Chronic low-grade inflammation plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). To investigate the ability of different inflammatory blood cell parameters in predicting the development of GDM and pregnancy outcomes, 258 women with GDM and 1,154 women without were included in this retrospective study. First-trimester neutrophil count outperformed white blood cell count and the neutrophil-to-lymphocyte ratio in the predictability for GDM. Subjects were grouped based on tertiles of neutrophil count during their first-trimester pregnancy. The results showed that as the neutrophil count increased, there was a stepwise increase in GDM incidence as well as in glucose and glycosylated hemoglobin levels, HOMA for insulin resistance (HOMA-IR), macrosomia incidence, and newborn weight. Neutrophil count was positively associated with prepregnancy BMI, HOMA-IR, and newborn weight. Additionally, neutrophil count was an independent risk factor for the development of GDM, regardless of the history of GDM. Spline regression showed that there was a significant linear association between GDM incidence and the continuous neutrophil count when it was >5.0 × 10⁹/L. This work suggested that the first-trimester neutrophil count is closely associated with the development of GDM and adverse pregnancy outcomes.

Context The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. Objective Here, we investigated the potential effect of monocytes in GDM. Methods Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages, and their products were measured. Results Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and was closely associated with glucose level, insulin resistance, and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia both in the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level, and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 10⁹/L. Notably, CD206 and interleukin 10 (IL-10) were significantly lower, whereas CD80, CD86, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) were higher both in GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α, and IL-6. Conclusion Decreased monocyte count throughout pregnancy was closely associated with the development of GDM, macrosomia, and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.

The efficacy and safety of a lower dose of vitamin E for metabolic dysfunction-associated steatohepatitis (MASH) treatment are unclear. This multi-center, randomized, double-blind, placebo-controlled study includes 124 non-diabetic participants with biopsy-proven MASH. Participants are randomly assigned to receive oral vitamin E 300 mg or the placebo in a 1:1 ratio. The primary outcome is improvement in hepatic histology. In the modified intention-to-treat population, 29.3% of participants in the vitamin E group achieve the primary outcome compared with 14.1% in the placebo group. Significant improvement in steatosis, lobular inflammation, and fibrosis stages is observed in the vitamin E group. 12 serious adverse events are reported in this trial but are not considered to be related to the treatment. Vitamin E 300 mg daily achieves sound improvements in liver histology in the Chinese population with MASH. This study is registered at ClinicalTrials.gov (NCT02962297).

Context: Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease, associated with fibrosis and an increased risk of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Objective: This work aimed to investigate the association of NAFLD fibrosis with the development of CKD in aged patients with T2DM. Methods: This cross-sectional study enrolled 13 915 participants. A further 1734 individuals who had been followed annually for 5 years comprised the retrospective cohort study. Noninvasive markers, NAFLD fibrosis score (NFS), and fibrosis index based on 4 factors (FIB-4) were applied to determine NAFLD fibrosis risk. Results: In the cross-sectional study, there was an additive interaction for NAFLD with increased risk of fibrosis and T2DM on CKD incidence. Logistic regression demonstrated that as NAFLD fibrosis risk progressed from low to intermediate and high, there was a stepwise increase in CKD in patients with NAFLD, T2DM, and those with coexistent NAFLD and T2DM when stratified by diabetes and fibrosis stage. FIB-4 had a much higher odds ratio (OR) value than NFS for prediction of CKD incidence. In the cohort study, individuals were grouped according to FIB-4 and NFS. Cox regression analysis showed that FIB-4 intermediate risk (hazard ratio [HR] 1.268; 95% CI, 1.056-1.521) and high risk (HR 2.516; 95% CI, 1.970-3.214) were significant predictors of CKD progression. When NFS was applied, only high risk was a significant predictor. Conclusion: NAFLD with an increased risk of fibrosis and presence of T2DM had an additive interaction on CKD incidence. Increased risk of NAFLD fibrosis was closely associated with CKD incidence and progression in aged T2DM patients. FIB-4 outperformed NFS as a noninvasive means to predict CKD development.

Background: This study aimed to investigate the association of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis with osteoporosis in postmenopausal women and men over 50 years of age with type 2 diabetes (T2DM). Methods: In this study, 1243 patients with T2DM (T2DM with coexistent NAFLD, n = 760; T2DM with no NAFLD, n = 483) were analysed. Non-invasive markers, NAFLD fibrosis score (NFS) and fibrosis index based on four factors (FIB-4), were applied to evaluate NAFLD fibrosis risk. Results: There was no significant difference in bone mineral density (BMD) between the NAFLD group and the non-NAFLD group or between males and females after adjusting for age, BMI and gender. In postmenopausal women, there was an increased risk of osteoporosis (odds ratio (OR): 4.41, 95% CI: 1.04–18.70, P = 0.039) in the FIB-4 high risk group compared to the low risk group. Similarly, in women with high risk NFS, there was an increased risk of osteoporosis (OR: 5.98, 95% CI: 1.40–25.60, P = 0.043) compared to the low risk group. Among men over 50 years old, there was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group and no significant difference between bone mineral density and incidence of osteopenia or osteoporosis among those with different NAFLD fibrosis risk. Conclusion: There was a significant association of high risk for NAFLD liver fibrosis with osteoporosis in postmenopausal diabetic women but not men. In clinical practice, gender-specific evaluation of osteoporosis is needed in patients with T2DM and coexistent NAFLD.