Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women-a secondary analysis of the DALI study.

BACKGROUND/OBJECTIVES: Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women. SUBJECTS/METHODS: In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness. RESULTS: 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011). CONCLUSIONS: As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.

Lipid profile in women of different ethnicity with gestational diabetes: Relationship with fetal growth.

AIMS/INTRODUCTION: Pregnancy complicated by gestational diabetes mellitus (GDM) is characterized by excessive insulin resistance that impairs the metabolism of glucose and lipids. the aim of the study was to examine lipid profiles during pregnancy of women with GDM, and its impact on fetal growth in a multiethnic population. MATERIALS AND METHODS: The study included 322 pregnant women of different ethnicity with GDM attending a clinical unit specializing in metabolic diseases. RESULTS: The area under the curve for the 75-g oral glucose tolerance test and glycated hemoglobin were significantly different among all groups. At the time of being diagnosed with GDM, Asian and African mothers had significantly lower levels of total and low-density liprotein cholesterol than European mothers (P < 0.001). The trend for high-density liprotein cholesterol was similar. Triglycerides levels in the Asian group (193.6 ± 65.5 mg/dL) were higher than in the African group (133.2 ± 49.6 mg/dL, P < 0.001), whereas the European group presented intermediate values (175.8 ± 58.8 mg/dL), which differed significantly only versus the African group (P < 0.001). Pre-partum lipid profiles showed a trend quite similar to that observed at diagnosis. The newborn's birthweight was significantly different, with that of African women (3,437 ± 503 g) being the highest, followed by that of European women (3,294 ± 455 g) and of Asian women (3,006 ± 513 g). The rates of macrosomia showed a trend with higher values in the African group (13.5%), followed by the European group (5.7%, P = 0.1162), whereas that of the Asian group was zero (P = 0.0023 vs African). CONCLUSIONS: Our data show that lipid profiles in women with GDM differ by ethnicity. The impact of lipid profile on fetal growth is limited and uninfluenced by ethnicity.

Pregnancy after Bariatric Surgery: Nutrition Recommendations and Glucose Homeostasis: A Point of View on Unresolved Questions.

Obesity is increasing in all age groups and, consequently, its incidence has also risen in women of childbearing age. In Europe, the prevalence of maternal obesity varies from 7 to 25%. Maternal obesity is associated with short- and long-term adverse outcomes for both mother and child, and it is necessary to reduce weight before gestation to improve maternal and fetal outcomes. Bariatric surgery is an important treatment option for people with severe obesity. The number of surgeries performed is increasing worldwide, even in women of reproductive age, because improving fertility is a motivating factor. Nutritional intake after bariatric surgery is dependent on type of surgery, presence of symptoms, such as pain and nausea, and complications. There is also a risk of malnutrition after bariatric surgery. In particular, during pregnancy following bariatric surgery, there is a risk of protein and calorie malnutrition and micronutrient deficiencies due to increased maternal and fetal demand and possibly due to reduction of food intake (nausea, vomiting). As such, it is necessary to monitor and manage nutrition in pregnancy following bariatric surgery with a multidisciplinary team to avoid any deficiencies in each trimester and to ensure the well-being of the mother and fetus.

Can the First Fasting Plasma Glucose Test in Pregnancy Predict Subsequent Gestational Complications?

Objective: To determine the best cut-off level of pregnant women's first fasting plasma glucose (FFPG) test results for the prediction of subsequent onset of gestational diabetes mellitus (GDM) and to examine the association between FFPG and maternal and neonatal outcomes in a large Caucasian population. Methods: 1437 medical records of women with singleton pregnancies followed up between 2015 and 2018 were retrospectively analyzed. Data on FFPG tested in the first trimester and 75 g oral glucose tolerance test (OGTT) findings performed according to IADPSG criteria and Italian guidelines were collected and evaluated. The women's clinical and metabolic characteristics (age, prepregnancy body mass index (BMI), previous pregnancies complicated by GDM, timing of delivery, and gestational hypertension) were also recorded. The fetal variables considered were being large for gestational age (LGA) or small for gestational age (SGA), macrosomia, and hypoglycemia. Results: Among the 1437 pregnant women studied, 684 had a normal glucose tolerance (NGT) and 753 developed GDM. In a univariate analysis FFPG ≥92 mg/dl predicts the risk of GDM with an OR = 2.36 (95% CI 1.930-3.186; p < 0.001). In multivariate analysis, after adjusting for principal risk factors of GDM (BMI, previous GDM, age >35 years, family history of diabetes) FFPG ≥92 mg/dl was associated with the risk of GDM (OR = 1.92; 95% CI 1.488-2.492; p < 0.001). In univariate analysis, FFPG ≥92 mg/dl predict the risk of insulin therapy in GDM women with a OR = 1.88 (95% CI 1.230-2.066; p < 0.001). As regards LGA, in a multivariate analysis, after adjusting for BMI, FFPG ≥92 mg/dl was associated with the risk of LGA only in NGT women (OR = 2.34; 95% CI 1.173-4.574; p=0.014), but not in GDM women. FFPG was not associated with other maternal or neonatal outcomes. Conclusions: FFPG ≥92 mg/dl is related to GDM diagnosis and to the need of insulin therapy if GDM is diagnosed. An early diagnosis and a prompt start of insulin therapy are essential to prevent maternal and fetal complications.

Weight gain during pregnancy: A narrative review on the recent evidences.

Gestational weight gain is necessary for the normal fetus development, in fact a series of studies have evidenced that both low and excessive gestational weight gain is associated with negative fetal-neonatal outcomes. So, evidences on the optimal gestational weight gain across the ranges of the pre-pregnancy maternal body mass index are necessary. In this context, while for normal weight and underweight the recommendations of IOM are clearly stated and supported by well designed and conducted clinical studies, those for the obese pregnant women are even today debated. Pre-pregnancy obesity is associated with high risk to develop hypertension, gestational diabetes, cesarean section and high birth weight. The Institute of Medicine guidelines, in 2009, recommended that women with obesity gain 11-20 lb at a rate of 0.5 lb/week during the second and third trimesters of pregnancy. Successively, taking into account a series of meta-analysis, the American College of Obstetricians and Gynecologists emphasized that the IOM weight gain targets for obese pregnant women are too high. However the high risk to have babies small for gestational age, related to a low weight gain or a losing of weight during pregnancy, has also been demonstrated. More recent studies have taken into consideration the maternal and fetal outcomes of obese pregnant women with different obesity class (I,II,III) and different weight gain during pregnancy. The analysis of these studies, discussed in this narrative review, show that the appropriate gestational weight gain should be personalized considering the three obesity class; furthermore both an upper and lower limit of gestational weight gain should be reconsidered in order to prevent the negative maternal and fetal outcomes in these women.

Elevated insulin sensitivity and ß-cell function during pregnancy in mothers of growth-restricted newborns.

The "Barker hypothesis" suggests that low birth weight might predict future risk of developing obesity, cardiovascular disease, and type 2 diabetes. Identification of the causes of fetal growth restriction (FGR) is critical for preventive and management strategies. Some studies indicate that maternal carbohydrate metabolism might be involved in FGR development. We aimed to evaluate, in a large number of normotensive pregnant women with normal glucose tolerance, the effect of insulin sensitivity and ß-cell function on unexplained fetal growth. A total of 1,814 Caucasian pregnant women with normal prepregnancy body mass index were tested with a 75-g, 2-h glucose load (24-28 gestation wk). Insulin sensitivity was evaluated with fasting (QUICKI) and dynamic index (OGIS) and ß-cell function with a modified insulinogenic index as ΔAUC(insulin)/ΔAUC(glucose) and disposition index. FGR was a birth weight below the 5th percentile for gestational age. FGR developed in 99 (5.5%) pregnant women that showed significantly higher QUICKI, OGIS, insulinogenic, and disposition index with respect to women with normal-weight babies (P < 0.0001). By using multiple regression analysis in the FRG group, QUICKI and OGIS appeared as significant independent variables (P < 0.0001 and P < 0.0366, respectively). We conclude that elevated insulin sensitivity seems to be one of the factors involved in determining unexplained fetal growth retardation; its assessment, even only in the fasting state, could be useful to guide any possible monitoring and therapeutic strategies to reduce fetal complications.

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.

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.

Genetics and Epigenetics: New Insight on Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy, with a prevalence that has increased significantly in the last decade, coming to affect 12-18% of all pregnancies. GDM is believed to be the result of a combination of genetic, epigenetic and environmental factors. Following the identification of susceptibility genes for type 2 diabetes by means of genome-wide association studies, an association has also been demonstrated between some type 2 diabetes susceptibility genes and GDM, suggesting a partial similarity of the genetic architecture behind the two forms of diabetes. More recent genome-wide association studies, focusing on maternal metabolism during pregnancy, have demonstrated an overlap in the genes associated with metabolic traits in gravid and non-gravid populations, as well as in genes apparently unique to pregnancy. Epigenetic changes-such as DNA methylation, histone modifications and microRNA gene silencing-have also been identified in GDM patients. Metabolomics has been used to profile the metabolic state of women during pregnancy, based on the measurement of numerous low-molecular-weight metabolites. Measuring amino acids and conventional metabolites has revealed changes in pregnant women with a higher insulin resistance and high blood glucose levels that resemble the changes seen in non-gravid, insulin-resistant populations. This would suggest similarities in the metabolic profiles typical of insulin resistance and hyperglycemia whether individuals are pregnant or not. Future studies combining data obtained using multiple technologies will enable an integrated systems biology approach to maternal metabolism during a pregnancy complicated by GDM. This review highlights the recent knowledge on the impact of genetics and epigenetics in the pathophysiology of GDM and the maternal and fetal complications associated with this pathology condition.

Adherence to a follow-up program after gestational diabetes.

AIM: The aim of this study was to examine attendance for early postpartum follow-up among women with gestational diabetes mellitus (GDM), and to identify factors that influenced their likelihood of attending. METHODS: One thousand eight hundred and nineteen women with GDM were retrospectively analyzed. During pregnancy, the following data were collected: age, family history of diabetes, ethnicity, prepregnancy BMI, fasting plasma glucose, glycated hemoglobin, gestational week of GDM diagnosis, timing and mode of delivery, newborn's birth weight and length. Glycemia and insulinemia during OGTT, lipid profile and postpartum BMI were assessed at follow-up. Based on the OGTT, women were classified as having normal glucose tolerance (NGT) or abnormal glucose tolerance (AGT), which included impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and DM2. Factors predicting postpartum attendance for follow-up and onset of AGT were considered. RESULTS: Of the 889 (48.9%) who attended the scheduled postpartum OGTT, 741 (83.4%) had NGT, while 148 (16.6%) had AGT (IFG 6.7%, IGT 7.7%, IFG + IGT 0.8%, DM2 1.5%). The predictors of adherence to follow-up were: not belonging to an immigrant group; family history of DM2; and insulin therapy in pregnancy. The same factors were also predictive of AGT. Our data suggest a role of ethnicity in both attendance for postpartum follow-up and its outcome. CONCLUSION: Despite efforts to provide care for women with GDM, postpartum screening rates are still low among Italian women, and especially among immigrants. Hence, the need to improve these patients' awareness of the severe risk of developing diabetes after pregnancy, concentrating efforts especially on women belonging to the most at risk ethnic groups.

Celiac Disease and Pregnancy Outcomes in Patients with Gestational Diabetes Mellitus.

AIM: Gestational diabetes mellitus (GDM) and celiac disease, if not diagnosed and properly treated, are associated with adverse outcomes of pregnancy. The aim of our study was to examine pregnancies complicated by GDM in celiac and nonceliac women in terms of their metabolic parameters and maternal and fetal outcomes. METHODS: The study involved 60 women with GDM, 20 with and 40 without celiac disease. Maternal clinical and metabolic parameters (glucose and insulin levels in the oral glucose tolerance test (OGTT), fasting plasma glucose, HbA1c, lipid profile, prepregnancy BMI, gestational weight gain, and chronic diseases), pregnancy outcomes (gestational hypertension, pre-eclampsia, eclampsia, time, and mode of delivery), and fetal parameters (weight and length at birth, and neonatal complications) were recorded. RESULTS: The two groups did not differ significantly in maternal parameters other than blood glucose levels at 120' in the diagnostic OGTT (141.2 ± 35.2 vs 161.2 ± 35.4, mg/dl, p=0.047), prepartum cLDL (127.2 ± 43.5 vs 179.6 ± 31.7 mg/dl, p ≤ 0.001), and total cholesterol (229.0 ± 45.9 vs 292.5 ± 42.1 mg/dl, p ≤ 0.001), which were significantly lower in celiac women than in nonceliac controls. Children born from celiac women had a significantly higher birth weight (3458.1 ± 409.8 vs 3209.0 ± 432.7 g, p=0.044) and ponderal index (2.89 ± 0.32 vs 2.66 ± 0.25 g/cm3, p=0.006) and were more likely to be large for gestational age (27.8% vs 2.5%, p=0.012). Analyzing the composition of the celiac and nonceliac women's diet showed that, for the same amount of kilocalories, the gluten-free diet was associated with a slight increase in the amount of carbohydrates (49.75% vs 48.54%) and a reduction in the amount of protein (21.10% vs 23.31%) and especially of fiber (9.84% vs 12.71%). CONCLUSIONS: Celiac women with GDM have much the same pregnancy outcomes as nonceliac women with GDM, except for fetal overgrowth. Gluten-free food, being richer in carbohydrates and less rich in fiber and protein, could have a role in fetal growth in celiac women.

Is the placental proteome impaired in well-controlled gestational diabetes?

In pregnancy complicated by gestational diabetes mellitus (GDM), the human placenta shows several pathological functional and structural changes, but the extent to which maternal glycemic control contributes to placental abnormalities remains unclear. The aim of this study was to profile and compare the proteome of placentas from healthy pregnant women and those with GDM, to investigate the placenta-specific protein composition and possible changes of its function in presence of GDM. Quantitative proteomic analysis, based on LC-MSE approach, revealed that higher (approximately 15% increase) levels of galectin 1 and collagen alpha-1 XIV chain (although the difference regarding the latter was at the limit of significance) were present in GDM samples, while heat shock 70 kDa protein 1A/1B was less abundant in GDM placental tissue. These data seem to indicate that GDM, when well controlled, did not markedly affect the placental proteome.

Mediators of Lifestyle Behaviour Changes in Obese Pregnant Women. Secondary Analyses from the DALI Lifestyle Randomised Controlled Trial.

A better understanding of what drives behaviour change in obese pregnant overweight women is needed to improve the effectiveness of lifestyle interventions in this group at risk for gestational diabetes (GDM). Therefore, we assessed which factors mediated behaviour change in the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) Lifestyle Study. A total of 436 women, with pre-pregnancy body mass index ≥29 kg/m², ≤19 + 6 weeks of gestation and without GDM, were randomised for counselling based on motivational interviewing (MI) on healthy eating and physical activity, healthy eating alone, physical activity alone, or to a usual care group. Lifestyle was measured at baseline, and at 24⁻28 and 35⁻37 weeks of gestation. Outcome expectancy, risk perception, task self-efficacy and social support were measured at those same time points and considered as possible mediators of intervention effects on lifestyle. All three interventions resulted in increased positive outcome expectancy for GDM reduction, perceived risk to the baby and increased task self-efficacy. The latter mediated intervention effects on physical activity and reduced sugared drink consumption. In conclusion, our MI intervention was successful in increasing task self-efficacy, which was related to improved health behaviours.

A multicenter Italian study on pregnancy outcome in women with diabetes.

BACKGROUND AND AIM: To determine pregnancy outcome in women with type 1 and type 2 diabetes. METHODS AND RESULTS: A prospective study was conducted in 33 centers in Italy between 1999 and 2003, mainly recording preterm delivery, stillbirths, neonatal mortality, congenital malformations and birthweight. Of the 668 women examined, 504 had type 1 diabetes and 164 had type 2. Pre-pregnancy counseling had been provided to 43.9% of the women who had type 1 diabetes and 29.1% of the women who had type 2 diabetes and correlated with a better HbA1c value throughout pregnancy. The preterm delivery rate was significantly higher in type 1 and 2 diabetics than in normal pregnant women and was related to HbA1c values higher than 8%, gestational hypertension, pre-eclampsia and the presence of retinopathy before pregnancy. The stillbirth and neonatal mortality rates were also higher in diabetic pregnant women (1.26% and 0.63%, respectively) than in Italian pregnancies in general (0.30% and 0.32%), and the same was true for major congenital malformations (4.9% for diabetic pregnancies, 0.86% for normal Italian pregnancies). CONCLUSIONS: In our population, pregnancy in diabetic women was still associated with a high rate of stillbirths, neonatal mortality and congenital malformations. Unplanned pregnancies and non-optimal glycemia control may help explain the high rates of maternal and neonatal complications.

Clinical and biochemical approach to predicting post-pregnancy metabolic decompensation.

The prevalence of gestational diabetes in the developed world is increased and parallels that of obesity. Apart from the maternal and fetal complications occurring during pregnancy, GDM is characterized by a high subsequent risk of type 2 diabetes, metabolic syndrome, and cardiovascular disease. In this paper, we outline the different factors to consider in assessing the future risk of diabetes developing in women with a history of GDM. Looking at the modifiable risk factors, it is worth noting that promoting a healthy diet and lifestyle before (physical activity), during and after pregnancy (breast feeding) in women of fertile age are fundamental to the success of efforts to reduce the burden of diabetes in these young people.

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.

Ketoacidosis in diabetic pregnancy.

Diabetic ketoacidosis (DKA) is a serious medical and obstetrical emergency previously considered typical of type 1 diabetes but now reported also in type 2 and GDM patients. Although it is a fairly rare condition, DKA in pregnancy can compromise both fetus and mother. Metabolic changes occurring during pregnancy predispose to DKA in fact it can develop even in setting of normoglycemia. This article will provide the reader with information regarding the pathophysiology underlying DKA, in particular euglycemic DKA, and will provide information regarding all possible effects of ketones on the fetus.

Diabetic pregnancy outcomes in mothers treated with basal insulin lispro protamine suspension or NPH insulin: a multicenter retrospective Italian study.

OBJECTIVE: The aim of this study was to study the efficacy and safety of long-acting insulin analog insulin lispro protamine suspension (ILPS) in diabetic pregnant women. METHODS: In a multicenter observational retrospective study, we evaluated pregnancy outcome in 119 women affected by type 1 diabetes and 814 with gestational diabetes (GDM) treated during pregnancy with ILPS, compared with a control group treated with neutral protamine hagedorn (NPH) insulin. RESULTS: Among type 1 diabetic patients, fasting blood glucose at the end of pregnancy was significantly lower in ILPS-treated than in NPH-treated patients. HbA1c levels across pregnancy did not differ between groups. Caesarean section and preterm delivery rates were significantly lower in the ILPS-women. Fetal outcomes were similar in the ILPS and NPH groups. Among GDM women, fasting blood glucose at the end of pregnancy was significantly lower in ILPS-treated than in NPH-treated patients. Duration of gestation was significantly longer, caesarian section and preterm delivery rates were lower in the ILPS-treated group. In addition, there were significantly fewer babies with an excessive ponderal index or neonatal hypoglycemic episodes in the ILPS group than in the NPH group. CONCLUSIONS: Association of ILPS with rapid-acting analogs in pregnancy is safe in terms of maternal and fetal outcomes.