2 | An updated standardized comprehensive program
How can an individual control and prevent T2D with a simple and effective method? We strongly recommend an updated classical standardized comprehensive iRT-ABCDEFG program (Figure 1) for clinical professional management and family health care of T2D. Here, G means goals; F means follow-up; E means examination; D means disease & risk factors control; C means changing unhealthy “environment-sleep-emotion-exercise-diet” intervention [E(e)SEEDi] lifestyle & Chinese medicine or control the source of infection & cutting genetic or spreading pathways during the COVID-19 pandemic; B means biohazard control; And A means antagonistic treatment, such as optimal anti-diabetic agents, which include traditional agents (for example, metformin and others), and novel chemical agents, such as [the glucagon-like peptide-1 receptor (GLPR) agonists, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, the ultralong-acting, once-daily basal insulin, and others]. As a novel strategy for Intervention of diabetes, this program can be used as a Reverse, Right, and Routine Treatment in clinical practice. The detailed tips are as follows (Table 1).
This iRT-ABCDEFG program is very suitable for not only control of risk factors and cardiovascular disease (CVD), eg., hypertension [12], AMI [13], CHF [14], and arrhythmogenic right ventricular cardiomyopathy [15] as well as cancer [16] and major virus-communicable diseases [17], but also T2D. Firstly, good goals help to work better. Moreover, as an updated classical, individualized, and concise “guideline”, if treated as “a law” in clinical practice, the vital goals which include less MACCE and diabetic complications, less medical costs, longer life expectancy, lower morbidity and mortality, and higher quality of life, will be realized by consistently practicing this iRT-ABCDEFG program due to early diagnosis, OMT, and overall prevention by healthy E(e)SEEDi lifestyle.
On the one hand, follow-up of both doctors with patients and patients with doctors will improve outcomes. For example, follow-up found that intensive glucose control reduces MACCE [18], but bariatric surgery plus intensive medical therapy is more effective for control hyperglycemia than intensive medical therapy alone [19]. Individuals’ comprehensive or targeted examinations or population-based large-scale screening (e.g., urinary glucose screening) will help the early diagnosis of both symptomatic and asymptomatic T2D [6,20]. For example, there are only 10% undiagnosed cases of diabetes in the United States due to large-scale screening, and diagnoses by the criteria of elevated levels of fasting glucose (≥7.0 mmol/L) and hemoglobin A1c (HbA1c, ≥6.5%) [21].
Since postpartum follow-up and screening of oral glucose tolerance test (OGTT) during the delivery hospitalization is helpful to control maternal T2D, follow-up of women after delivery and scheduled screening for preventing T2D is very important for against this public health issue. Whatever, early examination and screening will help the management of T2D and decreasing its complications. Some serum biomarkers are helpful to determine its severity and complications, such as fibroblast growth factor 21 (FGF21) [22], the receptor for advanced glycation end products (RAGE) [23], and salusin-α and salusin-β levels [24]. In addition, albuminuria level is also associated with higher risk of MACCE (AMI, stroke) in patients with T2D [25].
On the other hand, this program helps to control T2D-related complications and major risk factors by cutting genetic pathways and changing unhealthy lifestyles, which can also decrease diabetic gene mutation. Studies have already shown that intensive lifestyle intervention in patients with T2D is beneficial to control individuals’ glycemic levels [26], e.g. intensive body weight management [2]. Moreover, healthy lifestyle included five core elements — “environment-sleep-emotion-exercise-diet” intervention [E(e)SEEDi] [27,28] may achieve better goals in control and prevention of T2D (Table 2) [29-43].
As we already known, CVD and T2D are more common in some populations (such as taxi drivers) due to unhealthy lifestyle [44]. However, healthy lifestyle is associated with a lower risk of CVD incidence and mortality among adults with T2D [45], it plays a key role in risk factor management for primary prevention of CVD [46]. In fact, lifestyle modification can reduce risk factors in both CVD and T2D [47]. However, current lifestyle modification is still low among US adults with chronic conditions [48]. Therefore, healthy E(e)SEEDi lifestyle should be recommended to all individuals in the globe.
Previous studies showed that exercises were associated with significantly lower HbA1c and fasting blood glucose [49], and plant-based diets which include legumes, whole grains, vegetables, fruits, nuts, and seeds, not only reduce the risk of T2D but also help to prevent T2D [50]. However, there are no significant difference in MACCE from n-3 fatty acid supplementation among T2D patients without CVD [51], Vitamin D3 supplementation did not result in a significantly lower risk of T2D [52]. Without a doubt, individualized biohazard control and antagonistic treatment are necessary according to “5P” medical model [53], because T2D can easily result in injury of organs and a series of complications without long-term optimal glycemic control, for example, erectile dysfunction, lipoprotein (a) and microalbuminuria are predictors of vascular complications [54-56]. The EUCLID Trial showed that every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACCE in patients with diabetes and peripheral artery disease [57]. There are less costs and better quality of life among patients with individualized glycemic control than uniform intensive control (HbA1c level <7%) [58].
On antidiabetic medical treatment, clinical studies already showed that the GLPR agonists, semaglutide [59] and liraglutide [60-62] the SGLT2 inhibitors [63], canagliflozin [64,65] and empagliflozin [66-68], and an ultralong-acting, once-daily basal insulin degludec [69], are not only helpful to glycemic control but also reduce MACCE including cardiovascular death or hospitalization for heart failure (HHH) in subjects with T2D and/or slower progression of diabetic chronic kidney disease (CKD). Since both were not associated with high rates of venous thromboembolism [70], the SGLT2 inhibitors and the GLPR agonists had already been recommended by the 2019 guidelines of American Diabetes Association (ADA) [71]. It can be said that 2 new classes of antihyperglycemic agents [72], the GLPR agonists and the SGLT2 inhibitors, have indeed led to a paradigm shift of T2D treatment. However, a study found that, a selective SGLT2 inhibitor dapagliflozin [73], not result in a higher or lower rate of MACCE, but in a lower rate of cardiovascular death or HHH.
In addition, the nonsteroidal, selective mineralocorticoid receptor antagonist (MRA) finerenone can reduce the risk of new-onset atrial fibrillation or flutter (AF/AFL) in patients with T2D and CKD [74]. Of course, there is still improper use of aspirin for primary and secondary prevention of CVD in T2D [75]. According to its cost and safety profile, metformin should be the first line drug therapy for patients with newly diagnosed T2D [76]. Due to cardiovascular benefit and lower achieved LDL-C levels associated with lower risk of MACCE [77], statin therapy should be recommended for primary prevention in the elderly with or without T2D [78]. In fact, it is also easy to understand the treatment of T2D and its complications from other systematic reviews, including relatively complete existing drugs, therapeutic effects, adverse events, and other aspects. Therefore, we will not list and summarize here.