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\begin{document}

\title{A novel comprehensive program combining optimal medical treatment with
lifestyle for type 2 diabetes}



\author[1]{Chunsong Hu}%
\author[2]{Tengiz Tkebuchava}%
\author[2]{Qinghua Wu}%
\affil[1]{Nanchang University}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{June 14, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
This article introduces briefly current status in type 2 diabetes (T2D)
and an updated classical standardized comprehensive program which
combines optimal medical treatment (OMT) with lifestyle modification,
that is, intervention of RT-ABCDEFG (iRT-ABCDEFG) for control and
prevention of T2D, and discusses its advantages and prospects. Here, G
means goals, F follow-up, E examination, D disease \& risk factors
control, C changing unhealthy lifestyle \& Chinese medicine or control
the source of infection \& cutting genetic or spreading pathways, B
biohazard control, and A antagonistic treatment, such as anti-diabetic
agents, the glucagon-like peptide-1 receptor (GLPR) agonists, the
sodium-glucose cotransporter 2 (SGLT2) inhibitors, and the
ultralong-acting, once-daily basal insulin. As an effective
comprehensive program and strategy for Interventions of diabetes, this
program can be used as a Reverse, Right, and Routine Treatment (iRT).
Several pivotal goals which include less major adverse
cardiocerebrovascular events (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 program due to early diagnosis, OMT, and lifestyle modification for
overall prevention. Herein, this iRT-ABCDEFG program is worthy of
recommending for clinical professional management and health care of T2D
due to better cost-effectiveness.%
\end{abstract}%



\sloppy


REVIEW ARTICLE

\textbf{A novel comprehensive program combining optimal medical
treatment with lifestyle for type 2 diabetes}

Running title: A novel program for T2D

\textbf{Chunsong Hu\textsuperscript{a,*} \textbar{} Tengiz
Tkebuchava\textsuperscript{b} \textbar{} Qinghua Wu\textsuperscript{c}}

\textsuperscript{a} Department of Cardiovascular Medicine, Nanchang
University, Hospital of Nanchang University, Jiangxi Academy of Medical
Science, Nanchang 330006, Jiangxi, China. Tel: (+86) 189 70816800;
Email: cnhucs@ncu.edu.cn or cnhucs@163.com

\textsuperscript{b} Office of the President/CEO, Boston TransTec, LLC,
Boston, MA 02459, USA. Tel: direct +1-617-930-6088; Email:
tt@bostontranstec.com

\textsuperscript{c} Department of Cardiology, the Second Affiliated
Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Tel:
(+86) 136 0708 2828; Email: ncdxefywu@sina.com

Word count: 3,059 (Main text) + 200 (Abstract)

References: 140

Tables: 2

Figure: 1 Total pages: 31

\textsuperscript{*} Correspondence

Chunsong Hu, Department of Cardiovascular Medicine, Nanchang University,
Hospital of Nanchang University, Jiangxi Academy of Medical Science, No.
461 Bayi Ave, Nanchang 330006, Jiangxi, China.

Email: cnhucs@ncu.edu.cn or cnhucs@163.com

\textbf{Abstract}

This article introduces briefly current status in type 2 diabetes (T2D)
and an updated classical standardized comprehensive program which
combines optimal medical treatment (OMT) with lifestyle modification,
that is, intervention of RT-ABCDEFG (iRT-ABCDEFG) for control and
prevention of T2D, and discusses its advantages and prospects. Here, G
means goals, F follow-up, E examination, D disease \& risk factors
control, C changing unhealthy lifestyle \& Chinese medicine or control
the source of infection \& cutting genetic or spreading pathways, B
biohazard control, and A antagonistic treatment, such as anti-diabetic
agents, the glucagon-like peptide-1 receptor (GLPR) agonists, the
sodium-glucose cotransporter 2 (SGLT2) inhibitors, and the
ultralong-acting, once-daily basal insulin. As an effective
comprehensive program and strategy for Interventions of diabetes, this
program can be used as a Reverse, Right, and Routine Treatment (iRT).
Several pivotal goals which include less major adverse
cardiocerebrovascular events (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 program due to early diagnosis, OMT, and lifestyle modification for
overall prevention. Herein, this iRT-ABCDEFG program is worthy of
recommending for clinical professional management and health care of T2D
due to better cost-effectiveness.

\textbf{KEYWORDS}

iRT-ABCDEFG, lifestyle, prevention, treatment, type 2 diabetes

\textbf{1 \textbar{} INTRODUCTION}

Type 2 diabetes (T2D) is one of major non-communicable diseases (mNCDs)
that requires lifelong treatments and management of high glycemic level.
More than 400 million adults worldwide suffer from diabetes {[}1{]}.
Obesity, physical inactivity, and unhealthy diet are major risk factors
in adults diabetes {[}2{]}, and racial \& ethnic groups, maternal
obesity have also led to a relative increase in T2D. In fact, the
incidences of both type 1 and T2D increase significantly, particularly
among minority racial and ethnic groups {[}3{]}. Although mortality and
fatal outcomes declined in individuals with T2D in some developed
countries {[}4{]}, for example, in Sweden from 1998 through 2014, it's
still a big challenge and a heavy burden in developing countries.

Since high-quality care for individuals with T2D could decrease
unnecessary emergency visits {[}5{]}, for example, urine glucose
screening within community and schools may help to detect early
asymptomatic T2D {[}6{]}, and individuals with T2D need to exercise more
often (at least meeting physical activity guidelines) for reduction of
mortality {[}7{]}. However, considerable proportion of T2D patients in
some Asian countries and regions, for example, South Korea, were not
adequately managed and lack of high-quality care due to no reliable
comprehensive program {[}8{]}. In addition, a large-scale international
study showed that subjects with T2D frequently have depression and
psychological and psychiatric problems {[}9{]}. Thus, there is arising
evidence for better management of T2D, since it is an independent
predictor of revascularization and long-term mortality {[}10{]}.

Currently, treatment of T2D focuses on glucose-lowering medication and
non-pharmacological treatment. The former includes oral hypoglycemic
agents, insulin pump or injection therapy; The later includes surgical
treatment, for example, bariatric surgery for markedly obese individuals
with T2D, modification of unhealthy lifestyle. However, most patients
with T2D have not achieved optimal glycemic control with mono-therapies.
Moreover, some treatments may have side-effects {[}11{]}. Although
current guidelines for T2D are suitable for clinical doctors to use, it
isn't for individuals' self-management of T2D. Of course, there is still
a need for self-control of glucose levels in a new era of personnel
medicine.

\textbf{2 \textbar{} 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-\selectlanguage{greek}α \selectlanguage{english}and
salusin-\selectlanguage{greek}β \selectlanguage{english}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 D\textsubscript{3} 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 HbA\textsubscript{1c} 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 \textless{}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.

\textbf{3 \textbar{} Its advantages}

Since T2D is as dangerous as coronary heart disease and associates with
higher MACCE, which include cardiovascular and non-cardiovascular
hospitalizations, AMI, CHF, ischemic stroke/TIA recurrence, and death
{[}79{]}, abnormal glycemic levels link to high mortality and morbidity.
For example, on the one hand, maternal T2D highly links to arterial
stiffness, cardiac hypertrophy, and congenital heart defects; On the
other hand, there is increasing T2D in offspring in late adult life due
to maternal gestational hypertension. Thus, we think that there are
obvious advantages of this iRT-ABCDEFG for T2D, which will help to
realize the European Society of Cardiology's ambitious mission ``to
reduce the burden of CVD'' in countries worldwide {[}80{]}.

Most cases of new onset T1D in China occurred among adults {[}81{]},
this iRT-ABCDEFG program is suitable for not only T2D but also T1D
because it can help to decrease and delay onset of T1D by healthy
E(e)SEEDi lifestyle and cutting a genetic pathway in the early stage of
one's lifetime due to control of maternal risks. Thus, this iRT-ABCDEFG
program is worthy of conducting in the globe. In addition, since T2D is
surprisingly closely linked to AMI, CHF, and stroke, diabetic chronic
kidney disease (CKD), maximum effort must be made to control the
prevalence of T2D so as to halt CVD and its costs increasing. Since
policy initiatives can help controlling increases in health care
spending {[}82{]}, it's time for not only \emph{Health in All
Policies}but also \emph{Health in All Laws} {[}16,83{]}.

With the further studies on mechanisms and the continuing development of
new drugs and novel technologies for T2D, more precise and effective
management or self-management of T2D with this iRT-ABCDEFG program is
possible due to the role of structure-editing on unhealthy lifestyle
{[}84{]}, and long-term trends in mortality and the incidence of MACCE
will also decline. For example, a clinical trial confirmed that oral
insulin 338 can safely improve glycaemic control in insulin-naive
patients with T2D, although it isn't in place of subcutaneous insulin
glargine yet due to being not commercially viable at current stage
{[}85{]}.

In short, since some cardiovascular metabolic factors of T2D, such as
obesity, physical inactivity, obstructive sleep apnea (OSA),
hypertension, and other modifiable unhealthy E(e)SEEDi lifestyle-related
factors, may induce MACCE (AF, AMI, CHF, Stroke) and reduce health span
and life span{[}86,87{]}, control and prevention of these risk factors
according to this iRT-ABCDEFG program will get more clinical benefit and
improve cardiovascular outcomes. The SGLT2 inhibitors and GLP-1 receptor
agonists, the newer classes of antihyperglycemic agents with the
cardiorenal protective effects {[}88{]}, will add distinctly clinical
benefit. The MRA finerenone also reduces the composite kidney and
cardiovascular outcomes {[}89{]}.

\textbf{4 \textbar{} 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{]}.\textsuperscript{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.

\textbf{5 \textbar{} CONCLUSION AND PERSPECTIVES}

This iRT-ABCDEFG program combining OMT and healthy E(e)SEEDi lifestyle
for T2D is very suitable for healthcare among clinical doctors,
patients, and healthy individuals. This program is helpful to access
clinical vital goals, which include less MACCE and diabetic
complications, less medical costs, longer life expectancy, lower
morbidity and mortality, and higher quality of life due to early
diagnosis, OMT, and overall prevention by healthy E(e)SEEDi lifestyle.
Moreover, this program is not only effective but also not complicated,
and easy to perform in primary care centers. In addition, training the
professional members and individuals to carry out this program is so
easy. In fact, this program can also be developed as a mobile APP for
wide use among T2D individuals and general population. Herein, we highly
recommend this iRT-ABCDEFG program due to a good expected cost-effective
relationship and clinical outcomes, since T2D highly links to CVD (AMI,
CHF, and stroke) and cancer, as well as other MACCE and the CDC strips.

\textbf{ACKNOWLEDGMENTS}

No funding for this study was received. The reviewers and editors are
gratefully acknowledged for critical review.

\textbf{CONFLICT OF INTEREST}

The authors declare no conflict of interest.

\textbf{AUTHOR CONTRIBUTION}

C. H, T.T. and Q.W. have contributed to the development and review of
the manuscript and approved the final version of the manuscript for
submission.

\textbf{ETH ICS STATEMENT}

Not applicable.

\textbf{DATA AVAILABILITY STATEMENT}

The data included in this study are available upon request from the
corresponding author.

\textbf{ORCID}

\emph{Chunsong Hu} https://orcid.org/0000-0002-0590-3909

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\textbf{Table 1.}

iRT-ABCDEFG program as a standardized comprehensive program for T2D.\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
iRT-ABCDEFG & Tips\tabularnewline
G & \textbf{Goals} are less MACCE and diabetic complications, less
medical costs, longer life expectancy, lower morbidity and mortality,
and higher quality of life.\tabularnewline
F & \textbf{Follow-up} with registered subjects or patients, especially
populations with family history, IGT, and an unhealthy lifestyle for
primary and secondary prevention, tracking outcome and evaluating
effects of intensive medical therapy (oral drugs or insulin injection)
and~surgery. It's very important for a population-based
study.\tabularnewline
E & \textbf{Examination}~for early diagnosis, treatment, and prevention,
which includes large-scale screening and regular comprehensive or
targeted physical examinations, such as biomarkers (fasting
blood-glucose, postprandial blood glucose, hemoglobin Alc,~and others:
FGF21, lipoprotein(a), microalbuminuria, RAGE, salusin-\selectlanguage{greek}α \selectlanguage{english}and salusin-\selectlanguage{greek}β\selectlanguage{english}),
oral glucose tolerance test, \selectlanguage{ngerman}ß cell function, genetic variants (e.g.
nitric oxide synthase 1 adaptor protein, FOXO1 gene), ultrasonography,
histopathological analysis, coronary angiography, CT angiography \& MRI.
Risk stratification following these examinations and related scoring
will improve treatment and clinical outcomes.\tabularnewline
D & \textbf{Diseases and risk factor control}, which includes
prediabetes state or impaired glucose tolerance, hypertension,
dyslipidemia, chronic infection, and diabetic complications (e.g.
retinopathy or chronic kidney disease, hypoglycemia, peripheral
neuropathy, diabetic ketoacidosis and other CVDs), obesity, physical
inactivity, and heavy drinking or smoking.\tabularnewline
C & \textbf{Change unhealthy E(e)SEEDi~lifestyle}~with
SEEDi\textsuperscript{1.0-3.0} technologies, such as not staying up
late, being physically active, no smoking and drinking;~\textbf{Chinese
medicine} is a good choice; \textbf{Controlling the source of infection}
and \textbf{the}~\textbf{spread of pathways~~}during the pandemic are
vital strategies if accompanied by acute infectious diseases (e.g.
COVID-19); And \textbf{Cutting off the genetic pathways} by RNAi, gene
knockout or CRISP/Cas9 gene editing after an ethical approval and
patients consent due to a genetic predisposition to
diabetes.\tabularnewline
B & \textbf{Biohazard control}, which includes abnormal symptoms and
physiological indexes, HbA1c~level of bio-markers, family history,
intensive weight management for obesity, and control of diabetic
complications. Monitoring or self-monitoring of blood glucose levels is
important and necessary.\tabularnewline
A & \textbf{Antagonistic treatment,} which includes oral hypoglycemic
agents (such as GLPR agonists, SGLT2 inhibitors), insulin monotherapy,
statin-based treatment, bariatric surgery, guidelines and other related
methods.\tabularnewline
iRT & \textbf{intervention} with these strategies as \textbf{Routine},
\textbf{Right} \& \textbf{Reversible Treatment}.\tabularnewline
\bottomrule
\end{longtable}

\textbf{Notes} : SEEDi\textsuperscript{1.0-3.0} technologies were
developed based on core healthy elements; that is,
sleep-emotion-exercise-diet (SEED) intervention (SEEDi). When
E(e)SEED-BasED healthy lifestyle included external and internal
environment combines with RT-ABCDEF and Grade 210 prevention, it's 3.0
version of SEEDi (SEEDi\textsuperscript{3.0}) or General Formula (Health
\& Longevity equality) for major non-communicable diseases (mNCDs). GLPR
agonists: glucagon-like peptide-1 receptor agonists; SGLT2 inhibitors:
sodium-glucose cotransporter 2 inhibitors.

\textbf{Table 2.}

The effects of healthy or unhealthy E(e)SEEDi lifestyle on T2D:
Evidences from PubMed literatures.\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
E(e)SEEDi (healthy or unhealthy)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Linkage to T2D risk (lower or increase)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Environment (external or self-internal)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Clinical studies confirmed that long-term exposure to air pollution
links to the increased risk of both CVD and T2D
{[}29-33{]}.\textsuperscript{29-33}\textbf{~}And increased
transportation noise and e-noise exposures are associated with a
greater~risk of T2D {[}34-36{]}. Early growth status (short length and /
or thinness at birth and during infancy) also links to T2D
{[}37{]}.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Sleep\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Sleep breathing disorders (severe obstructive sleep apnea, OSA) may add
the risk of T2D {[}38{]}.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Emotion\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Work-related psychosocial stress may increase the risk of T2D
{[}39{]}.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Exercise\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Aerobic physical activity is associated with reduced risk of T2D and the
higher levels of muscle-strengthening activities, the lower risk of T2D
{[}40{]}. For example, leisure-time running is associated with a lower
risk of developing T2D in adults {[}41{]}.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Diet\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Smoking (nicotine intake) increases the risk of T2D, but there is a
protective role of habitual intake of filtered coffee on T2D development
{[}42,43{]}.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Notes:} If individuals can keep healthy E(e)SEEDi lifestyle,
they will basically get away from T2D or at least lower the risk of T2D.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1} . The iRT-ABCDEFG program for managing type-2 diabetes
(T2D).

According to this figure, it's easy to understand that this
comprehensive program is very helpful to control and prevent T2D and
reach several pivotal goals after consistently practice, which include
less major adverse cardiocerebrovascular events (MACCE) and diabetic
complications, less medical costs, longer life expectancy, lower
morbidity and mortality, and higher quality of life, due to early
diagnosis, OMT, and healthy E(e)SEEDi lifestyle for overall prevention.
Herein, this iRT-ABCDEFG program is worthy of recommending for clinical
professional management and health care of T2D due to better
cost-effectiveness. However, it needs to confirm by long-term follow-up
and clinical trials. In fact, it is suitable for not only acute diseases
or events, such as acute myocardial infarction (AMI), stroke, and
COVID-19 infection, but also chronic diseases, such as C-type
hypertension (CtH), chronic heart failure (CHF), chronic kidney disease
(CKD), neurodegenarative diseases (dementia or Alzheimer's disease and
Parkinson's disease), and cancer as well as the cardiovascular,
diabetes, and cancer (CDC) strips.

\selectlanguage{english}
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