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.