Prevalence of gestational diabetes mellitus risk factors in singleton pregnancies obtained by assisted reproductive technology: An observational, retrospective, real-world study from a pregnancy registry.

AIMS: Several studies showed that Assisted Reproductive Technology (ART) could affect gestational diabetes mellitus (GDM) onset. The aim of this study was to estimate the prevalence of GDM risk factors in a cohort of women with singleton pregnancy obtained by ART and complicated by GDM. Maternal and neonatal outcomes were explored. METHODS: We retrospectively collected data of pregnancies of women with singleton pregnancy obtained by ART and complicated by GDM consecutively cared for at a specialized center for diabetes and pregnancy care. Prevalence and combination of GDM risk factors, their combinations and maternal-fetal outcomes were estimated. RESULTS: Overall, our cohort included 50 women (mean age of 40.4 ± 4.7 years, mean pre-pregnancy BMI 26.3 ± 6.2 kg/m2). The most frequent GDM traditional risk factors were age ≥ 35 years (94 %), family history of diabetes (44 %), overweight (29 %) and obesity (19 %). Combining risk factors, 5 groups were identified with 1, 2, 3, 4, or 5 risk factors with a prevalence respectively of 28 %, 46 %, 20 %, 4 %, and 2 %. Examining features of the above groups, pre-pregnancy weight (p < 0.0001) and pre-pregnancy BMI (p < 0.0001) statistically significant differed in the 5 groups, increasing with higher numbers of risk factors. Regarding neonatal outcomes only neonatal hypoglycemia (p = 0.03) differed significantly among the groups, with higher percentages in women with higher numbers of combined risk factors. CONCLUSION: Prevalence of GDM traditional risk factors in singleton ART pregnancies complicated by GDM is considerable. Such pregnancies need appropriate clinical attention because of the risk of adverse outcomes.

Advancements in pharmacological treatment of NAFLD/MASLD: a focus on metabolic and liver-targeted interventions.

In the present narrative review, we have summarized evidence on the pharmacological treatment of non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD). We start by reviewing the epidemiology of the condition and its close association with obesity and type 2 diabetes. We then discuss how randomized-controlled trials are performed following guidance from regulatory agencies, including differences and similarities between requirements of the US Food and Drug Administration and the European Medicine Agency. Difficulties and hurdles related to limitations of liver biopsy, a large number of screening failures in recruiting patients, as well as unpredictable response rates in the placebo group are evaluated. Finally, we recapitulate the strategies employed for potential drug treatments of this orphan condition. The first is to repurpose drugs that originally targeted T2DM and/or obesity, such as pioglitazone, glucagon-like peptide 1 receptor agonists (liraglutide and semaglutide), multi-agonists (tirzepatide and retatrutide), and sodium-glucose transporter 2 inhibitors. The second is to develop drugs specifically targeting NAFLD/MASLD. Among those, we focused on resmetirom, fibroblast growth factor 21 analogs, and lanifibranor, as they are currently in Phase 3 of their clinical trial development. While many failures have characterized the field of pharmacological treatment of NAFLD/MASLD in the past, it is likely that approval of the first treatments is near. As occurs in many chronic conditions, combination therapy might lead to better outcomes. In the case of non-alcoholic steatohepatitis, we speculate that drugs treating underlying metabolic co-morbidities might play a bigger role in the earlier stages of disease, while liver-targeting molecules will become vital in patients with more advanced disease in terms of inflammation and fibrosis.

Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Screening, Diagnosis, and Treatment.

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~70% of patients with type 2 diabetes (T2D), with ~20% showing signs of advanced liver fibrosis. Patients with T2D are at an increased risk of developing cirrhosis, liver failure, and hepatocellular carcinoma and their liver-related mortality is doubled compared with non-diabetic individuals. Nonetheless, the condition is frequently overlooked and disease awareness is limited both among patients and among physicians. Given recent epidemiological evidence, clinical practice guidelines recommend screening for NAFLD/MASLD and advanced liver fibrosis in patients with T2D. While many drugs are currently being tested for the treatment of NAFLD/MASLD, none of them have yet received formal approval from regulatory agencies. However, several classes of antidiabetic drugs (namely pioglitazone, sodium-glucose transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and multi-agonists) have shown favorable effects in terms of liver enzymes, liver fat content and, in some occasions, on histologic features such as inflammation and fibrosis. Therefore, diabetologists have the opportunity to actively treat NAFLD/MASLD, with a concrete possibility of changing the natural history of the disease. In the present narrative review, we summarize evidence and clinical recommendations for NAFLD/MAFLD screening in the setting of T2D, as well as on the effect of currently available glucose-lowering drugs on hepatic endpoints.