Weight Management: Obesity to Diabetes Marion J. Franz FROM RESEARCH TO PRACTICE ■ IN BRIEF Evidence supports the effectiveness of nutrition therapy across the continuum of diabetes management—obesity to prediabetes to diabetes. For people who are overweight/obese or diagnosed with prediabetes, modest weight loss is important. However, the goals of nutrition therapy for type 2 diabetes are improved glycemia, lipids, and blood pressure. To achieve these goals, a reduced energy intake is essential. For some, reducing energy intake may lead to weight loss, while for others, it may maintain weight loss or prevent weight gain. Weight loss medications and metabolic surgery have been shown to be effective weight loss therapies across the continuum.

nfortunately, the prevalence of improve pancreatic β-cell function obesity continues to escalate, and the sensitivity of liver and skele- Uand solutions continue to be tal muscle to insulin, with larger rel- evasive. In 2015, two-thirds of the ative weight losses leading to graded U.S. population was reported as be- improvements in key adipose tissue ing overweight or obese (1). Health disturbances (3). care professionals in the diabetes field The American College of Cardi- are well aware of the impact and con- ology/American Heart Association sequences of obesity contributing to Obesity Expert Panel recommends the development of prediabetes and that patients receive high-intensity type 2 diabetes. This article reviews behavioral counseling, with ≥14 vis- the role of weight management in- its in 6 months (4). They report that terventions across the continuum of this type of comprehensive program obesity to prediabetes to diabetes, be- results in a mean weight loss of 5–8% ginning with management of obesity. and that ~60–65% of patients lose Readers are reminded that weight loss ≥5% of initial weight (4). However, is an outcome and not a weight man- weight regain is common after com- agement intervention. Interventions pletion of such programs, and they include reduced energy intake, reg- note that the most effective behav- ular physical activity, education and ioral method for preventing weight support, pharmacotherapy, and/or regain is continued support on an Nutrition Concepts by Franz, Minneapolis, metabolic (bariatric) surgery. MN every-other-week or monthly basis, Corresponding author: Marion J. Franz, Weight Management of whether in person or by telephone. [email protected] Obesity Unfortunately, long-term counsel- https://doi.org/10.2337/ds17-0011 Moderate weight loss, defined as ing is not widely available. They also a 5–10% reduction from baseline note that it is challenging to persuade ©2017 by the American Diabetes Association. Readers may use this article as long as the work weight, is associated with clinically patients to remain in counseling to is properly cited, the use is educational and not meaningful improvements in obesity- maintain a weight loss that is usually for profit, and the work is not altered. See http:// creativecommons.org/licenses/by-nc-nd/3.0 related metabolic risk factors (2). A smaller than they had desired (4). It is for details. 5% weight loss has been shown to important that all health profession-

VOLUME 30, NUMBER 3, SUMMER 2017 149 FROM RESEARCH TO PRACTICE / THE ROLE OF WEIGHT MANAGEMENT IN DIABETES als help educate the public regarding loss for people with prediabetes. glucagon-like peptide receptor ago- the benefits of moderate weight loss. People with overweight or obesity nists, and thiazolidinediones can The other treatment options for who received intensive lifestyle inter- also prevent progression from predi- overweight and obesity are weight vention in the Diabetes Prevention abetes to diabetes (8). The ADA now loss medications and metabolic Program (DPP) had a mean weight recommends that metformin should (bariatric) surgery. In 1-year trials, loss of 5.6 kg at 2.8 years and a 58% be considered for prevention of dia- total weight losses for three mono- relative reduction in the risk of type betes in those with prediabetes and pharmacotherapies (orlistat, lorcase- 2 diabetes compared to a 31% risk re- especially for individuals with a BMI rin, and liraglutide), whose effects are duction with metformin (6). Perhaps ≥35 kg/m2, those <60 years of age, mediated by different mechanisms, most encouraging was the finding that women with prior gestational dia- ranged from 5.8 to 8.8 kg (5.8 to the incidence of type 2 diabetes re- betes, and those with a rising A1C 8.8% of initial body weight) (2). In mained 34% less than the incidence in despite lifestyle intervention (8). They 1-year trials of two combination med- the control group at 10 years’ follow- note that metformin has the strongest ications (phentermine-topiramate and up, even though the participants in evidence base and has demonstrated naltrexone-bupropion), whose effects the intervention group had, on aver- long-term safety for diabetes preven- are on neural weight loss mecha- age, returned to close to their baseline tion. For other medications, cost, side nisms, weight loss ranged from 6.2 weight (7). effects, and durable efficacy require to 10.2 kg (6.4–9.8% of initial body The American Diabetes Associa- consideration. weight) (2). tion (ADA) recommends that people The Swedish Obese Subjects (SOS) Mean weight losses of 16–32% with prediabetes be referred to an trial reported the strongest evidence of baseline weight are produced by intensive behavioral lifestyle interven- that metabolic surgery can reduce the metabolic surgery in patients with tion modeled after the DPP (8). The incidence of type 2 diabetes in obese severe obesity and may lead to dis- goal is to achieve and maintain a 7% individuals (10). Ten-year data from ease remission, including remission loss of initial weight and to increase the SOS trial, which included 407 of type 2 diabetes (2). Limitations of moderate-intensity physical activity morbidly obese people who under- current metabolic surgeries include to at least 150 min/week. They also went metabolic surgery and matched high initial costs; at 1 year, risks of state that technology-assisted tools, control subjects, showed that the short- and long-term complications; including Internet-based social net- incidence of diabetes was 7% in the and weight regain in ~5–20% of works, distance learning, DVD-based metabolic surgery group and 24% in patients (2). However, Roux-en-Y content, and mobile applications may the control group (10). Similar results gastric bypass and vertical-sleeve be useful elements of effective lifestyle were reported from another study in gastrectomy are by far the most effec- modification to prevent diabetes. Sweden, in which 1,658 obese peo- tive long-term treatments of severe Combining lifestyle interven- ple underwent metabolic surgery and obesity. Unfortunately, only a small tions to prevent type 2 diabetes is 1,771 obese people received usual fraction of patients who would benefit reported to be helpful. Of interest care (11). At 15 years, the incidence from these three classes of treatment is a population-based cohort study of type 2 diabetes was 7% in the met- (lifestyle intervention, weight loss that examined lifestyle factors and abolic surgery group and 22% in the medications, and metabolic surgery) the risk of new-onset diabetes (9). control group. actually receive them (2). For all individuals, a healthy eating pattern, participation in regular phys- Weight Management of Type 2 Of interest is a recent position state- Diabetes ment from the American Association ical activity, maintenance of normal Although one of the goals for pre- of Clinical Endocrinologists and weight, and moderate alcohol intake vention of diabetes, as noted above, American College of Endocrinology, were reported to lower the risk of is weight loss, for treatment of type 2 which recommends a new diagnos- developing type 2 diabetes. However, diabetes, the goals of nutrition ther- tic term for obesity: adiposity-based adherence to a combination of these apy shift to glucose, lipid, and blood chronic disease, or ABCD (5). The factors in this study was reported to pressure management (12). To deter- reason cited for the new term is reduce that risk by as much as 84% mine the effectiveness of weight loss to avoid the stigma and confusion in women and 72% in men. Although interventions (WLIs) implemented related to the differential use and mul- weight was one of the most import- in overweight and obese adults with tiple meanings of the term “obesity.” ant factors, the researchers noted that even overweight individuals could type 2 diabetes, a systematic review Weight Management of lower their risk of type 2 diabetes by and meta-analysis was conducted Prediabetes adopting other healthy lifestyle habits. of randomized clinical trials with a Readers of this article are likely aware Medications such as metformin, minimum of 12 months’ duration of the effectiveness of modest weight α-glucosidase inhibitors, orlistat, and an 80% completion rate (13). In

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11 trials (8 comparing two WLIs and Focusing on a reduced energy marily on encouraging a healthy 3 comparing a WLI to a usual care intake for people with type 2 diabe- eating pattern, with careful attention control group, n = 6,754), weight loss tes, rather than on the scale (weight to portion sizes and energy intake; plateaued at 6 months. At 12 months, loss), is supported by a review of the participation in regular physical 17 WLIs (n = 1,365) reported weight effectiveness of medical nutrition activity; and education and support losses of <5% of initial weight (~3.2 therapy (MNT) provided by regis- to improve metabolic outcomes. For kg) resulting in nonsignificant bene- tered dietitian nutritionists (RDNs) some, this may lead to weight loss, ficial effects of A1C, lipids, or blood (17,18). In adults with type 2 diabe- while for others, it may maintain pressure. Only two trials (n = 2,676) tes, 21 study arms from 18 studies weight loss or prevent weight gain. reported weight losses ≥5% at 12 (n = 4,181) reported that, at 3 months, Weight loss studies using the five months: a Mediterranean-style diet A1C levels decreased from baseline approved weight loss medications implemented in newly diagnosed by 0.3–2.0%, and at >12 months, have been conducted in people with adults and an intensive WLI imple- with continued support, decreases type 2 diabetes. Table 1 summarizes

mented in the Look AHEAD trial. ranged from 0.6 to 1.8%. Although the trials comparing weight loss FROM RESEARCH TO PRACTICE Both included regular physical activ- MNT interventions were effective medication therapy to a placebo and ity and frequent contact with health throughout the disease process, the their 52- to 56-week weight loss and professionals and reported significant decreases in A1C were largest in A1C outcomes (19). When used as an beneficial effects on A1C, lipids, and studies in which participants were adjunct to lifestyle intervention, these blood pressure. newly diagnosed and/or had base- agents may help individuals sustain Additionally, compared to people line A1C levels >8.0%, for whom weight loss for a longer period of time. without diabetes, it appears more dif- decreases ranged from 0.5 to 2.0%. The weight loss resulting from the use ficult for those with diabetes to lose A variety of MNT interventions, of the medications resulted in better weight. In another systematic review including individualized nutrition glycemic control, while reducing the of WLIs in people primarily without therapy, energy restriction, portion number and doses of glucose-lowering diabetes, weight loss also plateaued at control, sample menus, carbohydrate medications and often lowering blood 6 months, and the mean weight loss counting, exchange lists, simple meal pressure and improving lipids. The at 12 months was 4.5–7.5 kg (5–8%) plans, and a low-fat vegan diet, were ADA states that weight loss medica- (14), whereas in 17 of the 19 WLI implemented and effective. However, tions may be effective adjuncts to an groups in people with diabetes, mean all MNT interventions resulted in energy-reduced eating plan, physical weight loss was 1.9–4.8 kg (3.2%). reduced energy intake. activity, and behavioral counseling Weight loss of >5% appears neces- Of importance, eating plans for for selected individuals with type 2 sary for beneficial effects on A1C, people with type 2 diabetes must be diabetes and a BMI ≥27 kg/m2 (20). lipids, and blood pressure. Achieving based on their current food intake It further recommends that, if an this level of weight loss appears to be and on the changes the individual is individual’s response to weight loss difficult because it requires intense willing and able to make to improve medications is <5% after 3 months interventions, including energy blood glucose control and other or if there are any safety or tolerabil- restriction, regular physical activity, metabolic outcomes. Blood glucose ity issues at any time, the medication and very frequent contact with health monitoring must then be used to should be discontinued and alterna- professionals. evaluate outcomes of lifestyle changes tive medications should be considered Improvement in glycemia from on pre- and postmeal glucose levels. (20). weight loss is most likely to be effec- It can then be determined whether The ADA also states that a sub- tive in the early stage of diabetes, food/eating and activity changes have stantial body of evidence has now when individuals still have a rela- achieved the target goals or whether accumulated, including data from tively preserved insulin secretion pharmacotherapeutic additions or numerous randomized controlled capacity (15). However, for many, it adjustments are needed. Because clinical trials, demonstrating that may be too late to improve hypergly- medications—including insulin— metabolic surgery achieves superior cemia through weight loss alone (16), need to be combined with nutrition glycemic control and reduction of and not all individuals with type 2 therapy, weight gain often occurs; cardiovascular risk factors in obese diabetes are overweight or obese. thus, preventing this weight gain people with type 2 diabetes (20). The Furthermore, any beneficial effects on becomes important. However, glyce- ADA’s 2017 recommendations state blood glucose levels begin to occur mic control must still take precedence that metabolic surgery should be rec- early, before much weight is lost (15), over concerns about weight. ommended to treat type 2 diabetes suggesting that the benefits are from Nutrition therapy for overweight in appropriate surgical candidates the reduced energy intake rather than and obese individuals with type 2 with a BMI ≥40 kg/m2 (BMI ≥37.5 from the weight loss. diabetes therefore should focus pri- kg/m2 in Asian Americans), regard-

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TABLE 1. Weight Loss Medications in People With Type 2 Diabetes: Weight Loss and Glucose Outcomes (19) Orlistat Lorcaserin Phentermine/ Naltrexone/ Liraglutide (Xenical, Alli*) (Belviq) Topiramate Bupropion (Saxenda) (Qsymia) (Contrave) Weight loss (%) Drug 6.2 4.5 9.6 5.0 6.0 Placebo 4.3 1.5 2.6 1.8 2.0 A1C change (%) Drug −0.3 −0.9 −1.6 −0.6 −1.3 Placebo +0.2 −0.4 −1.2 −0.1 −0.3 Brand names are in parentheses; study lengths were 52–56 weeks. *Over-the-counter brand name. less of the level of glycemic control ous effects of hyperglycemia. Over 4. American College of Cardiology/ American Heart Association Task Force on or complexity of glucose-lowering time, glucose-lowering medication(s) Practice Guidelines, Obesity Expert Panel, regimens, and in adults with a BMI and eventually exogenous insulin will 2013. Expert panel report: guidelines (2013) of 35.0–39.9 kg/m2 (32.5 –37.4 k g/m 2 for the management of overweight and be needed, but nutrition therapy con- obesity in adults. Obesity (Silver Spring) in Asian Americans) when hyper- tinues to be important for diabetes 2014;22(Suppl. 2):S41–S410 glycemia is inadequately controlled management. Both weight loss med- 5. Mechanick JI, Hurley DL, Garvery WT. despite lifestyle modification and ications and metabolic surgery have Adiposity-Based Chronic Disease as a new optimal medical therapy. Metabolic diagnostic term: American Association of recent research proving effectiveness Clinical Endocrinologists and the American surgery should be considered for for weight loss and other metabolic College of Endocrinology position state- adults with type 2 diabetes and a outcomes in people who are over- ment. Endocr Pract 2017;23:372–378 2 BMI of 30.0–34.9 kg/m (27.5–32.4 weight/obese or have been diagnosed 6. DPP Research Group. Reduction in the kg/m2 in Asian Americans) if hyper- incidence of type 2 diabetes with lifestyle with prediabetes or type 2 diabetes. intervention or metformin. N Engl J Med glycemia is inadequately controlled Knowledge of outcomes and 2002;346:393–403 despite optimal medical treatment by benefits from weight management 7. Knowler WC, Fowler SE, Hamman RF, et either oral or injectable medications interventions can assist individuals al. 10-year follow-up of diabetes incidence (including insulin). They note that, who are overweight/obese or who and weight loss in the Diabetes Prevention in patients undergoing metabolic sur- Program Outcomes Study. Lancet have prediabetes or type 2 diabe- 2009;374:1677–1686 gery, younger age, shorter duration tes, and professionals should work 8. American Diabetes Association. of diabetes (e.g., <8 years), nonuse collaboratively with patients in mak- Prevention or delay of type 2 diabe- of insulin, and better glycemic con- tes. Sec. 5 in Standards of Medical ing decisions regarding the role of trol are consistently associated with Care in Diabetes—2017. Diabetes Care higher rates of diabetes remission and weight management interventions in 2017;40(Suppl. 1):S44–S47 patients’ care. 9. Reis JP, Loria CM. Sorlie PD, et al. a lower risk of recidivism (21). Lifestyle factors and risk of new-onset dia- Summary betes: a population-based cohort study. Ann Duality of Interest Intern Med 2011;155:292–299 Weight loss interventions are import- No potential conflicts of interest relevant to 10. Sjostrom L, Lindroos A-K, Peltonen M, ant for the prevention and treatment this article were reported. et al. Lifestyle, diabetes, and cardiovascular of overweight/obesity and prediabe- disease risk factors 10 years after bariatric tes. Progressive β-cell loss necessitates References surgery. N Engl J Med 2004;351:2683–2693 11. Carlsson LM, Peltonen M, Ahlin S, et al. changes in nutrition therapy just as it 1. National Center for Health Statistics. Bariatric surgery and prevention of type 2 requires changes in medical therapy, Health, United States, 2015: with special diabetes in Swedish obese subjects. N Engl J including changes in pharmacother- feature on racial and ethnic health dispar- Med 2012;367:695–704 ities (Report No. 2016-1232). Hyattsville, apy. As type 2 diabetes is diagnosed Md., National Center for Health Statistics, 12. Evert AB, Boucher JL, Cypress M, et and progresses, nutrition therapy 2016 al. Nutrition therapy recommendations for the management of adults with diabetes. interventions focus on attaining and 2. Heymsfield SB, Wadden TA. Mechanism, Diabetes Care 2013;36:3821–3842 maintaining treatment goals for gly- pathophysiology, and management of obe- sity. N Engl J Med 2017;376:254–266 13. Franz MJ, Boucher JL, Ruten-Ramos cemia, lipids, and blood pressure. It is S, VanWormer JJ. Lifestyle weight-loss important that effective therapies low- 3. Magkos F, Fraterrigo G, Yoshino J, et al. intervention outcomes in overweight Effects of moderate and subsequent pro- and obese adults with type 2 diabetes: a er elevated blood glucose concentra- gressive weight loss on metabolic function systematic review and meta-analysis of tions as early as possible to slow β-cell and adipose tissue biology in humans with randomized clinical trials. J Acad Nutr Diet exhaustion and prevent the deleteri- obesity. Cell Metab 2016;23:591–601 2015;115:1447–1463

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14. Franz MJ, VanWormer JJ, Crain AL, 17. Academy of Nutrition and Dietetics. Advances in the science, treatment, and pre- et al. Weight-loss outcomes: a systematic Diabetes mellitus type 1 and 2 system- vention of the disease of obesity: reflections review and meta-analysis of weight-loss atic review and guideline, 2015 [Internet]. from a Diabetes Care editors’ expert forum. clinical trials with a minimum of 1-year fol- Available from http://www.andeal.org/topic. Diabetes Care 2015;38:1567–1582 low-up. J Am Diet Assoc 2007;107:1755–1767 cfm?menu-5305. Accessed January 2017 20. American Diabetes Association. Obesity 15. U.K. Prospective Diabetes Study Group. 18. Franz MJ, MacLeod J, Evert A, et management for the treatment of type 2 Response of fasting plasma glucose to diet al. Academy of Nutrition and Dietetics diabetes. Sec. 7 in Standards of Medical therapy in newly presenting type II diabetic nutrition practice guideline for type 1 and Care in Diabetes—2017. Diabetes Care patients. Metabolism 1990;39:905–912 type 2 diabetes in adults: systematic review 2017;40(Suppl. 1):S57–S63 of evidence for medical nutrition therapy 16. Weyer C, Bogardus C, Mott DM, Pratley 21. Schauer PR, Kashyap SR, Wolski K, et effectiveness and recommendations for inte- RE. The natural history of insulin secre- al.; STAMPEDE Investigators. Bariatric gration into the nutrition care process. tory dysfunction and insulin resistance in surgery versus intensive medical therapy in J Acad Nutr Diet. In press the pathogenesis of type 2 diabetes. J Clin obese patients with diabetes. N Engl J Med Invest 1999;104;787–794 19. Cefalu WT, Bray GA, Home PD, et al. 2012;366:1567–1576 FROM RESEARCH TO PRACTICE Why Weight Loss Maintenance Is Difficult Alison B. Evert1 and Marion J. Franz2

■ IN BRIEF This article reviews studies related to biological mechanisms that make weight loss maintenance difficult. Approximately 50% of weight variance is reported to be determined by genetics and 50% by the environment (energy-dense foods and reduced physical activity). Body weight is tightly regulated by hormonal, metabolic, and neural factors. Hormonal adaptations (decreases in leptin, peptide YY, cholecystokinin, and insulin and increases in ghrelin, glucagon-like peptide 1, gastric inhibitory polypeptide, and pancreatic polypeptide) encourage weight gain after diet-induced weight loss and continue for at least 1 year after initial weight reduction. Weight loss also results in adaptive thermogenesis (decreased resting metabolic rate), which is also maintained long-term. Neural factors such as dopamine also signal the need to respond to an increased desire for fatty foods after weight loss.

ealth care providers (HCPs) of- so simple! Yet, anyone dealing with ten find that people trying to weight loss maintenance issues real- “solve” a weight loss mainte- izes it is not that simple. The cycle 1University of Washington Medical Center– H Diabetes Care Center, Seattle, WA nance problem feel guilty about their of less weight loss than expected or 2Nutrition Concepts by Franz, Minneapolis, weight issues. They have been told by wanted and subsequent weight re- MN family, friends, the public, and, yes, gain continues, despite individuals’ Corresponding author: Marion J. Franz, even HCPs that it is their fault— best efforts to prevent it. In fact, we [email protected] that they simply lack willpower—or would probably all agree that, if they https://doi.org/10.2337/ds017-0025 have decided on their own that it were so simple to solve, the issues of is their fault that they are regaining weight loss and maintenance would ©2017 by the American Diabetes Association. the weight they have worked so hard not continue to be problems. Readers may use this article as long as the work is properly cited, the use is educational and not to lose. If they would just continue It is claimed that “many clinicians for profit, and the work is not altered. See http:// to eat less and exercise more, the are not adequately aware of the rea- creativecommons.org/licenses/by-nc-nd/3.0 for details. problem would be solved. It sounds sons that individuals with obesity

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