1. Prevention of Type 2 Diabetes Mellitus
Key Questions
and
A Call to Action
This slide set focuses on prevention of type 2 diabetes mellitus, addressing key questions with respect to why such prevention is imperative
Included are studies supporting how type 2 diabetes may be prevented or delayed and a call to action

2. Prevention of Type 2 Diabetes Mellitus: Table of Contents
Section
Topic
Slide No. 1
Why is prevention of type 2 diabetes imperative?
3-5 2
What is the evidence that type 2 diabetes can be prevented or delayed?
6-23 3
Do prevention interventions have sustained effects?
24-30 4
Are we preventing type 2 diabetes or delaying it?
31-32 5
Is diabetes prevention cost-effective?
33-36 6
Can evidence-based interventions be delivered effectively in lower-cost settings?
37-40 7
Will diabetes prevention “bend the curve” of the epidemic?
41-42 8
How can we most effectively prevent or delay type 2 diabetes?
43-51 9
Conclusions: call to action
52-53
This slide set takes a unique approach to addressing the prevention of type 2 diabetes
Each section ask questions, then provides studies and recommendations based on those questions
As outlined on this slide, the sections focus on each of the following eight questions
Why 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

3. Why is prevention of type 2 diabetes imperative?
Section 1
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 diabetes
Additional 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
Why is prevention of type 2 diabetes imperative?

4. Projecting the Future Diabetes Population: The Imperative for Change
U.S. Population with Diabetes (%)
This slide illustrates the projected future percentage of the U.S. population with diabetes
The 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
Boyle JP, et al. Popul Health Metr. 2010;8(29):1-12.
Reference
Boyle 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.

5. Percentage of U.S. Adults Who Were Obese or Had Diagnosed Diabetes
Obesity (BMI ≥30 kg/m2)
1994
2000
2008
No Data <14.0% % % % %
Diabetes
1994
2000
2008
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 are highlighted on this slide
The prevalence of diagnosed diabetes and selected risk factors by county was estimated using data from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System (BRFSS)1 and data from the U.S. Census Bureau’s Population Estimates Program2
The BRFSS is an ongoing, monthly, state-based telephone survey of the adult population
The survey provides state-specific information on behavioral risk factors and preventive health practices
Respondents 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 diabetes
Respondents were considered obese if their BMI was ≥30 kg/m2, derived from self-report of height and weight
Between 1994 and 2008, the percentage of individuals defined as obese increased, as did the percentage of those with diagnosed diabetes
No Data <4.5% % % % ≥9.0%
Centers for Disease Control and Prevention: National Diabetes Surveillance System. Available online at: Accessed 10/3/2011.
References
Centers for Disease Control and Prevention: National Diabetes Surveillance System. Available online at: Accessed 10/3/2011.
U.S. Census Bureau.

6. whaT IS THE EVIDENCE THAT TYPE 2 DIABETES CAN BE PREVENTED OR DELAYED?
Section 2
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
whaT IS THE EVIDENCE THAT TYPE 2 DIABETES CAN BE PREVENTED OR DELAYED?

7. Lifestyle Interventions Can Prevent Type 2 Diabetes Onset
Several randomized trials have shown interventions (lifestyle, medications) can decrease rate of onset of diabetes
Lifestyle: Da Qing, Finnish Diabetes Prevention Study, Diabetes Prevention Program
Medications: Diabetes Prevention Program (metformin), The Stop-NIDDM (acarbose), DREAM (rosiglitazone), ACT-NOW (pioglitazone)
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 diabetes
Results of the studies highlighted here are explored in subsequent slides
Reference
American Diabetes Association. Standards of Medical Care—2011. Diabetes Care. 2011;34(suppl 1):S16.

8. Lifestyle Interventions Da Qing Study Methods
110,660 adults from 33 Da Qing, China, health care clinics screened in 1986 for IGT, type 2 diabetes mellitus
577 adults with IGT (WHO criteria) randomized to control (n=138) or one of three lifestyle interventions (n=438)
Diet only
Exercise only
Diet + exercise
Follow-up at 2-year intervals over 6 years to identify those who developed diabetes
In 1986, the Da Qing study screened 110,660 adults from 33 health care clinics for impaired glucose tolerance (IGT) and type 2 diabetes mellitus
Using 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 women
The 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 intake
The goal of the exercise intervention was for participants to increase leisure time physical activity
Those in the diet + exercise group applied the goals from both the diet only and exercise only intervention groups
The effect of the intervention was assessed at 2-yearly intervals for 6 years to determine incidence of type 2 diabetes
Pan XR, et al. Diabetes Care. 1997;20:
Reference
Pan 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:

9. Lifestyle Interventions Da Qing Study Results
Cumulative incidence of diabetes at 6 years was significantly decreased in the active intervention groups (P<0.05)
When analyzed by clinic, each active intervention group differed significantly from the control (P<0.05)
Control
67.7% (95% CI, )
Diet
43.8% (95% CI, )
Exercise
41.1% (95% CI, )
Diet + exercise
46.0% (95% CI, )
At 6 years, the cumulative incidence of diabetes was significantly decreased in each of the active intervention groups compared with the control group
The percentage decrease in diabetes incidence and 95% confidence intervals are summarized in the Table
The diet + exercise lifestyle intervention led to the most significant decrease, followed by diet alone and then exercise alone
Control: 67.7% (95% CI, )
Diet + exercise: 46.0% (95% CI, )
Diet: 43.8% (95% CI, )
Exercise: 41.1% (95% CI, )
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<0.05).
Pan XR, et al. Diabetes Care. 1997;20:
Reference
Pan 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:

10. Lifestyle Interventions Da Qing Study Results
When stratified as lean or overweight (BMI < or ≥25 kg/m2), relative decrease in rate of development of diabetes in lifestyle intervention groups was similar
After adjusting for differences in baseline BMI and fasting glucose, all interventions were associated with diabetes risk reduction
When the Da Qing study participants were stratified as lean (BMI <25 kg/m2) or overweight (≥25 kg/m2), the relative decrease in rate of developing diabetes in each of the lifestyle intervention groups was similar
In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, each intervention was associated with a reduction in risk of developing diabetes: diet, 31% (P<0.03); exercise, 46% (P<0.0005), and diet + exercise, 42% (P<0.005)
Diet
31% (P<0.03)
Exercise
46% (P<0.0005)
Diet + exercise
42% (P<0.005)
Pan XR, et al. Diabetes Care. 1997;20:
Reference
Pan 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:

11. Lifestyle Interventions Da Qing Study Conclusions
Active intervention with diet and/or exercise led to a significant decrease in incidence of diabetes over a 6-year period ( ) among those with IGT
Diabetes incidence (per 100 person years) per year
Control: 14.1 (95% CI )
Lifestyle intervention: 7.9 (95% CI, )
The Da Qing study concluded that among those with IGT, the lifestyle interventions of diet and/or exercise led to a significant decrease in the incidence of diabetes over a 6-year period 1
For the period, incidence (per 100 person years per year) of diabetes was 14.1 (95% CI, ) in the control group, compared with 7.9 (95% CI, ) in the lifestyle intervention groups2
Pan XR, et al. Diabetes Care. 1997;20:
References
Pan 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:
Li G, Zhang P, Wang J, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371:

12. Lifestyle Interventions Finnish Diabetes Prevention Study
522 subjects, years of age
BMI ≥25 kg/m2; IGT: 2-h PPG mg/dL
Control group: general oral and written information diet and exercise
Intervention group: individualized
Reduce weight ≥5%
Decrease fat ≤30%, saturated fat ≤10% energy
Increase fiber to at least 15 g/1000 kcal
Moderate exercise ≥30 minutes/day
Primary end point: diagnosis of diabetes
In the Finnish Diabetes Prevention Study, 522 overweight (BMI ≥25 kg/m2) men and women ages 40 to 65 years with impaired glucose tolerance (IGT, defined as plasma glucose concentration mg/dL 2 hours following an oral glucose challenge) were randomly assigned to either a control group or to a lifestyle intervention group
In the control group, 91 men and 174 women were given general oral and written information about diet (a 2-page leaflet) and exercise at baseline and at annual visits
No specific individualized programs were offered
A 3-day food diary was completed at baseline and at each annual visit; nutrient intakes were computed
In the intervention group, 81 men and 176 women were given detailed advice about how to achieve the goals of the intervention, which were to
Reduce weight by 5% or more
Reduce total intake of fat to <30% and saturated fat to <10% of energy consumed
Increase fiber intake to at least 15 g/1,000 kcal
Moderate exercise for at least 30 minutes/day
Dietary advice was tailored to each subject on the basis of 3-day food records completed 4 times annually; participants had 7 sessions with a nutritionist during the first year of the study and 1 session every 3 months thereafter and received individual guidance on increasing level of physical activity
Primary end point was diagnosed diabetes: a FPG of 140 mg/dL or higher or a plasma glucose concentration of 200 mg/dL or higher 2 hours following an oral glucose challenge
Tuomilehto J, et al for the Finnish Diabetes Prevention Study Group. N Engl J Med. 2001;344:
Reference
Tuomilehto J, Lindström J, Eriksson JG, et al for the Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:

13. Lifestyle Interventions Finnish Diabetes Prevention Study
172 men, 350 women; mean age 55 y
Mean BMI 31 kg/m2
Mean duration of follow-up 3.2 years
Weight Loss, Kg
Mean ± SD
Cumulative Incidence of Diabetes
After 4 Years
Year 1
Year 2
Control
0.8±3.7
0.8±4.4
23% (95% CI, 17-29)
Intervention
4.2±5.1*
3.5±5.5*
11% (95% CI, 6-15)
Risk Reduction
58%*
The objective of the Finnish Diabetes Prevention Study was to determine the feasibility and effects of lifestyle changes designed to prevent or delay the onset of type 2 diabetes in those with IGT
Mean duration of study follow-up was 3.2 years
At the end of Year 1, weight loss was 0.8±3.7 kg (mean±SD) in the control group and 4.2±5.1 in the intervention group; at Year 2, weight loss was 0.8±4.4 kg in the control group and 3.5±5.5 in the intervention group (P<0.001 for both comparisons between groups)
After 4 years, the cumulative incidence of diabetes was 11% (95% CI, 6-15) in the intervention group compared with 23% (95% CI, 17-29) in the control group
Cox regression analysis of all person-years accumulated results in a cumulative incidence of diabetes that was 58% lower in the intervention group than in the control group (hazard ratio, 0.4; 95% CI, ; P<0.001)
Among those in the intervention group, incidence of diabetes was 63% lower among men (95% CI, 18-79; P=0.01) and 54% lower among women (95% CI, 26-81; P=0.008)
*P<0.001
Tuomilehto J, et al for the Finnish Diabetes Prevention Study Group. N Engl J Med. 2001;344:
Reference
Tuomilehto J, Lindström J, Eriksson JG, et al for the Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:

14. Lifestyle Interventions Finnish Diabetes Prevention Study
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 diabetes
These 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 diabetes
The authors concluded that type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects, defined as those with impaired glucose tolerance, which represented an intermediate category between normal glucose tolerance and overt diabetes
Strong evidence suggests modifiable risk factors (eg, obesity, physical inactivity) are the primary nongenetic determinants of type 2 diabetes
Results of this study have found that to prevent 1 case of diabetes, 22 subjects with IGT must be treated with lifestyle intervention for 1 year, or 5 subjects for 5 years
Tuomilehto J, et al for the Finnish Diabetes Prevention Study Group. N Engl J Med. 2001;344:
Reference
Tuomilehto J, Lindström J, Eriksson JG, et al for the Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:

15. Lifestyle Interventions Diabetes Prevention Program
3,234 nondiabetic persons in 27 clinical centers
BMI ≥24 kg/m2 (≥22 kg/m2 in Asians)
IGT: FPG mg/dL or 2-h PPG mg/dL
From , randomly assigned to
Standard 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)
From , the Diabetes Prevention Program Research Group randomly assigned 3,234 nondiabetic persons at high risk for diabetes (eg, with elevated fasting and postload plasma glucose concentrations) with a BMI ≥24 kg/m2 (or ≥22 kg/m2 in Asians) to
Standard lifestyle + placebo (n=1082)
Standard lifestyle + metformin (initiated at 850 mg orally once daily and, at one month, increased to twice daily)
Intensive lifestyle intervention (n=1079)
The study initially included a fourth intervention, troglitazone, which was discontinued in 1998 due to the potential for liver toxicity
“Standard lifestyle” included written information and an annual minute individual session that emphasized the importance of a healthy lifestyle (eg, follow the food pyramid guide, reduce weight, and increase physical activity)
Primary outcome was diabetes, diagnosed on the basis of an annual oral glucose-tolerance test or a semiannual fasting plasma glucose test
The intensive lifestyle intervention is described on the next slide
Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:
Reference
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:

16. Lifestyle Interventions Diabetes Prevention Program
Goals of intensive lifestyle intervention
7% loss of body weight
Dietary fat goal: 25% of calories from fat
Calorie intake goal: kcal/day based on initial body weight
>150 minutes of physical activities weekly
Similar in intensity to brisk walking; at least 700 kcal/week
Group received 16-lesson curriculum
This slide describes the goals of the intensive lifestyle intervention arm of the Diabetes Prevention Program study
Subjects were asked to lose 7% of their body weight and maintain it by keeping dietary fat to 25% of calories, which were calculated at kcal/day based on a patient’s initial body weight, and to engage in physical activity at least 150 minutes weekly
The fat and calories goals were used to achieve weight loss, rather than as specific goals
A 16-lesson curriculum designed to help participants achieve their goals was taught on a one-to-one basis during the first 24 weeks following enrollment and was individualized
Subsequent individual (monthly) and group sessions helped to reinforce behavioral changes
Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:
Reference
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:

17. Lifestyle Interventions Diabetes Prevention Program
Mean age 50.6 years
67.7% women; 45.3% members of minority groups
Mean BMI 34.0 kg/m2
69.4% had a family history of diabetes
Average follow-up: 2.8 years (range, )
Mean age of the subjects in the Diabetes Prevention Study was 50.6 years
67.7% of the subjects were women and 45.3% were members of minority groups (19.9% African American, 15.7% Hispanic, 5.3% American Indian, and 4.4% Asian)
Average follow-up was 2.8 years (range, years)
Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:
Reference
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:

18. Lifestyle Interventions Diabetes Prevention Program
Those assigned to lifestyle intervention had greater weight loss and increase in physical activity than participants receiving metformin or placebo
Lifestyle intervention more effective in restoring normal post-load glucose values
Results: average weight loss (P<0.001)
Participants in the Diabetes Prevention Program who were assigned to lifestyle intervention had much greater weight loss and a greater increase in physical activity than those assigned to treatment with metformin or placebo
Metformin and lifestyle intervention were similarly effective in restoring normal fasting glucose values; however, lifestyle intervention was more effective in restoring normal post-load glucose values
Average weight loss was 5.6 kg in the lifestyle group, 2.1 kg in the metformin group, and 0.1 kg in the placebo group (P<0.001)
Lifestyle
Metformin
Placebo
5.6 kg
2.1 kg
0.1 kg
Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:
Reference
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:

19. Lifestyle Interventions Diabetes Prevention Program
Results: intensive lifestyle intervention
At 24 Weeks
At Final Study Visit
Weight loss ≥7%
50%
38%
Exercise >150 minutes/week
58%
In the intensive lifestyle intervention group, half (50%) of the patients had achieved the goal of weight loss of 7% or more by the end of the curriculum (24 weeks) and 38% had a weight loss of at least 7% at the most recent study visit
Assessed by logs the participants kept, 74% had met the goal of at least 150 minutes of physical activity/week at 24 weeks and 58% at the most recent study visit
Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:
Reference
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:

20. Medications DPP: Metformin Intervention
Metformin, intensive lifestyle modification delayed or prevented type 2 diabetes vs placebo (11%/year incidence)
Placebo: 11%/year incidence
Metformin: 7.8%/year incidence*
Lifestyle intervention: 4.8%/year incidence*
Risk reduction:
31% by metformin
58% by lifestyle
39% lifestyle vs metformin
Results of the Diabetes Prevention Program study showed that treatment with metformin and intensive lifestyle modification both delayed or prevented type 2 diabetes compared with placebo
Risk reduction was 58% (95% CI, 17-43) by lifestyle intervention, 31% (95% CI, 48-66) by metformin, and 39% (95% CI, 24-51) by lifestyle compared with metformin
Rate of gastrointestinal symptoms were highest in the metformin group and musculoskeletal symptoms highest in the lifestyle intervention group
*P<0.001 vs placebo
Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:
Reference
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:

21. Medications DPP: Metformin Intervention
Intensive lifestyle intervention more effective than either metformin or placebo
By subgroup, metformin more effective if:
FPG >110 mg/dL
Age <60 years
BMI >35 kg/m2
Gender, ethnicity, 2-h PGG, NOT predictive of response
Use metformin in high-risk individuals
In general, the intensive lifestyle intervention was more effective than either metformin or placebo1
When the effect of metformin or intensive lifestyle intervention was examined by subgroup, the effect of metformin was less in those who had a lower BMI or a lower fasting glucose concentration than in those with higher value for those variables; neither interaction was explained by the other variable or by age, gender, or ethnicity1
Metformin was observed to be more effective in those with a fasting plasma glucose >110 mg/dL, in younger individuals (ie, less than 60 years of age), and in those with a higher BMI (>35 kg/m2); however, metformin was not significantly better than placebo in those >60 years of age1
Based on these findings, metformin may reasonably be recommended for very high-risk individuals; ie, those with risk factors for diabetes and/or more severe or progressive hyperglycemia2
Knowler WC, et al. for the Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:
References
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:
American Diabetes Association. Standards of Medical Care—2011. Diabetes Care. 2011;34(suppl 1):S16.

22. Medications The STOP-NIDDM: Acarbose
Acarbose reduced risk of new
Hypertension >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=682
Placebo n=686
25% Relative Risk Reduction P=0.0022
In the multicenter, double-blind, placebo-controlled randomized STOP-NIDDM trial conducted in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel and Spain from July 1998 to August 2001, 1429 patients with impaired glucose tolerance were randomized to placebo or acarbose 100 mg 3 times/day
The figure on this slide shows the effect of acarbose vs placebo on cumulative probability of remaining free of diabetes over time
Treatment with acarbose decreased progression to diabetes by 25% and improved glucose tolerance in patients who reverted to normal glucose tolerance
The probability of reverting to normal glucose tolerance over time was significantly higher in patients on acarbose than in those on placebo (P<0.0001)
Acarbose also significantly reduced risk of hypertension, myocardial infarction, and any cardiovascular disease events, including coronary heart disease (CHD), cardiovascular death or stroke, congestive heart failure (CHF), and peripheral vascular disease
No serious adverse events were related to treatment with acarbose; the most frequent side effects were flatulence and diarrhea
Reprinted with permission from Chiasson JL, et al. Lancet. 2002;359(9323): ; Chiasson JL, et al. JAMA. 2003;290(4):
References
Chiasson JL, Josse RG, Gomis R, et al for The STOP-NIDDM Trial Research Group Members. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359(9323):
Chiasson JL, Laakso M, Karasik A, for The STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance. JAMA. 2003;290(4):
Figure reprinted from The Lancet, 359, Chiasson JL, Josse RG, Gomis R, et al for The STOP-NIDDM Trial Research Group Members, Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial, , Copyright (2002), with permission from Elsevier.

23. Medications DREAM: Rosiglitazone
60% Relative Risk Reduction
HR 0.40 (0.35–0.46) P<0.0001
The aim of the prospective DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) study was to assess whether rosiglitazone could reduce the frequency of diabetes in individuals with impaired glucose tolerance or impaired fasting glucose, or both
5269 adults aged ≥30 years with impaired fasting glucose or impaired glucose tolerance, or both and no previous cardiovascular disease were randomized to rosiglitazone 8 mg/day (n=2635) or placebo (n=2634) and followed for a median of 3 years
Compared with placebo, treatment with rosiglitazone resulted in a 60% relative risk reduction in type 2 diabetes mellitus (HR 0.40 [95% CI 0.35–0.46]; P<0.0001)
A total of 1330 adults (50.5%) in the rosiglitazone group and 798 (30.3%) in the placebo group became normoglycaemic (HR 1.71, [95% CI 1.57–1.87]; P<0.0001)
Heart failure occurred in 14 adults (0.5%) in the rosiglitazone group and two (0.1%) in the placebo group (P=0.01)
The investigators concluded that rosiglitazone 8 mg/day for 3 years substantially reduced incident type 2 diabetes and increased likelihood of regression to normoglycemia in adults with IFG, IGT, or both
Reprinted with permission from DREAM Trial Investigators. Lancet. 2006;368(9541):
Reference
The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368(9541):
Figure reprinted from The Lancet, 368, The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators, Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial, , Copyright (2006), with permission from Elsevier.

24. Medications ACT NOW: Pioglitazone
Pioglitazone reduced risk of type 2 diabetes mellitus by 72% vs placebo (HR 0.28; 95% CI 0.16–0.49 P<0.001)
Conversion to normal glucose tolerance: 48% of patients with pioglitazone vs 28% with placebo (P<0.001)
Pioglitazone reduced fasting glucose, 2-hour glucose, HbA1c
Weight gain, edema observed in the pioglitazone arm
Interventions that may prevent or delay impaired glucose tolerance, which is associated with cardiovascular disease and conversion to type 2 diabetes mellitus are clinically important
The double-blind, placebo-controlled Act Now for Prevention of Diabetes (ACT NOW) study randomly assigned 602 adults with type 2 diabetes mellitus with impaired glucose tolerance to pioglitazone (n=303) or placebo (n=299) to determine whether pioglitazone could reduce the risk of type 2 diabetes
Median follow-up was 2.4 years
Fasting glucose was measured quarterly and oral glucose tolerance tests, annually
Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group vs 7.6% in the placebo arm; compared with placebo, pioglitazone reduced the risk of type 2 diabetes mellitus by 72% (HR 0.28 [95% CI 0.16–0.49]; P<0.001)
Conversion to normal glucose tolerance occurred in 48% of patients in the pioglitazone group vs 28% in the placebo group (P<0.001)
Treatment with pioglitazone vs placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg/dL vs 8.1 mg/dL; P<0.001), 2-hour glucose (a decrease of 30.5 mg/dL vs 15.6 mg/dL; P<0.001), and HbA1c (a decrease of 0.04 percentage points vs an increase of 0.20 percentage points; P<0.001)
Weight gain was greater with pioglitazone, 3.9 kg vs 0.77 kg for placebo (P<0.001), and edema was more frequent (12.9% vs 6.4%; P=0.007)
DeFronzo RA, et al, for the ACT NOW Study. N Engl J Med. 2011;364:
Reference
DeFronzo RA, Tripathy D, Schwenke DC, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011;364:

25. DO PREVENTION INTERVENTIONS HAVE SUSTAINED EFFECTS?
Section 3
Section 3, “Do Prevention Interventions Have Sustained Effects,” includes a review of lifestyle interventions , metformin, and rosiglitazone on preventing, and delaying type 2 diabetes mellitus
DO PREVENTION INTERVENTIONS HAVE SUSTAINED EFFECTS?

26. Lifestyle Interventions Da Qing Study 20-Year Follow-Up
Combined lifestyle intervention vs control
51% lower incidence of diabetes during active intervention
43% lower incidence over 20 years
3.6 years fewer with diabetes
Average Annual Incidence
20-Year Cumulative Incidence
Controls
11%
93%
Combined lifestyle intervention 7%
80%
The Da Qing study 20-year follow-up assessed the long-term effect of interventions
Primary outcomes: diabetes and CVD incidence, mortality, all-cause mortality
Compared with the control arm, combined lifestyle intervention resulted in a 51% lower incidence of diabetes during active intervention and a 43% lower incidence over 20 years, which translated to 3.6 fewer years with diabetes
The 20-year cumulative incidence of diabetes was 93% in the controls vs 80% among those who received the combined lifestyle intervention
Li G, et al. Lancet. 2008;371:
Reference
Li G, Zhang P, Wang J, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371:

27. Lifestyle Interventions Da Qing Study 20-Year Follow-Up
No significant difference in rate of
First CVD event (HR 0.98; 95% CI, )
CVD mortality (HR 0.83; )
All-cause mortality (HR 0.96; )
Study had limited statistical power to detect differences in these outcomes
Lifestyle interventions over 6 years can prevent, delay diabetes for up to 14 years after active intervention
Unclear whether lifestyle interventions also lead to reduced CVD, mortality
The Da Qing study found that at 20-year follow-up, there was no significant difference in the rate of first CVD event, CVD mortality, or all-cause mortality; however, the study had limited statistical power to detect differences in these outcomes
While it is unclear whether lifestyle interventions also led to reduced CVD mortality, this study showed that lifestyle interventions over 6 years were able to delay and/or prevent diabetes for up to 14 years after active intervention
Li G, et al. Lancet. 2008;371:
Reference
Li G, Zhang P, Wang J, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371:

28. Lifestyle Interventions Finnish DPS 7-Year Follow-Up
43% Relative Risk Reduction
Extended follow-up of the Finnish Diabetes Prevention Study assessed the extent to which the originally achieved lifestyle changes and risk reduction remained after discontinuation of active counseling
After a median of 4 years of active intervention, participants who were still free of diabetes were further followed up for a median of 3 years; median total follow-up was 7 years
The investigators measured diabetes incidence, body weight, physical activity, and dietary intakes of fat, saturated fat, and fiber
At 7 years, incidence of type 2 diabetes was 4.3 years per 100 person-years in the intervention arm vs 7.4 years per 100 person-years in the control arm (log-rank test P=0.0001), a 43% reduction in relative risk
Risk reduction was found to be related to success in achieving intervention goals of weight loss, reduced intake of total and saturated fat , increased intake of dietary fiber, and increased physical activity
These beneficial lifestyle changes were maintained after intervention discontinuation; corresponding incidence rates during postintervention follow-up were 4.6 and 7.2 (P=0.0401), a 36% reduction in relative risk
The investigators concluded that lifestyle intervention in people at high risk for type 2 diabetes resulted in sustained lifestyle changes and a reduction in diabetes incidence that remained after individual lifestyle counseling ceased
Reprinted with permission from Lindström J, et al. Lancet. 2006;368(9548):
Reference
Lindström J, Ilanne-Parikka P, Peltonen M, et al for the Finnish Diabetes Prevention Study Group. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006;368(9548):
Figure reprinted from The Lancet, 368, Lindström J, Ilanne-Parikka P, Peltonen M, et al for the Finnish Diabetes Prevention Study Group, Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study, , Copyright (2006), with permission from Elsevier.

29. DPP: Metformin Had Sustained Effect After Drug Washout
Brief (1-2 week) drug washout study at end of Diabetes Prevention Program trial
After 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 metformin
Postwashout: diabetes reduced by 25%
Metformin significantly reduced risk of diabetes in individuals with impaired glucose tolerance who participated in the Diabetes Prevention Program (DPP)
Diabetes status was assessed by oral glucose tolerance tests (OGTTs) in participants still taking metformin
A repeat OGTT was performed after a brief (1-2 week) washout period in which study medication was withheld
Primary analysis of the DPP demonstrated that metformin decreased risk of diabetes by 31%
This study shows that 26% of this effect can be accounted for by a pharmacological effect of metformin that did not persist when the drug was stopped
After the washout the incidence of diabetes was still reduced by 25%
Diabetes Prevention Program Research Group. Diabetes Care. 2003;26:
Reference
The Diabetes Prevention Program Research Group. Effects of withdrawal from metformin on the development of diabetes in the Diabetes Prevention Program. Diabetes Care. 2003;6:977–980.

30. Rosiglitazone Had No Sustained Effect After Drug Washout: DREAM
During rosiglitazone vs placebo washout
Primary 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, days)
Rosiglitazone substantially reduced incidence of type 2 diabetes (DREAM); however, when withdrawn, this effect is not sustained
The Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial found that new-onset diabetes could be slowed 60% vs placebo with the use of rosiglitazone but not with ramipril
This study sought to determine whether rosiglitazone had sustained benefit after the drug was withdrawn
3262 DREAM trial participants who had not developed diabetes and were still taking study medication were enrolled in a prospective 2- to 3-month posttrial medication washout to determine the rate of new-onset diabetes or death (primary outcome)
Patients were given single-blind placebo and scheduled for an OGTT 2- to 3-months later
During the washout period alone, for the groups that were allocated to rosiglitazone or placebo, the primary outcome (10.5% vs 9.8%; P=0.59) and the secondary outcome, regression to normoglycemia (21.5% vs 23.8%; P=0.33), were similar
Median follow-up was 71 days (range, days)
These results confirm that when taken, rosiglitazone can substantially reduce incidence of type 2 diabetes; however, when the drug is withdrawn, this effect is not sustained
The DREAM Trial Investigators. Diabetes Care. 2011;34:
Reference
The DREAM Trial Investigators. Incidence of diabetes following ramipril or rosiglitazone withdrawal. Diabetes Care. 2011;34:

31. Lifestyle Interventions Summary
Lifestyle intervention continues to have an effect; most drugs do not
Study N
Intervention
Treatment
Risk Reduction
Da Qing
IGT
577
Lifestyle
6 years 20 years
34% - 69%
Finnish DPS
523
3+ years 7 years
58%
DPP
3324
3 years
Lifestyle
Study N
Intervention
Treatment
Risk Reduction
DPP
IGT
3324
Metformin
3 years
31%
DREAM
5269
Rosiglitazone
60%
STOP-NIDDM
1429
Acarbose
21%
ACT NOW
IFG
~600
Pioglitazone
81%
This slide summarizes results of the studies presented in Section 2, “What is the Evidence That Type 2 Diabetes Can Be Prevented or Delayed?” and Section 3, “Do Prevention Interventions Have Sustained Effects?”
As results have shown, lifestyle interventions appear to continue to have a long-term, sustained effect compared with pharmacologic treatments
Pharmacologic
References
Lifestyle
Pan 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:
Li G, Zhang P, Wang J, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371:
Tuomilehto J, Lindström J, Eriksson JG, et al for the Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:
Lindström J, Ilanne-Parikka P, Peltonen M, et al for the Finnish Diabetes Prevention Study Group. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006;368(9548):
Knowler WC, Barrett-Connor E, Fowler SE, et al for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:
Pharmacologic
The Diabetes Prevention Program Research Group. Effects of withdrawal from metformin on the development of diabetes in the Diabetes Prevention Program. Diabetes Care. 2003;6:977–980.
The DREAM Trial Investigators. Incidence of diabetes following ramipril or rosiglitazone withdrawal. Diabetes Care. 2011;34:
Chiasson JL, Josse RG, Gomis R, et al for The STOP-NIDDM Trial Research Group Members. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359(9323):
Chiasson JL, Laakso M, Karasik A, for The STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance. JAMA. 2003;290(4):
DeFronzo RA, Tripathy D, Schwenke DC, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011;364:
Diabetes Care. 1997;20: ; N Engl J Med. 2002;344: ; N Engl J Med. 2002;346; ; Diabetes Care. 2011;34: ; Lancet. 2002;359(9323): N Engl J Med. 2011;364:

32. Are we preventing type 2 diabetes or delaying it?
Section 4
Section 4, “Are We Preventing Type 2 Diabetes or Delaying It?” examines results of the 10-year follow-up of the Diabetes Prevention Program
Are we preventing type 2 diabetes or delaying it?

33. Diabetes Prevention Program 10-Year Follow-Up Study
During 10-year follow-up since randomization
Original lifestyle group lost, then partly regained weight
Modest weight loss with metformin maintained
Diabetes incidence per 100 person-years
Lifestyle
5.9 (5.1, 6.8)
34%* (24, 42)
Metformin
4.9 (4.2, 5.7)
18%* (7, 28)
Placebo
5.6 (4.8, 6.5)
10-year follow-up after the Diabetes Prevention Program found that prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years
In the former placebo and metformin group, diabetes incidences fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group
*vs placebo
Diabetes Prevention Program. Lancet. 2009;374:
Reference
Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:

34. Is diabetes prevention cost-effective?
Section 5
Section 5, “Is Diabetes Prevention Cost-Effective?” looks at the cost-effectiveness of lifestyle modification or metformin compared with placebo based on results from the Diabetes Prevention Program
Is diabetes prevention cost-effective?

35. Cost-Effectiveness of Lifestyle Modification or Metformin: DPP
Active interventions (vs placebo) would:
Intensive Lifestyle
Metformin
Delay onset of type 2 diabetes by
11.1 years
3.4 years
Reduce incidence of type 2 diabetes by
20% 8%
Increase life expectancy by
0.5 years
0.2 years
Cost per QALY
$1,124
$31,286
Published in 2005, this study estimated the lifetime cost-utility of lifestyle modification or metformin based on data from the Diabetes Prevention Program
Intensive lifestyle intervention not only delayed onset and reduced the incidence of type 2 diabetes substantially compared with metformin, but life expectancy increased slightly
Overall, cost per quality adjusted life year (QALY) was $1,124 for lifestyle intervention compared with $31,286 for metformin
QALY = Quality Adjusted Life Years
Herman WH, et al for the Diabetes Prevention Program Research Group. Ann Intern Med. 2005:142:
Reference
Herman WH, Hoerger TJ, Brandle M, et al, for the Diabetes Prevention Program Research Group. The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance. Ann Intern Med. 2555;142:

36. Diabetes Prevention Program 10-Year Cost-Effectiveness
10-year within-trial cost-effectiveness of the interventions
Intensive lifestyle
Metformin
Data on resource utilization, cost, and quality of life collected prospectively
Economic analyses performed from health system and societal perspectives
The Diabetes Prevention Program (DPP) and its Outcomes Study (DPPOS) demonstrated that either intensive lifestyle intervention or metformin could prevent type 2 diabetes in high-risk adults for at least 10 years after randomization
This study reported the 10-year within trial cost-effectiveness of the interventions, either intensive lifestyle or treatment with metformin
Prospective data on resource utilization, cost, and quality of life were collected
Economic analyses were performed from health system and societal perspectives
Diabetes Prevention Program Research Group. Diabetes Care. 2012;35:
Reference
Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention. Diabetes Care. 2012;35:

37. Diabetes Prevention Program 10-Year Cost-Effectiveness
Lifestyle cost-effective, metformin marginally cost-saving vs placebo
Investment in lifestyle, metformin interventions for diabetes prevention in high-risk adults provides good value
Societal Perspective*
Lifestyle vs Placebo
Metformin vs Placebo
Lifestyle vs Metformin
DPP Group Lifestyle vs Placebo
Undiscounted
11,274
Cost-saving
44,562
Discounted†
14,365
42,753
1,681
As implemented during the Diabetes Prevention Program, the cumulative, undiscounted per capita direct medical costs of the interventions were greater for lifestyle ($4,601) than metformin ($2,300) or placebo ($769) over 10 years
Cumulative direct medical costs of care outside the study were least for lifestyle ($24,563 lifestyle vs. $25,616 metformin vs. $27,468 placebo)
Cumulative, combined total direct medical costs were greatest for lifestyle and least for metformin ($29,164 lifestyle vs. $27,915 metformin vs. $28,236 placebo)
Cumulative quality-adjusted life-years (QALYs) accrued over 10 years were greater for lifestyle (6.81) than metformin (6.69) or placebo (6.67)
When costs and outcomes were discounted at 3%, lifestyle cost $10,037 per QALY, and metformin had slightly lower costs and nearly the same QALYs as placebo
The study found that from a payer perspective, lifestyle was cost-effective and metformin was marginally cost-saving compared with placebo over 10 years
From a societal perspective, as illustrated on this slide, DPP group lifestyle vs. placebo was cost-saving when undiscounted and had an incremental cost-effectiveness ratio of 1,681 at a 3% discount
Investment in lifestyle and metformin interventions for diabetes prevention in high-risk adults provides good value for the money spent
Incremental cost-effectiveness ratios from three different perspectives; ∆cost/∆QALY
*Includes direct medical costs and direct nonmedical costs including participant time
†Both costs and QALYs are discounted at 3%
Diabetes Prevention Program Research Group. Diabetes Care. 2012;35:
Reference
Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention. Diabetes Care. 2012;35:

38. Section 6
Section 6, “Can Evidence-Based Interventions Be Delivered Effectively in Lower-Cost Settings?” examines three studies
DEPLOY, the first study to demonstrate the YMCA is a promising vehicle for disseminating Diabetes Prevention Program lifestyle intervention into the community, demonstrated a significant reduction in weight, BMI, and total cholesterol after 4-6 month
POWER found that significant weight loss can be sustained over 2 years with both in-person and remote-only behavioral weight-loss interventions
Employing Diabetes TeleHealth to institute a diabetes self-management education (DSME) intervention was found to improve metabolic control and reduce cardiovascular risk in an ethnically diverse, rural population
Can evidence-based interventions be delivered effectively in lower-cost settings?

39. DEPLOY Pilot Study: Diabetes Prevention in the Community
Adults BMI ≥24 kg/m2, ≥2 diabetes risk factors, blood glucose mg/dL
Randomized to group-based DPP lifestyle intervention or brief counseling (control)
Outcome, 4-6 months
Control (n=38)
Intervention (n=39)
P value (vs control)
% change in weight
−2 (−3.3, −0.6)
−6 (−7.3, −4.7)
< 0.001
% change BMI
−2.3 (−3.7, −0.8)
−5.8 (−7.3, −4.4)
0.001
Change total cholesterol
+6 mg/dL (−2.8, 14.8)
−21.6 mg/dL −29.9, −13.3)
<0.001
This is the first study to demonstrate the YMCA is a promising vehicle for disseminating DPP lifestyle intervention into the community
The DEPLOY (Diabetes Education & Prevention with a Lifestyle Intervention Offered at the YMCA) Pilot Study randomized 92 adults to either a group lifestyle intervention (n=46) or control (brief counseling; n=46) at two YMCA facilities in the greater Indianapolis, IN, area
The control group had more women (61% vs 50%) and more adults who were nonwhite (29% vs 6%) than the intervention group
Adults had a BMI ≥24 kg/m2, ≥2 diabetes risk factors, and a casual capillary blood glucose mg/dL
The 4–6-month follow-up visit was completed by 83% of those in the control group and 85% in the intervention group
Compared with the control group, adults at high risk for developing diabetes significantly achieved and maintained
Mean 6% reduction in baseline body weight
Mean 5.8% reduction in BMI
Mean 21.6 mg/dL in change in total cholesterol
These differences were sustained after 12 months
Adjustments for differences in race, gender did not alter the findings
Ackermann RT, et al. Am J Prevent Med. 2008;35:
Reference
Ackermann RT, Finch EA, Brizendine E, Zhou H, Marrero DG. Translating the Diabetes Prevention Program into the community, The DEPLOY Pilot Study. Am J Prev Med. 2008;35:

40. Practice-Based Opportunities for Weight Reduction (POWER)
Obese patients achieve, sustain significant weight loss with behavioral interventions
2-Year Outcome
Control
Remote Support Only
In-Person Support
Mean change in weight from baseline
−0.8 kg
−4.6 kg*
−5.1 kg*
% patients losing ≥5% of initial weight
18.8%
38.2%
41.4%
This 2-year trial, one of three independent studies in the Practice-based Opportunities for Weight Reduction (POWER) trials, each supported by a grant from the National Heart, Lung, and Blood Institute, randomized 415 patients with a baseline body-mass index (BMI) of 36.6 and a mean weight of kg and at least one cardiovascular risk factor to one of two behavioral weight-loss interventions in which primary care providers reinforced participation at routinely scheduled visits
1) Remote weight-loss support via telephone, a study-specific Web site, and
2) In-person support during group and individual sessions plus remote support as above
In the control arm, weight loss was self-directed
Mean age was 54.0 years; 63.6% were women and 41.0% of participants were black
At 2 years, mean change in weight from baseline was −0.8 kg in the control group, −4.6 kg in the remote support only group (P<0.001 vs. control), and −5.1 kg in the in-person support group (P<0.001 vs. control)
The percentage of those losing ≥5% of initial weight was 18.8% in the control group, 38.2% in the remote-support only group, and 41.4% in the in-person support group
Weight change from baseline did not differ significantly between the two behavioral weight-loss intervention groups
The study concluded that behavioral interventions, both in-person and remotely, can help obese patients achieve and sustain significant weight loss
*P<0.001 vs control arm
Appel LJ, et al. N Engl J Med. 2011;365:
Reference
Appel LJ, Clark JM, Hsin-Chieh Yeh H-C, et al. Comparative effectiveness of weight-loss interventions in clinical practice. N Engl J Med. 2011;365:

41. Diabetes TeleHealth Improves Diabetes Self-Management
1-year remote DSME intervention, Diabetes TeleCare (dietitian, nurse/certified diabetes educator
Improved metabolic control, reduced CV risk
Reduction in Glycated Hemoglobin
Baseline
6 Months
12 Months
Diabetes TeleCare group
9.4±0.3
8.3±0.3*
8.2±0.4†
Usual care group
8.8±0.3
8.6±0.3
This 1-year randomized trial evaluated a remote comprehensive diabetes self-management education (DSME) intervention, Diabetes TeleCare, in a population treated at a federally qualified health center in rural South Carolina
Participants were randomized to Diabetes TeleCare, a 12-month, 13-session curriculum delivered by a dietitian and nurse/certified diabetes educator using telehealth strategies, or usual care
As shown on this slide, improvement in glycated hemoglobin (GHb) was significantly greater in the intervention group compared with usual care from baseline to 6 and 12 months
In a posthoc analysis of a subset of the randomized sample who completed a 24-month follow-up visit, GHb was reduced from baseline to 12 and 24 months in the Diabetes TeleCare group
Improvement in LDL cholesterol was also significantly greater in the intervention group vs. usual care
No difference was observed in improvement in systolic blood pressure, diastolic blood pressure, BMI, waist circumference, or albumin-to-creatinine ratio
The study found that employing Diabetes TeleHealth to institute a diabetes self-management education (DSME) intervention improved metabolic control and reduced cardiovascular risk in an ethnically diverse, rural population
*P=0.003 vs. baseline
†P=0.004 vs. baseline
Davis RM, et al. Diabetes Care. 2010;33:1712–1717.
Reference
Davis RM, Hitch AD, Salaam MM, Herman WH, Zimmer-Galler IE, Mayer-Davis EJ. TeleHealth improves diabetes self-management in an underserved community. Diabetes TeleCare. Diabetes Care. 2010;33:1712–1717.

42. Will diabetes prevention “bend the curve” of the epidemic?
Section 7
Section 7, “Will Diabetes ‘Bend the Curve’ of the Epidemic?” focuses on a prevention model that suggests widespread implementation of reasonably effective preventive interventions that focus on high-risk subgroup can considerably reduce—if not eliminate—future increases in prevalence of diabetes
Will diabetes prevention “bend the curve” of the epidemic?

43. CDC Modeling Study to Reduce Future Diabetes Prevalence
Five-state model
Potential effect of hypothetical preventive intervention delivered to all with IFG
If 50% participated and incidence reduced by 50%, would equal 25% reduction in annual incidence of diabetes in the population with IFG
Would lower the increase in prevalence by to 1 in 4 (vs 1 in 3)
Equations developed to model future burden of diabetes on US adults through 2050
Effect of a hypothetical, large-scale preventive intervention considered
Preliminary results from a five-state model that would deliver preventive intervention to all participants with impaired fasting glucose (IFG), a group at high risk for future development of diabetes
If half of the people with IFG participated and incidence was reduced by 50%, this would be approximately equivalent to a 25% reduction in all people with IFG
The assumption is therefore that this hypothetical intervention would reduce annual incidence of diabetes in people with IFG by 25%
Widespread implementation of reasonably effective preventive interventions that focus on high-risk subgroups may not eliminate, but might considerably reduce, future increases in diabetes prevalence; for example, from 1 in 3 to 1 in 4 people
Boyle JP, et al. Popul Health Metr. 2010;8(29):1-12.
Reference
Boyle 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.

44. How can we most effectively prevent or delay type 2 diabetes?
Section 8
Section 8, “How Can We Most Effectively Prevent or Delay Type 2 Diabetes?” underscores that most people with diabetes are unaware of their condition
Therefore, people at risk need to be tested—including those who are asymptomatic– their prediabetes managed, and effective tools employed to promote lifestyle modifications
How can we most effectively prevent or delay type 2 diabetes?

45. Most People with Diabetes Are Unaware of Their Condition
Data analyzed from 1,402 adults without diabetes
2005–2006 NHANES participants
Valid fasting plasma glucose, oral glucose tolerance tests
Almost 30% of the US adult population had prediabetes in 2005–2006; only 7.3% were aware they had it
Adoption of risk reduction behaviors suboptimal
To study lifestyle changes consistent with reducing diabetes risk and factors associated with their adoption among adults with prediabetes, data were analyzed from 1,402 adults participating in the National Health and Nutrition Examination Survey (NHANES)
Valid fasting plasma glucose and oral glucose tolerance tests were available
Three risk reduction behaviors were assessed over the previous year: whether participants had tried to control or lose weight, reduce the amount of fat or calories in their diet, or increase physical activity or exercise
Although almost 30% of the US adult population had prediabetes in 2005–2006, only 7.3% were aware they had prediabetes
In the previous year, approximately 50% of adults with prediabetes reported performing diabetes risk reduction behaviors, but only about 33% of those with prediabetes had received healthcare provider advice about these behaviors
Provider advice, female gender, and being overweight or obese were positively associated with all three risk reduction behaviors
The study concluded that adoption of risk reduction behaviors among U.S. adults with prediabetes is suboptimal; to slow the growth in new cases of diabetes, efforts are needed to improve awareness of prediabetes, increase promotion of healthy behaviors, and improve availability of evidence-based lifestyle programs
Geiss LS, et al. Am J Prevent Med. 2010;38:
Reference
Geiss LS, James C, Gregg EW, Albright A, Williamson DF, Cowie CC. Diabetes risk reduction behaviors among U.S. adults with prediabetes. Am J Prevent Med. 2010;38:

46. We Need to Test People at Risk
Categories of increased risk for diabetes (Prediabetes)*
FPG mg/dl ( mmol/l): IFG or
2-h plasma glucose in the 75-g OGTT mg/dl ( mmol/l): IGT
A1C %
In 1997 and 203, The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus1,2 recognized an intermediate group of individuals whose glucose levels, although not meeting criteria for diabetes, are nevertheless too high to be considered normal
This group was defined as having impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
IFG: fasting plasma glucose (FPG) of mg/dL ( mmol/L)
IGT: two-hour plasma glucose (2-h PG) on the 75-g oral glucose tolerance test (OGTT) of mg/dL ( mmol/L)
It should be noted that the World Health Organization (WHO) and a number of other diabetes organizations define the cutoff for IFG at 110 mg/dL (6.1 mmol/L)
Individuals with IFG and/or IGT have been referred to as having prediabetes, indicating a relatively high risk for future development of diabetes
IFG and IGT should not be viewed as clinical entities in their own right but rather risk factors for diabetes as well as cardiovascular disease (CVD)
IFG and IGT are associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension
Individuals with an A1C of % should be informed of their increased risk for diabetes as well as CVD and counseled about effective strategies to lower their risks
*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.
References
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:
Genuth S, Alberti KG, Bennett P, et al., for the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003;26:
American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care 2012;35(suppl 1):S13. Table 3.

47. Recommendations: Testing for Diabetes in Asymptomatic Patients
Consider testing overweight/obese adults with one or more additional risk factors
In those without risk factors, begin testing at age 45 years (B)
If tests are normal
Repeat 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 diabetes
Identify and, if appropriate, treat other CVD risk factors (B)
Recommendations for testing for diabetes in asymptomatic patients are summarized on this slide
For many illnesses, there is major distinction between screening and diagnostic testing; however, for diabetes, the same tests are used for “screening” as for diagnosis
A1C, fasting plasma glucose (FPG), or two-hour oral glucose tolerance test (2-h OGTT) are appropriate to test for diabetes
The 2-h OGTT identifies people with either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT); therefore, more people at increased risk for the development of diabetes and cardiovascular disease (CVD)
Type 2 diabetes has a long asymptomatic phase and significant clinical risk markers
Testing for diabetes will also detect individuals at increased future risk for diabetes; ie, those who may have prediabetes
ADA. II. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S13.
Reference
American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(suppl 1):S13.

48. Criteria for Testing for Diabetes in Asymptomatic Adult Individuals (1)
1. Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2*) and have additional risk factors:
Physical inactivity
First-degree relative with diabetes
High-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 GDM
Hypertension (≥140/90 mmHg or on therapy for hypertension)
HDL cholesterol level <35 mg/dl (0.90 mmol/l) and/or a triglyceride level >250 mg/dl (2.82 mmol/l)
Women with polycystic ovarian syndrome (PCOS)
A1C ≥5.7%, IGT, or IFG on previous testing
Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
History of CVD
The three primary criteria for testing for diabetes in asymptomatic adult individuals (Table 4) are summarized on two slides; this slide (Slide 1 of 2) includes:
Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2) and have additional risk factors
Testing should be considered in adults of any age with BMI ≥25 kg/m2 and one or more of the known risk factors listed on this slide
It is important to know that the at-risk BMI may be lower in some ethnic groups, such as Asians
*At-risk BMI may be lower in some ethnic groups.
ADA. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S14. Table 4.
Reference
American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care 2012;35(suppl 1):S14. Table 4.

49. 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
The three primary criteria for testing for diabetes in asymptomatic adult individuals (Table 4) are summarized on two slides; this slide (Slide 2 of 2) includes:
In the absence of criteria (risk factors on previous slide), testing diabetes should begin at age 45 years
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
Age is a major risk factor for diabetes; therefore, testing of individuals without other risk factors should begin no later than at age 45 years
The rationale for the 3-year interval is that false negatives will be repeated before substantial time elapses, and there is little likelihood that an individual will develop significant complications of diabetes within 3 years of a negative test result
Given the need for follow-up and discussion of abnormal results, testing should be conducted within the health care setting
Community screening outside a health care setting is not recommended because people with positive tests may not seek, or have access to, appropriate follow-up testing and care
Conversely, there may be failure to ensure appropriate repeat testing for individuals who test negative
Community screening may also be poorly targeted; i.e., it may fail to reach the groups most at risk and inappropriately test those at low risk (the worried well) or even those already diagnosed
ADA. Testing in Asymptomatic Patients. Diabetes Care. 2012;35(suppl 1):S14. Table 4.
Reference
American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35(suppl 1):S14. Table 4.

50. DPP: Managing Prediabetes
For those found to have prediabetes, provide support or referral to encourage
Weight loss of at least 7%
Moderate exercise of at least 150 minutes per week
Consider metformin for certain patients
Obese (BMI ≥35 kg/m2)
<60 years (most effective, years)
Lifestyle interventions feasible, more cost-effective than medications
As outlined in slides in Sections 2, 3, and 4, the Diabetes Prevention Program (DPP), lifestyle intervention to lose weight and increase physical activity reduced development of type 2 diabetes by 58% during a 3-year period
This reduction was even greater—71%—among adults ≥60 years of age
Metformin reduced risk of diabetes by 31% overall and was most effective in younger (ages years) and in heavier adults
Prevention or delay of type 2 diabetes with either lifestyle or metformin intervention was effective in all racial and ethnic groups studied and has been shown to persist for at least 10 years
Interventions to prevent or delay type 2 diabetes in individuals with prediabetes can be feasible and cost-effective; lifestyle interventions are more cost-effective than medications
American Diabetes Association, 2012.
Reference
National Diabetes Information Clearinghouse. National Diabetes Statistics, Available at:

51. Clinical Tools Effective in Promoting Lifestyle Modification: AGREE
Steps in the lifestyle change process: AGREE
Assess
Generate goals
Record
Evaluate and Empower
Re-assess
The lifestyle change process typically works best when the patient and the health care provider meet on common ground to assess a problem, set behavioral change goals, monitor progress, and provide follow-up
Generating goals includes steps illustrated in the next slide
American Diabetes Association
Reference
American Diabetes Association. Facilitating behavior change: key strategies for empowering your patients

52. Clinical Tools Effective in Promoting Lifestyle Modification: FIRM
Steps to setting behavioral goals, objectives
1. Focus on developing specific objectives
2. Let the patient take the lead
3. Keep the objectives “FIRM”
Few in number
Individualized
Realistic
Measurable (frequency and duration)
The health care provider can help the patient keep behavioral objectives FIRM: few in number, individualized, realistic, and measurable.
Few in number. Keep the number of changes down to increase likelihood of success
Individualized, tailored to the patient and his/her lifestyle, income, habits, likes/dislikes
Realistic. Help the patient choose practical, attainable goals
Measurable. Set specific metrics for success—walking 3 days/week for 30 minutes, not “exercise more”
Advise patients to choose a few (one to three) behavioral objectives to focus on, rather than several. A good plan is to set one eating goal and one goal aimed at increasing physical activity. Opting for too many changes at once is less realistic and difficult to sustain
The objectives should be individualized, tailored to the specific needs of the patient. For example, patients with physical limitations, who do shift work or who live in dangerous neighborhoods may need to be creative about finding ways to increase activity
The objectives should be realistic. Patients may have high expectations of themselves and want to make major changes they believe may be necessary to achieve better health. However, even small changes can have a significant impact on health: improvements can be achieved with 5% weight loss, but patients may believe they have to achieve a normal body weight. Setting small initial goals, such as walking 20 minutes every other day or switching from regular to diet soda, may result in greater initial success
Objectives should be measurable, such as making lunchtime sandwiches on whole-grain bread 3 days/week or trying a dance class that meets every Tuesday and Thursday for 8 weeks
Saunders JT, Pastors JG. Curr Diabetes Rep. 2008;8;
Reference
Saunders JT, Pastors JG. Practical tips on lifestyle management of type 2 diabetes for the busy clinician. Curr Diabetes Rep. 2008;8:

53. cONCLUSIONS: Call to Action
Section 9
Section 9, Conclusions, provides Action Items to help prevent or delay type 2 diabetes
cONCLUSIONS: Call to Action

54. Conclusions: Call to Action
We must identify patients at highest risk (prediabetes)
Modest lifestyle changes are most effective
Sustain interventions
Increase opportunities for community programs to support prevention
Delaying or preventing type 2 diabetes is cost-effective and will help turn the tide on the diabetes epidemic
This “Call to Action” slide emphasizes the role clinicians need to employ to prevent and reduce the burden of diabetes
We must identify patients at highest risk (prediabetes)
Modest lifestyle changes are most effective
Sustain interventions
Increase opportunities for community programs to support prevention
Delaying or preventing type 2 diabetes is cost-effective and will help turn the tide on the diabetes epidemic