The essential role of exercise in the management of type 2 diabetes

Exercise is typically one of the first management strategies advised for patients newly
diagnosed with type 2 diabetes. Together with diet and behavior modification, exercise is an
essential component of all diabetes and obesity prevention and lifestyle intervention programs.
Exercise training, whether aerobic or resistance training or a combination, facilitates improved
glucose regulation. High-intensity interval training is also effective and has the added benefit of
being very time-efficient. While the efficacy, scalability, and affordability of exercise for the
prevention and management of type 2 diabetes are well established, sustainability of exercise
recommendations for patients remains elusive.
Type 2 diabetes has emerged as a major public health and economic burden of the 21st
century. Recent statistics from the Centers for Disease Control and Prevention suggest that
diabetes affects 29.1 million people in the United States, 1 and the International Diabetes
Federation estimates diabetes effects 366 million people worldwide. As these shocking numbers
continue to increase, the cost of caring for patients with diabetes is placing enormous strain on
the economies of the US and other countries. In order to manage and treat a disease on the scale
of diabetes, the approaches need to be efficacious, sustainable, scalable, and affordable. Of all
the treatment options available, including multiple new medications and bariatric surgery (for
patients who meet the criteria, discussed elsewhere in this supplement),3–5 exercise as part of a
lifestyle approach is a strategy that meets the majority of these criteria. The health benefits of
exercise have a long and storied history. Hippocrates, the father of scientific medicine, was the
first physician on record to recognize the value of exercise for a patient with “consumption.”
Today, exercise is recommended as one of the first management strategies for patients newly
diagnosed with type 2 diabetes and, together with diet and behavior modification, is a central
component of all type 2 diabetes and obesity prevention programs.
The evidence base for the efficacy, scalability, and affordability of exercise includes
multiple large randomized controlled trials; and these data were used to create the recently
updated exercise guidelines for the prevention and treatment of type 2 diabetes, published by the
American Diabetes Association (ADA), American College of Sports Medicine (ACSM), and
other national organizations.
 Herein, we highlight the literature surrounding the metabolic effects and clinical
outcomes in patients with type 2 diabetes following exercise intervention, and point to future
directions for translational research in the field of exercise and diabetes.

It is known that adults who maintain a physically active lifestyle can reduce their risk of
developing impaired glucose tolerance, insulin resistance, and type 2 diabetes. It has also been
established that low cardiovascular fitness is a strong and independent predictor of all-cause
mortality in patients with type 2 diabetes.11,12 Indeed, patients with diabetes are 2 to 4 times
more likely than healthy individuals to suffer from cardiovascular disease, due to the metabolic
complexity and underlying comorbidities of type 2 diabetes including obesity, insulin resistance,
dyslipidemia, hyperglycemia, and hypertension. Additionally, elevated hemoglobin A1c
(HbA1c) levels are predictive of vascular complications in patients with diabetes, and regular
exercise has been shown to reduce HbA1c levels, both alone and in conjunction with dietary
intervention. In a meta-analysis of 9 randomized trials comprising 266 adults with type 2
diabetes, patients randomized to 20 weeks of regular exercise at 50% to 75% of their maximal
aerobic capacity (VO2max) demonstrated marked improvements in HbA1c and cardiorespiratory
fitness.11 Importantly, larger reductions in HbA1c were observed with more intense exercise,
reflecting greater improvements in blood glucose control with increasing exercise intensity. In
addition to greater energy expenditure, which aids in reversing obesity-associated type 2
diabetes, exercise also boosts insulin action through short-term effects, mainly via insulin-
independent glucose transport. For example, our laboratory and others have shown that as little
as 7 days of vigorous aerobic exercise training in adults with type 2 diabetes results in improved
glycemic control, without any effect on body weight.15,16 Specifically, we observed decreased
fasting plasma insulin, a 45% increase in insulin-stimulated glucose disposal, and suppressed
hepatic glucose production (HGP) during carefully controlled euglycemic hyperinsulinemic
clamps. Although the metabolic benefits of exercise are striking, the effects are short-lived and
begin to fade within 48 to 96 hours.17 Therefore, an ongoing exercise program is required to
maintain the favorable metabolic milieu that can be derived through exercise.
EXERCISE MODALITIES
Aerobic exercise
 The vast majority of the literature about the effects of exercise on glycemic parameters in
type 2 diabetes has been centered on interventions involving aerobic exercise. Aerobic exercise
consists of continuous, rhythmic movement of large muscle groups, such as in walking, jogging,
and cycling. The most recent ADA guidelines state that individual sessions of aerobic activity
should ideally last at least 30 minutes per day and be performed 3 to 7 days of the week (Table
1).18 Moderate to vigorous (65%–90% of maximum heart and rate) aerobic exercise training
improves VO2max cardiac output, which are associated with substantially reduced
cardiovascular and overall mortality risk in patients with type 2 diabetes.19

TABLE 1
American Diabetes Association recommendations for exercise in type 2 diabetes
Aerobic exercise: At least 150 minutes/week of moderate to vigorous exercise
Spread over 3 to 7 days/week, with no more than 2 consecutive days between exercise bouts
Daily exercise is suggested to maximize insulin action
Shorter durations (at least 75 minutes/week) of vigorous-intensity or interval training may be
sufficient for younger and more physically fit patients
May be performed continuously, or as high-intensity interval training
Resistance exercise: Progressive moderate to vigorous resistance training should be completed 2
to 3 times/week on nonconsecutive days.
At least 8 to 10 exercises, with completion of 1 to 3 sets of 10 to 15 repetitions
Flexibility and balance training are recommended 2 to 3 times/week for older adults
Participation in supervised training programs is recommended to maximize health benefits of
exercise in type 2 diabetes.
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Notably, aerobic exercise is a well-established way to improve HbA1c, and strong evidence
exists with regard to the effects of aerobic activity on weight loss and the enhanced regulation of
lipid and lipoprotein metabolism.8 For example, in a 2007 report, 6 months of aerobic exercise
training in 60 adults with type 2 diabetes led to reductions in HbA1c (−0.63% ± 0.41 vs 0.31% ±
0.10, P < .001), fasting plasma glucose (−18.6 mg/dL ± 4.4 vs 4.28 mg/dL ± 2.57, P < .001),
insulin resistance (−1.52 ± 0.6 vs 0.56 ± 0.44, P = .023; as measured by homeostatic model
assessment), fasting insulin (−2.91 mU/L ± 0.4 vs 0.94 mU/L ± 0.21, P = .031), and systolic
blood pressure (−6.9 mm Hg ± 5.19 vs 1.22 mm Hg ± 1.09, P = .010) compared with the control
group.
Furthermore, meta-analyses reviewing the benefits of aerobic activity for patients with
type 2 diabetes have repeatedly confirmed that compared with patients in sedentary control
groups, aerobic exercise improves glycemic control, insulin sensitivity, oxidative capacity, and
important related metabolic parameters.11 Taken together, there is ample evidence that aerobic
exercise is a tried-and-true exercise modality for managing and preventing type 2 diabetes.
Resistance training
During the last 2 decades, resistance training has gained considerable recognition as a viable
exercise training option for patients with type 2 diabetes. Synonymous with strength training,
resistance exercise involves movements utilizing free weights, weight machines, body weight
exercises, or elastic resistance bands. Primary outcomes in studies evaluating the effects of
resistance training in type 2 diabetes have found improvements that range from 10% to 15% in
strength, bone mineral density, blood pressure, lipid profiles, cardiovascular health, insulin
sensitivity, and muscle mass.18,20 Furthermore, because of the increased prevalence of type 2
diabetes with aging, coupled with age-related decline in muscle mass, known as sarcopenia,21
resistance training can provide additional health benefits in older adults.
Dunstan et al 21 reported a threefold greater reduction in HbA1c in patients with type 2
diabetes ages 60 to 80 compared with nonexercising patients in a control group. They also noted
an increase in lean body mass in the resistance-training group, while those in the nonexercising
control group lost lean mass after 6 months. In a shorter, 8-week circuit weight training study
performed by the same research group, patients with type 2 diabetes had improved glucose and
insulin responses during an oral glucose tolerance test.
These findings support the use of resistance training as part of a diabetes management
plan. In addition, key opinion leaders advocate that the resistance-training-induced increase in
skeletal muscle mass and the associated reductions in HbA1c may indicate that skeletal muscle is
a “sink” for glucose; thus, the improved glycemic control in response to resistance training may
be at least in part the result of enhanced muscle glycogen storage. These discoveries support the
utilization of obstruction preparing as a component of a diabetes the executives plan. Also, key
assessment pioneers advocate that the opposition preparing incited expansion in skeletal bulk and
the related decreases in HbA1c might show that skeletal muscle is a "sink" for glucose; in this
way, the improved glycemic control in light of obstruction preparing might be essentially to a
limited extent the aftereffect of upgraded muscle glycogen capacity.
In view of expanding proof supporting the job of obstruction preparing in glycemic
control, the ADA and ACSM as of late refreshed their activity rules for treatment and avoidance
of type 2 diabetes to incorporate opposition preparing.

Consolidating vigorous and opposition preparing

The mix of high-impact and opposition preparing, as suggested by current ADA rules, might be
the best activity methodology for controlling glucose and lipids in type 2 diabetes.
Sleeve et al 24 assessed whether a joined preparation program could further develop insulin
responsiveness past that of high-impact practice alone in 28 postmenopausal ladies with type 2
diabetes. Without a doubt, four months of consolidated preparing prompted fundamentally
expanded insulin-intervened glucose take-up contrasted and a gathering performing just oxygen
consuming activity, reflecting more noteworthy insulin responsiveness.

Balducci et al25 showed that consolidated high-impact and obstruction preparing uniquely
further developed HbA1c (from 8.31% ± 1.73 to 7.1% ± 1.16, P < .001) contrasted and the
benchmark group and universally further developed risk factors for cardiovascular illness,
supporting the thought that joined preparation for patients with type 2 diabetes might have added
substance benefits.
Of note, Snowling and Hopkins played out a straight on meta-investigation of 27
controlled preliminaries on the metabolic impacts of high-impact, opposition, and blend
preparing in an aggregate of 1,003 patients with diabetes. Each of the 3 activity modes gave ideal
consequences for HbA1c, fasting and postprandial glucose levels, insulin awareness, and fasting
insulin levels, and the distinctions between practice modalities were paltry. Conversely,
Schwingshackl and associates played out a deliberate survey of 14 randomized controlled
preliminaries for the very 3 activity modalities in 915 grown-ups with diabetes and revealed that
consolidated preparation delivered an essentially more noteworthy decrease in HbA1c than
vigorous or obstruction preparing alone.
Future examination is important to measure the added substance and synergistic clinical
advantages of joined practice contrasted and vigorous or obstruction preparing regimens alone;
nonetheless, proof proposes that mix exercise might be the ideal technique for overseeing
diabetes.

Stop and go aerobic exercise

Intense cardio exercise (HIIT) has arisen as one of the quickest developing activity programs
lately. HIIT comprises of 4 to 6 rehashed, short (30-second) episodes of maximal exertion
sprinkled with brief periods (30 to 60 seconds) of rest or dynamic recuperation. Practice is
commonly performed on an exercise bike, and a solitary meeting goes on around 10 minutes.
HIIT increments skeletal muscle oxidative limit, glycemic control, and insulin
responsiveness in grown-ups with type 2 diabetes.28,29 A new meta-investigation that evaluated
the impacts of HIIT programs on glucose guideline and insulin obstruction revealed predominant
impacts for HIIT contrasted and vigorous preparation or no activity as a control.28 Specifically,
in 50 preliminaries with mediations enduring something like fourteen days, members in HIIT
bunches had a 0.19% decline in HbA1c and a 1.3-kg decline in body weight contrasted and
control gatherings.
Elective focused energy practice programs have likewise arisen lately, for example,
CrossFit, which we assessed in a gathering of 12 patients with type 2 diabetes. Our evidence of-
idea investigation discovered that a 6-week CrossFit program decreased muscle to fat ratio,
diastolic pulse, lipids, and metabolic condition Z-score, and expanded insulin aversion to
glucose, basal fat oxidation, VO2max, and high-sub-atomic weight adiponectin.30 HIIT seems,
by all accounts, to be one more powerful method for working on metabolic wellbeing; and for
patients with type 2 diabetes who can endure HIIT, it could be a period productive, elective way
to deal with nonstop high-impact work out.

Advantages OF EXERCISE FOR SPECIFIC METABOLIC TISSUES

In something like 5 years of the revelation of insulin by Banting and Best in 1921, the primary
report of activity initiated upgrades in insulin activity was distributed, however the particular cell
and sub-atomic components that support these impacts stay obscure. There is general
arrangement that the intense or momentary activity impacts are the aftereffect of insulin-ward
and insulin-autonomous instruments, while longer-term impacts likewise include "organ
crosstalk, for example, from skeletal muscle to fat tissue, the liver, and the pancreas, all of which
intercede ideal foundational consequences for HbA1c, blood glucose levels, pulse, and serum
lipid profiles.
An outside record that holds an image, delineation, and so forth.
FIGURE 1
Tissue-explicit metabolic impacts of practice in patients with type 2 diabetes.

Skeletal muscle
Following a dinner, skeletal muscle is the essential site for glucose removal and take-up. Fringe
insulin opposition beginning in skeletal muscle is a significant driver for the turn of events and
movement of type 2 diabetes.
Practice upgrades skeletal muscle glucose take-up utilizing both insulin-ward and insulin-
free components, and customary activity brings about supported enhancements in insulin
responsiveness and glucose removal.
Of note, intense episodes of activity can likewise briefly upgrade glucose take-up by the
skeletal muscle up to fivefold through expanded (insulin-free) glucose transport.33 As this
transient impact blurs, it is supplanted by expanded insulin awareness, and after some time, these
2 variations to practice bring about enhancements in both the insulin responsiveness and insulin
awareness of skeletal muscle. The fuel-detecting catalyst adenosine monophosphate-enacted
protein kinase (AMPK) is the significant insulin-autonomous controller of glucose take-up, and
its actuation in skeletal muscle by practice initiates glucose transport, lipid and protein
combination, and supplement metabolism.35 AMPK remains momentarily actuated after practice
and manages a few downstream targets associated with mitochondrial biogenesis and capacity
and oxidative limit.
In such manner, vigorous preparation has been displayed to increment skeletal muscle
mitochondrial content and oxidative compounds, bringing about sensational upgrades in glucose
and unsaturated fat oxidation10 and expanded articulation of proteins engaged with insulin
flagging.

Fat tissue
Practice gives various beneficial outcomes in fat tissue, specifically, diminished fat mass,
improved insulin awareness, and diminished irritation. Persistent second rate aggravation has
been necessarily connected to type 2 diabetes and builds the gamble of cardiovascular illness.
A few incendiary adipokines have arisen as original indicators for the improvement of
atherosclerosis, and fat-cell expansion from unnecessary caloric admission prompts expanded
creation of favorable to fiery cytokines, changed adipokine discharge, expanded circling
unsaturated fats, and lipotoxicity accompanying with insulin opposition.
It has been recommended that exercise might stifle cytokine creation through diminished
incendiary cell invasion and improved adipocyte work. Levels of the key favorable to incendiary
marker C-receptive protein is especially diminished by exercise and standardization of adipokine
flagging and related cytokine discharge has been approved for a considerable length of time
modalities.

Additionally, Ibañez et al showed that notwithstanding critical enhancements in insulin

responsiveness, obstruction practice preparing diminished instinctive and subcutaneous fat mass
in patients with type 2 diabetes.

Liver
The liver manages fasting glucose through gluconeogenesis and glycogen capacity. The liver is
likewise the essential site of activity for pancreatic chemicals during the change from pre-to
postprandial states. Similarly as with skeletal muscle and fat tissue, insulin obstruction is
additionally present inside the liver in patients with type 2 diabetes. In particular, hindered
concealment of HGP by insulin is a sign of type 2 diabetes, prompting supported hyperglycemia.
Approaches utilizing fasting proportions of glucose and insulin don't recognize fringe and
hepatic insulin opposition. All things considered, hepatic insulin responsiveness and HGP are
best evaluated by the hyperinsulinemic-euglycemic clasp strategy, alongside isotopic glucose
tracers.
Albeit more intricate, attractive reverberation spectroscopy may likewise be utilized to
evaluate intrahepatic lipid content, as its amassing has been displayed to drive hepatic insulin
opposition. Circuitous proportions of hepatic brokenness might be produced using expanded
levels of the coursing hepatic proteins soluble phosphatase, alanine transaminase, and aspartate
transaminase.
According to an activity viewpoint, we have shown that 7 days of oxygen consuming
preparation, without a trace of weight reduction, further develops hepatic insulin responsiveness.
It has additionally been shown that hepatic AMPK is invigorated during exercise, recommending
that an AMPK-incited versatile reaction to exercise might work with further developed
concealment of HGP. We have additionally shown that a more drawn out 12-week high-impact
practice intercession lessens hepatic insulin obstruction, with and without confined caloric
intake.48 Further, HGP connected with decreased instinctive fat, recommending that this fat
station might assume a significant unthinking part in better hepatic capacity.

Pancreas
Insulin obstruction in fat tissue, muscle, or the liver puts more noteworthy expectation on insulin
discharge from pancreatic beta cells. For some, this hypersecretory state is impractical, and the
resulting loss of beta-cell work denotes the beginning of type 2 diabetes. Fasting plasma glucose,
insulin, and glucagon levels are for the most part unfortunate marks of beta-cell work.
Clinical examination concentrates commonly utilize the oral glucose resilience test and
hyperglycemic clip procedure to all the more precisely measure the powerful guideline of
glucose homeostasis by the pancreas.50 However, scarcely any investigations have analyzed the
impacts of activity on beta-cell work in type 2 diabetes. Dela and associates showed that 3
months of vigorous preparation further developed beta-cell work in type 2 diabetes, yet just in
the people who had some lingering capacity and were less seriously diabetic. We have shown
that a 12-week high-impact practice intercession further develops beta-cell work in more
established stout grown-ups and in patients with type 2 diabetes. We have additionally tracked
down that enhancements in glycemic control that happen with practice are better anticipated by
changes in insulin emission rather than fringe insulin sensitivity.54 It has likewise been shown
that a generally short (8-week) HIIT program further developed beta-cell work in patients with
type 2 diabetes.55 And we as of late observed that a 6-week CrossFit preparing program further
developed beta-cell work in grown-ups with type 2 diabetes.
Synopsis, CONCLUSIONS, AND FUTURE DIRECTIONS
Customary activity produces medical advantages past enhancements in cardiovascular wellness.
These incorporate upgraded glycemic control, insulin flagging, and blood lipids, as well as
decreased second rate aggravation, worked on vascular capacity, and weight reduction.
Both oxygen consuming and obstruction preparing programs advance better skeletal
muscle, fat tissue, liver, and pancreatic function.18 Greater entire body insulin awareness is seen
following activity and endures for as long as 96 hours. While a discrete episode of activity gives
significant metabolic advantages in diabetic companions, upkeep of glucose control and insulin
awareness are expanded by physiologic transformations that just happen with weeks, months,
and long periods of activity preparing. Practice intensity,11 volume, and recurrence are related
with decreases in HbA1c; notwithstanding, an agreement has not been reached on whether one is
a preferable determinant over the other. The main thought while prescribing activity to patients
with type 2 diabetes is that the power and volume be enhanced for the best metabolic advantage
while staying away from injury or cardiovascular gamble. By and large, the gamble of activity
actuated unfriendly occasions is low, even in grown-ups with type 2 diabetes, and there is no
present proof that screening techniques past normal diabetes care are expected to recommend
practice in asymptomatic patients in this populace securely.
Future clinical examination in this space will give a more extensive appreciation to the
connections (positive and negative) among exercise and diabetes meds, the collaboration among
practice and bariatric medical procedure, and the possibility to utilize exercise to diminish the
wellbeing weight of diabetes inconveniences, including nephropathy, retinopathy, neuropathy,
and fringe blood vessel infection. In addition, fundamental examination will probably distinguish
the nitty gritty atomic deformities that add to diabetes in insulin-designated tissues. The arising
science encompassing cytokines, adipokines, myokines, and, most as of late, exerkines is
probably going to extend how we might interpret the robotic connections among exercise and
diabetes the board.
At long last, despite the fact that we have more than adequate proof that exercise is a
powerful, adaptable, and reasonable way to deal with forestall and oversee type 2 diabetes, we
actually need to conquer the test of finding how to make practice feasible for patients.
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