Clinical Focus Series: Diabetes Mellitus [1 ed.] 9789390020133, 9789352701803

Citation preview

CLINICAL FOCUS SERIES

Diabetes Mellitus

CLINICAL FOCUS SERIES

Diabetes Mellitus Series Editor Romesh Khardori MD PhD FACP FRCP(C) Professor Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Editors David C Lieb MD FACE FACP Associate Professor Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Jagdeesh Ullal MD MS FACP FACE Clinical Associate Professor of Medicine Division of Endocrinology and Metabolism Department of Internal Medicine Director, In-Patient Diabetes Program University of Pittsburgh Pittsburgh, Pennsylvania, United States

The Health Sciences Publisher New Delhi | London | Panama

Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: [email protected]

Overseas Offices J.P. Medical Ltd 83 Victoria Street, London SW1H 0HW (UK) Phone: +44 20 3170 8910 Fax: +44 (0)20 3008 6180 Email: [email protected]

Jaypee-Highlights Medical Publishers Inc City of Knowledge, Bld. 237, Clayton Panama City, Panama Phone: +1 507-301-0496 Fax: +1 507-301-0499 Email: [email protected]

Jaypee Brothers Medical Publishers (P) Ltd 17/1-B Babar Road, Block-B, Shaymali Mohammadpur, Dhaka-1207 Bangladesh Mobile: +08801912003485 Email: [email protected]

Jaypee Brothers Medical Publishers (P) Ltd Bhotahity, Kathmandu Nepal Phone: +977-9741283608 Email: [email protected]

Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2018, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity.

Inquiries for bulk sales may be solicited at: [email protected] Clinical Focus Series Diabetes Mellitus / Romesh Khardori, David C Lieb, Jagdeesh Ullal First Edition: 2018 ISBN: 978-93-5270-180-3

Contributors SERIES EDITOR Romesh Khardori MD PhD FACP FRCP(C) Professor Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

EDITORS David C Lieb MD FACE FACP

Jagdeesh Ullal MD MS FACP FACE

Associate Professor Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Clinical Associate Professor of Medicine Division of Endocrinology and Metabolism Department of Internal Medicine Director, In-Patient Diabetes Program University of Pittsburgh Pittsburgh, Pennsylvania, United States

CONTRIBUTING AUTHORS Joseph A Aloi MD FACE FACP

Anca D Dobrian PhD FAHA

Professor Department of Internal Medicine Wake Forest School of Medicine Winston-Salem, North Carolina, United States

Associate Professor Department of Physiological Sciences Eastern Virginia Medical School Norfolk, Virginia, United States

Roni Bright RN MSN ACNP

Kathleen B Erezo RN BSN MSN FNP-BC

Diabetes Nurse Practitioner Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Gwendolyn G Brown MSN RN CPNP-PC Diabetes Nurse Practitioner Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Sheri R Colberg PhD FACSM Professor Emerita Department of Human Movement Sciences Old Dominion University Norfolk, Virginia, United States

Nurse Practitioner Department of Endocrine and Metabolic Diseases Eastern Virginia Medical School Norfolk, Virginia, United States

Suzan Gharaibeh MD Dip ABIM Consultant Advanced Cure Diagnostic Center Al Bateen, Abu Dhabi, UAE

Brock Hashim BS MS Student Eastern Virginia Medical School Norfolk, Virginia, United States

Diabetes Mellitus

Yumi Imai MD

Margaret A Morris PhD

Associate Professor Department of Internal Medicine University of Iowa, Carver College of Medicine Iowa City, Iowa, United States

Associate Professor Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Kapil G Kapoor MD Assistant Professor Department of Ophthamology Eastern Virginia Medical School Vitreoretinal Surgeon Wagner Macula and Retina Centre Virginia Beach, Virginia, United States

Ajay Kher FASN Senior Consultant Department of Nephrology and Renal Transplant Medicine Fortis Escorts Hospital New Delhi, India

Vijay Kher MD DM Chairman Department of Nephrology and Renal Transplant Medicine Fortis Escorts Hospital New Delhi, India

Jennifer L Kirby MD PhD Assistant Professor Department of Internal Medicine University of Virginia School of Medicine Charlottesville, Virginia, United States

Sichen Liu MS Student Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Anthony L McCall MD PhD FACP

vi

James M Moss Professor Department of Internal Medicine University of Virginia School of Medicine Charlottesville, Virginia, United States

Jerry L Nadler MD MACP FAHA FACE Harry H. Mansbach Professor Vice Dean of Research and Chair Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Joseph L Nadler BS MS Student Eastern Virginia Medical School Norfolk, Virginia, United States

Aaron Nelson MD Assistant Professor Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Donald W Richardson MD Associate Professor Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Marta S Satin-Smith MD Assistant Professor Department of Pediatrics Eastern Virginia Medical School Children’s Hospital of the King’s Daughters Norfolk, Virginia, United States

Margarita de Veciana MD MS FACOG Professor Department of Obstetrics and Gynecology Director Diabetes in Pregnancy Program Eastern Virginia Medical School Norfolk, Virginia, United States

Contibutors

Alan L Wagner MD FACS FICS

Phyllis A Woodson MS RD CDE

Assistant Professor Department of Ophthalmology Eastern Virginia Medical School Norfolk, Virginia, United States

Dietitian The Strelitz Diabetes Center and MaternalFetal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

Stephen Wohlgemuth MD FACS FASMBS Assistant Professor Department of of Clinical Surgery Eastern Virginia Medical School Medical Director Sentara Metabolic and Weight Loss Surgery Center, Sentara Medical Group Norfolk, Virginia, United States

Mark A Ziegler MS Student Department of Internal Medicine Eastern Virginia Medical School Norfolk, Virginia, United States

vii

Preface We are facing a pandemic of diabetes. The International Diabetes Federation estimates that over 400 million adults worldwide have diabetes, and that the number will rise to over 600 million by 2040. Every country is affected by this disease and its many complications, including heart disease, kidney disease, blindness, and neuropathy. There are over 340 million individuals with impaired glucose tolerance who are at significant risk of converting to diabetes without proper diagnosis and treatment. While these numbers are staggering, there have been tremendous advances in our understanding of diabetes and its pathogenesis over the last 30 years, with the consequent development of new therapies and practice strategies for reducing not just hyperglycemia, but also diabetes-related complications.   This volume is our attempt to provide practitioners with a complete and updated review of the state of diabetes care. We chose not only to focus on practical management issues (the prescription of exercise in diabetes, approaches to medical nutrition therapy, and an update in current pharmacologic therapies available for type 2 diabetes mellitus), but also on prevention and management of the most common comorbid conditions seen in patients (including retinopathy, nephropathy, hypoglycemia, neuropathy, and cardiovascular disease). We discuss type 1 diabetes mellitus and exciting current concepts with respect to its development and potential  options for its cure, as well as the potential benefits of bariatric surgery in the management of type 2 diabetes mellitus. We review management strategies for both pregnant patients and those who are hospitalized. Importantly, we have a chapter devoted to the role of nonphysician healthcare providers in the management of patients with diabetes.   Our authors are experts in their particular fields, and we have asked that they write chapters which address common questions that come up in clinical practice. Our hope is that readers will find useful current, practical advice for managing diabetes and its complications, and will be able to utilize this book as a reference for many years to come.   In addition to our authors and editors, we would like to thank Ms Barkha Arora, without whose editing and involvement, this volume would not be possible.

David C Lieb Jagdeesh Ullal

Contents

1. Exercise and Diabetes: Personal Prescriptions

1

Sheri R Colberg



2. Medical Nutrition Therapy for Adults with Diabetes and Related Topics

16

Phyllis A Woodson



3. Type 1 Diabetes Mellitus: Is a Cure in Sight?

26

Margaret A Morris, Marta S Satin-Smith



4. Management of Type 2 Diabetes Mellitus: A Pathophysiologic Approach

37

Romesh Khardori, Aaron Nelson, Suzan Gharaibeh



5. Inpatient Management of Diabetes

58

Jennifer L Kirby, Anthony L McCall



6. Clinical Pearls for the Management of Diabetes in Pregnancy

67

Margarita de Veciana



7. Diabetes and Cardiovascular Disease: Tackling the Problem

85

Jerry L Nadler, Joseph L Nadler, Brock Hashim



8. Update on the Management of Diabetic Retinopathy

97

Kapil G Kapoor, Alan L Wagner



9. Diabetic Neuropathy: Emphasis on Neuropathic Pain

112

Jagdeesh Ullal

10. Diabetic Nephropathy

125

Ajay Kher, Vijay Kher

11. Hypoglycemia in Diabetes

134

Donald W Richardson

12. Bariatric Surgery and Its Role in the Management of Diabetes David C Lieb, Stephen Wohlgemuth, Anca D Dobrian

145

Diabetes Mellitus

13. Retaining and Regaining Pancreatic β-Cells to Treat Diabetes

158

Yumi Imai, Mark A Ziegler, Sichen Liu

14. Role of Nonphysician Healthcare Providers in Diabetes Management

168

Kathleen B Erezo, Gwendolyn G Brown, Roni Bright, Joseph A Aloi

Index179

xii

CHAPTER

1

Exercise and Diabetes: Personal Prescriptions Sheri R Colberg

INTRODUCTION Implementing and maintaining a physical activity program is a cornerstone of diabetes self-management, especially for those with type 2 diabetes mellitus (T2DM) or gestational diabetes who need to enhance insulin action. In fact, physical activity may prevent or reverse “double diabetes” in anyone with type 1 diabetes mellitus (T1DM), which can result from insulin resistance related to a sedentary lifestyle and weight gain.1 It is recommended that healthcare providers use the broader term “physical activity” in place of the narrower term “exercise” because many types of movements have been proven to have a positive impact on both health and physical fitness. More than one type of physical activity may be required to gain optimal glycemic and health benefits.2 The purpose of this chapter, therefore, is to recommend the types and quantities of physical activities that can and should be undertaken by people with diabetes, as well as appropriate precautions related to medication use and diabetes-related health complications.

PRE-EXERCISE EVALUATION Safe exercise participation can be complicated by the presence of diabetes-related health complications like cardiovascular disease, hypertension, neuropathy, or microvascular changes.3 Nevertheless, no current evidence suggests that any screening protocol beyond usual diabetes care reduces risk of exercise-induced adverse events in asymptomatic individuals with diabetes.4,5 Thus, pre-exercise medical clearance is not necessary for asymptomatic individuals receiving diabetes care consistent with  guidelines who wish to begin low- or moderateintensity physical activity not  exceeding the demands of brisk walking or everyday living. However,  some  individuals desiring to exercise at a higher intensity (more vigorous  than brisk walking) or with greater cardiovascular risk may benefit from referral to a healthcare provider for a checkup and possible exercise stress test before starting such activities.6

Diabetes Mellitus

Assessments may include a graded exercise test depending on the age of the person, diabetes duration, and the presence of additional cardiovascular disease risk factors.7,8 Although exercise stress testing may be done on anyone, most young individuals with a low cardiovascular disease risk may not benefit from doing it, and even the systematic detection of silent ischemia (using exercise testing or other methods) in high-risk asymptomatic patients with diabetes is unlikely to predict cardiovascular disease-related events or early mortality when risk is controlled with medical treatment. Exercise testing, therefore, should rarely be mandatory.4

DAILY MOVEMENT For individuals with diabetes, many of whom are physically unfit and sedentary; it may be beneficial to start by encouraging them to find ways to incorporate more unstructured physical activity into daily living.8 Both high levels of sedentary time and low levels of moderate to vigorous physical activity are strong and independent predictors of early death from any cause in adults ages 50 years or older.9 Physical activity during weight loss also prevents weight regain in this population.10

EXERCISE PRESCRIPTION BY TYPE OF ACTIVITY Prescribed exercise should meet the individual’s unique preferences, lifestyle, and desired physical fitness and other health-related goals. For most with diabetes, exercise acutely reduces blood glucose levels and can be undertaken safely. Initial instructions and periodic supervision by a qualified exercise trainer is recommended for most beginning exercisers undertaking structured exercise programs, particularly resistance exercise training, to ensure optimal health benefits and to minimize injury risk.11 Overall exercise recommendations by type are summarized in table 1.12

Aerobic Exercise Cardiorespiratory or aerobic exercise is defined as continuous, dynamic exercise that uses large muscle groups and requires aerobic metabolic pathways to sustain the activity and includes activities like walking, jogging, biking, swimming, and cycling.13 Aerobic exercise has been the mode traditionally prescribed for T2DM management and prevention, although it carries many health benefits for people with any type of diabetes.

Type of Aerobic Activity Although walking is the most commonly prescribed exercise, undertaking a variety of modes of physical activity is recommended.14 When people have comorbid health issues like peripheral neuropathy, obesity, and osteoarthritis, low-impact or nonweightbearing types of activity (e.g., cycling, swimming, and aquatic or chair exercises) may be a better alternative.6

Intensity of Aerobic Activity

2

Moderate to vigorous intensity physical activity is generally recommended to achieve greater aerobic fitness and metabolic improvements.6,13,14 For most people with T2DM, brisk walking is a moderate-intensity exercise. While more cardiovascular benefits may be gained by engaging in exercise, beginning exercisers should be encouraged to start

• A minimum of 2 nonconsecutive days/week, but preferably 3

• Intensity should be moderate to start, • Continue to work on flexibility and involving 10–15 repetitions per set, with balance training, increasing duration increases in weight or resistance undertaken and/or frequency to progress over with a lower number of repetitions (8–10) time only after the target number of repetitions per set can be exceeded; increase in resistance can be followed by a greater number of sets and lastly by increased training frequency

• 3–7 days/week, with no more than two consecutive days without exercise

• A greater emphasis should be placed on vigorous exercise if fitness is a primary goal and not contraindicated; both high-intensity interval and continuous exercise training may be appropriate activities for most individuals with diabetes

Frequency

Progression

• Flexibility: ≥2–3 days/week • Balance: ≥2–3 days/week

• At least 8–10 exercises with completion of 1–3 • Hold static or do dynamic stretch sets of 10–15 repetitions to near fatigue per for 10–30 s; 2–4 repetitions of each set on every exercise early in training exercise • Balance training can be any duration

• At least 150 min/week at moderate-tovigorous intensity for most adults with diabetes. For adults able to job steadily at 6 miles per hour (9.7 km/h) for 25 minutes, 75 minutes/week of vigorous activity may provide similar benefits

• Stretch to the point of tightness or slight discomfort • Balance exercises light to moderate intensity

• Moderate to vigorous (subjectively • Moderate (e.g., 15 repetitions) to vigorous experienced as “moderate” to “very hard”) (e.g., 6–8 repetitions)

Intensity

Duration

• Stretching: Static, dynamic, and other stretching, yoga • Balance (for adults ages 50+): Practice standing on one leg; exercises using balance equipment; lower-body and core resistance exercises; tai chi

Flexibility and balance

• Prolonged, rhythmic activities using large • Resistance machines, free weights, resistance muscle groups (e.g., walking, swimming, bands, and/or body weight as resistance cycling, etc.) exercises • May be done continuously or as highintensity interval training

Resistance

Type of exercise

Aerobic

TABLE 1:  Physical activity and exercise training recommendations for people with diabetes12

Exercise and Diabetes: Personal Prescriptions

3

Diabetes Mellitus

at an easy-to-moderate pace, particularly since a low fitness level limits self-efficacy and is a perceived barrier to exercise participation.15,16 When matched for energy cost, prolonged continuous low- to moderate-intensity aerobic exercise training is equally effective as moderate- to high-intensity training in improving overall glycemic control.17 For individuals already exercising moderately, undertaking some vigorous physical activity in place of moderate activity will likely result in additional health benefits.18 For example, interspersing some faster intervals during an aerobic training session, particularly a lower intensity one, may increase fitness gains.19 A recent training trend is low-volume high-intensity interval training (HIIT), which involves short bursts of very intense activity interspersed with longer periods of recovery at low to moderate intensity.20,21 However, its safety and efficacy remain unclear for some adults with diabetes.22,23 Before undertaking such training, people should be clinically stable and likely be supervised at least initially.24 The risks with advanced disease are unclear,24 and continuous, moderate-intensity exercise may be safer.25 Estimating exercise intensity using heart rate: Exercise intensity can be estimated by using heart rate measures. Recommended exercise intensity ranges from 40 to 89% of heart rate reserve (HRR, where HRR equals maximal minus resting heart). Intensity can be most accurately prescribed when a maximal heart rate is measured during an exercise stress test. The HRR formula is commonly used to calculate heart rate targets or ranges (see example in box 1). In general, moderate aerobic exercise corresponds to a HRR range of 40–59%, while vigorous exercise is 60–89% of HRR. Target heart rate = (HRR × Desired intensity percentage) + Resting heart rate If the actual maximal heart rate cannot be measured, target ranges can be formulated using an estimated maximal heart rate using one of the following: Estimated maximal heart rate = 220 − Age (years) Estimated maximal heart rate = 208 − (0.7 × Age) The latter equation is usually more accurate in older adults; however, either equation may overestimate or underestimate maximal heart rate in some adults, particularly in Box 1: Example using heart rate reserve to determine target heart rate range

• • • •

Patient: 50-year-old female Resting HR: 70 beats/min Maximum HR: 170 beats/min (estimated from formula, 220 − Age) Formula for sample calculation: Target HR = [(Max HR − Resting HR) × Desired intensity)] + Resting HR • Lower end of HR range (40%) (Moderate) = [(170 − 70) × 0.40] + 70 = [100 × 0.40] + 70 = 40 + 70 = 110 bpm • Higher end of HR range (85%) (Vigorous) = [(170 − 70) × 0.85] + 70 = [100 × 0.85] + 70 = 85 + 70 = 155 beats/min • Target HR range (40−85% HRR) = 110–155 beats/min

4

HRR, heart rate reserve; HR, heart rate.

Exercise and Diabetes: Personal Prescriptions

anyone with autonomic neuropathy.6 With autonomic neuropathy, intensity is better prescribed with maximal heart rate measured directly as it may be blunted.26 Exercise intensity can also be monitored subjectively, with reasonable validity.26,27

Duration of Aerobic Activity Exercise energy expenditure is a function of both duration and intensity. For caloric and glycemic benefits, a lower intensity exercise would need to be performed for longer periods of time compared to higher intensity sessions, although physical activity may be broken down into multiple sessions throughout the day and still lead to a cumulative effect.2,13,14 Deconditioned individuals may need to start with more sessions of short duration (5–10 minutes), begin at low levels (i.e., 30–39% HRR) with brief rest intervals, and progress slowly to doing longer durations or higher intensity exercise. It is recommended that most adults with diabetes engage in at least 150 minutes per week of aerobic activity done at a moderate to vigorous intensity, with a goal of approximately 30 minutes per day or more, most days of the week.12 For adults able to jog steadily at 6 miles per hour (9.7 km/h) or faster for 25 minutes, 75 minutes per week of vigorous activity may provide similar cardioprotective and metabolic benefits. These include engaging in 60 minutes per day or more of moderate- or vigorous-intensity aerobic activity, with vigorous, muscle-strengthening, and bone-strengthening activities included at least 3 days per week.14

Frequency of Aerobic Activity Since the duration of increased insulin action after an exercise session is usually greater than 24 hours but less than 72 hours, regular physical activity is needed for it to continue to lower blood glucose in people with insulin resistance.28,29 Daily exercise, or at least not allowing more than 2 days to elapse between exercise sessions, is recommended to decrease insulin resistance, regardless of diabetes type.20,21 For weight loss, the American College of Sports Medicine recommends 225–420 minutes of moderate-intensity aerobic exercise per week to lose 5–7.5 kg,30 which can be divided into 5 or 6 sessions per week.

Progression of Aerobic Activity Initially, adults should be advised to focus on increasing frequency and duration of exercise, rather than intensity, to reach target volumes of physical activity slowly over 4–6 months.31,32 Doing so increases the likelihood of creating and sustaining an activity habit. Beginning exercise at an intensity that is too high and progressing too quickly can both lead to higher dropout and injury rates.31,32

Resistance Training Prescription Given that diabetes is an independent risk factor for low muscular strength33 and accelerated decline in muscle strength and functional status,34 the primary goal of resistance or strength training in this population is increased muscular fitness, including both muscular strength and endurance. Resistance exercise has also been shown to improve glycemic control, possibly even more so than aerobic training in adults with T2DM, particularly in the early stages.35 In adults with T1DM, the effects on overall glycemic control levels are more variable,20 although immediate declines in blood glucose are less during such training sessions.36 Resistance training can also prevent falls and increase mobility in older adults, allowing

5

Diabetes Mellitus

them to remain more independent and self-sufficient for longer.37 Moreover, coronary ischemia is less likely to occur during resistance compared to aerobic exercise eliciting the same heart rate, and resistance exercise may not induce ischemia.38

Type of Resistance Activity Resistance exercises include weight lifting, use of resistance machines, and free weights (e.g., dumbbells and barbells) can result in fairly equivalent gains in strength and mass of targeted muscles.39 However, heavier weights or resistance may be needed for optimization of insulin action and blood glucose control.40

Intensity of Resistance Activity The prescribed resistance is determined by the individual’s one-repetition maximum (1-RM), defined as the maximal amount of weight successfully lifted one time. Training  should ideally be moderate (50% of 1-RM) or vigorous (75–80% of 1-RM) to optimize gains in strength and insulin action;2,13 lighter weights are not as effective. Home-based resistance training is adequate for maintaining muscle mass and strength, but less effective than supervised, gym-based training for improving blood glucose control and optimizing insulin action.39,40

Duration of Resistance Activity Resistance exercises should ideally be performed to fatigue during each set and consist of 10 to 15 repetitions to near fatigue per set early in training, progressing over time  to  heavier weights (or resistance) that can be lifted only eight to ten times.2 A minimum of 1 set of repetitions to near fatigue, but as many as 3 to 4 sets, is recommended for optimal strength gains. Individuals should perform at least 8 to 10 exercises that cover all of the major muscle groups in the upper body, lower body, and core.14

Frequency of Resistance Activity Resistance exercise should be undertaken at least twice weekly on nonconsecutive days,13,14,41 but more ideally three times a week,42,43 along with regular aerobic activities. Adequate rest periods between sets during a workout session should be included.

Progression of Resistance Activity To avoid injury and burnout, the intensity, frequency, and duration of training sessions  should progress slowly, particularly for people new to exercise or with a low fitness level or multiple perceived barriers to being active.15 In most progressive training, increases in weight or resistance are undertaken only once the target number of repetitions per set can consistently be exceeded, followed by a greater number of sets and lastly by increased training frequency. Progression over 6 months to thrice weekly sessions of 3 sets of 8 to 10 repetitions done at 75–80% of 1-RM on 8 to 10 exercises may be an optimal goal for most adults.42

Combined Aerobic and Resistance Training 6

Prescribing both aerobic and resistance exercise training is recommended. Combined training thrice weekly in individuals with T2DM may be of greater benefit to glycemic control than either aerobic or resistance exercise alone.44-47

Exercise and Diabetes: Personal Prescriptions

Flexibility and Balance Training Flexibility and balance exercises are likely equally important for health and well-being, particularly in older adults with diabetes. Limited joint mobility resulting in part from formation of advanced glycation end-products, which accumulate during normal aging, are accelerated by the presence of hyperglycemia.48 Stretching increases range of motion around joints and flexibility,49 but does not affect glycemic control. Such exercise should be undertaken regularly, although not necessarily as a substitute for other types of training.6 Traditional static and dynamic stretching, as well as yoga and tai chi, can provide fitness benefits, as can balance training. With basic stretching as part of the activity, yoga has the potential to improve glycemic control, lipid levels, and body composition in adults with T2DM,50 whereas tai chi training may improve glycemic control, balance, neuropathic symptoms, and some dimensions of quality of life (QOL) in adults with diabetes and neuropathy.51 Flexibility exercise combined with resistance training can increase joint range-of-motion in individuals with diabetes and allow them to more easily engage in activities that require flexibility.49 Older adults with diabetes should also undertake exercises that maintain or improve balance.14,41 Balance training can reduce falls risk by improving balance and gait, even with peripheral neuropathy present.52

ADOPTION AND MAINTENANCE OF AN ACTIVE LIFESTYLE The promotion of regular exercise among individuals with any type of diabetes or at risk for developing T2DM is important. Fear of hypoglycemia is the strongest reported barrier to regular physical activity in individuals with T1DM, highlighting the importance of information and support regarding hypoglycemia management.53 However, many of the other barriers to exercise are similar among people with and without diabetes, but those with diabetes need appropriate education about exercise effects on diabetes control and complications.54 Greater levels of activity are frequently related to higher levels of self-efficacy, which reflect confidence in the ability to be more active.16,55 Developing realistic goals, selecting appropriate types of activity, progressing slowly (to avoid injury or burnout), and getting supportive feedback can increase confidence.15,16,56 Counseling done by healthcare professionals may also be a meaningful and effective source of support.57 Likewise, supervision of exercise sessions by qualified exercise trainers improves compliance and glycemic control,11 and individuals engaging in supervised training likely gain benefits that exceed those of exercise counseling and increased activity undertaken alone.58 Pedometers promote physical activity by providing motivation and visual feedback.59

EXERCISE GLYCEMIC MANAGEMENT Hyperglycemia Exercise-induced hyperglycemia is more common in T1DM since most people with T2DM still produce endogenous insulin. Purposeful insulin omission before exercise can promote a rise in glycemia, as can malfunctioning infusion sets,60 overconsumption of carbohydrates prior to or during physical activities.61

7

Diabetes Mellitus

Anyone with diabetes may experience increases in blood glucose after aerobic or resistance exercise particularly with vigorous exercise,62 particularly when the activity is more intense or if they are starting out with blood glucose levels that are elevated.63 This effect may be mitigated by interspersing easier activities between more intense ones.64,65 To correct postexercise hyperglycemia, a conservative (50% of usual) correction may work,66 or an aerobic cool down may help lower blood glucose levels naturally. Individuals with T1DM should, tested for blood ketones.12 If blood glucose is over 300  mg/dL (16.7 mM) without ketones and people feel well, they can undertake exercise, but need to stay adequately hydrated.6 Even with meal-induced hyperglycemia, undertaking mild- to moderate-intensity aerobic work will likely reduce glycemic levels given that circulating insulin levels will likely be higher.67,68

Hypoglycemia In individuals managing diabetes with diet and exercise alone, the risk of developing hypoglycemia during or after any physical activity is minimal.6 Undertaking longer duration and lower intensity physical activity generally reduces glycemic levels, but does not result in hypoglycemia.69-71 While intense activity can cause transient blood glucose elevations,72-74 intermittent high-intensity exercise done immediately after breakfast in individuals treated with diet only reduces blood glucose levels and insulin secretion.75 Glucose monitoring should be performed before and after physical activity.

Factors Affecting Glycemic Responses in Type 1 Diabetes Mellitus For anyone using insulin or oral insulin secretagogues, physical activity may complicate diabetes management.76-78 For people with T1DM in particular, a number of factors can increase the risk for exercise-associated hypoglycemia, including the timing, duration, and intensity of the activity.79 Engaging in a new or unfamiliar activity may also increase the risk, while endurance training may lower it.80 However, resistance exercise may minimize the risk of exercise-induced hypoglycemia due to its  intensity.81 When both aerobic and resistance exercise are undertaken in one exercise session, performing resistance exercise first results in less hypoglycemia than when aerobic exercise is performed first.82 Many individuals with T1DM may have an impaired counter-regulatory hormone response reduced by prior hypoglycemia and/or exercise, placing them at high risk for severe hypoglycemia.83 In older individuals with T2DM, unawareness of hypoglycemia increases probability of severe hypoglycemia in these individuals.84

Strategies to Prevent Activity-related Hypoglycemia Carbohydrate intake will vary with insulin regimens, timing of exercise, type of activity, and more,79 but also be impacted by blood glucose levels at the start of the activity. For low- to moderate-intensity aerobic activities lasting 30–60 minutes undertaken under fasting or basal conditions, approximately 10–15 g of carbohydrate may suffice to prevent hypoglycemia.85 However, while exercising when insulin levels are higher (such as after a bolus of rapid-acting insulin), 30–60 g of carbohydrate per hour of exercise may be needed.86

8

Insulin adjustment: Decreasing circulating insulin levels enough during any activity may reduce or eliminate the need for carbohydrate intake. For example, a 20% or greater

Exercise and Diabetes: Personal Prescriptions Box 2: Medications with a higher risk of activity-related hypoglycemia

• • • •

Glimepiride Glipizide and extended release Glipizide and metformin Glyburide and combinations

• • • •

Glyburide and metformin Nateglinide Repaglinide Insulin: All types and delivery methods

reduction in basal insulin for individuals on multiple daily injections can be made for doses both before and after exercise.61 People using an insulin pump can choose to reduce87 or suspend88 insulin delivery at the start of exercise, or reduce it starting 30–60 minutes beforehand.89 For exercise performed within 2–3 hours after any bolus of rapid-acting insulin, making dose reductions of 25–75% may assist in lowering the risk of hypoglycemia. Prevention of delayed hypoglycemia: Repeated interval or intense resistance training in particular can cause substantial depletion of muscle glycogen and increase risk of postexercise hypoglycemia in insulin or insulin secretagogues users.90 Consuming 5–30 g of carbohydrate during and within 30 minutes following exhaustive, glycogendepleting exercise will lower the risk and allow for more efficient restoration of muscle glycogen.91

Medication Effects Some individuals may need to reduce their oral medications or insulin dosing before (and possibly after) exercise.92 Meglitinides are the main class of oral medications that can be readily adjusted due to their short durations of action (Box 2); they can be reduced or omitted if physical activity is planned within a few hours after eating. Doses of sulfonylureas may also need to be lowered in response to regular physical activity if the frequency of hypoglycemia increases.78,90 Users of rapid-acting insulin analogs will need to monitor glucose levels before and after exercise and make appropriate dietary and/or medication changes. If only longer-acting basal insulins are used, exerciseinduced hypoglycemia is less likely.93 Medications prescribed for comorbid conditions, including antihypertensive agents, aspirin, and lipid-lowering agents, generally do not affect exercise responses, with some notable exceptions. Beta-blockers blunt heart rate responses to exercise and lower maximal exercise capacity by approximately 13%,94 and they frequently mask the symptoms of hypoglycemia. However, β-blockers may increase exercise capacity in those with heart disease by reducing coronary ischemia during activity.95 Diuretics lower overall blood and fluid volumes and may result in dehydration and electrolyte imbalances, particularly during exercise in the heat. Lipid-lowering drugs (e.g., statins) carry an elevated relative risk of myalgia and myositis, particularly when combined with use of fibrates and niacin.96

EXERCISE WITH COMPLICATIONS Vascular Disease Diabetic individuals with known coronary disease and exercise-induced ischemia should exercise in a supervised cardiac rehabilitation program, at least initially.97 For

9

Diabetes Mellitus

anyone with peripheral artery disease, with and without intermittent claudication and pain in the extremities during exercise, low to moderate walking, arm-crank, and cycling exercise can enhance mobility, functional capacity, exercise pain tolerance, and QOL.98,99 Lower extremity resistance training also improves functional performance.100

Peripheral Neuropathy Peripheral neuropathy, with an associated decrease in sensation, carries with it an increased risk of injury, along with greater discomfort from painful neuropathy during physical activity. Sensations connected to balance and strength can be diminished and gait altered, contributing to development of orthopedic issues and a greater risk of falling.101 However, participation in mild to moderate exercise may help prevent the onset of peripheral neuropathy.102 Moderate walking does not appear to increase risk of foot ulcers or reulceration in those with peripheral neuropathy.103,104

Autonomic Neuropathy Cardiac autonomic neuropathy (CAN) results in more frequent silent myocardial ischemia,105 orthostatic hypotension, and resting tachycardia,106 but also impaired exercise tolerance and lower maximal heart rate.105 Cardiac autonomic neuropathy also greatly increases mortality risk.26,105 Given the likelihood of heart rate abnormalities in CAN, these individuals should be medically cleared and possibly undergo stress testing before starting an exercise training program.105 Moderate-intensity aerobic training can improve autonomic function in individuals with and without CAN.107-109 Exercise intensity may be accurately prescribed using the HRR method with maximal heart rate directly measured, or subjective ratings of perceived exertion can be used.26,105

Diabetic Eye Disease Exercise should never be undertaken during an ongoing retinal hemorrhage. Macular edema and glaucoma should be evaluated by an ophthalmologist or optometrist and activity guidelines determined by the results of the examination.

Diabetic Kidney Disease

10

Microalbuminuria, or minute amounts of albumin in the urine, is a common risk factor for more severe kidney dysfunction110 and cardiovascular mortality.111 Although urinary albumin excretion rates can rise proportionally with increasing exercise intensity during  the period following the activity, such changes should not be interpreted to mean that exercise is causing additional damage.112 Most people with overt nephropathy have diminished capacity for physical activity, but can benefit from staying physically active. Physical activity during dialysis sessions is possible and often recommended to increase functional capacity.113 Both aerobic and resistance training improve physical function and QOL in those with kidney disease.114 Resistance exercise training is especially effective in improving muscle function and activities of daily living, which are normally severely impacted by later stage kidney disease.114 Individuals with overt nephropathy should be screened, have physician approval, and possibly undergo stress testing to detect cardiovascular disease and abnormal responses.115

Exercise and Diabetes: Personal Prescriptions

CONCLUSION This chapter discusses exercise prescription for individuals with diabetes, based on the current physical activity and exercise guidelines. The basic elements of the exercise prescription serve as a guide to creating safe and effective physical activity programs, even when complicated by the use of certain medications and presence of diabetesrelated health issues. Most adults will benefit from engaging in both aerobic exercise (for at least 150 minutes per week spread over at least 3 days of the week, or a lesser amount of more intense activity) and resistance exercise training, along with flexibility and balance training if older. Healthcare professionals can prescribe appropriate physical activities and promote individual adoption of lasting behavior changes that benefit diabetes management and prevent health complications.

REFERENCES 1. Kilpatrick ES, Rigby AS, Atkin SL. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: “double diabetes” in the Diabetes Control and Complications Trial. Diabetes Care. 2007;30:707-12. 2. Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011;43:1334-59. 3. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C. Physical activity/exercise and type 2 diabetes. Diabetes Care. 2004;27:2518-39. 4. Lievre MM, Moulin P, Thivolet C, Rodier M, Rigalleau V, Penfornis A, et al. Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening. Trials. 2011;12:23. 5. Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301:1547-55. 6. Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33:e147-67. 7. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C, White RD. Physical activity/exercise and type 2 diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:1433-8. 8. American Diabetes Association. Physical activity/exercise and diabetes. Diabetes Care. 2004;27:S58-62. 9. Schmid D, Ricci C, Leitzmann MF. Associations of objectively assessed physical activity and sedentary time with allcause mortality in US adults: the NHANES study. PLoS One. 2015;10:e0119591. 10. Wang X, Lyles MF, You T, Berry MJ, Rejeski WJ, Nicklas BJ. Weight regain is related to decreases in physical activity during weight loss. Med Sci Sports Exerc. 2008;40:1781-8. 11. Balducci S, Zanuso S, Fernando F, Fallucca S, Fallucca F, Pugliese G, et al. Physical activity/exercise training in type 2 diabetes. The role of the Italian Diabetes and Exercise Study. Diabetes Metab Res Rev. 2009;25 Suppl 1:S29-33. 12. Colberg S, Sigal RJ, Yardley JE, Riddell MC, Dunstan DW, Dempsey PC, et al. Physical activity/exercise and diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2016;39(11):2065-79. 13. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007;39:1423-34. 14. Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report, 2008. Washington, DC: U.S. Department of Health and Human Services; 2008. 15. Aljasem LI, Peyrot M, Wissow L, Rubin RR. The impact of barriers and self-efficacy on self-care behaviors in type 2 diabetes. Diabetes Educator. 2001;27:393-404. 16. Dutton GR, Tan F, Provost BC, Sorenson JL, Allen B, Smith D. Relationship between self-efficacy and physical activity among patients with type 2 diabetes. J Behav Med. 2009;32:270-7. 17. Hansen D, Dendale P, Jonkers RA, Beelen M, Manders RJ, Corluy L, et al. Continuous low- to moderate-intensity exercise training is as effective as moderate- to high-intensity exercise training at lowering blood HbA(1c) in obese type 2 diabetes patients. Diabetologia. 2009;52:1789-97.

11

Diabetes Mellitus

12

18. Boulé NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia. 2003;46:1071-81. 19. Johnson ST, McCargar LJ, Bell GJ, Tudor-Locke C, Harber VJ, Bell RC. Walking faster: distilling a complex prescription for type 2 diabetes management through pedometry. Diabetes Care. 2006;29:1654-5. 20. Tonoli C, Heyman E, Roelands B, Buyse L, Cheung SS, Berthoin S, et al. Effects of different types of acute and chronic (training) exercise on glycaemic control in type 1 diabetes mellitus: a meta-analysis. Sports Med. 2012;42:1059-80. 21. Jelleyman C, Yates T, O’Donovan G, Gray LJ, King JA, Khunti K, et al. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis. Obes Rev. 2015;16:942-61. 22. Biddle SJ, Batterham AM. High-intensity interval exercise training for public health: a big HIT or shall we HIT it on the head? Int J Behav Nutr Phys Act. 2015;12:95. 23. Mitranun W, Deerochanawong C, Tanaka H, Suksom D. Continuous vs interval training on glycemic control and macroand microvascular reactivity in type 2 diabetic patients. Scand J Med Sci Sports. 2014;24:e69-76. 24. Levinger I, Shaw CS, Stepto NK, Cassar S, McAinch AJ, Cheetham C, et al. What doesn’t kill you makes you fitter: a systematic review of high-intensity interval exercise for patients with cardiovascular and metabolic diseases. Clin Med Insights Cardiol. 2015;9:53-63. 25. Holloway TM, Spriet LL. CrossTalk opposing view: high intensity interval training does not have a role in risk reduction or treatment of disease. J Physiol. 2015;593:5219-21. 26. Colberg SR, Swain DP, Vinik AI. Use of heart rate reserve and rating of perceived exertion to prescribe exercise intensity in diabetic autonomic neuropathy. Diabetes Care. 2003;26:986-90. 27. Chen MJ, Fan X, Moe ST. Criterion-related validity of the Borg ratings of perceived exertion scale in healthy individuals: a meta-analysis. J Sports Sci. 2002;20:873-99. 28. Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001;286:1218-27. 29. O’Gorman DJ, Karlsson HK, McQuaid S, Yousif O, Rahman Y, Gasparro D, et al. Exercise training increases insulinstimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes. Diabetologia. 2006;49:2983-92. 30. Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK, et al. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009;41:459-71. 31. Gilchrist J, Jones BH, Sleet DA, Kimsey CD; CDC. Exercise-related injuries among women: strategies for prevention from civilian and military studies. MMWR Recomm Rep. 2000;49:15-33. 32. Pollock ML, Carroll JF, Graves JE, Leggett SH, Braith RW, Limacher M, et al. Injuries and adherence to walk/jog and resistance training programs in the elderly. Med Sci Sports Exerc. 1991;23:1194-200. 33. Nishitani M, Shimada K, Sunayama S, Masaki Y, Kume A, Fukao K, et al. Impact of diabetes on muscle mass, muscle strength, and exercise tolerance in patients after coronary artery bypass grafting. J Cardiol. 2011;58:173-80. 34. Anton SD, Karabetian C, Naugle K, Buford TW. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults? Exp Gerontol. 2013;48:888-97. 35. Ishiguro H, Kodama S, Horikawa C, Fujihara K, Hirose AS, Hirasawa R, et al. In search of the ideal resistance training program to improve glycemic control and its indication for patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Sports Med. 2016;46:67-77. 36. Garcia-Garcia F, Kumareswaran K, Hovorka R, Hernando ME. Quantifying the acute changes in glucose with exercise in type 1 diabetes: a systematic review and meta-analysis. Sports Med. 2015;45:587-99. 37. Tofthagen C, Visovsky C, Berry DL. Strength and balance training for adults with peripheral neuropathy and high risk of fall: current evidence and implications for future research. Oncol Nurs Forum. 2012;39:E416-24. 38. Ghilarducci LE, Holly RG, Amsterdam EA. Effects of high resistance training in coronary artery disease. Am J Cardiol. 1989;64:866-70. 39. Dunstan DW, Daly RM, Owen N, Jolley D, Vulikh E, Shaw J, et al. Home-based resistance training is not sufficient to maintain improved glycemic control following supervised training in older individuals with type 2 diabetes. Diabetes Care. 2005;28:3-9. 40. Willey KA, Singh MA. Battling insulin resistance in elderly obese people with type 2 diabetes: bring on the heavy weights. Diabetes Care. 2003;26:1580-8. 41. Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007;39:1435-45. 42. Dunstan DW, Daly RM, Owen N, Jolley D, De Courten M, Shaw J, et al. High-intensity resistance training improves glycemic control in older patients with type 2 diabetes. Diabetes Care. 2002;25:1729-36.

Exercise and Diabetes: Personal Prescriptions 43. Snowling NJ, Hopkins WG. Effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients: a meta-analysis. Diabetes Care. 2006;29:2518-27. 44. Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W, Kramer K, et al. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2010;304:2253-62. 45. Marcus RL, Smith S, Morrell G, Addison O, Dibble LE, Wahoff-Stice D, et al. Comparison of combined aerobic and high-force eccentric resistance exercise with aerobic exercise only for people with type 2 diabetes mellitus. Phys Ther. 2008;88:1345-54. 46. Cuff DJ, Meneilly GS, Martin A, Ignaszewski A, Tildesley HD, Frohlich JJ. Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care. 2003;26:2977-82. 47. Sigal RJ, Kenny GP, Boulé NG, Wells GA, Prud’homme D, Fortier M, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147:357-69. 48. Abate M, Schiavone C, Pelotti P, Salini V. Limited joint mobility in diabetes and ageing: recent advances in pathogenesis and therapy. Int J Immunopathol Pharmacol. 2011;23:997-1003. 49. Herriott MT, Colberg SR, Parson HK, Nunnold T, Vinik AI. Effects of 8 weeks of flexibility and resistance training in older adults with type 2 diabetes. Diabetes Care. 2004;27:2988-9. 50. Innes KE, Selfe TK. Yoga for adults with type 2 diabetes: a systematic review of controlled trials. J Diabetes Res. 2016;2016:6979370. 51. Ahn S, Song R. Effects of tai chi exercise on glucose control, neuropathy scores, balance, and quality of life in patients with type 2 diabetes and neuropathy. J Altern Complement Med. 2012;18:1172-8. 52. Morrison S, Colberg SR, Mariano M, Parson HK, Vinik AI. Balance training reduces falls risk in older individuals with type 2 diabetes. Diabetes Care. 2010;33:748-50. 53. Brazeau AS, Rabasa-Lhoret R, Strychar I, Mircescu H. Barriers to physical activity among patients with type 1 diabetes. Diabetes Care. 2008;31:2108-9. 54. Lascar N, Kennedy A, Hancock B, Jenkins D, Andrews RC, Greenfield S, et al. Attitudes and barriers to exercise in adults with type 1 diabetes (T1DM) and how best to address them: a qualitative study. PLoS One. 2014;9:e108019. 55. Delahanty LM, Conroy MB, Nathan DM. Psychological predictors of physical activity in the diabetes prevention program. J Am Diet Assoc. 2006;106:698-705. 56. McAuley E, Blissmer B. Self-efficacy determinants and consequences of physical activity. Exerc Sport Sci Rev. 2000;28:85-8. 57. Armit CM, Brown WJ, Marshall AL, Ritchie CB, Trost SG, Green A, et al. Randomized trial of three strategies to promote physical activity in general practice. Prev Med. 2009;48:156-63. 58. Gordon BA, Benson AC, Bird SR, Fraser SF. Resistance training improves metabolic health in type 2 diabetes: a systematic review. Diabetes Res Clin Pract. 2009;83:157-75. 59. Lauzon N, Chan CB, Myers AM, Tudor-Locke C. Participant experiences in a workplace pedometer-based physical activity program. J Phys Act Health. 2008;5:675-87. 60. Yardley JE, Zaharieva DP, Jarvis C, Riddell MC. The “ups” and “downs” of a bike race in people with type 1 diabetes: dramatic differences in strategies and blood glucose responses in the Paris-to-Ancaster Spring Classic. Can J Diabetes. 2015;39:105-10. 61. Campbell MD, Walker M, Bracken RM, Turner D, Stevenson EJ, Gonzalez JT, et al. Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care. 2015;3:e000085. 62. Gordon BA, Bird SR, MacIsaac RJ, Benson AC. Does a single bout of resistance or aerobic exercise after insulin dose reduction modulate glycaemic control in type 2 diabetes? A randomised cross-over trial. J Sci Med Sport. 2016;19(10):795-9. 63. Marliss EB, Vranic M. Intense exercise has unique effects on both insulin release and its roles in glucoregulation: implications for diabetes. Diabetes. 2002;51 Suppl 1:S271-83. 64. Guelfi KJ, Jones TW, Fournier PA. The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes. Diabetes Care. 2005;28:1289-94. 65. Guelfi KJ, Ratnam N, Smythe GA, Jones TW, Fournier PA. Effect of intermittent high-intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes. Am J Physiol Endocrinol Metab. 2007;292:E865-70. 66. Turner D, Luzio S, Gray BJ, Bain SC, Hanley S, Richards A, et al. Algorithm that delivers an individualized rapid-acting insulin dose after morning resistance exercise counters post-exercise hyperglycaemia in people with type 1 diabetes. Diabet Med. 2016;33:506-10. 67. Poirier P, Mawhinney S, Grondin L, Tremblay A, Broderick T, Cléroux J, et al. Prior meal enhances the plasma glucose lowering effect of exercise in type 2 diabetes. Med Sci Sports Exerc. 2001;33:1259-64.

13

Diabetes Mellitus

14

68. Colberg SR, Zarrabi L, Bennington L, Nakave A, Thomas Somma C, Swain DP, et al. Postprandial walking is better for lowering the glycemic effect of dinner than pre-dinner exercise in type 2 diabetic individuals. J Am Med Dir Assoc. 2009;10:394-7. 69. Bajpeyi S, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Hickner RC, et al. Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation. J Appl Physiol (1985). 2009;106:1079-85. 70. Evans EM, Racette SB, Peterson LR, Villareal DT, Greiwe JS, Holloszy JO. Aerobic power and insulin action improve in response to endurance exercise training in healthy 77-87 yr olds. J Appl Physiol. 2005;98:40-5. 71. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS, Kraus WE. Effect of the volume and intensity of exercise training on insulin sensitivity. J Appl Physiol. 2004;96:101-6. 72. Kreisman SH, Halter JB, Vranic M, Marliss EB. Combined infusion of epinephrine and norepinephrine during moderate exercise reproduces the glucoregulatory response of intense exercise. Diabetes. 2003;52:1347-54. 73. Szewieczek J, Dulawa J, Strzalkowska D, Batko-Szwaczka A, Hornik B. Normal insulin response to short-term intense exercise is abolished in type 2 diabetic patients treated with gliclazide. J Diabetes Complications. 2009;23(6):380-6. 74. Szewieczek J, Dulawa J, Strzalkowska D, Hornik B, Kawecki G. Impact of the short-term, intense exercise on postprandial glycemia in type 2 diabetic patients treated with gliclazide. J Diabetes Complications. 2007;21:101-7. 75. Larsen JJ, Dela F, Madsbad S, Galbo H. The effect of intense exercise on postprandial glucose homeostasis in type II diabetic patients. Diabetologia. 1999;42:1282-92. 76. Kennedy JW, Hirshman MF, Gervino EV, Ocel JV, Forse RA, Hoenig SJ, et al. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes. 1999;48:1192-7. 77. Musi N, Fujii N, Hirshman MF, Ekberg I, Fröberg S, Ljungqvist O, et al. AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes. 2001;50:921-7. 78. Rosenstock J, Hassman DR, Madder RD, Brazinsky SA, Farrell J, Khutoryansky N, et al. Repaglinide versus nateglinide monotherapy: a randomized, multicenter study. Diabetes Care. 2004;27:1265-70. 79. Colberg SR, Laan R, Dassau E, Kerr D. Physical activity and type 1 diabetes: time for a rewire? J Diabetes Sci Technol. 2015;9:609-18. 80. Murillo S, Brugnara L, Novials A. One year follow-up in a group of half-marathon runners with type-1 diabetes treated with insulin analogues. J Sports Med Phys Fitness. 2010;50:506-10. 81. Yardley JE, Kenny GP, Perkins BA, Riddell MC, Balaa N, Malcolm J, et al. Resistance versus aerobic exercise: acute effects on glycemia in type 1 diabetes. Diabetes Care. 2013;36:537-42. 82. Yardley JE, Kenny GP, Perkins BA, Riddell MC, Malcolm J, Boulay P, et al. Effects of performing resistance exercise before versus after aerobic exercise on glycemia in type 1 diabetes. Diabetes Care. 2012;35:669-75. 83. Davis SN, Tate D, Hedrington MS. Mechanisms of hypoglycemia and exercise-associated autonomic dysfunction. Trans Am Clin Climatol Assoc. 2014;125:281-91; discussion 291-2. 84. Bremer JP, Jauch-Chara K, Hallschmid M, Schmid S, Schultes B. Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care. 2009;32:1513-7. 85. Riddell MC, Milliken J. Preventing exercise-induced hypoglycemia in type 1 diabetes using real-time continuous glucose monitoring and a new carbohydrate intake algorithm: an observational field study. Diabetes Technol Ther. 2011;13:819-25. 86. Francescato MP, Stel G, Stenner E, Geat M. Prolonged exercise in type 1 diabetes: performance of a customizable algorithm to estimate the carbohydrate supplements to minimize glycemic imbalances. PLoS One. 2015;10:e0125220. 87. Franc S, Daoudi A, Pochat A, Petit MH, Randazzo C, Petit C, et al. Insulin-based strategies to prevent hypoglycaemia during and after exercise in adult patients with type 1 diabetes on pump therapy: the DIABRASPORT randomized study. Diabetes Obes Metab. 2015;17:1150-7. 88. Diabetes Research in Children Network (DirecNet) Study Group, Tsalikian E, Kollman C, Tamborlane WB, Beck RW, Fiallo-Scharer R, et al. Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin. Diabetes Care. 2006;29:2200-4. 89. Heinemann L, Nosek L, Kapitza C, Schweitzer MA, Krinelke L. Changes in basal insulin infusion rates with subcutaneous insulin infusion: time until a change in metabolic effect is induced in patients with type 1 diabetes. Diabetes Care. 2009;32:1437-9. 90. Larsen JJ, Dela F, Madsbad S, Vibe-Petersen J, Galbo H. Interaction of sulfonylureas and exercise on glucose homeostasis in type 2 diabetic patients. Diabetes Care. 1999;22:1647-54. 91. Stellingwerff T, Boon H, Gijsen AP, Stegen JH, Kuipers H, van Loon LJ. Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use. Pflugers Arch. 2007;454:635-47.

Exercise and Diabetes: Personal Prescriptions 92. Galbo H, Tobin L, van Loon LJ. Responses to acute exercise in type 2 diabetes, with an emphasis on metabolism and interaction with oral hypoglycemic agents and food intake. Appl Physiol Nutr Metab. 2007;32:567-75. 93. Plockinger U, Topuz M, Riese B, Reuter T. Risk of exercise-induced hypoglycaemia in patients with type 2 diabetes on intensive insulin therapy: comparison of insulin glargine with NPH insulin as basal insulin supplement. Diabetes Res Clin Pract. 2008;81:290-5. 94. Sigal RJ, Purdon C, Bilinski D, Vranic M, Halter JB, Marliss EB. Glucoregulation during and after intense exercise: effects of beta-blockade. J Clin Endocrinol Metab. 1994;78:359-66. 95. de Muinck ED, Lie KI. Safety and efficacy of beta-blockers in the treatment of stable angina pectoris. J Cardiovasc Pharmacol. 1990;16 Suppl 5:S123-8. 96. Nichols GA, Koro CE. Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and nondiabetic patients. Clin Ther. 2007;29:1761-70. 97. Smith SC Jr, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113:2363-72. 98. Pena KE, Stopka CB, Barak S, Gertner HR Jr, Carmeli E. Effects of low-intensity exercise on patients with peripheral artery disease. Phys Sportsmed. 2009;37:106-10. 99. Zwierska I, Walker RD, Choksy SA, Male JS, Pockley AG, Saxton JM. Upper- vs lower-limb aerobic exercise rehabilitation in patients with symptomatic peripheral arterial disease: a randomized controlled trial. J Vasc Surg. 2005;42:1122-30. 100. McDermott MM, Ades P, Guralnik JM, Dyer A, Ferrucci L, Liu K, et al. Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: a randomized controlled trial. JAMA. 2009;301:165-74. 101. Ko SU, Stenholm S, Chia CW, Simonsick EM, Ferrucci L. Gait pattern alterations in older adults associated with type 2 diabetes in the absence of peripheral neuropathy—results from the Baltimore Longitudinal Study of Aging. Gait Posture. 2011;34:548-52. 102. Balducci S, Iacobellis G, Parisi L, Di Biase N, Calandriello E, Leonetti F, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complications. 2006;20:216-23. 103. Lemaster JW, Mueller MJ, Reiber GE, Mehr DR, Madsen RW, Conn VS. Effect of weight-bearing activity on foot ulcer incidence in people with diabetic peripheral neuropathy: feet first randomized controlled trial. Phys Ther. 2008;88:1385-98. 104. Lemaster JW, Reiber GE, Smith DG, Heagerty PJ, Wallace C. Daily weight-bearing activity does not increase the risk of diabetic foot ulcers. Med Sci Sports Exerc. 2003;35:1093-9. 105. Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007;115:387-97. 106. Ewing DJ, Clarke BF. Diabetic autonomic neuropathy: present insights and future prospects. Diabetes Care. 1986;9:648-65. 107. Howorka K, Pumprla J, Haber P, Koller-Strametz J, Mondrzyk J, Schabmann A. Effects of physical training on heart rate variability in diabetic patients with various degrees of cardiovascular autonomic neuropathy. Cardiovasc Res. 1997;34:206-14. 108. Loimaala A, Huikuri HV, Koobi T, Rinne M, Nenonen A, Vuori I. Exercise training improves baroreflex sensitivity in type 2 diabetes. Diabetes. 2003;52:1837-42. 109. Pagkalos M, Koutlianos N, Kouidi E, Pagkalos E, Mandroukas K, Deligiannis A. Heart rate variability modifications following exercise training in type 2 diabetic patients with definite cardiac autonomic neuropathy. Br J Sports Med. 2008;42:47-54. 110. Coccheri S. Approaches to prevention of cardiovascular complications and events in diabetes mellitus. Drugs. 2007;67:997-1026. 111. Gimeno Orna JA, Boned Juliani B, Lou Arnal LM, Castro Alonso FJ. Microalbuminuria and clinical proteinuria as the main predictive factors of cardiovascular morbidity and mortality in patients with type 2 diabetes. Rev Clin Esp. 2003;203:526-31. 112. Kornhauser C, Malacara JM, Macias-Cervantes MH, Rivera-Cisneros AE. Effect of exercise intensity on albuminuria in adolescents with type 1 diabetes mellitus. Diabet Med. 2012;29:70-3. 113. Makhlough A, Ilali E, Mohseni R, Shahmohammadi S. Effect of intradialytic aerobic exercise on serum electrolytes levels in hemodialysis patients. Iran J Kidney Dis. 2012;6:119-23. 114. Johansen KL. Exercise and chronic kidney disease: current recommendations. Sports Med. 2005;35:485-99. 115. Braden C. Nephropathy: advanced. In: RudermanN, Devlin JT. The Health Professional’s: Guide to Diabetes and Exercise. Alexandria, VA: American Diabetes Association; 1995. pp. 177-80.

15

CHAPTER

2

Medical Nutrition Therapy for Adults with Diabetes and Related Topics Phyllis A Woodson

INTRODUCTION According to the Institute of Medicine, “The registered dietitian is currently the single identifiable group of healthcare professionals with standardized education, clinical training, continuing education, and national credentialing requirements necessary to be directly reimbursed as a provider of nutrition therapy.” Medical nutrition therapy  (MNT) provided by the registered dietitian leads to improved clinical outcomes and decreased costs associated with physician time, use of medication, and hospital admissions of individuals with obesity, diabetes, lipid disorders, and other chronic diseases.1 Medical nutrition therapy has long been considered the foundation or cornerstone of managing diabetes and many other nutrition-related conditions. This chapter will address the origins of MNT and its comparison to diabetes selfmanagement training (DSMT) which can also be provided by the registered dietitian. Current nutrition recommendations for diabetes and gestational diabetes mellitus (GDM); weight management; cost savings associated with weight maintenance and glycemic control and expenses associated with weight gain and poor glycemic control; bariatric surgery; and a review of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and low-carbohydrate diets will be presented. The controversies surrounding these recommendations will remind the reader that there is often a lack of agreement on the best diet approach.

MEDICAL NUTRITION THERAPY, DIABETES SELF-MANAGEMENT TRAINING, AND PREVALENCE OF DIABETES The term MNT can be traced back to 1994 when the Academy of Nutrition and Dietetics, previously the American Dietetic Association, was pursuing reimburse­ ment  for this service.2 The pathway to coverage by Medicare in the United States of these services is a complicated one (due to requirements of the referral process, MNT  and DSMT cannot be received by a patient on the same day, DSMT rules for individual or group education, place of service restrictions, etc.) resulting in limited access by those in need of these services. It is estimated that only 5% of individuals with newly diagnosed diabetes and eligible for Medicare coverage in the United

Medical Nutrition Therapy for Adults with Diabetes and Related Topics

States utilize the DSMT benefit.3 For additional information, the reader may wish to review Diabetes Self-Management Education and Support in Type 2 Diabetes Mellitus (T2DM): A Joint Position Statement.4 The Centers for Disease Control and Prevention (CDC) states that 86 million adults in the United States have prediabetes, 90% do not know it, and that structured lifestyle change resulting in weight loss could reduce this risk by as much as 58%, well worth any effort undertaken.5 It is estimated that half of all adults 65 years or older have prediabetes.6 About 29 million adults have diabetes and 25% do not know it.5 It is estimated that at least 25% of adults 65 years or older have diabetes.7 The annual cost of diabetes in this older group is over $104 billion, threatening to increase significantly if the prevalence of diabetes grows as expected, two- to threefold by the year 2050.8 The benefit of any intervention to reduce the prevalence of diabetes in the aging population would include huge cost savings.

Medical Nutrition Therapy Goals and Recommendations for Diabetes In the 2016 Standards of Medical Care, the American Diabetes Association (ADA) recommends four goals of MNT for adults with diabetes:9 1. Encourage eating a variety of nutritious foods in the recommended portion sizes to promote health by achieving and maintaining an appropriate body weight and improving individualized glucose, lipid, and blood pressure control in order to delay or prevent diabetes complications. 2. Consider the individual’s personal and cultural environment, health literacy and numeracy, access to recommended foods, and interest and ability to make the necessary efforts including overcoming any barriers to meet nutrition needs. 3. Encourage pleasure in eating with acceptance. 4. Facilitate the individual’s ability to independently plan healthy meals. The ADA recommends that all persons with diabetes receive MNT by a registered dietitian with in-depth diabetes knowledge and experience. Medical nutrition therapy should be a major  part in the treatment of prediabetes, diabetes, and patient self-care. Studies have shown that when MNT is an intervention variable and delivered by a registered dietitian, glycosylated hemoglobin (HbA1c) decreases by 0.3–1% in individuals with type 1 diabetes mellitus (T1DM)10-12 and by 0.5–2% in individuals with T2DM.13-16 The ADA recommends that all diabetes team members be familiar with and supportive of MNT recommendations. The ADA promotes nutrition recommendations in the areas of effectiveness of nutrition therapy, energy balance, eating patterns and macronutrient  distribution, and micronutrients and herbal supplements.9 Alcohol, sodium intake, and lipid management are also discussed. These recommendations provide significant detail with respect to nutrition in the patient with diabetes, covering such areas as nutrition education, the role that caloric intake plays in weight loss and weight management, and the importance of healthy food choices, such as whole grains and vegetables as opposed to higher sugarcontaining foods and high-calorie beverages.

WEIGHT MANAGEMENT AND DIABETES Strong evidence shows that weight control is important to better manage T2DM and prevent it.17,18 As little as 5–7% sustained weight loss in overweight and obese

17

Diabetes Mellitus

individuals can improve glucose control and avoid medication for this control.19-21 It has been shown that about 1,200–1,500 calories for women and about 1,500– 1,800 calories for men (considering initial body weight) can achieve this weight loss. Please see the plate we use to guide patients in selecting a variety of healthy foods with portion control (Fig. 1). Weight loss is a complicated, multifaceted, and ongoing effort by the individual, so understanding and modifying behavior will take time and require support. It is recommended for more successful weight loss, that intensive behavioral lifestyle intervention be utilized. This approach would include at least 16 sessions over 6  months, covering diet, physical activity, and behavioral strategies to reduce daily caloric intake by the above-recommended 500–750 calories. Trained interventionists should provide this education and support, either individually or in groups.22 When overweight and obese individuals with T2DM have completed the 16 sessions and have lost weight, they should participate in an ongoing follow-up program for at least 1 year receiving at least monthly support for weight loss maintenance. Weekly monitoring of weight is recommended with the ongoing reduced calorie diet. At this time, it would be expected that physical activity or exercise has safely progressed to 3–5 hours weekly.

Cost Savings and Expenses Associated with Weight Maintenance or Gain In patients with T2DM who maintained weight within 5% of baseline over time, regardless of HbA1c, a reduction in related medical costs of about $400 or 5% has

sl, slice; c, cup; tsp, teaspoon; tbsp, tablespoon; oz, ounce.

FIG. 1:  Plate of health (For color version, see Plate 1)

18

With permission from: Copyright© 2011–2016 Eastern Virginia Medical School/The Strelitz Diabetes Center. All Rights Reserved.

Medical Nutrition Therapy for Adults with Diabetes and Related Topics

been observed compared to an increase in medical costs of about $1,473 or 14% (p 1.5 L/day PO)

√

√

√

√

Monitor blood glucose if diabetes, hypoglycemia symptoms

√

√

√

√

LAGB, laparoscopic adjustable gastric banding; LSG, laparoscopic sleeve gastrectomy; RYGB, Roux-en-Y gastric bypass; BPDDS, laparoscopic biliopancreatic diversion duodenal switch; RD, registered dietitian.

Table 1 represents the micronutrient recommendations per surgery type.

MEDITERRANEAN, DIETARY APPROACHES TO STOP HYPERTENSION, AND LOW-CARBOHYDRATE DIETS

20

The Mediterranean diet continues to receive recognition as a good choice for those with diabetes since a study of nearly 5 years showed a relative risk reduction of 30% for heart attack, stroke or death due to cardiovascular causes in persons at high risk for heart disease.28 The diet associated with the study, conducted by 18 investigators in Spain, included a complementary supplementation of either nuts (this group did better) or extra-virgin olive oil. The participants were encouraged to eat three servings of fruit daily, two servings of vegetables daily, three servings of fish weekly, three servings of legumes weekly, and to consume less red meat, sweets, soda drinks, and dairy foods. It was optional to include seven servings of wine weekly if the participant already drank wine. This multicenter trial utilized randomly assigned participants and a control group. The DASH diet effectively prevents and treats hypertension.29 This diet study showed that blood pressure was decreased substantially in persons consuming a diet reduced in saturated fat and total fat, rich in fruits and vegetables, and consisting of low fat dairy foods. Strict exclusion criteria were utilized in regards to medical diagnoses, weight, medications, and food supplements. After a 3-week control period, patients were randomly assigned to one of three 8-week groups (2-diet groups and 1-control group). Caffeine (no more than three servings daily) and alcohol (no more than two servings daily) intake were limited. Weight (caloric intake was altered as needed) and sodium intake (3,000 mg/day) were maintained across groups. At least 1 meal a day was provided. A goal of the study was to have at least two-thirds minority participation. There were no significant differences in blood pressure outcomes when comparing males and females or membership in a minority group or not. A more moderate low-carbohydrate diet may be helpful. Carbohydrate intake is probably one of the most controversial issues in the management of diabetes. The ADA30 states that managing carbohydrate intake can be instrumental in both weight

Medical Nutrition Therapy for Adults with Diabetes and Related Topics

and glycemic control. However, a very low carbohydrate intake has been questioned for its safety, effectiveness, sustainability, and potentially negative effect on kidneys, bones, lipids, and thyroid function.31 The Recommended Dietary Allowance (RDA) for carbohydrate, determined by the Institute of Medicine’s Food and Nutrition Board, is 130 g/day, this is also the minimum intake recommended by the ADA for persons with diabetes. What we see on food labels is based on a selected 300 g for an individual consuming 2,000 calories per day or 60% of calories. The optimal amount of carbohydrate has not been determined and depends on factors such as weight, activity, and postprandial glucose response. One approach, moderately restricted in carbohydrate, is 20–25% calories from carbohydrate (100–125 g carbohydrate per 2,000 calories), 20–30% calories from protein, and 45–60% calories from fat with nutrient-dense food selections.31 To obtain the benefits of a lower carbohydrate intake (but not too low) and based on the above recommendation, one could aim for the following macronutrient balance per meal: 30–35 g carbohydrate, about 4–6 oz meat/protein, several cups of vegetables, and include moderate amounts of monounsaturated fats such as olive oil, avocado, and unsalted nuts. The carbohydrate could include whole grains, fruit, and milk or yogurt. It would be best to choose less processed and more whole foods.

GESTATIONAL DIABETES MELLITUS The Academy of Nutrition and Dietetics has published recommendations for the management of patients with GDM.32 These recommendations include macronutrient composition (carbohydrate, protein, and fat), non-nutritive sweeteners, caloric intake, and physical activity.

A Review of the Literature of Medical Nutrition Therapy for Gestational Diabetes Mellitus The goals of MNT for GDM: Adequate weight gain and fetal growth, euglycemia, and prevention of ketones.33 The Institute of Medicine recommends at least 175 g carbohydrate per day during pregnancy.34 Another group of authors, in preparing a clinical practice guideline, recommends reducing by one-third the calories consumed prior to pregnancy but not eating less than a minimum of 1,800–2,000 calories per day with 35–45% of these calories as carbohydrate consumed in 3 meals and 2–4 snacks.35 Even though carbohydrate restriction has been used most often, other approaches are also being considered such as a more liberal carbohydrate intake and use of the glycemic index.33 These authors state that more studies are needed using randomized controlled trials (RCT) to yield stronger evidence regarding the best composition of the GDM diet. This same source summarizes that present guidelines overall indicate a daily minimum of 175 g carbohydrate representing 35–50% of total calories from mostly lowglycemic index foods and spread out over 3 meals and 2–4 snacks. Below is a review of four studies of the GDM diet composition. A RCT examining a 40% carbohydrate and 40% fat compared to a 55% carbohydrate and 25% fat composition showed no significant differences in need for insulin treatment or obstetrical and perinatal outcomes.36 It is proposed that a higher-complex carbohydrate low-fat diet may improve insulin resistance and infant adiposity. A RCT (n = 63) examined the effect of a low-glycemic index diet on insulin require­ ment which resulted in a 50% reduction in need for insulin compared to women on a high-to-moderate glycemic index diet including high-fiber low-sugar foods (p