minimally invasive surgery symposium modest weight loss in t2 dm: lessons from the look ahead trial...

Minimally Invasive Surgery SymposiumModest Weight Loss in T2 DM: Lessons

from the Look AHEAD Trial

Donna H. Ryan, MDPennington Biomedical Research CenterBaton Rouge, LA

Donna.Ryan@pbrc.edu

OUTLINE

The relationship between weight and diabetes

Look AHEAD – what it means for obesity and for diabetes

Looking ahead – what have we learned to date from the study?

There is a diabetes epidemic.Crude and Age-Adjusted Prevalence of Diagnosed Diabetes per 100 Population, US, 1980-2005

Source: CDC website

There is an obesity epidemic.Prevalence of Overweight and Obesity by Age, 1960-2004

Source CDC/NCHS, Health, US, 2006

0

25

50

75

100

Relationship Between BMI and Risk of Type 2 Diabetes

Chan J et al. Diabetes Care 1994;17:961.Colditz G et al. Ann Intern Med 1995;122:481.

Age

-Adj

uste

d R

elat

ive

Ris

k

Body Mass index (kg/m2)

MenMen

WomenWomen

<22 <23 23-

23.9

24-

24.9

25-

26.9

27-

28.9

29-

30.9

31-

32.9

33-

34.9

35+

1.0

2.91.0

4.31.0

5.01.5

8.12.2

15.8

4.4

27.6

40.3

54.0

93.2

6.711.6

21.3

42.1

0

1

2

3

4

5

6

Relationship Between Weight Gain in Adulthood and Risk of Type 2 Diabetes Mellitus

Re

lativ

e R

isk

Weight Change (kg)Willett et al. N Engl J Med 1999;341:427.

-10 -5 0 5 10 15 20

MenMen

WomenWomen

Weight Loss Benefits For acute weight loss phase:

Strong benefit in glycemic control Reduction in LDL, reduction in HDL, reduction

in BP For reduced stable weight:

Strong benefit in glycemic control Increase in HDL, reduction in BP; ~20% weight

loss is needed to see reduction in LDL

Mechanisms of Glycemia Improvement with Weight Loss Negative energy balance during acute

weight loss improves glycemia After weight loss plateaus, reduced state

with less visceral adiposity improves glycemia

The behaviors that promote weight loss maintenance, low fat diet, energy neutral diet, & physical activity improve glycemia.

0

50

100

150

Insulin Sensitivity Improves with Weight Loss in Patients with Type 2 Diabetes

Insu

lin (

pmol

/L)

Before

Weight Loss at 1 Year (%)

Wing et al. Arch Intern Med 1987;147:1749.*P<0.01 vs before.

* *

*

0-2.4 2.5-6.9 7.0-14.0 >15

0

2

4

6

8

10

12

DPP Results

Diabetes Prevention Program Research Group. N Engl J. Med 2002: 346, 393.

Diet + ExerciseDiet + Exercise

Dia

bete

s In

cide

nce

Dia

bete

s In

cide

nce

per

100

Per

sons

-Yea

rspe

r 10

0 P

erso

ns-Y

ears

Placebo Placebo MetforminMetformin

58% reduction58% reduction58% reduction58% reduction

4.84.8

7.87.8

1111

Redrawn from: Hamman, et al Diabetes Care 29:2102-2107, 2006

Change in weight from baseline (kg)

0-10 -5 +5

Inci

den

ce r

ate

pe

r 1

00 p

ers

on-

year

s

10

20

15

5

0

How much weight loss is needed to prevent type 2 diabetes – the DPP experience

Adding it up Being obese is bad for you. Overweight and

obesity are associated with increased mortality.

Is losing weight good for you? Losing weight is associated with Improvements in risk factors Prevention of diabetes But what about reduction in mortality? The SOS

study showed mortality reduction with intentional, surgical weight loss, but many epi studies show that weight loss is associated with increased mortality.

OUTLINE

The relationship between weight and diabetes

Look AHEAD – what it means for obesity and for diabetes

Looking ahead – what have we learned to date from the study?

Why conduct the Look AHEAD Study? Randomized clinical trial of a lifestyle

intervention designed to produce and maintain weight loss and effects on so-called hard endpoints – cardiovascular events and mortality. Look AHEAD also gathers data on benefits/risks over 14 years in diabetics.

Look AHEAD is important to everyone in the weight loss community.

Look AHEAD is important to everyone in the diabetes community.

OUTLINE

The relationship between weight and diabetes

Look AHEAD – what it means for obesity and for diabetes

Looking ahead – what have we learned to date from the study?

Study Design 5145 overweight subjects with type 2

diabetes 2 arms

Usual care (Diabetes Support and Education) Usual care + Lifestyle Intervention

Study duration: up to 13.5 years (with 4 years of intensive intervention).

Primary outcome: Cardiovascular death (fatal MI and stroke), nonfatal MI, and stroke; hospitalization for angina

Look AHEAD Research Group. Controlled Clin Trials. 2003;24:61-28.

Lifestyle Intervention:Phase I, Weight Loss Induction

Months 1-6 Weekly contact

3 group sessions/month 1 individual session/month

Personal weight loss goal = 10% Study weight loss goal > 7%

Phase II, Weight Loss Maintenance Months 7-12 Reduced contact

2 group sessions/month 1 individual session/month 2 face-to-face contacts/month required;

3 recommended Individual weight loss goal

continue weight loss if < 10% weight maintenance if > 10%

Diabetes Support and Education

3-4 meetings / year to promote retention

health education topicsdietexercisesocial support

Attendance At Year 1 Examination

ILI Cohort: 97%

DSE Cohort: 96%

P=0.004

% Weight Loss at 1-Year

-9

ILI 0

-1

-2

-3

-4

-5

-6

-7

-8

DSE

p < 0.0001

% W

eigh

t Cha

nge

8.6%

0.7%

% Reduction in Initial Weight by Gender

N=872

N=1229N=1197

N=830

-12

-10

-8

-6

-4

-2

0

0 2 4 6 8 10 12

Months

% R

educ

tion

in In

itial

Wei

ght

MenWomen

P<0.001

Weight Loss in Insulin Users vs. Non-Users within ILI Group

0

1

2

3

4

5

6

7

8

9

10

Insulin No Insulin

Mea

n %

Wei

ght L

oss

7.6%8.7%

Medication Use At Baseline

P=0.002

Fitness Change (%) at 1-Year

0

5

10

15

20

25

Mea

n %

Fitn

ess

Cha

nge

UnadjustedP<0.001

Adjusted for 1 Year Weight Change

P<0.001

5.8

20.9

10.8

15.9

DSE ILI ILIDSE

1-Year Changes in Markers of Diabetes Control

Markers of Diabetes Control ILI DSE P-value

Hemoglobin A1c (%), BLHemoglobin A1c (%), Y1Y1 – Baseline

7.256.61-0.64

7.297.15-0.14

0.26<0.001<0.001

Fasting glucose (mg/dl), BLFasting glucose (mg/dl), Y1Y1 – Baseline

151.9130.4-21.5

153.6146.4-7.2

0.21<0.001<0.001

Diabetes medications, BLDiabetes medications, Y1Y1 – Baseline

86.5%78.6%-7.8%

86.5%88.7%2.2%

0.93<0.001<0.001

1-Year Changes in Markers of Blood Pressure Control

Markers of Blood Pressure Control ILI DSE P-value

Systolic BP (mmHg), BLSystolic BP (mmHg), Y1Y1 – Baseline

128.2121.4-6.8

129.4126.6-2.8

0.26<0.001<0.001

Diastolic BP (mmHg), BLDiastolic BP (mmHg), Y1Y1 – Baseline

69.967.0-3.0

70.468.6-1.8

0.11<0.001<0.001

Antihypertensive medications, BLAntihypertensive medications, Y1Y1 – Baseline

75.3%75.2%-0.1%

73.7%75.9%2.2%

0.230.540.02

1-Year Changes in Markers of Lipid Control

Markers of Lipid Control ILI DSE P-value

LDL-cholesterol (mg/dl), BLLDL-cholesterol (mg/dl), Y1Y1 – Baseline

112.2107.0-5.2

112.4106.7-5.7

0.780.740.49

HDL-cholesterol (mg/dl), BLHDL-cholesterol (mg/dl), Y1Y1 – Baseline

43.546.93.4

43.644.91.4

0.80<0.001<0.001

Triglycerides (mg/dl), BLTriglycerides (mg/dl), Y1Y1 – Baseline

182.8152.5-30.3

180.0165.4-14.6

0.38<0.001<0.001

Lipid lowering medications, BLLipid lowering medications, Y1Y1 – Baseline

49.4%53.0%3.7%

48.4%57.8%9.4%

0.52<0.001<0.001

1-Year Changes in Percent of Participants Meeting ADA Goals

ADA Goal ILI DSE P-value

Hemoglobin A1c < 7%, BLHemoglobin A1c < 7%, Y1Y1 – Baseline

46.3%72.7%26.4%

45.4%50.8%5.4%

0.50<0.001<0.001

Blood pressure < 130/80 mmHg, BLBlood pressure < 130/80 mmHg, Y1Y1 – Baseline

53.5%68.6%15.1%

49.9%57.0%7.0%

0.01<0.001<0.001

LDL-cholesterol < 100 mg/dl, BLLDL-cholesterol < 100 mg/dl, Y1Y1 – Baseline

37.1%43.8%6.7%

36.9%44.9%8.0%

0.870.450.34

All three goals, BLAll three goals, Y1Y1 – Baseline

10.8%23.6%12.8%

9.5%16.0%6.5%

0.13<0.001<0.001

Trying Look AHEAD at Home The ILI was a program

Derived from DPP Manuals for interventionists and participants

Dietary Intake 1200-1500 kcal/day < 250 lb 1500-1800 kcal/day > 250 lb < 30% calories from fat Meal replacements Menu plans provided

Physical Activity Gradual increases to 175 min/wk 10,000 steps

Trying Look AHEAD at Home Algorithm for medication management while in

negative energy balance.

Obesity Vol 14 No 5 May, 2006  

Thank you

www.pbrc.edudonna.ryan@pbrc.edu