The prevalence of elderly pregnancy and maternal obesity is increasing worldwide. In old and obese women, metabolic derangement affecting fetal growth might be present earlier than the diagnosis of gestational diabetes mellitus (GDM) or even before pregnancy. We thus investigated whether GDM diagnosed at 24–28 weeks of gestation had already affected fetal abdominal growth and, if so, whether elderly pregnancy and/or maternal obesity aggravate fetal abdominal obesity. We retrospectively reviewed the medical records of 7820 singleton pregnant women who had been universally screened using a 50-g glucose challenge test (GCT) at 24–28 weeks of gestation, and underwent a 3-h 100-g oral glucose tolerance test (OGTT) if GCT were ≥140mg/dl. GDM and normal glucose tolerance (NGT) were diagnosed using the Carpenter-Coustan criteria. Fetal abdominal obesity was investigated by assessing the fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference per actual GA by the last menstruation period, biparietal diameter or femur length, respectively. Fetal abdominal overgrowth was defined as FAOR ≥ 90^th percentile. The subjects were divided into four study groups: group 1 (age < 35 years and pre-pregnancy body mass index [BMI] < 25 kg/m²), group 2 (age < 35 years and ≥ 25), group 3 (age ≥ 35 years and BMI < 25), and group 4 (age ≥ 35 years and ≥ 25). The overall prevalence of GDM was 5.1%, with old and obese group 4 exhibiting the highest prevalence (22.4%). FAORs were significantly higher in the fetus of those with GDM than in the NGT subjects. But, in the subgroup analysis, only old and nonobese group 3 and old and obese group 4 with GDM exhibited significantly higher FAORs than the NGT subjects. Also, risk of fetal abdominal overgrowth was increased in group 3 and 4 subjects with GDM but not in young and nonobese group 1 GDM. The risk of fetal abdominal overgrowth significantly increased with maternal age >35 years, pre-pregnancy BMI >20kg/m², and HbA1c >37.7 mmol/mol (5.6%). In multivariate analyses, maternal age and HbA1c were significantly associated with FAORs. GDM diagnosed at 24–28 weeks of gestation already affected fetal abdominal obesity in older and/or obese women, but not in younger and nonobese women. Our data suggest that selective screening and appropriate intervention of GDM earlier than 24–28 weeks of gestation might be necessary for high-risk old and/or obese women.

Kim HJ, et al. Cardiometab Syndr J. 2024 Aug;4:e14. https://doi.org/10.51789/cmsj.2024.4.e14

Background: Fetal abdominal obesity (FAO) has been reported to be affected at gestational diabetes mellitus (GDM) diagnosis at 24 to 28 weeks of gestation in older and/or obese women. This study investigated whether the management of GDM improves FAO in GDM subjects near term.Methods: Medical records of 7,099 singleton pregnant women delivering at CHA Gangnam Medical Center were reviewed retrospectively. GDM was diagnosed by 100-g oral glucose tolerance test after 50-g glucose challenge test based on Carpenter–Coustan criteria. GDM subjects were divided into four study groups according to maternal age and obesity. FAO was defined as ≥90th percentile of fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference per actual GA by the last menstruation period, biparietal diameter, or femur length, respectively.Results: As compared with normal glucose tolerance (NGT) subjects near term, FAORs and odds ratio for FAO were significantly higher in old and/or obese women with GDM but not in young and nonobese women with GDM. For fetuses of GDM subjects with FAO at the time of GDM diagnosis, the odds ratio for exhibiting FAO near term and being large for GA at birth were 7.87 (95% confidence interval [CI], 4.38 to 14.15) and 10.96 (95% CI, 5.58 to 20.53) compared with fetuses of NGT subjects without FAO at GDM diagnosis.Conclusion: Despite treatment, FAO detected at the time of GDM diagnosis persisted until delivery. Early diagnosis and treatment might be necessary to prevent near term FAO in high-risk older and/or obese women.

Background: This study aimed to investigate whether sleep duration and/or quality are associated with incident diabetes mellitus (DM). Methods: A total of 8816 of 10,030 healthy participants were enrolled in a prospective cohort study. Sleep duration and quality questionnaires were completed. Sleep quality was assessed using the Epworth Sleepiness Scale (ESS), which measures excessive daytime sleepiness in individuals. Results: During the 14-year follow-up period, 18% (1630/8816) were diagnosed with DM. A U-shaped relationship was observed between sleep duration and incident DM, with the highest risk observed when sleep duration was ≥10 h/day (hazard ratios (HR) 1.65 [1.25–2.17]). This group exhibited decreased insulin glycogenic index, a marker of insulin secretory function, during the study period. Among study participants who slept less than 10 h/day, the risk of incident DM increased when the ESS score was >10. Conclusions: We found that the association between sleep duration and incident DM was U-shaped; both short (≤5 h) and long (≥10 h) sleep durations were associated with an increased risk for the occurrence of incident DM. When sleep duration was 10 h or longer per day, there was a tendency to develop DM due to decreased insulin secretory function.

Background: Crosstalk between tumors and their microenvironment plays a crucial role in the progression of hepatocellular carcinoma (HCC). However, there is little existing information about the key signaling molecule that modulates tumor-stroma crosstalk. Methods: Complementary DNA (cDNA) microarray analysis was performed to identify the key molecule in tumor-stroma crosstalk. Subcutaneous xenograft in vivo murine model, immunoblotting, immunofluorescence, and real-time polymerase chain reaction using HCC cells and tissues were performed. Results: The key molecule, regenerating gene protein-3A (REG3A), was most significantly enhanced when coculturing HCC cells and activated human hepatic stellate cells (HSCs) (+8.2 log) compared with monoculturing HCC cells using cDNA microarray analysis. Downregulation of REG3A using small interfering RNA significantly decreased the proliferation of HSC-cocultured HCC cells in vitro and in vivo, and enhanced deoxycholic acid-induced HCC cell apoptosis. Crosstalk-induced REG3A upregulation was modulated by platelet-derived growth factor ββ (PDGF-ββ) in p42/44-dependent manner. REG3A mRNA levels in human HCC tissues were upregulated 1.8-fold compared with non-tumor tissues and positively correlated with PDGF-ββ levels. Conclusions: REG3A/p42/44 pathway/PDGF-ββ signaling plays a significant role in hepatocarcinogenesis via tumor-stroma crosstalk. Targeting REG3A is a potential novel therapeutic target for the management of HCCs by inhibiting crosstalk between HCC cells and HSCs.