Assisted reproductive technology, risk of gestational diabetes, and perinatal outcomes in singleton pregnancies.

AIMS: To evaluate the impact of assisted reproductive technology (ART) on the risk of gestational diabetes mellitus (GDM) in single pregnancies. MATERIALS AND METHODS: We 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. RESULTS: There 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. Among ART-women, age over 40 years was associated with GDM. Preterm delivery was more common in ART-women; gestational week at delivery, birth weight, ponderal index, and Apgar score were lower in ART-women than in SC-women, both in the whole cohort and in GDM women. CONCLUSIONS: Among women undergoing ART treatment, at least one in two develops GDM. ART appears to be an independent risk factor for GDM in single pregnancies, particularly above the age of 40. ART treatment seems to be associated with an increased rate of preterm delivery and lower neonatal birth weight and Apgar score, especially in GDM women. CLINICAL TRIAL REGISTRATION: The study was not registered as it is an observational retrospective evaluation.

Short sleep duration and risk of gestational diabetes.

ObjectiveSleep disturbances and short sleep duration are common in pregnancy and might contribute to the development of hyperglycemia. Therefore, we evaluated the association of sleep disturbances and gestational diabetes (GDM) in a cohort of women.MethodsWe collected data of 386 women consecutively screened for GDM in 2019 by 75 gr OGTT, according with IDPSG criteria. Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to assess self-reported poor sleep quality (PSQI score >5) and short nocturnal sleep duration (<6 h).ResultsOf 386 women, 148 (38.3%) had poor sleep quality and 87 (22.5%) short sleep duration. GDM prevalence was 26.9%. There was no difference in GDM prevalence between women with poor or good sleep quality (26% vs. 28%; n.s.), while GDM was more frequent in women with short sleep duration (35.6% vs. 24.4%; p = 0.038). On univariate logistic regression analysis, short sleep duration (OR 1.71; 95%CI: 1.03-2.86; p = 0.039), previous GDM (OR 3.52; 95%CI: 1.83-6.76; p < 0.0001), family history of diabetes (OR 1.96; 95%CI: 1.21-3.91; p = 0.007), pre-pregnancy overweight (OR 1.85; 95%CI: 1.06-3.23; p = 0.031) or obesity (OR 2.56; 95%CI: 1.40-4.70; p = 0.002) were associated to GDM. However, after adjustment for confounders, short sleep duration did not persist as an independent risk factor for GDM (OR: 1.55; 95%CI: 0.91-2.65; ns).ConclusionsSleep disturbances are relative common among pregnant women. Although GDM seems more common among women with short sleep duration, this sleep disturbance does not seem to be an independent risk factor for GDM in women at high risk.

Accuracy of intermittently scanned continuous glucose monitoring during caesarean delivery in pregnant women with insulin-treated diabetes.

AIM: Continuous Glucose Monitoring (CGM) systems are not currently recommended to guide intrapartum glucose and insulin infusion, due to insufficient data. In this study, intrapartum accuracy of intermittently scanned CGM (isCGM), compared to simultaneously measured capillary glucose (CG), was evaluated. METHODS: Paired isCGM (Freestyle Libre 2) - CG data during caesarean delivery in pregnant women with insulin-treated diabetes were prospectively collected. The isCGM accuracy was assessed by MARD and Clarke Error Grid analysis. Moreover, the impact on intrapartum management was evaluated. RESULTS: Sixty-eight paired isCGM-CG data of 19 women were evaluated. The overallMARD was 9.28 %. All values were in A and B zones of Clarke Error Grid. Forty-six (68 %) isCGM-CG pairs were in the same glycemic range, meaning the same intrapartum management. All discordant data were identified by checking CG in case of isCGM above 110 mg/dL or less than 70 mg/dL [chi-square 21.76, p < 0.001]. At ROC curve, isCGM above 110 mg/dL was associated with 100 % sensitivity to discordant result at CG (AUC 0.859, p < 0.001). CONCLUSION: The accuracy of isCGM during caesarean delivery was good, particularly for glucose values between 70 and 110 mg/dL, when CG confirmation could be safely avoided.

Predicting the Risk of Adverse Neonatal Outcomes in Women With Insulin-Treated Diabetes: Is It Time for a Pregnancy-Specific Glycemic Risk Index (GRI)?

BACKGROUND: The Glycemia Risk Index (GRI) describes the quality of glycemic control, emphasizing extreme hypoglycemia and hyperglycemia more than less extreme values. However, a pregnancy-specific GRI (pGRI), tailored to the tighter target glucose range required during pregnancy, has not been established. METHODS: We retrospectively evaluated clinical, metabolic, and Continuous Glucose Monitoring (CGM) data across pregnancy in women with insulin-treated diabetes, managed between September 2021 and March 2024 at the University Hospital of Pisa. First and second levels of hyperglycemia (TAR1: 140-180 mg/dL, TAR2: >180 mg/dL) and hypoglycemia (TBR1: 63-54 mg/dL, TBR2: <54 mg/dL) were used to calculate the pGRI at each trimester. Logistic regression analysis investigated the association between pGRI and risk of at least one adverse neonatal outcome (among preterm delivery, macrosomia, large for gestational age, small for gestational age, neonatal hypoglycemia, neonatal jaundice, and neonatal intensive care unit admission). RESULTS: Of 45 pregnant women, 25 (56%) experienced at least one adverse neonatal outcome. In the third trimester, women with adverse outcomes had significantly higher total TAR (26 [12-32]% vs 10 [4-23]%, P = .018) and lower TIR (71 [64-83]% vs 88 [75-92]%, P = .007). Specifically, the difference was notable in TAR2 (6 [2-15]% vs 1 [0-4]%, P = .004), whereas TAR1 was comparable between the 2 groups. Accordingly, third trimester pGRI was higher in women with adverse neonatal outcomes (38 [18-49]% vs 18 [10-31]%, P = .013) and, at logistic regression, slightly but significantly increased the risk of adverse neonatal outcomes (1.044 [1.004-1.086], P = .024). CONCLUSIONS: Pregnant women with insulin-treated diabetes reporting adverse neonatal outcomes spent more time in hyperglycemia, particularly in extreme hyperglycemia. Therefore, the level of hyperglycemia should always be assessed during pregnancy. The pGRI, emphasizing extreme hyperglycemia, may be a novel comprehensive tool for assessing the risk of adverse neonatal outcomes.

Advances in diabetes management: have pregnancy outcomes in women with type 1 diabetes changed in the last decades?

AIMS: Over the recent years multiple therapeutic and management opportunities have been made available to treat pregnant women with Type 1 diabetes (T1DM). However, analyses assessing whether these different approaches may have any specific advantage/disadvantage in metabolic control and neonatal outcomes is still limited. The aim of this study was to compare metabolic control and neonatal outcomes in pregnant women with T1DM among different basal insulins (NPH vs. analogue), insulin administration ways [Multiple Daily Injections (MDI) vs. Continuous Subcutaneous Insulin Infusion (CSII)] and glucose monitoring systems [Self-Monitoring of Blood Glucose (SMBG) vs. real-time/intermittently scanned Continuous Glucose Monitoring (rtCGM/isCGM)]. METHODS: A retrospective analysis on metabolic data and neonatal outcomes of 136 T1DM pregnant women (76% on MDI, based on NPH (51%) or analogue (49%); 24% on CSII; 24% using rtCGM/isCGM), managed between 2008 and 2020, was performed, comparing different therapeutic approaches. RESULTS: Metabolic data and neonatal outcomes were comparable among women treated with different basal insulins. Women on CSII planned their pregnancy more frequently (82 vs. 60%; p = 0.043) and had better pregestational HbA1c (52 ± 5 vs. 60 ± 13 mmol/mol; p = 0.044) and first trimester HbA1c (48 ± 4 vs. 51 ± 8 mmol/mol; p = 0.047). Pregestational and first trimester HbA1c were also lower in women using rtCGM/isCGM (53 ± 8 vs. 58 ± 13 mmol/mol; p = 0.027 and 46 ± 5 vs. 51 ± 7 mmol/mol; p = 0.034, respectively). In the whole cohort, LGA risk was directly correlated to HbA1c at third trimester (correlation coefficient: 0.335, p = 0.001) and inversely correlated to the achievement of HbA1c target (≤6% [<42 mmol/mol]) at third trimester (correlation coefficient: - 0.367, p < 0.001). CONCLUSION: Treatment with insulin analogs didn't significantly change metabolic control and neonatal outcomes in T1DM women, while CSII and rtCGM/isCGM can optimize preconception and first trimester pregnancy glycemic control. Irrespective of the therapeutic management, third trimester HbA1c remains the strongest risk factor for LGA.

De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes.

AIMS: To evaluate the impact of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in people with type 2 diabetes (T2D) in basal-bolus (BB) insulin regimen, on insulin requirement, HbA1c, weight loss up to 24 months. METHODS: Data on subjects with T2D on BB who initiated a GLP-1 RA have been retrospectively collected. HbA1c, body weight, and insulin dose were recorded at baseline, 6, 12, and 24 months after initiation of GLP-1 RA therapy. A linear mixed model for repeated measures was used to evaluate the changes in HbA1c, body weight, and insulin requirement over time. RESULTS: We included 156 subjects (63.5% males; age 62 ± 11 years, HbA1c 70 ± 22.0 mmol/mol; 8.6 ± 4.2%). Compared to baseline, HbA1c and body weight were significantly lower at 6 months after introducing a GLP-1RA and remained stable up to 24 months (all p < 0.0001 vs. baseline). At 24 months, 81% of subjects discontinued prandial insulin, while 38.6% discontinued basal insulin as well. Insulin requirement at baseline (aOR 0.144; 95% CI, 0.046-0.456; P = 0.001) was the only significant predictor of prandial insulin discontinuation. CONCLUSIONS: Replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen while improving glycaemic control and promoting weight loss in subjects with T2D.

BRAF K601E Mutation in Oncocytic Carcinoma of the Thyroid: A Case Report and Literature Review.

BACKGROUND: Thyroid carcinoma (TC) is the most common endocrine cancer, with papillary thyroid carcinoma (PTC) being the most common subtype. BRAF and RAS oncogene were characterized as the most frequently altered genes in PTC, with a strong association between genotype and histotype. The most common mutation in BRAF gene is V600E and is prevalent in classic and aggressive variants of PTC, while BRAF K601E mutation is the most common among the other rare BRAF mutations. BRAF K601E mutated thyroid carcinomas are usually characterized by low aggressiveness, except for anecdotal cases of poorly differentiated TC. CASE PRESENTATION: We described a case of oncocytic carcinoma of the thyroid (OCA) with an aggressive clinical course, including widespread metastasis and resistance to radioiodine treatment. Molecular analysis revealed the exclusive presence of the BRAF K601E mutation in both primary tumor and metastatic lesions. Accordingly, a revision of the literature about aggressive TC cases carrying BRAF K601E mutation was performed. CONCLUSION: Although rare, this case emphasizes the relevance of considering BRAF K601E mutation in advanced non-PTC thyroid carcinomas, since it can be considered an actionable mutation for target therapies.

Use of non-nutritive-sweetened soft drink and risk of gestational diabetes.

In this observational study, we assessed the association between use of non-nutritive-sweetened soft drink (NNSSD) and risk of gestational diabetes (GDM) in 376 pregnant women consecutively screened for GDM, observing that NNSSD consumption is common among pregnant women and is associated with an increased risk of GDM, independently from traditional risk factors.