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<br><strong>Record: 1</strong><dl class="print-citation"><dd data-
auto="citation_field_value"
xmlns:extendedmarkupcontroller="urn:ExtendedMarkupController"><span class="medium-
normal">Management of type 2 diabetes mellitus in self-motivated patients:
optimized diet, exercise, and medication for weight loss and cardiometabolic
fitness. (English) By: Nadeau DA, The Physician And Sportsmedicine [Phys
Sportsmed], ISSN: 0091-3847, 2014 Nov; Vol. 42 (4), pp. 49-59; Publisher: Taylor
& Francis; PMID: 25419888; <br>Type 2 diabetes mellitus (T2DM) is a growing
public health problem with significant lifetime health care costs. The majority of
Americans do not achieve minimal targets for exercise, and individuals with T2DM
typically engage in less exercise than the general adult population. However, those
patients with T2DM who are sufficiently self-motivated to manage their condition
have the potential to reverse diabetes and prevent its complications through
behavioral and pharmacologic interventions. Marked improvements are possible
through increased awareness and selection of healthy eating options, a willingness
to incorporate vigorous exercise into their lifestyle, and the use of newer
medications that essentially eliminate the risk of hypoglycemia while facilitating
weight loss and the achievement of ideal glucose targets. For self-motivated
patients, daily aerobic activity of 45 to 60 minutes per day may be a suitable
target. For those who have cardiovascular clearance, high-intensity interval
training accomplishes high levels of cardiometabolic fitness with shorter training
periods by alternating moderate and intense exertion. Suitable medications that
have a low risk of hypoglycemia during exercise include metformin, glucagon-like
peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose
linked transporter-2 inhibitors. Specific daily caloric goals and incorporation of
a mainly plant-based diet should be considered as a primary target for diabetes
management. Self-management is important to achieving diabetes treatment goals, and
mobile applications can be useful tools to support lifestyle changes in patients
with T2DM.</span></dd><dt
xmlns:extendedmarkupcontroller="urn:ExtendedMarkupController"><strong><span
class="medium-bold">Persistent link to this record (Permalink):
</span></strong></dt><dd
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direct=true&db=mdc&AN=25419888&site=ehost-
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direct=true&db=mdc&AN=25419888&site=ehost-live</a></span></dd><dt
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normal"> <A href="http://search.ebscohost.com/login.aspx?
direct=true&db=mdc&AN=25419888&site=ehost-live">Management of type 2
diabetes mellitus in self-motivated patients: optimized diet, exercise, and
medication for weight loss and cardiometabolic fitness.</A></span></dd><dt
class="medium-bold" data-auto="citation_field_label">Database:
</span></strong></dt><dd
normal" data-auto="citation_field_value">MEDLINE Complete</span></dd></dl><hr><div
class="print-citation"><h1 class="delivery-title" xmlns:translation="urn:EBSCO-
Translation">Management of Type 2 Diabetes Mellitus in Self-Motivated
Patients: Optimized Diet, Exercise, and Medication for Weight
Loss and Cardiometabolic Fitness </h1><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">Type 2 diabetes
mellitus (T2DM) is a growing public health problem with significant lifetime health
care costs. The majority of Americans do not achieve minimal targets for exercise,
and individuals with T2DM typically engage in less exercise than the general adult
population. However, those patients with T2DM who are sufficiently self-motivated
to manage their condition have the potential to reverse diabetes and prevent its
complications through behavioral and pharmacologic interventions. Marked
improvements are possible through increased awareness and selection of healthy
eating options, a willingness to incorporate vigorous exercise into their
lifestyle, and the use of newer medications that essentially eliminate the risk of
hypoglycemia while facilitating weight loss and the achievement of ideal glucose
targets. For self-motivated patients, daily aerobic activity of 45 to 60 minutes
per day may be a suitable target. For those who have cardiovascular clearance,
high-intensity interval training accomplishes high levels of cardiometabolic
fitness with shorter training periods by alternating moderate and intense exertion.
Suitable medications that have a low risk of hypoglycemia during exercise include
metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4
inhibitors, and sodium-glucose linked transporter-2 inhibitors. Specific daily
caloric goals and incorporation of a mainly plant-based diet should be considered
as a primary target for diabetes management. Self-management is important to
achieving diabetes treatment goals, and mobile applications can be useful tools to
support lifestyle changes in patients with T2DM.</p><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">CLINICAL
FEATURES</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">Keywords: diabetes mellitus, type 2;
motivation; exercise; weight loss; physical fitness</p><a id="AN0114328943-2"
xmlns:translation="urn:EBSCO-Translation"> </a><span class="medium-bold"
xmlns:translation="urn:EBSCO-Translation"><a data-auto="ep_link"
href="http://web.b.ebscohost.com/ehost/delivery?sid=85f99567-7978-4752-8a14-
16aa4d027d8d%40pdc-v-sessmgr01&vid=1&ReturnUrl=http%3a%2f
%253d#toc" id="hd_toc_6" title="Introduction">Introduction</a></span><p
class="body-paragraph" data-auto="body_paragraph" xmlns:translation="urn:EBSCO-
Translation">Type 2 diabetes mellitus (T2DM) is now a worldwide pandemic growing at
an alarming rate.1 In 2010, the prevalence of diabetes mellitus among children and
adults in the United States was an estimated 25.8 million, approximately 8.3% of
the population.1 The incidence is estimated to reach 21% to 33% of the population
by 2050.2 Proper nutrition and intense exercise, coupled with newer and better
pharmacotherapy, are integral components in the reduction of the risk of this
disease.3-5 Unfortunately, overall dietary patterns in the United States remain
poor, and approximately 80% of Americans do not achieve minimal targets for
exercise6; moreover, individuals with T2DM typically engage in less exercise than
the general adult population.7 However, some studies have shown that highly self-
motivated patients with T2DM have the potential to reverse diabetes and prevent
complications (eg, cardiovascular events, neuropathy, retinopathy) with vigorous
exercise,8,9 although the results are inconsistent.5,10 The 2013 American Diabetes
Association (ADA) nutrition guidelines recommend a healthy diet that contains
appropriate portion sizes of high nutritional density foods that help establish and
attain individualized glycemic, blood pressure, and lipid goals, and achieve and
maintain body weight goals; this may help to delay or prevent complications of
diabetes.11 Individuals with diabetes should be aware of caloric content, selection
of healthy eating options (eg, whole foods), and avoidance of processed foods and
saturated fat.11</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">Regular exercise in adults with T2DM has
been associated with improvement in blood glucose levels,7,12 metabolic profile
(ie, triglyceride and total cholesterol levels),13 adiposity and body mass
index,14,15 inflammatory markers,8,14 cardiovascular risk,14 and general well-
being.13 Furthermore, regular exercise can help reduce the risk of T2DM.16,17 When
only sulfonylureas and insulin were available for the treatment of T2DM, these
medications proved counterproductive for achievement of weight loss goals and
increased the risk of hypoglycemia. Newer medications, such as glucagon-like
peptide-1 receptor agonists (GLP-1-RAs), facilitate weight loss and have little to
no risk of hypoglycemia, while helping achieve ideal glucose targets. These novel
agents can assist motivated patients in achieving their weight loss goals.
Improvements in "patient empowerment," increased exercise, and better compliance
can result in better glycated hemoglobin (HbA<sub>1c</sub>) control.18</p><p
Translation">This review explores the literature in this challenging and emerging
area, and suggests a strategy that will make the role of exercise central to the
management of diabetes. This approach focuses on patients who are sufficiently
self-motivated to actively participate in the management of their diabetes. The
goal of this work is not to recommend methods through which physicians may attempt
to increase motivation in patients with low motivation, but rather to describe
options for behavioral and pharmacologic interventions that physicians may
recommend to patients who already have high levels of self-motivation. With active
participation in their diabetes management, such highly self-motivated patients may
be able to arrest or even reverse the development of T2DM.</p><a id="AN0114328943-
3" xmlns:translation="urn:EBSCO-Translation"> </a><span class="medium-bold"
%253d#toc" id="hd_toc_10" title="Motivation and Exercise in Patients With
Diabetes">Motivation and Exercise in Patients With Diabetes</a></span><p
Translation">Other than education and "self-empowerment," detailed information
about motivators that promote physical activity in individuals with T2DM are
limited. In clinical practice, only a small percentage of the population with T2DM
is sufficiently self-motivated to undertake a rigorous exercise program to increase
their cardiometabolic fitness level and to perhaps change the impact of T2DM on
their life. In a cross-sectional study of subjects at high risk for diabetes,
physically active individuals reported that exercise was a high priority, believed
that physical activity influenced weight, were less concerned about injuries, and
made time for physical activity.19 Individuals with at least a high school diploma
were more physically active than those without a high school diploma. Thus, more
education about the importance of physical activity may be needed, particularly in
people with a sedentary lifestyle. In the Finnish Diabetes Prevention Study, the
main motivator for physical activity was quality of life, including health and
mental and physical well-being, particularly among older individuals.20 Other
motivators included weight management, ability to exercise, and independence;
regular counseling was important for promoting exercise among older people.</p><p
Translation">The risk of T2DM increases with age. In older adults, the acceptance
of an exercise program may be more difficult because of their age and lower weight-
carrying capacity. A 12-month study in older adults (≥ 50 years) with T2DM who were
treated with insulin found that exercise itself elevated motivation for increased
exercise (≥ 3 hours/week) more than 2-fold.21 Regular exercise was confirmed in 67%
and 65% of the patients at 3- and 12-month poststudy follow-up sessions,
respectively, compared with 27% of patients who did not participate in any exercise
at the start of the study. Metabolic control improved and the use of insulin was
significantly reduced in those who exercised; better metabolic control may have
also been a factor in increasing exercise time.</p><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">In a focus group-
based assessment of physical activity and barriers compared with facilitators to
exercise in overweight adults with T2DM both during and after participation in a
supervised exercise program that included stretching for 15 minutes and exercise on
a treadmill, stationary bicycle, or cross trainer for 45 minutes, participants
reported that motivation was the most important factor in adhering to a simple
long-term exercise program (eg, walking). Patients' motivation was inferred through
questions about program attendance (ie, "What may explain the finding that some
patients were not able to attend at least 75% of the sessions?" "From your
experience with the program, what might have facilitated attending
at least 75% of the sessions?" "Why have you decided to continue [or stop]
exercising?") Other reported factors included fitting with the patient's daily
schedule and the proximity of the exercise location.22</p><p class="body-paragraph"
data-auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">A qualitative
study of couples aged > 50 years where one or both partners had T2DM used a
framework derived from social cognitive theory to assess the role of collective
efficacy in adhering to exercise for married adults living with diabetes.23 For
those with diabetes, motivation to exercise and the effort put forth to adhere to
an exercise regimen was higher when both individuals shared beliefs about
exercise.23 It is possible that there may be gender differences in motivation for
physical activity in patients with T2DM; among active members of a patients'
association in France who were contacted by the organizers for potential
participation in an interview-based study, females reported that the emotional
support from being part of group, positive body image, and a sense of well-being
were motivating factors, whereas males emphasized disease control and health-
promoting behaviors. 24 Thus, it may be necessary to individualize exercise
programs, especially in older patients.</p><a id="AN0114328943-4"
%253d#toc" id="hd_toc_15" title="Types of Exercise">Types of Exercise</a></span><p
Translation">The ADA recommends that individuals with diabetes perform ≥ 150
minutes of moderate-intensity aerobic physical activity (50%-70% of maximum heart
rate) per week, spread over ≥ 3 days, with ≤ 2 consecutive days without exercise,
and moderate-to-vigorous intensity resistance training ≥ 2 days a week in the
absence of contraindications.4 As discussed elsewhere,25 people who have succeeded
in maintaining considerable weight loss routinely achieve approximately 7 hours of
exercise each week; likewise, 40 to 60 minutes of aerobic physical activity per day
has been suggested as a goal for preventing and managing youth-onset T2DM.26
Increasing physical activity also improves cardiometabolic fitness and decreases
cardiovascular risk in subjects with or at risk for T2DM.26-28 The benefit of
physical exercise as a potential therapy for patients with T2DM, particularly as a
long-term regimen, is an area of increasing clinical interest.27</p><p class="body-
paragraph" data-auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">For
patients with cardiovascular clearance, high-intensity interval training (HIIT)
enables high levels of fitness to be achieved with shorter training periods by
alternating moderate (ie, 80% of maximal heart rate) and intense (ie, 95% of
maximal heart rate) exertion. For example, rather than 7 minutes of continuous
moderate exercise (CME) alone, one approach would be a 7-minute aerobic workout
comprising a warmup of 60 seconds of moderate exercise, followed by alternating 30-
second intervals of intense versus moderate exercise for an additional 6 minutes.
During exercise, pushing the body beyond its comfort zone has clear-cut benefits,29
which may at least partly explain the positive effects of HIIT. In a study
involving subjects with metabolic syndrome, after a 10-minute warm-up, the HIIT
group exercised at 90% maximal heart rate (HR<sub>max</sub>) for 4 minutes followed
by 3 minutes at 70% HR<sub>max</sub>; this was repeated 4 times, followed by a 5-
minute cool-down. The CME group exercised at 70% HR<sub>max</sub> for 45 minutes.
The HIIT group showed greater improvements in insulin sensitivity, aerobic
capacity, and high-density lipoprotein cholesterol levels, as well as lower blood
glucose levels than did the CME group. Aerobic capacity improved by 35% with HIIT
compared with 16% with CME.30 It has also been found that HIIT may provide a more
enjoyable workout than CME, with a feeling of exhilaration that makes regular
exercise easier.31,32</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">Resistance training engaging the upper
body, lower body, and core muscle groups on 2 to 3 nonconsecutive days per week has
been recommended for people with T2DM.25 Home-based training with resistance
machines and free weights alone may be insufficient to maintain blood glucose
control in the long term33; however, such training regimens increase strength and
mass of the muscle groups engaged. Increasing resistance or weight can attenuate
insulin resistance in obese adults with T2DM,34 and combining resistance training
with aerobic exercise in a physical activity regimen leads to greater benefits such
as the potential for cardiovascular risk reduction. Additionally, instruction and
supervision by a qualified trainer has been recommended for most individuals with
T2DM to maximize health benefits (eg, blood glucose control, blood pressure
management, and lipids), to reduce cardiovascular risk, and to minimize potential
injury.27</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">A combination of aerobic training and
resistance training has been shown both by the important Italian Diabetes and
Exercise Study (IDES) trial and by a systematic review to provide significant
benefits and is recommended for individuals with diabetes.35,36 Aerobic exercise
(eg, swimming, running, or using a bicycle, treadmill, or elliptical machine)
increases the function of the heart, lungs, and muscle through activation of large
muscle groups (eg, upper body, lower body, or core) to meet the heightened oxygen
demands while providing cardiorespiratory benefits. Because maintenance of weight
loss and increasing physical activity are key goals in managing T2DM and decreasing
cardiovascular risk, it is my opinion that for highly self-motivated patients an
optimal target for daily aerobic activity to increase cardiometabolic fitness may
be 40 to 60 minutes per day. Resistance training may appeal particularly to
individuals with T2DM, elderly individuals, or those with sedentary lifestyles; it
may include the use of various exercise machines, lifting free-weights (eg,
dumbbells), or doing calisthenics (eg, sit-ups, push-ups, crunches, and lunges).
Although multiple approaches may be taken by highly self-motivated patients, in my
opinion, with cardiovascular clearance, resistance training may be undertaken to
muscle exhaustion and might target major muscle groups (eg, upper body, lower body,
and core) 237-39 or, ideally, 340-42 times a week. Each session should include ≥ 1
set of 10 to 15 repetitions, with sufficient weight to lead to muscle fatigue by
the end of each set37,40,41,43; 3 to 4 sets is recommended for optimal strength
gains.44</p><a id="AN0114328943-5" xmlns:translation="urn:EBSCO-Translation">
</a><span class="medium-bold" xmlns:translation="urn:EBSCO-Translation"><a data-
auto="ep_link" href="http://web.b.ebscohost.com/ehost/delivery?sid=85f99567-7978-
4752-8a14-16aa4d027d8d%40pdc-v-sessmgr01&vid=1&ReturnUrl=http%3a%2f
%253d#toc" id="hd_toc_20" title="Medical Risks Associated With Exercise">Medical
Risks Associated With Exercise</a></span><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">Prevention of
hypoglycemia is important in the management of patients with diabetes mellitus,
particularly during and after intense exercise. Thus, a balance must be achieved
between insulin use, carbohydrate intake, and exercise. Exercise participation can
be further complicated by the presence of comorbidities (eg, cardiovascular disease
[CVD], hypertension, neuropathy, or microvascular changes). Before beginning an
exercise program, individuals with diabetes should be assessed for conditions that
may contraindicate exercise, predispose them to injury, require pre-exercise
treatment, or are associated with an increased risk of CVD.40 Current guidelines
recommend formal exercise stress testing before initiating a moderate-intensity
exercise program; electrocardiogram stress testing may be indicated for individuals
aged > 40 years, or those aged > 30 years with hypertension, a history of
smoking, dyslipidemia, retinopathy, neuropathy, or disease duration of > 10
years.25</p><a id="AN0114328943-6" xmlns:translation="urn:EBSCO-Translation">
%253d#toc" id="hd_toc_22" title="Role of Diet/Nutrition">Role of
Diet/Nutrition</a></span><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">In the United States, diets rich in
animal products have contributed to the increased incidence of obesity and T2DM.
The nutrition recommendations described here are supported primarily by findings of
the Harvard School of Public Health and the 2013 ADA nutrition guidelines. It
should be emphasized that early referral to
a registered dietitian or a certified diabetes educator is recommended to assist
patients through individualized nutritional counseling.</p><p class="body-
paragraph" data-auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">A
review and meta-analysis of 3 cohort studies, including data from Harvard's Nurses'
Health Studies I and II (n = 79 570 women and n = 87 504 women, respectively) and
Health Professionals' Follow-Up Study (n = 37 083 men), found that individuals who
ate red or processed meat had a higher risk of T2DM.45 Specifically, results of the
meta-analysis of follow-up data indicated that, among a total of 442 101 patients
and 28 228 cases of diabetes, 3.5 ounces of red meat or 1.8 ounces of processed
meat (ie, a hot dog or 2 slices of bacon) daily led to a 19% and 51% increase in
T2DM risk, respectively.45 Similarly, a meta-analysis of 12 cohort studies
estimated the relative risk of T2DM associated with high versus low total meat
consumption (17% risk) and high versus low consumption of red (21% risk) and
processed (41% risk) meat.46 Further, a small study (18 subjects were enrolled, 17
completed the study) suggested that eating processed foods results in increased
energy absorption,47 which may contribute to associated weight gain and increased
diabetes risk.</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">The 2013 ADA nutrition guidelines
recommend that distribution of protein, cholesterol, and fat (ie, macronutrients)
should be based on individualized assessment of current eating patterns,
preferences, and metabolic goals; evidence suggests that there is no ideal
percentage of calories from each macronutrient that is applicable to all people
with diabetes.11</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">Plant-based diets consisting of whole
grains, fruits, vegetables, legumes, and nuts, which have long been used for weight
loss,48 also increase insulin sensitivity and reduce CVD risk factors.49
Specifically, a 22-week randomized trial in 99 patients with T2DM who were stable
on medication and were assigned to a low-fat, low glycemic index, vegan diet, or a
portion-controlled omnivorous diet following the 2003 ADA guidelines found that the
vegan group had a significantly greater decrease in HbA<sub>1c</sub> compared with
the ADA diet group (1.23% vs 0.38%, respectively; P = 0.01). Moreover, average
weight loss was significantly higher with the vegan diet (6.5 kg vs 3.1 kg; P <
0.001). Furthermore, patients on the vegan diet had reduced diabetes medication
requirements (43% vs 26%).50 Such changes were generally maintained for more than
18 months,49 illustrating the importance of dietary choices for T2DM management.
Despite some clear health benefits, a strict vegan diet is not realistic for most
patients, and maintaining a restrictive or radically altered dietary profile may be
challenging for many patients in the long-term; a less restrictive, primarily
plant-based diet that includes fish and other healthy protein seems prudent in such
cases. In either case, in my experience, whole grains should be emphasized.
Eliminating refined carbohydrates and using whole grains is now supported by the
recent ADA recommendations to "minimize" intake of processed carbohydrates.11</p><p
Translation">The ADA recommends that people with prediabetes (impaired glucose
tolerance, impaired fasting glucose, or HbA<sub>1c</sub> levels between 5.7% and
6.4%, but not yet at the diagnostic threshold for T2DM) or confirmed T2DM should
receive ongoing support, which includes individualized nutritional guidance
targeting weight loss (7% of body weight), increased physical activity (150
min/week moderate activity). Metformin therapy should also be considered.51</p><p
Translation">Ideally, the nutritional guidance would be provided by a registered
dietitian familiar with the concepts of nutritional management of diabetes.4 Strong
counseling support is central to these programs; however, for most patients such a
system may not be available, limiting the longer term effectiveness of this
intervention in the "real world." In such situations, it may become necessary to
add drug therapy for patients with high glucose readings or those who are not
meeting their glycemic and weight targets. I recommend weight loss for overweight
or obese individuals at risk of or diagnosed with T2DM; strategies should include
behavior modification and physical activity. Setting specific daily caloric goals
is helpful in achieving targets. For most women, a target of 1200 kcal/ day is a
good starting point; for men, 1500 kcal/day is appropriate, but for patients
weighing > 100 kg (220 pounds), the target can be increased to 1800 kcal/day.
Therefore, healthy daily menus of 1200, 1500, and 1800 kcal provide guidance for
most patients. If weight loss of ≥ 1 to 2 pounds/week is not achieved, reducing
calories by 200 to 300 calories per day seems reasonable.</p><p class="body-
paragraph" data-auto="body_paragraph" xmlns:translation="urn:EBSCO-
Translation">Saturated fats (< 7% of total calories) should be a small part of
the overall calorie intake, and no amount of hydrogenated or "trans" fat should be
considered safe. A traditional Mediterranean diet, with its focus on vegetables,
fruits, whole grains, beans, legumes, and healthy proteins, in line with the new
ADA recommendations,11 may help patients achieve their glycemic control and weight
loss goals. Individuals at risk of T2DM should consume more whole fruit,
specifically blueberries, grapes, and apples; fruit juice alone has been associated
with a higher risk of developing T2DM in an analysis of data from the Nurses'
Health Studies and the Health Professionals Follow-Up Study involving almost 3.5
million person-years of follow-up.52 As noted previously, among individuals with
diabetes, adherence to dietary guidelines is much greater than adherence to an
exercise regimen.53</p><a id="AN0114328943-7" xmlns:translation="urn:EBSCO-
Translation"> </a><span class="medium-bold" xmlns:translation="urn:EBSCO-
Translation"><a data-auto="ep_link"
%253d#toc" id="hd_toc_30" title="Use of Technology to Manage Diet and Exercise">Use
of Technology to Manage Diet and Exercise</a></span><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">Self-management is
important for achieving diabetes treatment goals, and mobile applications (apps)
can be useful tools for lifestyle changes in patients with T2DM. To date, however,
published studies describing the specific role of these apps and devices in
improving diabetes control or promoting long-term adherence to exercise regimens
are limited, in part because many of these tools are relatively new. In a review of
mobile health apps, the management of diabetes had the greatest number of apps
available.54 A few years ago, expensive dietary analysis programs were not readily
available to patients. But now it is remarkably easy to capture calories associated
with diet and exercise on apps such as Loseit! and MyFitnessPal on smart phones and
computers. Other apps support self-management tasks, such as physical exercise,
insulin dosage or medication, blood glucose monitoring, blood pressure monitoring,
and diet.55 These apps also provide valuable notifications and alerts, enabling
health care provider feedback and decision support, and integration with social
media; their use has been shown to have a positive impact on HbA<sub>1c</sub>,
weight, and blood pressure.56 In addition, the perceived usefulness of these apps
among individuals with T2DM or those at risk for T2DM is high and implies a
potentially greater role in self-management.57</p><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">The use of mobile
technology, remote coaching, and incentives in sedentary adults with elevated
saturated fat and low fruit/vegetable intake has been associated with an increase
in consumption of fruits/vegetables and an increase in physical activity.58 The
elderly face particularly strong barriers to exercise, including comorbid
conditions, as well as impaired reaction time, coordination, cognition, gait, and
balance. Amobile training app called Active Lifestyle aims to improve balance and
strength in the elderly; it assists, monitors, and motivates the user to follow
personalized training plans autonomously at home while interacting socially with
other participants.59 In a pilot study of this app, adherence to the training plans
among users was 89% for balance exercises and 60% for strength exercises.59 The
majority of participants (64%) reported feeling increased motivation to exercise;
91% felt motivated by being part of a virtual exercise group and being able to
monitor their performance in real time; although baseline motivation was not
assessed, patients reported that they did not feel motivated to exercise without
the app.59 These findings indicate the clinical utility of mobile apps in
motivating individuals with T2DM to increase physical activity and consume a
healthy diet, but next-generation apps would ideally include behavior modification
techniques as well.</p><a id="AN0114328943-8" xmlns:translation="urn:EBSCO-
Translation"> </a><span class="medium-bold" xmlns:translation="urn:EBSCO-
Translation"><a data-auto="ep_link"
16aa4d027d8d%40pdc-v-sessmgr01&
vid=1&ReturnUrl=http%3a%2f%2fweb.b.ebscohost.com%2fehost%2fdetail%2fdetail
%3fvid%3d0%26sid%3d85f99567-7978-4752-8a14-16aa4d027d8d%2540pdc-v-sessmgr01%26bdata
%3dJnNpdGU9ZWhvc3QtbGl2ZQ%253d%253d#toc" id="hd_toc_33" title="Role of
Medications">Role of Medications</a></span><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">The goal of
pharmacotherapy in self-motivated patients is to control blood glucose without
causing hypoglycemia and to help facilitate weight loss to achieve a body weight as
close to ideal as possible. The relationship between HbA<sub>1c</sub> levels and
weight loss has been detailed elsewhere3; available T2DM medications are summarized
in Table 1.</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">At the time of diagnosis of T2DM,
initiation of lifestyle interventions should be coupled with diet and pharmacologic
therapy, unless contraindicated. One approach to pharmacologic therapy, termed the
MGI (metformin, GLP1-RA, and insulin) protocol has been described previously.3 In
brief, treatment of T2DM is begun with metformin; this drug is the first-line oral
therapy for T2DM according to guidelines from several medical professional
groups.60-64 An injectable GLP-1-RA could be added immediately if baseline
HbA<sub>1c</sub> is high (ie, > 7.5%)64 or if there is urgency in achieving
weight loss targets. For example, underlying weight-related sleep apnea and lower
extremity arthritic pain may compel urgent weight loss. As previously discussed,
because GLP-1-RAs address the core pathophysiologic defects of T2DM (Figure 1),3,65
their early use is reasonable.</p><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">The GLP-1-RAs
stimulate insulin secretion in a glucose-dependent manner via pancreatic ß cells
and enhance glucose sensitivity (defect III on Figure 1), prevent inflammation-
mediated apoptosis of pancreatic ß-cells (defect III), reduce glucagon secretion by
pancreatic a cells (defect VI), decrease hepatic glucose production (defect I),
replace a deficient GLP-1 response (defect V), initially delay gastric emptying,
induce satiety (defect VIII), and result in overall weight loss,65-68 which
suggests that the GLP-1-RAs address 5 of the 8 pathophysiologic defects. Moreover,
the GLP-1-RAs reduce triglyceride levels and blood pressure69-71; evidence also
suggests that the GLP-1-RAs may facilitate better food choices, aiding in further
weight loss,72 and potentially increasing exercise quantity.</p><p class="body-
Translation">Metformin and the GLP-1-RAs are helpful for self-motivated patients
with T2DM because they are weight-neutral or may induce weight loss.3 Insulin
therapy with or without additional pharmacotherapy may be considered in patients
with markedly symptomatic or elevated blood glucose levels or HbA<sub>1c</sub>.
Insulin, if needed, should be initiated in patients with T2DM as the long-acting
form at bedtime to reduce hepatic glucose production and reduce the risk of daytime
hypoglycemia during exercise. In my experience, dosing can begin at either 10 U at
bedtime or 0.2 U/kg and increased by 1 U every day until the morning glucose is
< 120 mg/dL. Allowing time for the achievement of weight loss may require slower
titration if dramatic alterations in lifestyle are occurring.</p><p class="body-
Translation">Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are newly
available, and when added to metformin and a GLP-1-RA, are powerful adjuncts to
current therapy. These agents prevent glucose reabsorption in the proximal tubule
of the kidney, leading to glucose (and calorie) loss, significant effects on
HbA<sub>1c</sub>, and overall glucose control; weight loss is observed in some
patients. Adverse events include an increased risk of bacterial and mycotic
infections; patients who develop mycotic infections may experience recurrent
infections.73 Additionally, elderly patients should be cautioned about the
possibility of symptoms related to orthostatic hypotension secondary to volume
contraction when using SGLT-2 inhibitors.73 The combination of metformin, GLP-1,
and SGLT-2 lowers glucose and facilitates weight loss with almost no risk of
hypoglycemia; however, the economic cost of treatment may be an important
consideration for some patients.</p><a id="AN0114328943-9"
%253d#toc" id="hd_toc_39" title="Case Report">Case Report</a></span><p class="body-
Translation">Patient Demographics and Clinical Characteristics Upon Clinic
Arrival</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">T.M. was a 260-lb (118 kg), 5'10" (178
cm; body mass index = 37.3), 43-year-old man diagnosed with T2DM 1 month
previously, with hypertension, hypercholesterolemia, and concomitant sleep apnea
for which he refused to use a continuous positive air pressure machine. He stated
he had gained an average of 3 to 5 pounds each year for the previous 5 years, and
had "never been able to lose weight." Current medication included metformin (1000
mg twice daily), plus 2 medications to lower blood pressure and cholesterol levels.
Fasting glucose readings were 200 to 230 mg/dL and HbA<sub>1c</sub> was 9.7%. He
was following the standard American diet and had no regular exercise program other
than working on his commercial boat. He described his diabetes as a "wake-up
call."</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">Treatment</p><p class="body-paragraph"
data-auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">After
screening for cardiac disease, T.M. was counseled on an aggressive diet and
exercise program. He was asked to begin walking for 20 minutes/day, which would
increase as he became able to do so. His metformin was continued at the same dose,
and liraglutide 0.6 mg daily was initiated and titrated to 1.2 mg after 1 week. The
patient had mild nausea that was resolved within 10 days of initiation of treatment
with liraglutide. He seemed eager to use a medication that would lower his
HbA<sub>1c</sub> and that might help with weight loss and lifestyle changes. He
adopted a whole food, mainly plant-based diet. As encouraged to do so after 3
weeks, he increased his exercise to 40 minutes/day of HIIT, which included a 10-
minute warmup and three 5-minute intervals of intense exercise, alternating with
three 5-minute moderate exercise intervals. He also included 4 days of resistance
training, with each session lasting approximately 20 minutes, focusing on chest,
back, legs, and shoulders on different days, with abdominal exercises twice weekly.
At a follow-up visit, his wife reported that his snoring had improved, and T.M.
reported being more awake during the day. A repeat polysomnographic study showed a
significant reduction in apnea.</p><a id="AN0114328943-10"
%253d#toc" id="hd_toc_44" title="Results">Results</a></span><p class="body-
Translation">After 7 weeks, T.M. had lost 12 pounds, his fasting blood glucose
levels were 100 to 110 mg/dL, and his HbA<sub>1c</sub> was 7.3%. He was optimistic
about continuing to lose weight now that his appetite was better controlled.</p><a
id="AN0114328943-11" xmlns:translation="urn:EBSCO-Translation"> </a><span
class="medium-bold" xmlns:translation="urn:EBSCO-Translation"><a data-
%253d#toc" id="hd_toc_46" title="Conclusion">Conclusion</a></span><p class="body-
Translation">Type 2 diabetes mellitus is a significant public health problem. For
motivated individuals, the severity/progression of the disease can at least be
alleviated by making positive changes in diet and exercise. New technology may
assist some patients with achieving their objectives, but for others, it may be
necessary to initiate pharmacotherapy: the MGI (metformin, GLP-1 RA, and insulin)
protocol3 may prove beneficial for many patients who are motivated to make the
lifestyle modifications necessary to assist in controlling T2DM.</p><a
id="AN0114328943-12" xmlns:translation="urn:EBSCO-Translation"> </a><span
class="medium-bold" xmlns:translation="urn:EBSCO-Translation"><a data-
4752-8a14-16aa4d027d8d%2540pdc-v-sessmgr01%26bdata%3dJnNpdGU
9ZWhvc3QtbGl2ZQ%253d%253d#toc" id="hd_toc_48"
title="Acknowledgments">Acknowledgments</a></span><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">Under the direction
of the author, medical editorial support was provided by Sylvia Hanna and Roderick
H. Sayce, BSc, MBA, at Complete Publications Solutions, LLC; this support was
funded by Novo Nordisk A/S.</p><a id="AN0114328943-13"
%253d#toc" id="hd_toc_50" title="Conflict of Interest Statement">Conflict of
Interest Statement</a></span><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">Daniel A. Nadeau, MD, has served as a
speaker for Astra-Zeneca, Bristol-Myers Squibb, Janssen, and Novo Nordisk. Dr
Nadeau is also an adviser to and stockholder in Novo Nordisk.</p><p class="body-
paragraph" data-auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">The
content of this manuscript has not been presented elsewhere in whole or in
part.</p><a id="AN0114328943-14" xmlns:translation="urn:EBSCO-Translation">
%253d#toc" id="hd_toc_53" title="Table 1. Medications Available to Treat
T2DM">Table 1. Medications Available to Treat T2DM</a></span><p class="body-
paragraph" data-auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">
</p><div class="table-size-normal table-border"><table border="1"> <tbody><tr>
<td>Class (medication)</td> <td>MOA/effects</td> <td>Advantages</td>
<td>Disadvantages</td> <td>Dosage</td> </tr> <tr> <td colspan="5">Recommended</td>
</tr> <tr> <td rowspan="6">Biguanides (metformin)</td> <td>Activates AMPK</td>
<td>Weight neutral</td> <td>GI AEs (diarrhea, cramping)</td> <td>500-2550 mg
daily</td> </tr> <tr> <td>↓ Hepatic glucose production</td> <td>No to low risk of
hypoglycemia</td> <td>Lactic acidosis (rare)</td> <td></td> </tr> <tr> <td>↑
Insulin sensitivity</td> <td>↓ CV events</td> <td>Vitamin B12 deficiency</td>
<td></td> </tr> <tr> <td>↓ Insulin resistance</td> <td>Low cost</td>
<td>Contraindications: reduced kidney, liver, cardiac function, history of lactic
acidosis, hypoxemia</td> <td></td> </tr> <tr> <td>↑ GLP-1 levels?</td> <td>Oral
administration</td> <td></td> <td></td> </tr> <tr> <td></td> <td>Long-term safety
known</td> <td></td> <td></td> </tr> <tr> <td rowspan="6">GLP-1 receptor agonists
(exenatide LAR, exenatide bid, liraglutide)</td> <td>Activates GLP-1 receptors</td>
<td>↓ Weight</td> <td>GI AEs (nausea, vomiting)</td> <td>Exenatide bid: 10-20 μg
daily; exenatide LAR: 2 mg weekly; liraglutide: 0.6, 1.2, 1.8 mg/day</td> </tr>
<tr> <td>↑ GLP-l response</td> <td>No to low risk of hypoglycemia</td> <td>Cases of
acute pancreatitis and medullary thyroid cell carcinoma observed</td> <td></td>
</tr> <tr> <td>↑ Insulin secretion</td> <td>Improved (β-cell function/survival</td>
<td>Injectable</td> <td></td> </tr> <tr> <td>↓ Glucagon secretion</td>
<td>Potential CV benefit</td> <td>Long-term safety unknown</td> <td></td> </tr>
<tr> <td>↓ Gastric emptying</td> <td></td> <td></td> <td></td> </tr> <tr> <td>↑
Satiety</td> <td></td> <td></td> <td></td> </tr> <tr> <td rowspan="4">DPP-4
inhibitors (sitagliptin. saxagliptin, linagliptin)</td> <td>Inhibits DPP-4
activity</td> <td>Weight neutral</td> <td>Cases of pancreatitis observed</td>
<td>Saxagliptin: 2.5-5 mg daily; sitagliptin: 100 mg daily; linagliptin: 5 mg
daily</td> </tr> <tr> <td>↑Active GLP-1 concentration</td> <td>No to low risk of
hypoglycemia</td> <td>Allergic and hypersensitivity reactions</td> <td></td> </tr>
<tr> <td>↑ Insulin secretion</td> <td>Oral administration</td> <td>Long-term safety
unknown</td> <td></td> </tr> <tr> <td>↓ Glucagon secretion</td> <td>β-cell
survival</td> <td></td> <td></td> </tr> <tr> <td rowspan="6">Long-acting insulin
analogues (glargine, detemir)</td> <td>Directly activates insulin receptor</td>
<td>Sustained glycemic improvements</td> <td>↑ Weight</td> <td>Varies</td> </tr>
<tr> <td>↓ Hepatic glucose production</td> <td></td> <td>Injectable</td> <td></td>
</tr> <tr> <td>↓ Lipolysis</td> <td></td> <td>Hypoglycemia</td> <td></td> </tr>
<tr> <td></td> <td></td> <td>Training required</td> <td></td> </tr> <tr> <td></td>
<td></td> <td>Associated stigma</td> <td></td> </tr> <tr> <td></td> <td></td>
<td>Fluid retention</td> <td></td> </tr> <tr> <td rowspan="3">SGLT-2 inhibitors
(dapagliflozin, canagliflozin, empagliflozin)</td> <td>Inhibits SGLT-2, responsible
for glucose reabsorption</td> <td>↓ Weight</td> <td>Vulvovaginitis, balanitis, and
lower UTIs</td> <td>NA</td> </tr> <tr> <td>↑ Urinary glucose excretion</td> <td>No
hypoglycemia</td> <td></td> <td></td> </tr> <tr> <td>↓ Plasma glucose</td>
<td></td> <td></td> <td></td> </tr> <tr> <td colspan="5">Acceptable</td> </tr> <tr>
<td rowspan="4">Dopamine agonists (bromocriptine)</td> <td>Activates dopaminergic
receptors</td> <td>Weight neutral</td> <td>Dizziness/syncope</td> <td>0.8-4.8 mg
daily</td> </tr> <tr> <td>Alters hypothalamic regulation of metabolism</td> <td>No
hypoglycemia</td> <td>Nausea</td> <td></td> </tr> <tr> <td>↓ Hepatic glucose
production</td> <td>↓ CV events</td> <td>Fatigue</td> <td></td> </tr> <tr>
<td></td> <td></td> <td>Rhinitis</td> <td></td> </tr> <tr> <td colspan="5">Not
recommended</td> </tr> <tr> <td rowspan="4">Sulfonylureas (glyburide, glipizide,
glimepiride)</td> <td>Closes KATP channels on β-cell plasma membranes</td> <td>Low
cost</td> <td>↑ Weight</td> <td>1-40 mg daily</td> </tr> <tr> <td>↑ Insulin
secretion</td> <td>Long-term safety established</td> <td>Hypoglycemia</td>
<td></td> </tr> <tr> <td></td> <td></td> <td>HbA1c reductions not durable</td>
<td></td> </tr> <tr> <td></td> <td></td> <td>Conflicting data on CVD risk</td>
<td></td> </tr> <tr> <td rowspan="5">Thiazolidinediones (pioglitazone,
rosiglitazone)</td> <td>Activates PPAR-γ</td> <td>No hypoglycemia</td> <td>↑
Weight</td> <td>Pioglitazone: 15-45 mg daily</td> </tr> <tr> <td>↑ Insulin
sensitivity</td> <td>Durable</td> <td>Edema, heart failure</td> <td>Rosiglitazone:
# 8 mg/day</td> </tr> <tr> <td></td> <td>↑ HDL-C levels</td> <td>↑ Risk of
myocardial infarction</td> <td></td> </tr> <tr> <td></td> <td>↓ TG levels</td>
<td>Bone fractures</td> <td></td> </tr> <tr> <td></td> <td>↓ All-cause mortality
(pioglitazone)</td> <td>↑ LDL-C levels</td> <td></td> </tr> <tr> <td
rowspan="4">Alpha-glucosidase inhibitors (acarbose, miglitol)</td> <td>Inhibit
carbohydrate degradation</td> <td>↓ TG levels</td> <td>Hypoglycemia likely in
combination with other drugs</td> <td>25-100 mg 3 times daily</td> </tr> <tr> <td>↑
Secretion of GLP-1</td> <td>↓ Weight</td> <td>GI AEs</td> <td></td> </tr> <tr>
<td></td> <td>No hypoglycemia</td> <td></td> <td></td> </tr> <tr> <td></td> <td>Low
cost</td> <td></td> <td></td> </tr> <tr> <td rowspan="6">Amylin (pramlintide)</td>
<td>Amylinomimetic; stimulates amylin receptors</td> <td>↓ Weight</td> <td>GI AEs:
nausea, vomiting</td> <td>60-120 μg daily</td> </tr> <tr> <td>↓ Gastric
emptying</td> <td></td> <td>Hypoglycemia</td> <td></td> </tr> <tr> <td>↑
Satiety</td> <td></td> <td>Injectable</td> <td></td> </tr> <tr> <td>↓ Glucagon
secretion</td> <td></td> <td>Long-term safety unknown</td> <td></td> </tr> <tr>
<td></td> <td></td> <td>Only used with insulin</td> <td></td> </tr> <tr> <td></td>
<td></td> <td>Administration frequency</td> <td></td> </tr> <tr> <td
rowspan="4">Meglitinides (repaglinide. nateglinide)</td> <td>Closes KATP channels
on β-cell plasma membranes</td> <td>Rapid, short acting</td> <td>↑ Weight</td>
<td>Repaglinide:</td> </tr> <tr> <td>↑ Insulin secretion</td> <td></td>
<td>Hypoglycemia</td> <td>1.5-12 mg daily</td> </tr> <tr> <td></td> <td></td>
<td>Administration frequency</td> <td>Nateglinide:</td> </tr> <tr> <td></td>
<td></td> <td></td> <td>120-360 mg daily</td> </tr> <tr> <td colspan="5">Emerging
treatments</td> </tr> <tr> <td rowspan="4">Ultra-long-acting insulin analogues
(insulin degludec)</td> <td>Multihexamer solubilization technology</td> <td>Less
hypoglycemia than with long-acting insulin analogues</td> <td>↑ Weight similar to
long-acting analogues</td> <td>N/A</td> </tr> <tr> <td>Directly activates insulin
receptor</td> <td></td> <td>Injectable</td> <td></td> </tr> <tr> <td>↓ Hepatic
glucose production</td> <td></td> <td>Training required</td> <td></td> </tr> <tr>
<td>↓ Lipolysis</td> <td></td> <td>Associated stigma</td> <td></td> </tr>
</tbody></table></div> <p></p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">Adapted from Nadeau DA. Physiologic and
weight-focused treatment strategies for managing type 2 diabetes mellitus: the
metformin, glucagon-like peptide-1 receptor agonist, and insulin (MGI) approach.
Postgrad Med. 2013;125(<a id="bib3up
"> </a><a data-auto="ep_link"
%253d#bib3" id="ref_linkbib3" title="3">3</a>): 112-126.3 Abbreviations: AE,
adverse event; AMPK, adenosine monophosphate-activated protein kinase; CV,
cardiovascular; CVD, cardiovascular disease; DPP-4, dipeptidyl peptidase-4; GI,
gastrointestinal; GLP-1, glucagon-like peptide-1; HbA1c, glycated hemoglobin; HDL-
C, high-density lipoprotein cholesterol; KATP, adenosine triphosphate-sensitive
potassium; LAR, long-acting release; LDL-C, low-density lipoprotein cholesterol;
MOA, mechanism of action; NA, not applicable; PPAR, peroxisome proliferator-
activated receptor; SGLT-2, sodium-glucose cotransporter; T2DM, type 2 diabetes
mellitus; TG, triglyceride; UTI, urinary tract infection.</p><p class="body-
Translation">Figure 1. The multifactorial pathogenesis of T2DM. X, T2DM pathologies
directly addressed by GLP-1-RAs; x, anecdotal evidence suggests that weight loss
induced by GLP-1-RAs may correspond with positive changes in food and exercise
choices.</p><a id="AN0114328943-15" xmlns:translation="urn:EBSCO-Translation">
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Pharmaceuticals, Inc.; 2013. </em></p><p xmlns:translation="urn:EBSCO-
Translation">~~~~~~~~</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation">By Daniel A. Nadeau, MD, Kris V. Iyer
Endowed Chair in Diabetes Care, Mary and Dick Allen Diabetes Center, Hoag Hospital,
Newport Beach, CA</p><p class="body-paragraph" data-auto="body_paragraph"
xmlns:translation="urn:EBSCO-Translation"></p><p class="body-paragraph" data-
auto="body_paragraph" xmlns:translation="urn:EBSCO-Translation">Correspondence:
Daniel A. Nadeau, MD, Mary and Dick Allen Diabetes Center at Hoag Hospital, 520
Superior Avenue, #150, Newport Beach, CA 92663. Tel: 949-764-6204 Fax: 949-642-7703
E-mail: dan.nadeau@hoag.org</p><div><hr width="25%" noshade="noshade"><span
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