Prevention of Type 2 Diabetes MellitusKey QuestionsandA Call to Action

Prevention of Type 2 Diabetes Mellitus: Table of Contents

SectionTopicSlide No.1Why is prevention of type 2 diabetes imperative?3-52What is the evidence that type 2 diabetes can be prevented or delayed?6-233Do prevention interventions have sustained effects?24-304Are we preventing type 2 diabetes or delaying it?31-325Is diabetes prevention cost-effective?33-366Can evidence-based interventions be delivered effectively in lower-cost settings?37-407Will diabetes prevention bend the curve of the epidemic?41-428How can we most effectively prevent or delay type 2 diabetes?43-519Conclusions: call to action52-53

WHY IS PREVENTION OF TYPE 2 DIABETES IMPERATIVE?Section 1

Projecting the Future Diabetes Population: The Imperative for ChangeU.S. Population with Diabetes (%)Boyle JP, et al. Popul Health Metr. 2010;8(29):1-12.

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Percentage of U.S. Adults Who Were Obese or Had Diagnosed DiabetesCenters for Disease Control and Prevention: National Diabetes Surveillance System. Available online at: http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Accessed 10/3/2011. Obesity (BMI 30 kg/m2)Diabetes No Data

WHAT IS THE EVIDENCE THAT TYPE 2 DIABETESCAN BE PREVENTED OR DELAYED?Section 2

Lifestyle Interventions Can Prevent Type 2 Diabetes OnsetSeveral randomized trials have shown interventions (lifestyle, medications) can decrease rate of onset of diabetesLifestyle: Da Qing, Finnish Diabetes Prevention Study, Diabetes Prevention ProgramMedications: Diabetes Prevention Program (metformin), The Stop-NIDDM (acarbose), DREAM (rosiglitazone), ACT-NOW (pioglitazone)

110,660 adults from 33 Da Qing, China, health care clinics screened in 1986 for IGT, type 2 diabetes mellitus577 adults with IGT (WHO criteria) randomized to control (n=138) or one of three lifestyle interventions (n=438)Diet onlyExercise onlyDiet + exerciseFollow-up at 2-year intervals over 6 years to identify those who developed diabetes

Lifestyle Interventions Da Qing Study MethodsPan XR, et al. Diabetes Care. 1997;20:537-544.

Cumulative incidence of diabetes at 6 years was significantly decreased in the active intervention groups (P

When stratified as lean or overweight (BMI < or 25 kg/m2), relative decrease in rate of development of diabetes in lifestyle intervention groups was similarAfter adjusting for differences in baseline BMI and fasting glucose, all interventions were associated with diabetes risk reduction

Lifestyle Interventions Da Qing Study ResultsPan XR, et al. Diabetes Care. 1997;20:537-544.

Diet31% (P

Active intervention with diet and/or exercise led to a significant decrease in incidence of diabetes over a 6-year period (1986-1992) among those with IGTDiabetes incidence (per 100 person years) per yearControl: 14.1 (95% CI 11.2-17.0)Lifestyle intervention: 7.9 (95% CI, 6.8-9.1)

Lifestyle Interventions Da Qing Study ConclusionsPan XR, et al. Diabetes Care. 1997;20:537-544.

Lifestyle InterventionsFinnish Diabetes Prevention Study522 subjects, 40-65 years of ageBMI 25 kg/m2; IGT: 2-h PPG 140-200 mg/dLControl group: general oral and written information diet and exerciseIntervention group: individualizedReduce weight 5%Decrease fat 30%, saturated fat 10% energyIncrease fiber to at least 15 g/1000 kcalModerate exercise 30 minutes/dayPrimary end point: diagnosis of diabetesTuomilehto J, et al for the Finnish Diabetes Prevention Study Group. N Engl J Med. 2001;344:1343-1350.

172 men, 350 women; mean age 55 yMean BMI 31 kg/m2Mean duration of follow-up 3.2 years

Lifestyle Interventions Finnish Diabetes Prevention StudyTuomilehto J, et al for the Finnish Diabetes Prevention Study Group. N Engl J Med. 2001;344:1343-1350.*P

Reduction in incidence of type 2 diabetes was directly associated with changes in lifestyles of high-risk subjects (ie, those with IGT)Modifiable risk factors such as obesity, physical inactivity, suggested as main nongenetic determinants of diabetesThese results demonstrate that 22 subjects with IGT must be treated with lifestyle intervention for 1 year (or 5 subjects for 5 years) to prevent 1 case of diabetesTuomilehto J, et al for the Finnish Diabetes Prevention Study Group. N Engl J Med. 2001;344:1343-1350.Lifestyle Interventions Finnish Diabetes Prevention Study

3,234 nondiabetic persons in 27 clinical centersBMI 24 kg/m2 (22 kg/m2 in Asians)IGT: FPG 95-125 mg/dL or 2-h PPG 140-199 mg/dLFrom 1996-1999, randomly assigned toStandard lifestyle + placebo (n=1082)Standard lifestyle + metformin, initiated at 850 mg orally once daily; at 1 month, increased to 850 mg twice daily (n=1073)Intensive lifestyle intervention (n=1079)Lifestyle Interventions Diabetes Prevention ProgramKnowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.

Goals of intensive lifestyle intervention7% loss of body weightDietary fat goal: 25% of calories from fatCalorie intake goal: 1200-1800 kcal/day based on initial body weight>150 minutes of physical activities weeklySimilar in intensity to brisk walking; at least 700 kcal/weekGroup received 16-lesson curriculum

Lifestyle Interventions Diabetes Prevention ProgramKnowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.

Mean age 50.6 years67.7% women; 45.3% members of minority groupsMean BMI 34.0 kg/m269.4% had a family history of diabetesAverage follow-up: 2.8 years (range, 1.8-4.6)Lifestyle Interventions Diabetes Prevention ProgramKnowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.

Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403. Lifestyle Interventions Diabetes Prevention ProgramResults: average weight loss (P

Results: intensive lifestyle interventionLifestyle Interventions Diabetes Prevention ProgramKnowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.

At 24 WeeksAt Final Study VisitWeight loss 7%50%38%Exercise >150 minutes/week38%58%

Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403. Medications DPP: Metformin InterventionMetformin, intensive lifestyle modification delayed or prevented type 2 diabetes vs placebo (11%/year incidence)Placebo: 11%/year incidenceMetformin: 7.8%/year incidence*Lifestyle intervention: 4.8%/year incidence*Risk reduction:31% by metformin58% by lifestyle39% lifestyle vs metformin*P

Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.Medications DPP: Metformin InterventionIntensive lifestyle intervention more effective than either metformin or placeboBy subgroup, metformin more effective if:FPG >110 mg/dLAge 35 kg/m2Gender, ethnicity, 2-h PGG, NOT predictive of responseUse metformin in high-risk individuals

Medications The STOP-NIDDM: AcarboseReprinted with permission from Chiasson JL, et al. Lancet. 2002;359(9323): 2072-2077; Chiasson JL, et al. JAMA. 2003;290(4):486-494.Acarbose reduced risk of newHypertension >140/90; 5.3% absolute risk reduction (P=0.006)Myocardial infarction (P=0.02)Any CVD event: CHD, CV death or stroke, CHF, PVD (P=0.03)Acarbose 100 mg TID n=682Placebo n=68625% Relative Risk Reduction P=0.0022

Reprinted with permission from DREAM Trial Investigators. Lancet. 2006;368(9541):1096-1105. Medications DREAM: Rosiglitazone60% Relative Risk Reduction HR 0.40 (0.350.46) P

DeFronzo RA, et al, for the ACT NOW Study. N Engl J Med. 2011;364:1104-1115.Medications ACT NOW: PioglitazonePioglitazone reduced risk of type 2 diabetes mellitus by 72% vs placebo (HR 0.28; 95% CI 0.160.49 P

DO PREVENTION INTERVENTIONS HAVE SUSTAINED EFFECTS?Section 3

Combined lifestyle intervention vs control51% lower incidence of diabetes during active intervention43% lower incidence over 20 years3.6 years fewer with diabetes

Lifestyle Interventions Da Qing Study 20-Year Follow-Up Li G, et al. Lancet. 2008;371:1783-1789.

Average Annual Incidence20-Year Cumulative IncidenceControls11%93%Combined lifestyle intervention7%80%

No significant difference in rate ofFirst CVD event (HR 0.98; 95% CI, 0-71-1.37)CVD mortality (HR 0.83; 0.48-1.40)All-cause mortality (HR 0.96; 0.65-1.41)Study had limited statistical power to detect differences in these outcomesLifestyle interventions over 6 years can prevent, delay diabetes for up to 14 years after active interventionUnclear whether lifestyle interventions also lead to reduced CVD, mortality

Lifestyle Interventions Da Qing Study 20-Year Follow-Up Li G, et al. Lancet. 2008;371:1783-1789.

Lifestyle Interventions Finnish DPS 7-Year Follow-UpReprinted with permission from Lindstrm J, et al. Lancet. 2006;368(9548):1673-1679.43% Relative Risk Reduction

Brief (1-2 week) drug washout study at end of Diabetes Prevention Program trialAfter washout, diabetes was more frequently diagnosed in metformin vs. placebo (1.49; 0.93, 2.38; P=0.098)DPP primary analysis: metformin decreased diabetes risk by 31%Washout: 26% accounted for by pharmacological effect of metforminPostwashout: diabetes reduced by 25%

DPP: Metformin Had Sustained Effect After Drug WashoutDiabetes Prevention Program Research Group. Diabetes Care. 2003;26:977-980.

During rosiglitazone vs placebo washoutPrimary outcome, new-onset diabetes or death: 10.5% vs 9.8% (P=0.59)Secondary outcome, regression to normoglycemia: 21.5% vs 23.8% (P=0.33)Median follow-up: 71 days (range, 63-86 days)Rosiglitazone substantially reduced incidence of type 2 diabetes (DREAM); however, when withdrawn, this effect is not sustained

Rosiglitazone Had No Sustained Effect After Drug Washout: DREAMThe DREAM Trial Investigators. Diabetes Care. 2011;34:1265-1269.

Lifestyle intervention continues to have an effect; most drugs do not

Lifestyle Interventions SummaryDiabetes Care. 1997;20:537-544; N Engl J Med. 2002;344:1343-1350; N Engl J Med. 2002;346;393-403; Diabetes Care. 2011;34:1265-1269; Lancet. 2002;359(9323): 2072-2077 N Engl J Med. 2011;364:1104-1115.LifestylePharmacologic

StudyNInterventionTreatmentRisk ReductionDPPIGT3324Metformin3 years31%DREAMIGT5269Rosiglitazone3 years60%STOP-NIDDMIGT1429Acarbose3 years21%ACT NOWIFG~600Pioglitazone3 years81%

StudyNInterventionTreatmentRisk ReductionDa QingIGT577Lifestyle6 years 20 years34% - 69% Finnish DPSIGT523Lifestyle3+ years 7 years58%DPPIGT3324Lifestyle3 years58%

ARE WE PREVENTING TYPE 2 DIABETES OR DELAYING IT?Section 4

During 10-year follow-up since randomizationOriginal lifestyle group lost, then partly regained weightModest weight loss with metformin maintainedDiabetes incidence per 100 person-yearsDiabetes Prevention Program 10-Year Follow-Up StudyDiabetes Prevention Program. Lancet. 2009;374:1677-1686.*vs placebo

Lifestyle5.9 (5.1, 6.8)34%* (24, 42)Metformin4.9 (4.2, 5.7)18%* (7, 28)Placebo5.6 (4.8, 6.5)

IS DIABETES PREVENTION COST-EFFECTIVE?Section 5

Active interventions (vs placebo) would:

Cost-Effectiveness of Lifestyle Modification or Metformin: DPPHerman WH, et al for the Diabetes Prevention Program Research Group. Ann Intern Med. 2005:142:323-332.QALY = Quality Adjusted Life Years

Intensive LifestyleMetforminDelay onset of type 2 diabetes by 11.1 years3.4 yearsReduce incidence of type 2 diabetes by20%8%Increase life expectancy by0.5 years0.2 yearsCost per QALY$1,124$31,286

10-year within-trial cost-effectiveness of the interventionsIntensive lifestyleMetforminData on resource utilization, cost, and quality of life collected prospectivelyEconomic analyses performed from health system and societal perspectives

Diabetes Prevention Program10-Year Cost-EffectivenessDiabetes Prevention Program Research Group. Diabetes Care. 2012;35:723-730.

Lifestyle cost-effective, metformin marginally cost-saving vs placeboInvestment in lifestyle, metformin interventions for diabetes prevention in high-risk adults provides good value

Diabetes Prevention Program10-Year Cost-EffectivenessIncremental cost-effectiveness ratios from three different perspectives; cost/QALY*Includes direct medical costs and direct nonmedical costs including participant timeBoth costs and QALYs are discounted at 3%

Diabetes Prevention Program Research Group. Diabetes Care. 2012;35:723-730.

Societal Perspective*Lifestyle vs PlaceboMetformin vs PlaceboLifestyle vs MetforminDPP Group Lifestyle vs PlaceboUndiscounted11,274Cost-saving44,562Cost-savingDiscounted14,365Cost-saving42,7531,681

CAN EVIDENCE-BASED INTERVENTIONS BE DELIVERED EFFECTIVELY IN LOWER-COST SETTINGS?Section 6

Adults BMI 24 kg/m2, 2 diabetes risk factors, blood glucose 110-199 mg/dLRandomized to group-based DPP lifestyle intervention or brief counseling (control)

DEPLOY Pilot Study: Diabetes Prevention in the CommunityAckermann RT, et al. Am J Prevent Med. 2008;35:357-363.

Outcome, 4-6 monthsControl (n=38)Intervention (n=39)P value (vs control)% change in weight2 (3.3, 0.6)6 (7.3, 4.7)< 0.001% change BMI2.3 (3.7, 0.8)5.8 (7.3, 4.4)0.001Change total cholesterol+6 mg/dL (2.8, 14.8)21.6 mg/dL 29.9, 13.3)

Practice-Based Opportunities for Weight Reduction (POWER)Appel LJ, et al. N Engl J Med. 2011;365:1959-68.*P

Diabetes TeleHealth Improves Diabetes Self-ManagementDavis RM, et al. Diabetes Care. 2010;33:17121717.1-year remote DSME intervention, Diabetes TeleCare (dietitian, nurse/certified diabetes educatorImproved metabolic control, reduced CV risk*P=0.003 vs. baselineP=0.004 vs. baseline

Reduction in Glycated HemoglobinBaseline6 Months12 MonthsDiabetes TeleCare group9.40.38.30.3* 8.20.4 Usual care group8.80.38.60.38.60.3

WILL DIABETES PREVENTION BEND THE CURVE OF THE EPIDEMIC?Section 7

Five-state modelPotential effect of hypothetical preventive intervention delivered to all with IFGIf 50% participated and incidence reduced by 50%, would equal 25% reduction in annual incidence of diabetes in the population with IFGWould lower the increase in prevalence by 2050 to 1 in 4 (vs 1 in 3)

CDC Modeling Study to Reduce Future Diabetes PrevalenceBoyle JP, et al. Popul Health Metr. 2010;8(29):1-12.

HOW CAN WE MOST EFFECTIVELY PREVENT OR DELAY TYPE 2 DIABETES?Section 8

Data analyzed from 1,402 adults without diabetes20052006 NHANES participantsValid fasting plasma glucose, oral glucose tolerance tests Almost 30% of the US adult population had prediabetes in 20052006; only 7.3% were aware they had itAdoption of risk reduction behaviors suboptimal

Most People with Diabetes Are Unaware of Their ConditionGeiss LS, et al. Am J Prevent Med. 2010;38:403-409.

We Need to Test People at Risk*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range.ADA. I. Classification and Diagnosis. Diabetes Care 2012;35(suppl 1):S13. Table 3.

Categories of increased risk for diabetes (Prediabetes)*FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFGor2-h plasma glucose in the 75-g OGTT 140-199 mg/dl (7.8-11.0 mmol/l): IGTorA1C 5.7-6.4%

Recommendations: Testing for Diabetes in Asymptomatic PatientsConsider testing overweight/obese adults with one or more additional risk factorsIn those without risk factors, begin testing at age 45 years (B)If tests are normalRepeat testing at least at 3-year intervals (E)Use A1C, FPG, or 2-h 75-g OGTT (B)In those with increased risk for future diabetesIdentify and, if appropriate, treat other CVD risk factors (B)ADA. II. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S13.

Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (1)HDL cholesterol level 250 mg/dl (2.82 mmol/l)Women with polycystic ovarian syndrome (PCOS)A1C 5.7%, IGT, or IFG on previous testingOther clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)History of CVD

*At-risk BMI may be lower in some ethnic groups.1. Testing should be considered in all adults who are overweight (BMI 25 kg/m2*) and have additional risk factors:

ADA. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S14. Table 4.

Physical inactivityFirst-degree relative with diabetesHigh-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)Women who delivered a baby weighing >9 lb or were diagnosed with GDMHypertension (140/90 mmHg or on therapy for hypertension)

ADA. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S14. Table 4.Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (2)

2. In the absence of criteria (risk factors on previous slide), testing for diabetes should begin at age 45 years

3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status

DPP: Managing PrediabetesFor those found to have prediabetes, provide support or referral to encourageWeight loss of at least 7%Moderate exercise of at least 150 minutes per weekConsider metformin for certain patientsObese (BMI 35 kg/m2)

Clinical Tools Effective in Promoting Lifestyle Modification: AGREESteps in the lifestyle change process: AGREE

AssessGenerate goalsRecordEvaluate and EmpowerAmerican Diabetes Association. 2008.Re-assess

Steps to setting behavioral goals, objectives1. Focus on developing specific objectives2. Let the patient take the lead3. Keep the objectives FIRMFew in numberIndividualizedRealisticMeasurable (frequency and duration)

Clinical Tools Effective in Promoting Lifestyle Modification: FIRMSaunders JT, Pastors JG. Curr Diabetes Rep. 2008;8;353-360.

CONCLUSIONS:CALL TO ACTIONSection 9

Conclusions: Call to ActionWe must identify patients at highest risk (prediabetes)Modest lifestyle changes are most effectiveSustain interventionsIncrease opportunities for community programs to support preventionDelaying or preventing type 2 diabetes is cost-effective and will help turn the tide on the diabetes epidemic

This slide set focuses on prevention of type 2 diabetes mellitus, addressing key questions with respect to why such prevention is imperativeIncluded are studies supporting how type 2 diabetes may be prevented or delayed and a call to action*This slide set takes a unique approach to addressing the prevention of type 2 diabetesEach section ask questions, then provides studies and recommendations based on those questionsAs outlined on this slide, the sections focus on each of the following eight questionsWhy is prevention of diabetes imperative?What is the evidence that type 2 diabetes can be prevented or delayed?Do prevention interventions have sustained effects?Are we preventing type 2 diabetes or delaying it?Is diabetes prevention cost-effective?Can evidence-based interventions be delivered effectively in lower-cost settings?Will diabetes prevention bend the curve of the epidemic?How can we most effectively prevent or delay type 2 diabetes?The Conclusion section provides a call to action for the prevention of type 2 diabetes*Section 1, Why is Prevention of Type 2 Diabetes Imperative?, presents slides focusing on the projected future U.S. diabetes population and suggests a link between the growing numbers of obese individuals and increase in diagnosed diabetesAdditional slides based on National Diabetes Statistics, 2011 and other sources are available in the The Impact of Diabetes Mellitus in the United States, a slide set that includes epidemiology, costs, and future projections of type 1 and type 2 diabetes*This slide illustrates the projected future percentage of the U.S. population with diabetesThe anticipated steady growth in diabetes, from 14.5% in 2010 to 25.6% in 2030 and 32.7% in 2050, or from approximately 1 in 7 to 1 in 3 individuals, underscores the imperative for change*ReferenceBoyle JP, Thompson TJ, Gregg EW, Barker LE, Williamson DF. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul Health Metr. 2010;8:29.Age-adjusted percentage of U.S. adults who were obese (defined as BMI 30 kg/m2; top row) or who had diagnosed diabetes (bottom row) for the years 1994, 2000, and 20081 are highlighted on this slideThe prevalence of diagnosed diabetes and selected risk factors by county was estimated using data from the Centers for Disease Control and Preventions Behavioral Risk Factor Surveillance System (BRFSS)1 and data from the U.S. Census Bureaus Population Estimates Program2The BRFSS is an ongoing, monthly, state-based telephone survey of the adult populationThe survey provides state-specific information on behavioral risk factors and preventive health practicesRespondents were considered to have diabetes (either type 1 or type 2) if they responded yes to the question, Has a doctor ever told you that you have diabetes? Women who indicated that they only had diabetes during pregnancy were not considered to have diabetesRespondents were considered obese if their BMI was 30 kg/m2, derived from self-report of height and weightBetween 1994 and 2008, the percentage of individuals defined as obese increased, as did the percentage of those with diagnosed diabetes*ReferencesCenters for Disease Control and Prevention: National Diabetes Surveillance System. Available online at: http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Accessed 10/3/2011. U.S. Census Bureau. http://www.census.gov/popest/estimates.php. Section 2, What is the Evidence That Type 2 Diabetes Can Be Prevented or Delayed, presents slides focusing on the interventions that have been shown to decrease rate of onset of diabetes significantly*Several randomized clinical trials have shown that individuals at high risk for developing diabetes (ie, those with impaired fasting glucose [IFG] or impaired glucose tolerance [IGT], or both) can be given interventions that significantly decrease rate of onset of diabetesResults of the studies highlighted here are explored in subsequent slides*ReferenceAmerican Diabetes Association. Standards of Medical Care2011. Diabetes Care. 2011;34(suppl 1):S16.In 1986, the Da Qing study screened 110,660 adults from 33 health care clinics for impaired glucose tolerance (IGT) and type 2 diabetes mellitusUsing World Health Organization (WHO) criteria, 577 men and women were classified as having IGT and randomized by clinic to either a control group (n=138) or one of three lifestyle interventions (n=438)The mean age of the control group was 46.6 years and included 79 men and 59 women; in the active treatment groups combined, mean age was 44.7 years and there were 233 men and 205 womenThe goal of the diet only intervention was to increase vegetable intake and lower alcohol and sugar intake; those overweight or obese were also encouraged to lose weight by reducing total calorie intakeThe goal of the exercise intervention was for participants to increase leisure time physical activityThose in the diet + exercise group applied the goals from both the diet only and exercise only intervention groupsThe effect of the intervention was assessed at 2-yearly intervals for 6 years to determine incidence of type 2 diabetes*ReferencePan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997;20:537-544.At 6 years, the cumulative incidence of diabetes was significantly decreased in each of the active intervention groups compared with the control groupThe percentage decrease in diabetes incidence and 95% confidence intervals are summarized in the TableThe diet + exercise lifestyle intervention led to the most significant decrease, followed by diet alone and then exercise aloneControl: 67.7% (95% CI, 59.8-75.2)Diet + exercise: 46.0% (95% CI, 37.3-54.7)Diet: 43.8% (95% CI, 35.5-52.3)Exercise: 41.1% (95% CI, 33.4-49.4)When data from each of the 33 clinics were analyzed, each active intervention group was found to differ significantly from those of the control clinic (P