minimally invasive surgery symposium modest weight loss in t2 dm: lessons from the look ahead trial...
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Minimally Invasive Surgery SymposiumModest Weight Loss in T2 DM: Lessons
from the Look AHEAD Trial
Donna H. Ryan, MDPennington Biomedical Research CenterBaton Rouge, LA
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
