Papers by Alessandra Bertolotto
International Journal of Obesity
Background/Objectives Obesity during pregnancy is associated with neonatal adiposity, which is a ... more Background/Objectives Obesity during pregnancy is associated with neonatal adiposity, which is a risk factor for childhood obesity. Maternal physical activity (PA) and sedentary behaviours during pregnancy might modify this risk. We therefore studied associations between maternal PA and sedentary time (ST) during pregnancy and neonatal anthropometry and cord blood parameters and investigated whether associations differed by offspring sex. Subjects/Methods Participants of the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) study with a BMI ≥ 29 kg/m2 were analysed as a cohort. Maternal moderate-to-vigorous PA (MVPA) and ST were measured repeatedly with accelerometers across pregnancy. Associations between mean levels and changes in MVPA and ST and birthweight, neonatal adiposity (fat mass (FM)%) and cord blood parameters, including C-peptide, leptin and lipids, were analysed in 213 mother-child pairs with Bayesian multilevel models. Interacti...
Diabetic Medicine, Feb 22, 2012
Gestational diabetes is associated with features of Type 2 diabetes, the metabolic syndrome and c... more Gestational diabetes is associated with features of Type 2 diabetes, the metabolic syndrome and cardiovascular disease. This suggests that these conditions may share common pathophysiological mechanisms, including insulin resistance and impaired insulin secretion [1]. Low socio-economic status has been shown to contribute to the risk for development of Type 2 diabetes, the metabolic syndrome and cardiovascular disease, but little is known regarding a potential association between maternal educational level and gestational diabetes [2–5]. During the period January 2006–February 2010, all pregnant women who attended our Diabetes and Pregnancy Clinic with a positive screening test (plasma glucose values 7.8 mmol ⁄ l 1 h after a standard 50-g glucose load, administered after an overnight fast), underwent a 3-h 100-g oral glucose tolerance test. According to the American Diabetes Association criteria, gestational diabetes was diagnosed when two or more plasma glucose levels exceeded cut-off values whereas impaired glucose tolerance was diagnosed by only one exceeded level [6]. We collected anthropometric and clinical variables and assessed the maternal educational level, based on school degree and an ad hoc questionnaire as a proxy of socio-economic status. Women were categorized into: low (primary school only), intermediate (high school) and high (university) educational level. Out of 1012 Caucasian pregnant women (mean age 33.8 4.4 years; 27.4 4 weeks of gestation) 135 had impaired glucose tolerance, 125 had gestational diabetes and 752 had normal glucose tolerance. All women gave informed consent and all procedures were in accordance with the Helsinki Declaration of 1975. With regard to maternal educational level, 201 women had only attended primary school (low) (19.8%), 494 had attended high school (intermediate) (48.8%) and 318 had graduated from university (high) (31.4%). Women in the primary-school-only group were younger (33.4 6.2 vs. 33.2 4.3 and 34.9 3.7 years; P < 0.0002), heavier (BMI 25.7 5.6 vs. 24.2 5 and 23 3.9 kg ⁄ m; P < 0.0001), with a higher rate of overweight (19.9 vs. 12 and 6.9%; P < 0.0001) or obesity (22.4 vs. 18.3 and 15.4%; P < 0.0001). They also gained more weight during pregnancy (10.9 4.9 vs. 10.4 5.8 and 9.7 3.6 kg; P < 0.01). In contrast, women who had had a university education were older (34.9 3.7 years) than both those in the primary-school-only group (33.4 6.1 years) and in the high-school (intermediate) group (33.2 4.3 years) (P < 0.002). No differences were observed in family history for Type 2 diabetes and parity. Impaired glucose tolerance and ⁄ or gestational diabetes was diagnosed in 58 (29%) women in the primary-school-only group, 124 (25%) in the high-school group and 80 (25%) in the university-graduate group, with no difference among the three groups. Impaired glucose tolerance and diagnosis of gestational diabetes were not related to maternal educational level, while, after a logistic binary regression model including all clinical and metabolic variables, only pre-pregnancy BMI [odds ratio 1.05 (1.02–1.08; P < 0.001) and age (odds ratio 1.05 (1.02–1.09; P < 0.002)] remained independently associated with impaired glucose tolerance or gestational diabetes (Table 1). We found no relationship between an abnormal oral glucose tolerance test and the degree of maternal education. Most likely, in our population, at variance with others, low educational level is not associated with deprivation and ⁄ or poor health awareness [7,8]. Our data stand against a direct effect of maternal educational level on the occurrence of gestational diabetes ⁄ impaired glucose
PubMed, Oct 1, 2011
Gestational diabetes mellitus (GDM) predisposes women to future development of Type 2 diabetes me... more Gestational diabetes mellitus (GDM) predisposes women to future development of Type 2 diabetes mellitus (DM2) and the two conditions share similar metabolic alterations. Recent observations suggest that a defective glucose stimulated insulin secretion by glucagon-like peptide-1 (GLP- 1) plays a role in the pathogenesis of DM2. Whether such a defect is impaired in GDM remains to be ascertained. Aim: We have determined GLP-1 secretion in response to oral glucose tolerance test (OGTT) in GDM and normal glucose tolerance (NGT) during and after pregnancy. Materials and methods: 100-g-3h OGTT was performed in 12 GDM and 16 NGT women at 27.3 ± 4.1 weeks of gestation, for determination of plasma GLP-1, glucose, insulin, and C-peptide. Insulin sensitivity (ISI) and insulin secretion (first and second phase); as well as ISI-secretion index (ISSI) were also derived. Results: NGT and GDM women were comparable for age pre-pregnancy body mass index (BMI) and weight gain. GDM had higher glucose area under the curve (AUC): 27,575.5 ± 3448 vs 20,685.88 ± 2715 mg/dl min (p<0.01), but lower first-phase insulin secretion (993.12±367 vs 1376.61 ± 423, p<0.05) and ISSI compared to controls (3873.23 ± 1185 vs 6232.13 ± 1734, p<0.001). When we examined GLP-1 mean levels in relation to mean glycemic values, GLP-1 secretion was inappropriately low with respect to mean glycemic values in GDM compared to NGT. At follow-up, AUCGLP-1 was significantly lower in post-partum GDM compared to post-partum NGT women (2542 ± 273 vs 10,092 ± 7367 pmol·l-1·min-1, p<0.05, respectively). Conclusions: Our study suggests that GLP-1 secretion in GDM women is inadequate for the prevailing glycemic levels both in pregnancy and post partum. Moreover, we cannot exclude that other important aspects of the incretin effect may be involved in GDM development.
Elsevier eBooks, 2011
During pregnancy, complex changes occur in lipid profiles. From the 12th week of gestation, phosp... more 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.
Nutrients, Aug 9, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Diabetes Care, May 1, 2008
Diabetes, Jun 1, 2022
Aim: Umbilical cord leptin is higher than expected in some babies (relative cord hyperleptinaemia... more Aim: Umbilical cord leptin is higher than expected in some babies (relative cord hyperleptinaemia) . We test the hypothesis that a higher cord leptin:fat mass ratio, putatively reflecting “leptin resistance” might be associated with adverse pregnancy outcomes. Methods: Secondary analyses from Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial a pan European study among women with a BMI ≥29 kg/m2 between 2012-14. Cord sampling and skin caliper measurements followed standardized methods. Serum cord leptin (µg/l) to fat mass ratio (kg) was classified into low, middle, and high tertiles across (where stated) and within sexes. Large/small for gestational age (SGA) used GROW. Pregnancy outcomes were compared between low and high tertiles adjusted for potential confounders using binomial logistic regression. Results: Among the 349 eligible babies (mean gestational age 39.7 ± 1.4 weeks, female 49%) the median (interquartile range) leptin-fat mass ratio (both sexes combined) was 20.2 (11.4-30.8) , top tertile (TT) was &gt;25.3 and low tertile (LT) was &lt;14.9 . Compared with babies in the LT group, those in the TT group had higher cord erythropoietin (30.2 (16.7-59.2) vs. 20.3 (12.4-35.6) µg/l p = 0.002, respectively, both sexes) with higher cord serum C peptide (0.7 (0.5-1.0) vs. 0.5 (0.3-0.8) µg/l p = 0.005) , lower birthweight (3435 ± 5vs. 37± 412 gm, p = 0.002) in boys but not in girls. Cord glucose was similar. Among males, those in the TT had higher risk of SGA (25.0% vs. 8.5%; OR 3.61 (95%CI 1.21-10.76)) but lower risk of cesarean section (0.39 (0.17-0.88)) . Among females, mothers in the TT had higher rate of pregnancy induced hypertension (3.93 (1.21-12.71)) . Conclusions: Relative cord hyperleptinaemia is associated with reduced fetal growth (boys only) , and possible relative fetal hypoxia (both sexes) . Further studies are required to evaluate the implications of these findings on future metabolism. Disclosure J.Immanuel: None. D.M.Jensen: None. E.R.Mathiesen: Consultant; Novo Nordisk A/S, Speaker's Bureau; Novo Nordisk A/S. D.J.Hill: None. P.Damm: Advisory Panel; Novo Nordisk A/S. F.J.Snoek: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Roche Diabetes Care, Research Support; Novo Nordisk A/S, Sanofi, Speaker's Bureau; Insulet Corporation. J.Adelantado: None. E.Wender-ozegowska: None. D.Simmons: Other Relationship; Elsevier, Research Support; Abbott, Hitachi, Ltd., Novo Nordisk, Speaker's Bureau; Sanofi. G.Desoye: None. M.Vanpoppel: None. A.Kautzky-willer: None. R.Corcoy: None. A.Bertolotto: Research Support; AstraZeneca, Novo Nordisk, Speaker's Bureau; Abbott Diagnostics, Lilly Diabetes. F.P.Dunne: None. J.Harreiter: None. L.Andersen: None. Funding EU FP7 (242187)
Gynecological Endocrinology, 2009
OBJECTIVE-Compare the efficacy, safety, and patient satisfaction of continuous subcutaneous insul... more OBJECTIVE-Compare the efficacy, safety, and patient satisfaction of continuous subcutaneous insulin infusion (CSII) therapy with multiple daily injection (MDI) therapy for patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 132 CSII-naive type 2 diabetic patients were randomly assigned (1:1) to CSII (using insulin aspart) or MDI therapy (bolus insulin aspart and basal NPH insulin) in a multicenter, open-label, randomized, parallel-group, 24-week study. Efficacy was assessed with HbA 1c and eight-point blood glucose (BG) profiles. Treatment satisfaction was determined with a self-administered questionnaire. Safety assessments included adverse events, hypoglycemic episodes, laboratory values, and physical examination findings. RESULTS-HbA 1c values decreased similarly for both groups from baseline (8.2 Ϯ 1.37% for CSII, 8.0 Ϯ 1.08% for MDI) to end of study (7.6 Ϯ 1.22% for CSII, 7.5 Ϯ 1.22% for MDI). The CSII group showed a trend toward lower eight-point BG values at most time points (only significant 90 min after breakfast; 167 Ϯ 48 vs. 192 Ϯ 65 mg/dl for CSII and MDI, respectively; P ϭ 0.019). A total of 93% of CSII-treated subjects preferred the pump to their previous injectable insulin regimen for reasons of convenience, flexibility, ease of use, and overall preference. Safety assessments were comparable for both treatment groups. CONCLUSIONS-Insulin aspart in CSII therapy provided efficacy and safety comparable to MDI therapy for type 2 diabetes. Patients with type 2 diabetes can be trained as outpatients to use CSII and prefer CSII to injections, indicating that pump therapy should be considered when initiating intensive insulin therapy for type 2 diabetes.
Diabetes/Metabolism Research and Reviews
AimsTo evaluate the impact of assisted reproductive technology (ART) on the risk of gestational d... more AimsTo evaluate the impact of assisted reproductive technology (ART) on the risk of gestational diabetes mellitus (GDM) in single pregnancies.Materials and MethodsWe retrospectively collected clinical and anthropometric data of 219ART‐ and 256 age‐ and body mass index (BMI)‐matched women with spontaneous conception screened for GDM. The primary outcome was to evaluate GDM prevalence in ART women.ResultsThere were no differences in age, BMI, and family history of diabetes in the two groups of women. ART‐women were more frequently primiparous, whereas the prevalence of previous GDM was higher in SC‐women. The prevalence of GDM in the whole cohort was 36.1% and was higher in ART‐women (52.3% vs. 23.4%; p < 0.0001). In the whole cohort, on multivariate analysis, family history of diabetes (OR 1.67; 95% CI: 1.03–2.69), previous GDM (OR 7.05; 95% CI: 2.92–17.04), pre‐pregnancy obesity (OR 2.72; 95% CI 1.21–6.13), and ART (OR 4.14; 95% CI 2.65–6.48) were independent risk factors for GDM...
Diabetes Research and Clinical Practice, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Diabetes, Obesity and Metabolism, 2019
AimTo investigate the effect of sitagliptin (SITA) and metformin (MET) monotherapy as well as in ... more AimTo investigate the effect of sitagliptin (SITA) and metformin (MET) monotherapy as well as in combination (MET+SITA) on beta‐cell function and insulin sensitivity in women with recent gestational diabetes (GDM) and impaired glucose regulation (IGR: impaired fasting glucose and/or impaired glucose tolerance).Material and MethodsForty women were randomly assigned to receive SITA (100 mg qd), MET (850 mg bid) or MET+SITA (50 + 850 mg bid) for 16 weeks. A 75 g oral glucose tolerance test (OGTT) and +125 mg/dL hyperglycaemic clamp followed by 5 g i.v. L‐arginine were performed at baseline and end of study. The primary outcome of the study was the mean change in arginine‐stimulated insulin secretion rate during the hyperglycaemic clamp test from baseline to 16‐week therapy.ResultsAt week 16, body mass index declined in all groups (−1.2 ± 0.2 kg/m2; P < 0.05). MET+SITA gave a greater increase of first phase(2–10 min) insulin secretion and arginine‐stimulated response (720.3 ± 299.0 t...
Gynecological Endocrinology, 2019
Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not ... more Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and b-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.
Nutrition, Metabolism and Cardiovascular Diseases, 2019
Background and aims: Screening for Gestational Diabetes (GDM) is usually recommended between 24 a... more Background and aims: Screening for Gestational Diabetes (GDM) is usually recommended between 24 and 28 weeks of pregnancy; however available evidence suggests that GDM may be already present before recommended time for screening, in particular among high-risk women as those with prior GDM or obesity. The purpose of this retrospective study was to evaluate whether early screening (16e18 weeks) and treatment of GDM may improve maternal and fetal outcomes. Methods and results: In 290 women at high-risk for GDM, we analyzed maternal and fetal outcomes, according to early or standard screening and GDM diagnosis time. Early screening was performed by 50% of high-risk women. The prevalence of GDM was 62%. Among those who underwent early screened, GDM was diagnosed at the first evaluation in 42.7%. Women with early diagnosis were more frequently treated with insulin and had a slightly lower HbA1c than women with who were diagnosed late. No differences were observed in the prevalence of Cesarean section, operative delivery, gestational age at the delivery, macrosomia, neonatal weight, Ponderal Index and Large-for-Gestational-Age among women with early or late GDM diagnosis or NGT. However, compared to NGT women, GDM women, irrespective of the time of diagnosis, had a lower gestational weight gain, lower prevalence of macrosomia (3.9% vs. 11.4%), small (1.7% vs. 8.3%) as well as large for gestational age (3.3% vs. 16.7%), but higher prevalence of pre-term delivery (8.9% vs. 2.7%). Conclusion: Early vs. standard screening and treatment of GDM in high-risk women is associated with similar short-term maternal-fetal outcomes, although women with an early diagnosis were treated to a greater extent with insulin therapy.
Diabetes Research and Clinical Practice, 2018
Aims: Both obesity and gestational diabetes (GDM) are risk factors for adverse pregnancy outcomes... more Aims: Both obesity and gestational diabetes (GDM) are risk factors for adverse pregnancy outcomes. The aim of our study is to ascertain the independent role of prepregnancy BMI (pp-BMI), gestational weight gain (GWG), and GDM on pregnancy outcomes. Methods: We analyzed data of 1198 pregnant women, who underwent selective screening for GDM. Data on pregnancy outcomes was collected from hospital discharge records. Results: Cesarean section (CS) was comparable in GDM and NGT women. Prevalence of fetal macrosomia was 5.9%, with no difference between GDM and normal glucose tolerance (NGT), neonatal hyperbilirubinemia were more frequent in newborns of GDM women (63.3% vs. 52.2%; p<0.01). Offspring of women with excessive GWG weighed more than those of women with regular GWG (3405±510g vs. 3287±524g; p<0.01). On a logistic regression analysis, GWG was an independent risk factor for macrosomia (OR 1.08, 95% CI 1.02-1.13; p<0.01) and delivery at a gestational age <37 weeks (OR 0.29, 95% CI 0.16-0.53; p<0.0001). GDM and pp-BMI were not independent risk factors for adverse outcomes in this cohort. Conclusions: GWG rather than GDM is associated with adverse pregnancy outcomes. These findings call for an early education and implementation of a healthy lifestyle in women planning a pregnancy.
Nutrition, Metabolism and Cardiovascular Diseases, 2017
Background and aim: In 2011, the Italian National Health System guidelines introduced a selective... more Background and aim: In 2011, the Italian National Health System guidelines introduced a selective screening for gestational diabetes (GDM) based on risk factors, recommending early evaluation in high risk women. The present study examined to which extent guidelines are applied and analyzed the effectiveness of GDM diagnosis according to risk profile. Subjects and methods: We analyzed 1338 pregnant women, consecutively screened for GDM with a 75g OGTT between January 2013 and December 2015, according to national guidelines. Diagnosis of GDM was based on IADPSG/WHO 2013 criteria. Results: The 14.4% of screened women was at high risk, 64% at medium, 21.6% didn't have any risk factor. Only 50% of high-risk women were appropriately screened at 16 th-18 th gestational weeks; 28% of them repeated the OGTT due to NGT. The overall prevalence of GDM was 39.9%, higher in high risk women (67% vs. 40% medium risk vs. 22% low risk; p<0.0001). An early GDM diagnosis was performed in 40.7% of high-risk women. In low risk women, gestational weight gain at the screening time was independently associated with GDM. Conclusions: The recommendations for the screening of GDM are still insufficiently implemented, especially for early evaluation in high risk women. Considering the high proportion of early GDM diagnosis, the poor adherence to screening recommendation may result in late diagnosis of GDM. Finally, our finding of 22% prevalence of GDM among low risk women suggests the need to consider additional risk factors, such as excessive weight gain during pregnancy.
Minerva ginecologica, 1989
The effects on carbohydrate metabolism by four low-dose oral contraceptives were evaluated in fou... more The effects on carbohydrate metabolism by four low-dose oral contraceptives were evaluated in four low-dose oral contraceptives were evaluated-66 young women randomly divided in four groups. In the various preparations there were a different dosage of estrogen (ethinylestradiol) together different doses and types of progestogen (desogestrel, gestodene, cyproterone acetate). After six months of treatment, in all groups a slight increase of glycemic and insulinemic responses during OGTT was observed; the significance was achieved with the preparation containing cyproterone acetate alone. Glycated hemoglobin did not change. Our results suggest that these new low-dose oral contraceptives induced negligible metabolic side effects.
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Papers by Alessandra Bertolotto