4 | Future prospects
It can be easily found that this comprehensive program will help to translate new technologies and research into clinical practice and reverse T2D due to strengthening prevention and management or self-management as well as personalized services. It will meet not only Healthy China 2030 Plan but also updated the National Health Service (NHS) Long Term Plan in the UK [90]. In short, this program can help to achieve global health goals.
In fact, this program has already been used for CVD and cancer in daily clinical practice, but there are more detailed on changing unhealthy lifestyle for T2D (Table 1). If there is a national registered centre for T2D which just likes major virus-communicable diseases, e.g. SARS and COVID-19 [17,91], more satisfactory effects will be got after reliable national clinical trials with this innovative classical comprehensive program, since it combines anti-diabetic agents, insulin use, metabolic surgery with mental health screenings and healthy E(e)SEEDi lifestyle [27,92,93], which includes plant-based dietary patterns, and will get better control of population-level HbA1c and cardiovascular risk among individuals with T2D.
With a better understanding in the pathophysiological mechanisms at the molecular level and the discovery of new targets for metabolism[94,95], the implications for existing guidelines and therapeutic options, as well combination with this iRT-ABCDEFG program and effective lifestyle interventions for T2D, for example, a precision dietary management and scientific dietary recommendations with respect to carbohydrate, fat and dietary fibre, and increases in physical activity and fitness, calorie restriction and weight loss [96,97], these individuals will improve greatly glycaemic control and better prevent its complications [98], such as CVD and neurodegenarative diseases (Alzheimer’s disease and Parkinson’s disease) [99]. In addition, the prevalence of both depression and thyroid abnormalities is high among individuals with T2D [100,101]. and coronary plaques [102], abnormal gene expression and serum biomarker levels in these patients mean higher risk and adverse clinical outcomes [103-105], hence, we should control and prevent these risk factors so as to reduce cardiovascular mortality.
Theoretically, this iRT-ABCDEFG program is more plausible for better management and self-management of T2D due to truly individualized glycaemic goals. It is helpful to individuals with T2D for early detection of ischemic heart disease, unrecognized CHF, and early statins and SGLT2 inhibitors treatment safely for improvement of lipids and endothelial function and lowering MACCE [106]. In fact, a biomarker score is helpful to stratify T2D and pre-diabetes related CHF risks [107]. Healthy E(e)SEEDi lifestyle may help to reduce these risks and improve clinical outcomes [108]. In addition, clinical trials already confirmed benefits of selective nonsteroidal MRA eplerenone [109] and finerenone [110] in CHF prevention and cardiovascular outcomes improvement. Obviously, a combination of these strategies in this novel comprehensive program is helpful to healthcare of individuals with T2D. Of course, both drug and non-drug management of T2D require more solid evidence-based studies [111].
Since there are more cardiovascular benefits in SGLT2 inhibitors, such as dapagliflozin [112], and new animal models and clinical trials had already confirmed the glucose-lowering potential of glucokinase activators [113], and there are more and better choices for T2D treatment, but we should pay more attention to both safety and efficacy of these novel hypoglycaemic drugs [114]. Because T2D links to significant abnormalities in cardiocerebrovascular system [115], such as atherosclerotic CVD, diabetic cardiomyopathy, CHF, stroke, CKD, peripheral neuropathy [116], our program may have a role of risk-reduction of MACCE and improvement of clinical outcomes. Herein, this program can be adopted as “a concise guideline” in clinical practice due to OMT and healthy E(e)SEEDi lifestyle.
Both T2D (diagnosed and undiagnosed) and IGT are important CVD risk factors [117] and have higher risk of coronary stenosis and coronary atherosclerotic plaques burden [118]. When there is fragmented QRS, it may predict complex VAs and the risk of sudden cardiac death [119], and LVDD is common [120] in T2D patients, it may also be detected by 3D speckle tracking echocardiography [121]. However, current SGLT2-inhibition remains to be at an underused status in these HF-population [122]. A combination of agents high-intensity statins (rosuvastatin) and more often with ezetimibe [123] and intensifying lifestyle measures is needed for stricter LDL-C and non-HDL-C targets.
Because good clinical investigations or programs could inform future diagnostic and therapeutic strategies, and enhance the understanding of a disease, just like myocardial infarction with nonobstructive coronary arteries (MINOCA) [124] and this iRT-ABCDEFG program. When combined with novel tools [125], new agents [126], fresh preventive and interventional strategies [127,128], it will help us to get better effects on management or self-management of T2D. However, “advances in science are not linear, they are zigzag” [129].129 Thus, we should keep enough patience and confidence from papers publication to practical application and try to expand related clinical coverage.
In fact, during the pandemic and post-COVID-19 era [130], as major OMT and particularly when combined with healthy E(e)SEEDi lifestyle, both GLP-1 receptor agonists and SGLT2 inhibitors are good choices for prevention of related complications in T2D (CHF, CKD, and AF/AFL-reduction benefit) and MACCE due to direct and favorable cardioprotective and nephroprotective effects [131-134], even if SGLT2 inhibitors have no significant effects on ischemic events stemming from atherosclerotic CVD in T2D [135]. With the development of new drug delivery systems [136-138] and novel technologies [139,140], it’s promising in applications for T2D and its complications.