Nobiletin exerts anti-diabetic and anti-inflammatory effects in an in vitro human model and in vivo murine model of gestational diabetes.

Gestational diabetes mellitus (GDM) is a global health issue, whereby pregnant women are afflicted with carbohydrate intolerance with first onset during pregnancy. GDM is characterized by maternal peripheral insulin resistance, thought to be driven by low-grade maternal inflammation. Nobiletin, a polymethoxylated flavonoid, possesses potent glucose-sensitizing and anti-inflammatory properties; however, its effects in GDM have not been assessed. The present study aimed to determine the effects of nobiletin on glucose metabolism and inflammation associated with GDM in both in vitro human tissues and an in vivo animal model of GDM. In vitro, treatment with nobiletin significantly improved TNF-impaired glucose uptake in human skeletal muscle, and suppressed mRNA expression and protein secretion of pro-inflammatory cytokines and chemokines in human placenta and visceral adipose tissue (VAT). Mechanistically, nobiletin significantly inhibited Akt and Erk activation in placenta, and NF-κB activation in VAT. In vivo, GDM mice treated with 50 mg/kg nobiletin daily via oral gavage from gestational day (gd) 1-17 or via i.p. injections from gd 10-17 significantly improved glucose tolerance. Pregnant GDM mice treated with nobiletin from either gd 1-17 or gd 10-17 exhibited significantly suppressed mRNA expression of pro-inflammatory cytokines and chemokines in placenta, VAT and subcutaneous adipose tissue (SAT). Using a quantitative mass spectrometry approach, we identified differentially abundant proteins associated with the effect of nobiletin in vivo. Together, these studies demonstrate that nobiletin improves glucose metabolism and reduces inflammation associated with GDM and may be a novel therapeutic for the prevention of GDM.

How do older adults with multimorbidity navigate healthcare?: a qualitative study in Singapore.

BACKGROUND: Patients living with multimorbidity may require frequent visits to multiple healthcare institutions and to follow diverse medical regimens and advice. Older adults with multimorbidity could face additional challenges because of declining cognitive capability, frailty, increased complexity of diseases, as well as limited social and economic resources. Research on how this population navigates the healthcare system in Singapore also remains unknown. This study investigates the challenges older adults with multimorbidity face in navigating healthcare in Singapore. METHODS: Twenty older adults with multimorbidity from a public primary care setting were purposively sampled. Interviews conducted inquired into their experiences of navigating the healthcare system with multiple conditions. Inductive thematic analysis was performed by independent coders who resolved differences through discussion. RESULTS: Older adults with multimorbidity form a population with specific characteristics and challenges. Their ability to navigate the healthcare system well was influenced by these themes including patient-related factors (autonomy and physical mobility, literacy and technological literacy, social support network), healthcare system-related factors (communication and personal rapport, fragmented system, healthcare staff as advocate) and strategies for navigation (fitting in, asking for help, negotiating to achieve goals, managing the logistics of multimorbidity). DISCUSSION: Older adults with multimorbidity should not be treated as a homogenous group but can be stratified according to those with less serious or disruptive conditions (less burden of illness and burden of treatment) and those with more severe conditions (more burden of illness and burden of treatment). Among the latter, some became navigational experts while others struggled to obtain the resources needed. The variations of navigational experiences of the healthcare system show the need for further study of the differential needs of older adults with multimorbidity. To be truly patient-centred, healthcare providers should consider factors such as the existence of family support networks, literacy, technological literacy and the age-related challenges older adults face as they interact with the healthcare system, as well as finding ways to improve healthcare systems through personal rapport and strategies for reducing unnecessary burden of treatment for patients with multimorbidity.

Experiences of older primary care patients with multimorbidity and their caregivers in navigating the healthcare system: A qualitative study protocol.

BACKGROUND: Patients with multimorbidity must bear not just the burden of their illness, but also the burden of treatment which is, in part, induced by their interactions with the healthcare system. The need to shuttle between different healthcare institutions and multiple healthcare providers can make navigating the healthcare system challenging, and this may be even more so for older patients with limited resources and support. OBJECTIVES: Few qualitative studies have explored the experiences of patients with multimorbidity in navigating the healthcare system. This study will explore the experiences of older patients with multimorbidity and their caregivers as they navigate through the healthcare system. We aim to arrive at a better understanding of patient experiences of possible gaps in the continuity of care and how the current system can be modified and adapted to better address the needs of older patients with multimorbidity. METHOD: Semi-structured, in-depth interviews will be conducted with purposively sampled older patients with multimorbidity, aged 60 and above seen in primary care, together with their caregivers. Interviews will be transcribed verbatim and analysed by the study team using inductive thematic analysis. CONCLUSIONS: Our study seeks to explore the navigational experiences within the healthcare system for older patients with multimorbidity in an Asian, multi-ethnic society. The findings will be shared with decision-makers in the healthcare setting in order to improve patient care for this population and ultimately maximise their positive health outcomes, and will add to better understanding how the burden of treatment arising from navigational challenges within the healthcare system may be reduced for older patients with multimorbidity.