The document discusses evidence from studies on the effect of lifestyle modifications such as caloric restriction, physical activity, and weight loss on health outcomes. It summarizes key findings from several studies: 1) The Diabetes Prevention Program clinical trial found that intensive lifestyle intervention reduced the risk of developing type 2 diabetes by 58% compared to 31% for treatment with metformin. 2) Studies on caloric restriction in primates showed decreased fasting glucose and insulin levels as well as reduced risk of age-related diseases like diabetes and cardiovascular disease. 3) Physical activity has been shown to increase lifespan in animal models, and a study of over 1300 male rats found a 10% reduction in body weight led to a 13.5

1. Effect of lifestyle modification
: search for evidence
Nayanjeet Chaudhury, MD,MPH
Director M&E and Health Services Delivery
Population Services International, India
Certified Personal Trainer (ACSM)
Certified Aerobics Trainer (Reebok)

2. Aging, Disease & Free Radicals,
• Aging is the accumulation of diverse deleterious
changes in the cells and tissues with advancing
age that increase the risk of disease and death.
(Harman, D. (2001) Aging: Overview. Annals of New York Academy of Sciences , 928, 1-21. )
• Our expected lifespan at birth and/or the rate of
aging are influenced by
– Individual genetic backgrounds and/or
– environmental factors influence.
(Gerstenblith G. Cardiovascular Aging: What We Can Learn From Caloric Restriction⁎. J Am Coll
Cardiol. 2006;47(2):403-404)

3. Ageing and lifespan
The inherent aging process limits
• Average life expectancy at birth to about 85 years
• and the Maximum life span to around 122 years.
Harman 2001
Improved nutrition
Economic and social uplift
Better living conditions
Improved sanitation
Housing
Environmental protection
Conventional methods of increasing life span
Although in developing countries, these are primary concerns, they
are progressively unsuccessful in prolonging life in developed countries
beyond a certain age limit.

4. Who’s the culprit?
• A possible determinant
– Overproducation of the Free Oxygen Radicals
or Reactive Oxygen Species)
• An important mediator of cell damage and
consequently many disease states :
– Cancer & Diabetes (mitochondrial Oxidative stress)
– Atherosclerosis and chronic inflammation
(inflammatory oxidative conditions )
– Ischemia (xanthine oxidase-induced damage)
Valko et al. Free radicals and antioxidants in normal physiological functions and human
disease. Int J Biochem Cell Biol. 2007;39(1):44-84. Epub 2006 Aug 4.

5. Caloric Restriction
• CR can greatly increase the longevity of
rodents and invertebrate model systems
(Frankel S and Rogina B (2006) Sir2, caloric restriction and aging.Pathol Biol (Paris) 54(2):55-7)
• precise biological mechanisms and
applicability to humans remain unknown.
[Roth, G. S., Ingram, D. K. and Lane, M. A.(2001) Caloric Restriction in Primates and Relevance
to Humans.Annals of the New York Academy of Sciences 928:305-315 (2001).]

6. Rodent studies
• Purified diet with 22% casein
was offered to rats from the
21st day of life in ad libitum or
in restricted amounts.
• These regimens were either
maintained throughout life or
changed at 70, 300, or 365
days of age.
21 days old rats
Restricted diet
from 21 to 70 days
Followed by
Ad libitum feed
Ad libitum
feed
Normal lifespan
Increased lifespan
400 + days
•Dietary experiences early in life influence Length of life in rats
Ross, M. H.( August, 1972).Length of life and caloric intake. The American Journal of Clinical Nutrition 25, 834-838

7. Primate studies on caloric
restriction and aging
• Conclusive evidence yet to come
• Results similar to rodent studies
• Promising outcomes shown in age related
diseases e.g.Diabetes, CVD, osteoporosis
• Monkeys on CR show
– Decreased Fasting glucose and insulin
– Increased insulin sensitivity
– Change in body fat to favor less risk for CVD
Lane, M.A., Black, A., Handy, A., Tilmont, E. M., Ingram, D.K., Roth, G.S.( 2001, April). Caloric
Restriction in Primates. Annals of the New York Academy of Sciences 928(1), 287-295.

8. Early life, CR and diseases
• Diseases that have origins in events of early life:
– Atherosclerosis, coronary heart disease, hypertension,
breast and prostate cancer, Alzheimer disease, Parkinson
disease, essential hypertension, cataracts, amyloidosis,
diabetes mellitus, and amyotrophic lateral sclerosis
(Many of these are diseases of adulthood that shorten life).
(Harman, D. (2001) Aging: Overview. Annals of New York Academy of Sciences , 928, 1-21. )
• CR primates will be less likely to incur these age-
related diseases and may in fact be aging more
slowly than fully fed counterparts.
[Roth, G. S., Ingram, D. K. and Lane, M. A.(2001) Caloric Restriction in Primates and Relevance to
Humans.Annals of the New York Academy of Sciences 928:305-315 (2001).]

9. • Caloric Restriction(CR) and CR-like effects can
significantly reduce mortality in primates by
inducing a physiological state that protects
against age-related disease in various tissues,
including the liver, heart, and the brain.
Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, et al. (2012) Impact of caloric restriction on
health and survival in rhesus monkeys from the NIA study. Nature 489: 318–321

10. Fructose controversy
Multivariate relative risk of incident gout in 46393 men from
health professionals follow-up study, according to fifths of free
fructose intake in subgroups. Reference group for comparisons
was men in lowest fifth of fructose intake and (top) with body
mass index <25 kg/m2, (middle) no alcohol use, and (bottom)
total daily dairy intake ≤1.6 servings. Relative risks were
adjusted for age, total energy intake, bodymass index, diuretic
use, history of hypertension, history of renal failure, intake of
alcohol, intake of total vitamin C,and percentage of energy from
total carbohydrate and protein
Choi and Curhan. Soft drinks, fructose
consumption, and the risk of gout in men:
prospective cohort study. BMJ. 2008; 336
Nayanjeet/Surat/16Dec2012

11. Intake of added sugars correlates closely with the
rise in obesity, metabolic syndrome, and diabetes
Johnson et al. ,Sugar, Uric Acid, and the Etiology of Diabetes and Obesity. Diabetes 62:3307–3315, 2013

12. Concept of Energy Balance

13. Physical Activity and Health
• Like Caloric Restriction, regular physical
activity has been shown to increase
lifespan in animal models
J Gerontol (1983) 38 (1): 36-45. doi: 10.1093/geronj/38.1.36
Philadelphia interdisciplinary longevity study of more than
1300 male rats showed:
• For every 10% reduction of Body weight there was a
13.5% gain in life expectancy
• For every 10% gain in body weight there was a 13.5%
reduction in life expectancy
Ross, M. H.( August, 1972).Length of life and caloric intake. The American Journal of Clinical Nutrition 25, 834-838

14. Lifestyle modification – evidence for prevention
Variable Evidence for
Inverse
Dose-Response
Relationship
Category of
Evidence
All-cause mortality Yes C
Cardiovascular and coronary heart disease Yes C
Blood pressure and hypertension Noa B
Blood lipids and lipoproteins Insufficient
data
Coagulation and hemostatic factors Insufficient
data
Overweight, obesity, and fat
distribution
Yes C
Type 2 diabetes mellitus Yesb C
Colon cancer Yes C
Low back pain, osteoarthritis, and
osteoporosis
Insufficient data
Quality of life and independent living
in older persons
Yes C
Depression and anxiety Noa B

15. Lifestyle modification – evidence for prevention
Variable Evidence for
Inverse
Dose-Response
Relationship
Category of
Evidence
All-cause mortality Yes C
Cardiovascular and coronary heart disease Yes C
Blood pressure and hypertension Noa B
Blood lipids and lipoproteins Insufficient
data
Coagulation and hemostatic factors Insufficient
data
Overweight, obesity, and fat
distribution
Yes C
Type 2 diabetes mellitus Yesb C
Colon cancer Yes C
Low back pain, osteoarthritis, and
osteoporosis
Insufficient data
Quality of life and independent living
in older persons
Yes C
Depression and anxiety Noa B
Category A: Evidence is from endpoints of well-designed randomized clinical trials (RCTs)
Category B: Evidence is from endpoints of intervention studies that include only a limited number of RCTs,
post hoc or subgroup analysis of RCT, or meta-analysis of RCTs.
Category C: Evidence is from outcomes of uncontrolled or nonrandomized trials or observational studies.
Category D: Expert judgment is based on the panel's synthesis of evidence from experimental research
described in the literature and/or derived from the consensus of panel members based on clinical
experience or knowledge that does not meet the listed criteria.
a No indicates a lack of evidence for a “dose response” for the relationship between the health outcome
and physical activity; it does not indicate the absence of a favourable relationship.
b Inverse dose response for primary prevention, but not for improvement in blood glucose control among
diabetics
AmericanCollegeofSportsMedicine;

16. Fatty Acid
Complement
administered in the
body
Diacyl Glycerol and
Ceramide
Highly Bioactive and
Activates pro
inflammatory
pathway
Inhibits Insulin
signaling and
promotes fatty acid
mediated Insulin
Resistance
Intra Muscular
Tri Glyceride
(IMTG)
Innocuous Fatty
acid metabolite
Increases
Insulin
sensitivity
Recent Studies in Immunology and Bio-signaling
(Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid–induced insulin resistance S. Schenk and
J.F. Horowitz; Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid–induced insulin resistance;
The Journal of Clinical Investigation, Volume 117 Number 6 June 2007)
Sedentary group Exercise group

17. Fatty Acid
Complement
administered in the
body
Diacyl Glycerol and
Ceramide
Highly Bioactive and
Activates pro
inflammatory
pathway
Inhibits Insulin
signaling and
promotes fatty acid
mediated Insulin
Resistance
Intra Muscular
Tri Glyceride
(IMTG)
Innocuous Fatty
acid metabolite
Increases
Insulin
sensitivity
Recent Studies in Immunology and Bio-signaling
Acute exercise increases triglyceride synthesis in skeletal
muscle and prevents fatty acid–induced insulin resistance
(S. Schenk and J.F. Horowitz; 2007)
Sedentary
group
Exercise group

18. REDUCTION IN THE INCIDENCE
OF TYPE 2 DIABETES WITH
LIFESTYLE INTERVENTION OR
METFORMIN
The New England Journal of Medicine.
Volume 346, Number 6, 2002
pp 393-403
Evidence of lifestyle modification

19. Objectives
 Does a lifestyle intervention or treatment
with Metformin, prevent or delay the onset
of Diabetes?
 Do these two interventions differ in
effectiveness ?
 Does their effectiveness differ according
to age, sex, race or ethnic group?

20. Inclusion Criteria
 Age : ≥ 25 years
 BMI : ≥ 24 kg/m2
 BMI : ≥ 22 kg/m2 for Asians
 FBS : 95-125 mg%
 PPBS : 140-199 mg%

21. Exclusion Criteria
 Taking medicines known to alter glucose
tolerance.
 Had illness which could seriously reduce
life expectancy or their ability to
participate in the trial.

22. The Four Step Screening and
Recruitment Process ( Ref. 6)

23. Interventions
 Random allocation of participants in three
groups :
 SLR plus Metformin
 SLR plus placebo
 Intensive lifestyle modification program

24. Randomized Clinical Trial: 27 centers
Four Step Screening & Recruitment
Process
Eligible Participants
Random Allocation in three groups
Standard lifestyle
& Metformin
N=1073
Standard lifestyle
& Placebo
N=1082
Intensive
Program of
lifestyle modifin
N=1079
Diabetes Prevention Programme Study

25. Goals for the Intensive lifestyle
intervention
 A weight reduction of 7 % of the initial
body weight.
 To engage in physical activity of moderate
intensity for at least 150 mins. per week.

26. Session No. Activity
1 Getting started being active
2 Move your muscles
3 Being active – a way of life
4 Be a fat detective
5 Three ways to eat less fat
6 Healthy eating
7 Take charge of what’s around you
8 Tip the calorie balance
9 Problem solving
10 Four keys to healthy eating out
11 Talk back to negative thoughts
12 The slippery slop of lifestyle change
13 Jump start your activity plan
14 Make social cues work for you
15 You can manage stress
16 Ways to stay motivated

27. Outcome Measures
 Diagnosis of Diabetes : FBS ≥ 126 mg%
or Post load test value of ≥ 200 mg%
 The values were also confirmed within six
weeks by same tests, done second time.
 The diagnosed participants would be
monitored with FBS.

28. Outcome Measures.. (contd.)
 Levels of leisure physical activity were assessed
with Modifiable Activity Questionnaire.
 The calculations were done by multiplying
duration with frequency as well as MET.
 Daily calorie intakes from various sources were
also assessed.

29. MET
Physical Activity MET
Light Intensity Activities < 3
sleeping 0.9
watching television 1.0
sexual activity 1.3
writing, desk work, typing 1.8
walking, less than 2.0 mph (3.2 km/h), level ground, strolling, very slow 2.0
Moderate Intensity Activities 3 to 6
bicycling, stationary, 50 watts, very light effort 3.0
calisthenics, home exercise, light or moderate effort, general 3.5
bicycling, <10 mph (16 km/h), leisure, to work or for pleasure 4.0
bicycling, stationary, 100 watts, light effort 5.5
Vigorous Intensity Activities > 6
jogging 7.0
General calisthenics (e.g. pushups, situps, pullups,jumping jacks), heavy,
vigorous effort
8.0
Running, jogging in place 8.0

30. Measuring Leisure Physical Activity

37. Discussion
 The incidence of Diabetes was reduced by 58% and
31% in lifestyle intervention group & metformin
group, respectively.
 The results were similar for all age, sex, race &
ethnic groups.
 The incidence of DM was higher in placebo groups,
than anticipated.
 Role of metformin as well as lifestyle intervention, in
prevention of T2DM was established.

38. DPP as the forerunner for the Look AHEAD trial
aDPPDiabetes Prevention Program.
bAHEADAction for Health in Diabetes.
cMean follow-up of 3.0 years (3,17).
dMean follow-up 1 year (4,7).
eHbA1chemoglobin A1c.
fNAspecific results not available;
g0.001 compared with control group.
hTo convert mg/dL glucose to mmol/L,
multiply mg/dL by 0.0555. To convert
mmol/L
glucose to mg/dL, multiply mmol/L by 18.
Glucose of 108 mg/dL6.00 mmol/L.
iLDLlow-density lipoprotein.
jTo convert mg/dL cholesterol to mmol/L,
multiply mg/dL by 0.0259. To convert
mmol/L
cholesterol to mg/dL, multiply mmol/L by
38.7. Cholesterol of 193 mg/dL5.00
mmol/L.
kNSnot significant.
lHDLhigh-density lipoprotein.
mTo convert mg/dL triglycerides to
mmol/L, multiply mg/dL by 0.0113. To
convert
mmol/L triglycerides to mg/dL, multiply
mmol/L by 88.6.
(Linda M., et al, Implications of the Diabetes Prevention Program and Look AHEAD Clinical Trials
for Lifestyle InterventionsJ. A. D. A, 2008, pp 66,72)

39. .
Mean percentage
reduction in initial
weight over 1 year
for participants
assigned to
sibutramine alone,
lifestyle modification
alone, combined
therapy, or
sibutramine plus
brief therapy.
Wadden et al 2005. Randomized Trial of Lifestyle Modification and Pharmacotherapy
for Obesity. N Engl J Med 2005; 353:2111-2120
Lifestyle modification vs pharmacotherapy

40. CHALLENGES WITH LIFESTYLE
MODIFICATION
• Lack of trained manpower
– Principally in research and hospital settings
• Needs multidisciplinary approach.
• Translating findings from clinical trials
into primary care and community
practice – greater challenge.