Screening of postpartum diabetes in women with gestational diabetes: high-risk subgroups and areas for improvements-the STRONG observational study.

AIMS: To assess the proportion of women with gestational diabetes (GDM) by performing postpartum Oral Glucose Tolerance Test (OGTT) and to identify GDM phenotypes at high-risk of postpartum dysglycemia (PPD). METHODS: Observational, retrospective, multicenter study involving consecutive GDM women. Recursive partitioning (RECPAM) analysis was used to identify distinct and homogeneous subgroups of women at different PPD risk. RESULTS: From a sample of 2,736 women, OGTT was performed in 941 (34.4%) women, of whom 217 (23.0%) developed PPD. Insulin-treated women having family history of diabetes represented the subgroup with the highest PPD risk (OR 5.57, 95% CI 3.60-8.63) compared to the reference class (women on diet with pre-pregnancy BMI < = 28.1 kg/m2). Insulin-treated women without family diabetes history and women on diet with pre-pregnancy BMI > 28.1 kg/m2 showed a two-fold PPD risk. Previous GDM and socioeconomic status represent additional predictors. Fasting more than post-prandial glycemia plays a predictive role, with values of 81-87 mg/dl (4.5-4.8 mmol/l) (lower than the current diagnostic GDM threshold) being associated with PPD risk. CONCLUSIONS: Increasing compliance to postpartum OGTT to prevent/delay PPD is a priority. Easily available characteristics identify subgroups of women more likely to benefit from preventive strategies. Fasting BG values during pregnancy lower than those usually considered deserve attention.

Risk and adverse outcomes of gestational diabetes in migrants: A population cohort study.

AIMS: To evaluate the risk of gestational diabetes (GDM) and of neonatal/maternal complications (macrosomia, large for gestational age (LGA), cesarean sections, preterm deliveries, neonatal distress and fetal malformations) among women coming from High Migration Pressure Countries (HMPC), compared to native (Italian) mothers. METHODS: Risks of GDM and related neonatal/maternal complications were evaluated in a cohort of 581,073 Italian compared with 105,111 HMPC women of age 15-45 yr, resident in Tuscany, Italy along years 2012-2017, delivering 122,652 singleton live births (18,596 from HMPC mothers). RESULTS: HMPC women, compared to Italian ones, were at higher risk of GDM (OR: 1.586; 1.509-1.666;p < 0.0001), peaking for women originating from South Asia (OR:3.0.49; 2.618-3.553;p < 0.0001). GDM was associated with increased risk of preterm delivery and cesarean sections, while migrants, regardless of GDM, were burdened by a higher risk of all considered complications. The rise in all these risks, including macrosomia or LGA however, disappeared, after addition of interaction term GDM × HMPC ethnicity. CONCLUSION: Compared to Italian mothers, HMPC women had higher risk of GDM and of all considered adverse events. The addiction of the interaction term GDM × HMPC ethnicity in the predictive model, however reversed the rise in risk of all HMPC associated adverse outcomes.

"MySweetGestation": A novel smartphone application for women with or at risk of diabetes during pregnancy.

Mobile health (mHealth) applications (apps) have been recently introduced as an easily accessible tool for providing information to pregnant women with diabetes. Despite the growing number of apps on the topic "diabetes & pregnancy", a smartphone app offering comprehensive and individualized information to both women (before and during gestation) and their healthcare professionals was still missing. To overcome this lack, the Italian Diabetes and Pregnancy Study Group conceived and realized in 2016 a novel mobile app called "MySweetGestation". It is designed to be an interactive educational tool for both patients and physicians not expert in the field. Through an interactive way of learning, it provides validated information to the user, focusing on different area of interest: from prevention and risk factors for developing diabetes during pregnancy to treatment and follow-up strategies after gestation. Three years since its publication, MySweetGestation has been downloaded in different western and eastern countries worldwide, suggesting a widespread social impact. Easily accessible personalized information made available via mHealth technology may be of great importance to spread controlled information among the pregnant population. MySweetGestation, being an interactive educational device for both patients and healthcare professionals, may contribute to improve the management of pregnant women with diabetes.

Guidelines for the screening and diagnosis of gestational diabetes in Italy from 2010 to 2019: critical issues and the potential for improvement.

AIMS: In 2010, Italian health professionals rapidly implemented the one-step screening for gestational diabetes mellitus (GDM) based on a 75 g OGTT, to comply with the diagnostic criteria proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). The change was promoted by the two main Italian scientific societies of diabetology, Associazione Medici Diabetologi (AMD) and Società Italiana di Diabetologia (SID), and it took just a few months for the Istituto Superiore di Sanità, together with several scientific societies, to revise the criteria and include them in the National Guidelines System. Over the last 9 years, the implementation of these guidelines has shown some benefits and some drawbacks. METHODS: In order to evaluate the critical issues arisen from the implementation of the current Italian guidelines for the diagnosis of GDM, the studies published on this topic have been reviewed. The search was performed using the following keywords: "gestational diabetes" AND "diagnostic criteria" OR screening AND Ital*. The study is an expert opinion paper, based on the relevant scientific literature published between 2010 and 2019. The databases screened for the literature review included PubMed, MEDLINE, and Scopus. RESULTS: The implementation of the Guidelines for Screening and Diagnosis of GDM in Italy present some strengths and some weaknesses. One of the positive aspects is that high-risk women are required to perform an OGTT early in pregnancy. By contrast, there are several aspects in need of improvement: (1) In spite of the current indications, only a minority of high-risk women perform OGTT early in pregnancy; (2) several low-risk women are screened for GDM; (3) in some low-risk women affected by GDM, the diagnosis might be missed with the application of the current guidelines; (4) there is a lack of homogeneity in the risk assessment data from different regions. CONCLUSIONS: In order to improve the current Italian GDM guidelines, some practical solutions have been suggested.

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study.

AIMS: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. METHODS: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. RESULTS: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59-3.87), large for gestational age (OR 3.99, 95% CI 2.40-6.63), fetal malformation (OR 2.66, 95% CI 1.00-7.18), and respiratory distress (OR 4.33, 95% CI 1.33-14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00-2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04-3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02-2.27) and obesity (OR 1.62, 95% CI 1.04-2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21-2.33 for obese; OR 1.38 95% CI 1.03-1.87 for overweight). CONCLUSIONS: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity.

Preventing type 2 diabetes and cardiovascular disease in women with gestational diabetes - The evidence and potential strategies.

Gestational Diabetes Mellitus is a condition strongly related to the development of type 2 diabetes later in life, although the risk and the onset have not been fully identified yet. Although glucose tolerance returns to normal levels after delivery in the majority of women with GDM, this condition represents an early stage in the natural history of T2DM. In addition, women with previous GDM exhibit an increased cardiovascular risk profile and a raised incidence of cardiovascular diseases. Lifestyle changes and pharmacological interventions might be able to reduce the incidence of type 2 diabetes in pGDM women, although results are still not conclusive. Long term continuous programs specifically addressed to women with pGDM should be implemented, with the ambitious target to encourage them to regularly check glucose tolerance, lipid profile and other parameters related to cardiovascular diseases, aimed at improving women's health. In this paper, we review the relationship between type 2 diabetes, cardiovascular diseases and a history of GDM.

Screening for gestational diabetes in Tuscany, Italy. A population study.

AIMS: According to current Italian guidelines, only women at higher risk of gestational diabetes (GDM) are eligible for receiving a glucose tolerance test (OGTT) during pregnancy. This study evaluates the compliance to national guidelines, additionally proposing an algorithm able to identify women with GDM. METHODS: The study included 23,270 pregnant women aged >15yr, resident in Tuscany, a region in central Italy, delivering in year 2015, identified by certificates of care at delivery. Eligibility to screening was evaluated by fulfillment to regional guidelines recommending a 2-h-75g-OGTT only in presence of risk factors. Additionally, a validated algorithm is proposed to diagnose GDM from regional administrative databases. RESULTS: Glucose tolerance was tested in 79.2% of women. Eligibility criteria were fulfilled in 55.6% of OGTT performers and in 40.2% of those who didn't perform any OGTT. Performers' rate increased with age, body weight, higher education degree and in those followed by a well defined clinical setting. Housewives and students had a lower chance of receiving an OGTT. Algorithm identified GDM in 11% of women, ranging from 14% among eligible and 7% among non-eligible ones. CONCLUSION: Selective screening for GDM is not being currently applied in Tuscany. Despite the percentage of eligible women by national guidelines was 55%, the rate of those who performed the screening was about 80%, with a 40% of low risk women continuing to be screened. Moreover, GDM rate, calculated by algorithm, was relatively large (7%) among non-eligible women, suggesting the need of universal glucose screening to adequately capture all GDM cases.

Prescribing exercise for prevention and treatment of gestational diabetes: review of suggested recommendations.

Exercise has been proved to be safe during pregnancy and to offer benefits for both mother and fetus; moreover, physical activity may represent a useful tool for gestational diabetes prevention and treatment. Therefore, all women in uncomplicated pregnancy should be encouraged to engage in physical activity as part of a healthy lifestyle. However, exercise in pregnancy needs a careful medical evaluation to exclude medical or obstetric contraindications to exercise, and an appropriate prescription considering frequency, intensity, type and duration of exercise, to carefully balance between potential benefits and potential harmful effects. Moreover, some precautions related to anatomical and functional adaptations observed during pregnancy should be taken into consideration. This review summarized the suggested recommendations for physical activity among pregnant women with focus on gestational diabetes.

Selective screening for GDM in Italy: application and effectiveness of National Guidelines.

In September 2011 the Italian Public Health Authority established selective screening for GDM to be performed based on the presence of risk factors. In a cohort of 2552 Caucasian pregnant women we evaluated to which extent the new national guidelines (NGL) are correctly applied; moreover we estimated the prevalence of GDM assessed by NGL. Our data show that the NGL are still properly implemented since the screening test was performed in nearly the totality of the women at 24th and 28th week of gestation. GDM prevalence is 10.9%, 25% greater as compared to the one determined with the old criteria 10 years ago.

1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women.

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL, n = 661; 120-139 mg/dL, n = 710; 140-159 mg/dL, n = 912; 160-179 mg/dL, n = 885; and ≥180 mg/dL, n = 996). We calculated incremental area under glucose (AUC(gluc)) and insulin curves (AUC(ins)), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUC(ins)/AUC(gluc). AUC(gluc) and AUC(ins) progressively increased according to 1-hour plasma glucose concentrations (both P < 0.0001 for trend). HOMA-B progressively declined (P < 0.001), and HOMA-R progressively increased across the five groups. AUC(ins)/AUC(gluc) decreased in a linear manner across the 5 groups (P < 0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: -29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (all P < 0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion.

Histopathology and ex vivo insulin secretion of pancreatic islets in gestational diabetes: A case report.

Gestational diabetes (GD) results from insufficient endogenous insulin supply. No information is available on features of islet cells in human GD. Herein, we describe several properties of islets from a woman with GD. Immunohistochemical stainings and EM analyses were performed on pancreatic samples. Islet isolation was achieved by enzymatic dissociation and density gradient centrifugation. Ex vivo insulin secretion was studied in response to fuel secretagogues. Control islets were obtained from matched non-pregnant, non-diabetic women. Total insulin positive area was lower in GD, mainly due to the presence of smaller islets. ß-cell apoptosis and the presence of Ki67 positive islet cells were similar in GD and controls, whereas the amount of insulin positive cells in or close to the ducts was decreased in GD. Ex vivo insulin secretion did not differ between GD and non-pregnant, non-diabetic islets. These findings suggest that in this case of human GD there might mainly be a defect of ß-cell amount, not due to increased apoptosis, but possibly to insufficient regeneration.

Glucose variability in diabetic pregnancy.

BACKGROUND: Fetal overgrowth is the most important complication of gestational (GDM) and pregestational diabetes mellitus. METHODS: We correlated maternal glucose profiles, as detected by continuous glucose monitoring (CGM), with fetal growth parameters for 80 pregnant women (32 with type 1 diabetes, 31 with GDM, and 17 healthy controls). Glucose profiles were monitored in the first, second, and third trimesters of pregnancy for type 1 diabetes women and in the second and third trimesters for GDM women and controls. To analyze glycemic variability, we considered the mean amplitude of glycemic excursion, mean glycemia, the continuous overlapping net glycemic action (CONGA), the SD, the High Blood Glucose Index (HBGI), the Low Blood Glucose Index, and the interquartile range (IQR). RESULTS: Mean age was the same for the three groups. Prepregnancy body mass index was higher for the women with diabetes (GDM and type 1) than for controls. The newborn's mean birth weight and ponderal index were higher, although not significantly so, for the women with diabetes than for controls. For the type 1 diabetes patients, ponderal index correlated with the HBGI in the first trimester, CONGA1 and IQR in the second, and mean glycemia and SD in the third. For GDM patients, ponderal index correlated with mean glycemia and the HBGI in the second trimester. CONCLUSIONS: Fetal exposure to glycemic variability and hyperglycemia seems to be important in determining fetal overgrowth in pregnant women with diabetes. Optimal glucose control and less glucose variability are needed as early as possible in both type 1 diabetes and GDM patients to ensure normal fetal growth.

Circulating endothelial progenitor cells in women with gestational alterations of glucose tolerance.

Endothelial progenitor cells (EPCs) play a role in angiogenesis during pregnancy. The aim of this study was to evaluate circulating EPCs in pregnant women with gestational alterations of glucose tolerance. Glucose tolerance, insulin sensitivity and ß-cell function were derived from oral glucose tolerance tests in 23 women with normal glucose tolerance (NGT), 18 with gestational impaired glucose tolerance (GIGT) and 24 with gestational diabetes mellitus (GDM). Circulating cells expressing CD34 in combination with CD133, kinase insert domain receptor (KDR) or both were quantified by flow cytometry. Women with GIGT and GDM had lower CD34(+)KDR(+) and CD34(+)CD133( +)KDR(+) cells at 27±3.2 weeks' gestation compared with NGT (ANOVA p<0.02 for both). CD34(+)KDR(+) and CD34(+)CD133(+)KDR(+) cells were inversely correlated with the area-under-the-glucose-curve (p<0.005, for both) and positively to insulin secretion-sensitivity index (p<0.05, for both). Alterations of glucose tolerance during pregnancy are associated with a decrease in EPCs. Hyperglycaemia might exert a direct effect on depletion of EPCs.

Does nuchal translucency thickness in the first trimester predict GDM onset during pregnancy?

BACKGROUND AND AIMS: This study was planned to evaluate whether increased nuchal translucency (NT) thickness in the first trimester of gestation can be related to onset of gestational diabetes mellitus (GDM) during pregnancy. METHODS: From January 2006 to August 2008, a group of 678 singleton pregnancies who had developed GDM has been selected as a study group among a total of 3966 pregnant women who had undergone first trimester screening for aneuploidies at 11-14 weeks of gestation. A group of 420 single pregnant women with physiological pregnancy were enrolled as control group. Both fetal structural and karyotype's anomalies were excluded in the two groups. NT was mesured by a Fetal Medicine Foundation certificated operator; GDM was diagnosed at 24-28 weeks of gestation following Carpenter and Coustan criteria. In the analyses of continuos variables, study and control group were compared by Student's t-test and Anova test. RESULTS: There was no significative difference (p = 0.585) between NT values in the study (mean = 1.56) and control group (mean = 1.54). CONCLUSIONS: NT thickness does not show a significative increase in those women who subsequently develop GDM. Therefore, NT assessment does not prove to be an useful ultrasound parameter for predicting GDM onset during pregnancy.

Physical activity and dietary habits during pregnancy: effects on glucose tolerance.

OBJECTIVES: We designed this study to assess the potential effects of physical activity and dietary habits on glucose tolerance during pregnancy. METHODS: This is an observational study involving 268 women who underwent a 50-g oral glucose challenge test (GCT) at 27±6.9 week of gestation. Plasma glucose level at 1-h GCT ≥ 140 mg/dl was used to define abnormal glucose tolerance (AGT). Physical activity was evaluated using the short form of the International Physical Activity Questionnaire (IPAQ), while for dietary habits we used a food frequency questionnaire linked to a computerised program. RESULTS: One hundred five women had AGT (AGT+) and 163 had normal glucose tolerance (AGT−). There was no difference between the two groups in demographic and clinical data, with the exception of pre-pregnancy BMI and weight gain both higher in AGT+ women. Also, all parameters referring to physical activity energy and diet (Kcal and diet components) were not statistically different between the two groups. After a multivariate analysis, only pre-pregnancy BMI (F-value 9.264, p=0.002) remained an independent predictor of 1-h plasma glucose. CONCLUSIONS: Our study suggests that high pre-pregnancy BMI confers a substantially high risk of AGT, independently of lifestyle during pregnancy.

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.

Beta-cell failure in type 2 diabetes mellitus.

Diabetes mellitus has been defined as a "group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both" and encompasses a wide range of heterogeneous conditions. Common type 2 diabetes mellitus (T2DM) results from a combination of genetic and acquired factors. However, lifestyle factors, particularly overeating and physical inactivity, are the major clinical determinants of T2DM. Insulin resistance is a common feature of T2DM, but it is unlikely to cause T2DM unless progressive loss of beta-cell function develops. Significant reduction in beta-cell function is already present at the time of T2DM diagnosis, and it continuously declines irrespective of treatment. As such, the progressive loss of beta-cell function dictates the rate of worsened glycemic control. Development of progressive deterioration accelerates via gluco- and lipotoxicity, loss of beta-cell function, and shrinkage of beta-cell mass. Understanding the causes for beta-cell failure is therefore of capital importance to develop new and more effective therapeutic strategies.

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 beta-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.