The Global Agenda for the Prevention of Diabetes: Research Opportunities

The Global Agenda for the Prevention of Diabetes: Research Opportunities William H. Herman, MD, MPH Stefan S. Fajans/GlaxoSmithKline Professor of Diabetes Professor of Internal Medicine and Epidemiology University of Michigan Director, Michigan Center for Diabetes Translational Research

Outline The global burden of type 2 diabetes The global costs of type 2 diabetes Research opportunities

The Global Burden of Type 2 Diabetes

Global Estimates and Projections of the Number of People with Diabetes Millions 500 450 400 350 300 250 200 150 100 50 0 1990 2000 2010 2020 2030 2040 Amos, McCarty & Zimmet, 1997 King, Aubert & Herman, 1998 Wild, Roglic, Green, Sicree & King, 2004 Shaw, Sicree & Zimmet, 2010 Year

Numerical Estimates Between 2010 and 2030, the number of adults with diabetes worldwide will increase 54% from 285 million to 439 million 20% increase in developed countries 20% in Europe 42% in North America 47% in Western Pacific 69% increase in developing countries 65% in South and Central America 72% in Asia 94% in MiddleEast 98% in Africa Shaw JE et al. Diabetes Res Clin Pract 87:4, 2010

Summary conservative estimates developing countries > developed countries middle aged > old epidemic has major implications for costs Shaw JE et al. Diabetes Res Clin Pract 87:4, 2010

The Global Costs of Type 2 Diabetes In 2010, the global cost of diabetes was estimated to be $376 billion or 12% of all health care costs Zhang et al. Diabetes Res Clin Pract 87:293, 2010

95% of global health expenditures for diabetes were from the world s richest countries: 57% North America 28% Europe 10% Western Pacific Zhang et al. Diabetes Res Clin Pract 87:293, 2010

Mean Annual Health Expenditure per Person with Diabetes by Region, 2010 Mean annual expenditure Region per person with diabetes North America $5,751 Europe $1,991 Western Pacific $508 South America and Central $458 America Eastern Mediterranean $210 Africa $112 Southeast Asia $53 Zhang et al. Diabetes Res Clin Pract 87:293, 2010

Expenditures for Diabetes by Development Status Developed Countries Developing Countries Antihyperglycemic therapy Treatment of complications and comorbidities Zhang et al. Diabetes Res Clin Pract 87:293, 2010

The Global Costs of Diabetes, 2030 By 2030, the global cost of diabetes will increase by 30%, from ~$376 billion to ~$490 billion* *assumes constant per capita health care expenditures for diabetes Zhang et al. Diabetes Res Clin Pract 87:293, 2010

Between 2010 and 2030, developed countries are projected to have a 27% increase in expenditures for diabetes and developing countries a 67% increase in expenditures for diabetes Zhang et al. Diabetes Res Clin Pract 87:293, 2010

Reasons for the Increasing Costs of Diabetes Population growth Aging of population Changing population demographics (urbanization, westernization) Increased incidence of diabetes Changing criteria for diagnosis of diabetes Increased access to care Decreased diabetes mortality

Economic development is associated with an increase in per capita health care expenditures

ESRD Treatment by National Economic Wealth The dashed line represents the boundary between high-income countries and low- and middle-income countries as classified by the World Bank Group Grassman et al. Artif Organs 30:895, 2006

The projected increase in health care costs attributable to diabetes and its complications is unsustainable!

What can be done?

What is the efficacy of interventions to delay or prevent the development of diabetes?

Interventions Proven to Delay or Prevent the Development of Type 2 Diabetes Intervention % Risk Reduction Lifestyle (4 trials) 29-58% Metformin (2 trials) 26-31% Lifestyle & Metformin (1 trial) 28% Acarbose (1 trial) 25% Voglibose (1 trial) 41% Troglitazone (1 trial) 55% Rosiglitazone (1 trial) 60% Pioglitazone (1 trial) 72% Orlistat (1 trial) 37%

Research opportunities

Can lifestyle interventions be translated into practice? Clinical trials with observational follow-up Primary care interventions Community interventions

Clinical Trials with Observational Follow-up Trial Chinese DaQing DPS 1 diet and exercise % DM Risk Reduction (follow-up) 43% (20 years) Finnish DPS 2 diet and exercise DPP/DPPOS 3 diet and exercise 43% (7 years) 34% (10 years) 1 Li. Lancet 371:1783, 2008 2 Lindstrom. Lancet 368:1673, 2006 3 DPP. Lancet 374:1677, 2009

Primary Care Interventions Intervention % Weight Loss (follow-up) In person and remote support 1 5.2% (2 years) Remote support (phone, email, web) 5.0% (2 years) Control 1.1% (2 years) Brief lifestyle, meals or meds 2 Brief lifestyle Usual care Coach led group 3 Self-directed DVD Control 4.7% (2 years) 2.9% (2 years) 1.6% (2 years) 6.6% (1.25 years) 5.0% (1.25 years) 2.6% (1.25 years) 1 Appel. N Engl J Med 365:1959, 2011 2 Wadden. N Engl J Med 365:1969, 2011 3 Ma. Arch Int Med Dec 10, 2012 doi.10.1001/2013.jamainternmed.987

Community Interventions YMCA Intervention Group lifestyle 1 Control % Weight Loss (follow-up) 6.0% (1 years) 1.8% (1 year) Group maintenance 2 Control and maintenance 6.0% (2.3 years) 3.6% (2.3 years) 1 Ackermann. Am J Prev Med 35:357, 2008 2 Ackermann. Chronic Illness 7:279, 2011

Albright. Am J Prev Med. 44(4S4):S346, 2013 www.cdc.gov/diabetes/prevention

Additional Research Challenges Case finding/generalizability Uptake and adherence Funding/sustainability Pharmacologic therapy

Case Finding/Generalizability Identifying at-risk individuals is a barrier to translation

U.S. Preventive Services Task Force Draft Recommendation Statement: Screening for Abnormal Glucose and Type 2 Diabetes Mellitus The USPSTF recommends screening for abnormal blood glucose and type 2 diabetes mellitus in adults who are at increased risk for diabetes (evidence level B). http://www.uspreventiveservicestaskforce.org/

Case Finding/Generalizability Applying mathematical models to existing health plan data may be a practical and inexpensive way to identify patients with IFG or IGT McEwen. J Diabetes Complications 27:580, 2013

Population Midwest independent practice association model HMO 700,000+ members West Coast integrated delivery system 3.3 million members Eligibility At least 18 years old Not pregnant No history of diabetes Fasting plasma glucose electronically available Continuously enrolled in the health plan for 12 consecutive months either before or after the fasting plasma glucose McEwen. J Diabetes Complications 27:580, 2013

Model development Developed 4 models using available data A: Demographic and claims/diagnoses data B: Demographic, claims/diagnoses, and pharmacy data C: Demographic, claims/diagnoses, pharmacy, and laboratory data D: Demographic, claims/diagnoses, pharmacy, laboratory, and clinical data McEwen. J Diabetes Complications 27:580, 2013

Conclusions Older age and male sex were consistent predictors of IFG or diabetes in all models in both health plans All models also included one or more indicators of Body size (either a claim/diagnosis for obesity or measured BMI) Blood pressure (either a claim/diagnosis for hypertension, at least one filled prescription for a BP medication or systolic blood pressure) Cholesterol (either a claim/diagnosis for dyslipidemia, at least one filled prescription for a lipid-lowering medication, or lipid levels) The models had a fairly low sensitivity (20-25%) but high specificity (~90%) and would be appropriate if implemented periodically to identify target populations for definitive testing and intervention McEwen. J Diabetes Complications 27:580, 2013

Uptake and Adherence Can incentives be designed to promote uptake and adherence to lifestyle interventions? Can diabetes prevention be integrated into mainstream medical care?

Behavioral Economics Reduce or eliminate out-of-pocket costs Provide financial incentives Invoke loss avoidance

Healthy Blue Living Healthy Blue Living (HBL) is a commercial health insurance program that provides strong incentives for patients, providers, and employers to work towards improved health in six high-impact areas Members must complete a HBL Qualification Form, adopt a healthy lifestyle, and work to achieve their wellness plan Members who adhere to HBL program requirements receive additional benefits and reduced co-payments with a savings of ~$800 per member per year HBL compensates providers and offers employers a 10% reduction in premiums Rothberg. Obesity 21:2157, 2013

HBL Pilot Project Beginning in 2009, HBL members with BMI 32 kg/m 2 with one or more comorbidities, or BMI 35 kg/m 2, who worked for employer groups that agreed to offer the University of Michigan Weight Management Program (WMP), were required to enroll in the WMP, Weight Watchers, or WalkingSpree to maintain enhanced benefits Rothberg. Obesity 21:2157, 2013

Weight Management Intervention Programs University of Michigan Weight Management Program Two year program that employs intensive energy restriction for the first 12 weeks to promote 15% weight loss, followed by interventions to support behavior change and promote regular physical activity Weight Watchers Commercial weight loss program that provides weekly structured in-person counseling WalkingSpree Commercial pedometer-based walking program that uses dual axial accelerometers and web-based interfaces to promote daily physical activity Rothberg. Obesity 21:2157, 2013

Results When a variety of weight management programs are offered to obese managed care enrollees and when failure to participate is associated with reduced benefits and increased out-of-pocket costs, participation is high ( 90%) and adherence at one year is excellent ( 70%) Rothberg. Obesity 21:2157, 2013

Results Participation in any one of the programs is associated with lower BMI and improved cardiovascular risk factor control After intervention costs are considered, program participation is associated with a lower rate of increase in per-member permonth direct medical costs compared to nonparticipation Rothberg. Obesity 21:2157, 2013

Conclusions Behavioral economic approaches invoking loss avoidance may promote uptake and adherence to lifestyle interventions within the mainstream healthcare delivery system Rothberg. Obesity 21:2157, 2013

Funding/Sustainability Lack of available programs is a barrier to diabetes prevention Lack of funding is a barrier to the implementation and maintenance of programs

In 2014, the USPSTF recommended offering interventions or referring adults who are overweight or obese and have additional CVD risk factors (hypertension, dyslipidemia, impaired fasting glucose, or the metabolic syndrome) to intensive behavioral counseling interventions to promote diet and physical activity for CVD prevention (evidence level B). LeFevre. Ann Intern Med 161:587, 2014

Conclusions Recent USPSTF level B recommendations should facilitate the implementation and sustainability of lifestyle intervention programs

Pharmacologic Therapy Some patients may prefer pharmacologic therapy for diabetes prevention

Diabetes Incidence Rate by Age and Treatment Group DPP. J Gerontol A Biol Sci Med Sci 61:1075, 2006

Use of Metformin in Two Large HMO Populations without a Diagnosis of Diabetes by Fasting Glucose Level FPG <110 mg/dl FPG 110 mg/dl Midwestern HMO 101/17,389 (1%) 45/1,138 (4%) California HMO 61/319,357 (0%) 28/48,668 (0%) McEwen. J Diabetes Complications 27:580, 2013

What are the Barriers to Pharmacologic Therapy? Provider endorsement Marketing

Conclusions Pharmacologic therapy should be endorsed and offered to appropriate atrisk patients as an alternative to lifestyle intervention Brook. JAMA 302:997, 2009

Conclusions

Lifestyle interventions for preventing diabetes are Effective in young and old, women and men, all racial and ethnic groups, less and more obese, less and more hyperglycemic Associated with improved quality-of-life Safe Cost-effective Barnato. Med Decis Making 23:177, 2003

The effectiveness, cost-effectiveness, and appropriateness of lifestyle interventions for diabetes prevention should not negate the importance of: Integrating lifestyle interventions into mainstream medical care Pharmacotherapy Societal interventions to address school health, food policy, and the built environment Early detection and intensive management of diabetes

Research must focus on how best to implement diabetes prevention in diverse populations and settings.