, 48-h CGM was performed in all three trimesters in 31 women with GDM, and showed a close relationship between babies’ ponderal index and their mothers’ glucose variability indicators and mean glycemia in the 2nd trimester, irrespective of their HbA1c levels. This study emphasized that fetal growth in the early stages of gestation could be affected even in patients whose glycemic variability indices were only slightly higher than in controls [7]. In this issue of Endocrine, Su et al. [8] set out to use 72-h CGM to analyze several glycemic variability parameters in 30 patients with GDM, as compared with 20 healthy pregnant women and 20 healthy non-pregnant women, seeking a possible association with markers of beta-cell function. As indicators of glucose variability, they took into account the mean amplitude of glycemic excursion (MAGE), the mean of daily differences (MODD), and the standard deviation of blood glucose (SDBG); the HOMA-IR index was calculated to assess insulin resistance. The early insulinogenic index (DI30/DG30) and the area under the curve of insulin (AUCI 180) derived from 75 g oral glucose tolerance test (OGTT) were calculated to A. Lapolla (&) N. C. Chilelli Department of Medicine (DIMED), University of Padua, Via Giustiniani n 2, 35128 Padua, Italy e-mail: annunziata.lapolla@unipd.it