Relationship between years since menopause and lipid variation in postmenopausal women: A cross-sectional study

Lipid alteration in postmenopausal women is commonly due to hormonal changes. This study aimed to explore the association between the years since menopause and lipid profiles in postmenopausal women. In this cross-sectional study, a total of 1033 postmenopausal women were recruited from the Women’s Hospital of Zhejiang University in China between 2015 and 2022. Each participant was interviewed using questionnaires regarding sociodemographic and reproductive data. Anthropometric measurements, lipid profiles, and reproductive hormone levels were assessed. Participants were divided into 3 groups based on the length of time since menopause: 2, 2 to 5.9, and 6 years. Differences in lipid profiles and reproductive hormones among the groups were compared. Logistic and linear regression analyses were used to examine the relationship between years after menopause and lipid profile. High-density lipoprotein cholesterol (HDL-C) and luteinizing hormone levels were significantly lower in postmenopausal women with time since menopause of ≥6 years than those <2 years (P < .05), whereas low-density lipoprotein cholesterol levels were significantly higher (P < .05). A longer time after menopause was independently associated with lower HDL-C levels (β, −0.059, standard error, 0.023, P = .01) after adjustment for age, body mass index, and other confounders. Compared to women who had menopause for <2 years, those who were postmenopausal for >6 years had lower HDL-C levels after adjustment for age, body mass index, and other covariates (β, −0.123, 95% confidence interval, [−0.221, −0.014], P = .014). Longer time since menopause was associated with an atherogenic lipid profile with appreciably low levels of HDL-C subfraction. Future multicenter studies are necessary to examine postmenopausal population and determine how differences in lipids influence the risk of cardiovascular disease in this group.     

Discovery and evaluation of biphenyl derivatives of 2-iminobenzimidazoles as prototype dual PTP1B inhibitors and AMPK activators with in vivo antidiabetic activity

This work describes the synthesis of series hydrobromides of N-(4-biphenyl)methyl–N′-dialkylaminoethyl-2-iminobenzimidazoles, which, due to the presence of two privileged structural fragments (benzimidazole and biphenyl moieties), can be considered as bi-privileged structures. Compound 7a proved to activate AMP-activated kinase (AMPK) and simultaneously inhibit protein tyrosine phosphatase 1B (PTP1B) with similar potency. This renders it an interesting prototype of potential antidiabetic agents with a dual-target mechanism of action. Using prove of concept in vivo study, we show that dual-targeting compound 7a has a disease-modifying effect in a rat model of type 2 diabetes mellitus via improving insulin sensitivity and lipid metabolism.