Bridging the Digital Divide in Diabetes Care With an AI-Powered Health Coaching Intervention: Qualitative Formative Study.

Among the many early life risk factors, maternal high-fat diet (mHFD) has become an increasingly serious nutritional problem during pregnancy worldwide. This dietary pattern usually refers to a diet with a fat-to-energy ratio of more than 35% (). From the perspective of nutritional epidemiology, the connotation of “high fat” is far more than the increase in energy supply ratio, and its core harm lies in the serious imbalance of dietary fatty acid composition (). Typical Western high-fat diet is rich in saturated fatty acids (SFA) such as palmitic acid and n-6 polyunsaturated fatty acids (PUFA), while long-chain n-3 PUFA, especially docosahexaenoic acid (DHA), are seriously deficient (). This high n-6/n-3 ratio state is not only a core nutritional incentive that drives maternal metabolic inflammation, but also directly changes the selective transport spectrum of essential fatty acids in the placenta, transforming a simple “calorie excess” into a far-reaching “nutritional programming signal” (, ). Animal experiments and population studies have shown that a high-fat diet can induce excessive fat accumulation and homeostasis disorders, leading to a variety of metabolic disorders (). With the globalization of Western dietary patterns, the dietary fat intake of women of childbearing age before and during pregnancy continues to rise, which has become a public health issue that cannot be ignored. The core pathological feature of mHFD is the continuous enhancement of maternal systemic low-grade chronic inflammation and oxidative stress (). This pathological state can reshape the fetal intrauterine microenvironment through the placental barrier, thereby interfering with the central nervous system. In particular, it causes selective damage to the mesencephalic dopaminergic (DAergic) system, which has extremely high energy metabolism requirements and is highly sensitive to inflammation and oxidative damage (, ). Studies have shown that maternal metabolic status during pregnancy increases the risk of autism or other neurodevelopmental disorders in their children (). At present, the global population is accelerating into an aging society. The prevalence of neurodegenerative diseases represented by Parkinson's disease (PD) continues to rise, and the disease burden is increasing. However, there is still a lack of effective early warning and radical treatment. In this context, it is of great scientific significance and public health value to explore the potential programming effect of early life environmental factors on PD susceptibility. PD is the world's second most common disease, and its incidence has continued to rise over the past half century (). Statistics show that between 1990 and 2015, the number of PD patients worldwide reached more than 6 million; affected by an aging population, this number is expected to double again to more than 12 million by 2040 (). Previous studies have focused on the role of environmental changes and genetic mutations in PD in adulthood. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposed by existing studies provides a new perspective for the analysis of PD. In 1986, Barker speculated based on historical data that the adverse environment in the early life will permanently affect the body structure and function, thereby increasing the risk of chronic diseases in later life. This argument was originally called the “fetal origin hypothesis” (). In 2003, the International DOHaD Society was established. Previously, some scholars have pointed out that environmental factors in early life, especially the intrauterine environment, can have a profound impact on the long-term health of individuals. As the direct environment of fetal development, the physiological state of the mother affects the development trajectory of the offspring through complex biological mechanisms (). The “fetal origin hypothesis” is extended to a more comprehensive “developmental origin” theory, and the influence window is extended to the early stage after birth. At present, the research on the correlation mechanism between mHFD and the susceptibility of offspring to PD is still in the exploratory stage. The existing animal experiments and clinical cohort studies have preliminarily revealed that insulin resistance-related signaling pathway disorders and mitophagy dysfunction may be the core regulatory links (). Based on the above background, this paper focuses on the exposure factor of mHFD, reviews its specific damage to the development of DAergic system in the midbrain of offspring, and focuses on the synergistic pathogenic mechanism of IR-NF-κB inflammatory pathway and PINK1/Parkin mitophagy pathway in increasing the susceptibility of offspring to PD. On this basis, this paper will also explore the prospects of the above mechanisms into clinical transformation, including the development of early warning biomarkers and the exploration of targeted intervention strategies, as well as the current core