1. Pre-Diabetes and Type 2 Diabetes Prevention: Is it possible
Pre-Diabetes and Type 2 Diabetes Prevention: Is it possible? What does science tell us, but also a little speculation!?
Dace Trence, MD
March 2016

2. Objectives What is the challenge in prevention
What has research shown us works, what does not
What benefit persists over time
What complications associated with diabetes are changing
What are future questions

3. Disclosures
Stockholder: Sanofi, Medtronic

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. Cardiovascular Disease
Metabolic Pulse Overview Mod 1 ( )
Long-term Complications of Diabetes Consequences of Sustained Hyperglycemia
Leading cause
of blindness
in working age adults
2- to 4-fold
increase in
cardiovascular
events and mortality
Diabetic Retinopathy
Stroke
Diabetic
Nephropathy
Cardiovascular Disease
Diabetes: Magnitude of Complications
Diabetic microvascular complications are most commonly manifested in the eyes, kidneys, and nerves.
Diabetes is the leading cause of new cases of blindness in adults between the ages of 20 and 74 years. Diabetic neuropathy causes 12,000 to 24,000 new cases of blindness each year.
Diabetes is the leading cause of kidney failure and was responsible for 44% of new cases in This represents over 150,000 people with end-stage renal disease due to diabetes.
Diabetes is also the leading cause of nontraumatic lower-extremity amputations, accounting for 60% of amputations in the United States. About 60% to 70% of people with diabetes have some degree of diabetic nerve damage.
There is also a high frequency of atherosclerosis (macrovascular disease) leading to increased risk of stroke and/or heart attack.
People with diabetes are 2 to 4 times more likely to die from heart disease than people without diabetes. Cardiovascular disease is responsible for 65% of diabetes-related deaths.
A person with diabetes is 2 to 4 times more likely to suffer a stroke than a person without diabetes.
Approximately 73% of adults with diabetes have hypertension (blood pressure 130/80 mm Hg or greater) or use medications for hypertension.
Reference
National Diabetes Information Clearinghouse. Diabetes Statistics–Complications of Diabetes. Available at: Accessed August 9, 2006.
Category: Diabetes
Keywords: diabetes, complications
Leading cause of end-stage renal disease
Diabetic Neuropathy
Leading cause of nontraumatic lower extremity amputations
National Diabetes Information Clearinghouse. At:

6. 2014 382 million adults (8·3%) worldwide living with diabetes
Estimated projected rise over 592 million by 2035
$147 billion spent on diabetes in Europe, 2013
$263 billion No America and Caribbean, 2013.
Diabetes has become a major cause of death in younger than 60 yrs.
Effective diabetes prevention and management necessary to battle this global epidemic

7. Glimmer of Hope
After more than doubling from 1990 to 2008, age-adjusted diabetes incidence among adults aged 18 to 79 years dropped between 2008 and 2014, from 8.5 to 6.6 per 1000.
But according to IDF atlas, United States still has highest prevalence of diabetes among developed nations, 11% of population aged 20 to 79 years
IDF Atlas, 7th edition2015

8. Prevention

9. Weight

10. Overweight and Obesity Prevalence Increasing Among U.S. Adults
Overweight is defined as a body mass index (BMI) of kg/m2 and obesity by a BMI > 30 kg/m2.[1] The prevalence of both conditions among U.S. adults remained relatively stable between 1960 and 1980.[2] Over the last two decades, however, the prevalence of obesity has doubled, such that 66% of Americans aged 20 or greater are either overweight or obese.[3,4] Similar increases in excess weight have been observed in children, suggesting that the epidemic of obesity will become even more widespread in the future.[3,4]
National Institutes of Health/National Heart Lung and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Obes Res ;6:51S–210S.
Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, JAMA. 2002;288:
Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, JAMA. 2004;291:
Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, JAMA ;295:
Flegal KM et al. JAMA 2002;288: ; Hedley AA et al. JAMA 2004;291: ; Ogden CL et al. JAMA 2006;295: ; Flegal KM et al. JAMA 2012;307(5):491-7.

11. Obesity Contributes to Diabetes Epidemic

12. Perspectives on Obesity
Moral problem?
NO. As clinicians, we must not blame an individual for issues they cannot have complete control over, such as their genes.
IT’S A DISEASE!
Psychological problem? Aesthetic problem?
Culture based – self-perception/esteem
Medical problem!
Should be recognized as a disease
Public health problem!
Results in increased Societal Cost

13. Health Benefits of Modest Weight Loss
Loss of 5-10% of body weight can result in:
Decreased cardiovascular risk, blood glucose and insulin levels, blood pressure, LDL cholesterol and triglycerides, sleep apnea severity, and degenerative joint disease symptoms
Increased HDL cholesterol
Improvement in multiple cardiovascular risk factors, and other complications, including gynecologic conditions
Source: The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults..

14. Weight Gain
Each unit increase in BMI (about kg) increases Type 2 diabetes risk by 12.1 percent
An estimated % of diabetes risk in the U.S. is attributable to or associated with excess weight
For every kilogram increase in weight over 10 years, Type 2 diabetes risk increases 4.5 %
The risk of diabetes increases with increasing BMI values in men and women [1,2]. Moreover, the age-adjusted relative risk for diabetes begins to increase at BMI values that are considered normal for men (24 kg/m2) and women (22 kg/m2) based on mortality risk. The marked increase in the prevalence of obesity is an important contributor to the 25% increase in the prevalence of diabetes in the United States over the last 20 years [3]. Increases in abdominal fat mass, weight gain since young adulthood, and a sedentary lifestyle are additional obesity-related risk factors for diabetes [1,4,5].
1. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:
2. Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994;17:
3. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, Diabetes Care 1998;21:
4. Ohlson LO, Larsson B, Svardsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes 1985;34:
5. Helmrich SP, Ragland DR, Leung RW, Paffenbarger Jr RS. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991;325:
Ford et al. Amer J Epidemiol 146:214,1997.

15. Relationship Between BMI and Risk of Type 2 Diabetes Mellitus
Age-Adjusted Relative Risk
Body Mass Index (kg/m2)
<23
24–24.9
25–26.9
27–28.9
33–34.9 25 50 75
100
1.0
2.9
4.3
5.0
8.1
15.8
27.6
40.3
54.0
93.2
<22
23–23.9
29–30.9
31–32.9
35+
1.5
2.2
4.4
6.7
11.6
21.3
42.1
Men
Women
The risk of diabetes increases with increasing BMI values in men and women [1,2]. Moreover, the age-adjusted relative risk for diabetes begins to increase at BMI values that are considered normal for men (24 kg/m2) and women (22 kg/m2) based on mortality risk. The marked increase in the prevalence of obesity is an important contributor to the 25% increase in the prevalence of diabetes in the United States over the last 20 years [3]. Increases in abdominal fat mass, weight gain since young adulthood, and a sedentary lifestyle are additional obesity-related risk factors for diabetes [1,4,5].
1. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:
2. Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994;17:
3. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, Diabetes Care 1998;21:
4. Ohlson LO, Larsson B, Svardsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes 1985;34:
5. Helmrich SP, Ragland DR, Leung RW, Paffenbarger Jr RS. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991;325:
Chan J et al. Diabetes Care 1994;17:961.; Colditz G et al. Ann Intern Med 1995;122:481.

16. Identification and Screening: BMI Is the Starting Point
2013 AHA/ACC/TOS Obesity Guidelines— identify patients who need to lose weight
Measure height and weight and calculate BMI at annual visits or more frequently for all patients
Use BMI cut points to classify patients with overweight or obesity
BMI is used as an estimate of increased adverse health consequences
A pt with a BMI of 30 with T2DM, OSA and HTN will require much more intensive mgmt than someone with the same BMI and no comorbidities. Yet both individuals are defined as having class 1 obesity.
ACC = American College of Cardiology; AHA = American Heart Association; TOS = The Obesity Society.
Jensen MD et al. Circulation. 2014;129(25 suppl 2):S102–S138.

17. No surprises
Obesity correlates with higher risk for development of diabetes (DM)
Waist circumference is better correlate with DM risk than BMI
Weight gain since young adulthood independent predictor of DM risk, even after adjustment for current BMI
Ley SH et al Lancet ;383:

18. Obesity Classification: Waist Circumference (WC)
Patients with overweight/obesity = increased body fat (adiposity)
Overweight and obesity classification: Waist Circumference (WC)
BMI advised to avoid wt gain
who have no indicators of increased CV risk should be advised to avoid additional wt gain
For overweight or obese pts, ask, “How prepared are you to make changes in your diet or to be more physically active. Are you willing to record food intake and weight?”
Look at priorities. Stopping drinking and cigs may supercede need for wt loss
If pt not willing to procede, attempts to counsel will be counterproductive
Measure WC at annual visits or more frequently in patients with overweight or obesity.
Men abdominal obesity
≥40 in. (≥102 cm)*
Women abdominal obesity
≥35 in. (≥88 cm)*
*Different WC abdominal obesity cutoff points may be appropriate for different races, such as ≥90 cm for Asian men and ≥80 cm for Asian women.
Seger JC et al. Obesity Algorithm, presented by the American Society of Bariatric Physicians, 2014– (Access = April 6, 2015).

19. Treatment: Modest Weight Loss = Major Health Benefits
T2DM prevention
With T2DM: better glycemic control/ medication reduction
Improvement in urinary stress incontinence, mobility, joint pain, weight-related QOL
Improvements in CVD risk factors (HDL-C, TG, BP)
Previous improvements
Sleep apnea
Diabetes remission?
Previous improvements
CVD mortality
All-cause mortality and reduction in cancer risk (with surgical weight loss)
Agree on wt loss goals. 3-5 % reduction can lead to clinically meaningful reductions in some CV risk factors.
Goal is to reduce 5-10 % from baseline within 6 mos
Create an energy deficit of 500 kcal/day.
As weight loss proceeds, monitor need to reduce meds including DM meds and HTN meds which may lead to hypo
Consider the benefits that a 5% to 10% weight loss will have on your patients with overweight or obesity.
Blackburn G. Obes Res. 1995;3(suppl 2):211s-216s.
Foster GD et al. Arch Intern Med. 2009;169(17):1619–1626.
Gregg EW et al. JAMA. 2012;308(23):2489–2496.
Sjostrom L et al. J Intern Med. 2013;273(3):219–234.
Christou NV et al. Surg Obes Relat Dis. 2008;4(6):691–695.

20. Reduction in Mortality with Modest Weight Loss
Effects of Weight Loss in Type 2 Diabetes
Every kg of weight loss is associated with 3 to 4 months of improved survival
In prospective analysis of 5000 people with type 2 diabetes, 35% reported intentional weight loss; this subgroup experienced a 25% reduction in mortality over 12 years
Alternately, a 5-kg weight gain increases coronary heart disease risk by 30%
Lean ME, et al. Diabet Med. 1990;7: ; Williamson DF, et al. Diabetes Care. 2000;23: Anderson JW et al. J Am Coll Nutr. 2003;22:331-9.

21. Regulation of Body Weight
Genes confer the potential for obesity
Environment determines whether the potential is realized, and to what extent

22. Thrifty Genes Contribute to Obesity
Genetic factors account for 80% of a person’s tendency to develop obesity
“Thrifty genes” are designed to protect us from starvation by allowing us to store large amounts of energy in the form of fat when food is abundant
This is the first time in human history that food has been so abundant
The age-old advantage of thrifty genes has been influenced by our unique environment to cause disease
Kaplan L. Body Weight Regulation and Obesity. J Gastrointestinal Surgery 2003;7(4):
Hales and Barker et al, Diabetologia (4;35: and 3;36:62-67)

26. Chefs’ Estimates of Serving Sizes
Condrasky M, et al Obesity 2007;15: 2086–2094

28. hp2010.nhlbihin.net/portion

29. Sedentary Lifestyles – Examples
Physical activity is…
To be avoided
Nearly unnecessary
Limited by infrastructure

30. Physical Activity
Adults with T2DM should be advised to perform at least 150 min/week of moderate-intense aerobic activity (50%-70% of maximum HR) spread over 3 days with no more than 2 consecutive days without exercising
In the absence of contraindications, resistance training should be performed at least twice weekly
Providers should use “clinical judgment” when deciding whether to screen asymptomatic patients for silent CAD”
High risk patients should be encouraged to start with short periods of low intensity exercise and progress slowly
HR, heart rate
ADA Clinical Practice Recommendations. Diabetes Care. 2013;36 (Suppl 1):S24.

31. AACE Physical Activity Recommendations
Patients
Healthcare Professionals
≥150 minutes per week of moderate-intensity (ie, “conversational”) exercise
Flexibility and strength training
Aerobic exercise (e.g., brisk walking)
Cross-train
Heart rate to 70% maximum (max HR = 220 – age)
Start slowly and build up gradually
Use exercise partners, organized activities, or professional trainer to help with motivation
Exude positive attitude
Evaluate for contraindications and/or limitations to increased physical activity before patient begins or intensifies exercise program
Develop exercise recommendations according to individual goals and limitations
Set realistic goals and schedules
Handelsman Y, et al. Endocr Pract. 2011;17(suppl 2):1-53.

32. Specific Dietary Components

33. Dietary factors for the prevention of diabetes
Ley SH et al Lancet ;383: .

34. Specific Nutrient Associations
Ley SH et al Lancet ;383:

35. Question 1:
A high dietary fat intake is directly associated with increased risk for the development of DM.
True or
False?

36. Dietary Fats Increased risk of DM indirectly by promoting weight gain
BUT studies in humans do not support high-fat diets have a detrimental effect on insulin sensitivity
Women’s Health Initiative, incidence of diabetes not reduced in women following low-fat diet compared to control group
Quality of fat important- diets high in plant-based over animal fats more protective : greater intake of omega-6
polyunsaturated fatty acids (PUFA) associated with lower
DM risk
Nurses’ Health Study: Replacement of saturated fat with PUFA associated with lower risk of developing DM
However, association between omega-3 PUFA and diabetes risk has been inconsistent

37. Question 2:
Higher carbohydrate intake has been associated with decreased risk of development of DM.
True
or False?

38. Dietary Carbohydrate
Prospective observational evidence suggests the relative carbohydrate proportion of diet does not affect DM risk
Diet rich in fiber, especially cereal fiber, might reduce risk of diabetes. Fruit fiber weaker inverse assoc. than cereal fiber
Carbohydrate quality can be measured by evaluation of glycemic response to carbohydrate-rich foods, such as glycemic index (GI) and glycemic load (GL, aproduct of GI and the amount of carbohydrates of a food).
In meta-analyses of prospective studies, low GI and GL diets were associated with lower risk of diabetes than were
diets with a higher GI and GL,
independent of
amount of cereal fiber

39. Question 3: Increased risk of developing diabetes is associated with:
A- Smoking
B- Coffee
C- Mediterranean Diet
D- Alcohol

40. Smoking Personal Hx Smoking Passive smoking
The ex- and heavy current smokers -highest incidence of diabetes of 12·5% and 11·1% respectively, compared with never-smokers (7·9%) during 4 years of follow-up.
Cho NH, et al. Clin Endocrinol (Oxf) 2009;71:679–85
Wei X, et al. Diabetes Res Clin Pract. 2015;107:9-14.

41. Coffee Consumption
Meta-analysis (15 epidemiological studies,9 prospective and 6 case-control, involving 200,000 participants): Compared with no consumption, four or more cups of coffee/day resulted in 35% reduced risk of DM2.
2nd meta-analysis(20 prospective studies total of 500,000 people with follow-up yrs) inverse association between coffee consumption and risk of DM2 and dose dependent.
Risk reduced 7% per cup of coffee/day. Decaffeinated or caffeinated

42. Analysis 6 studies, total of 225,000 individuals showed risk of developing DM2 about one-third lower in people who drink 3-4 cups of decaffeinated coffee per day than in people who do not drink coffee.
Natella F et al.Nutrition Reviews 2014:70;207–217

43. Alcohol

48. Pharmacologic Agents