the obesity/diabetes epidemic: perspectives, consequences, prevention, treatment stan schwartz md,...
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The Obesity/Diabetes Epidemic:Perspectives, Consequences,
Prevention, Treatment
Stan Schwartz MD, FACP, FACE
Private Practice, Ardmore
Obesity Program
Cardiometabolic Diabetes Center and Affiliate,
Main Line Health System
Emeritus, Clinical Associate Professor
University of Pennsylvania
Part 6
Cost of PreventionTotal cost $174.3 million Diet and exercise prevented diabetes in 162
peopleMetformin prevented diabetes in 77 people
(237 people did not develop diabetes over 3 yrs)
NNT = 7 for life style intervention
NNT= 14 for MetforminCosts per person over 3 yr excluding research cost
Metformin $2542
Life style intervention $2780
ACT NOWStudy Results: Time to Occurrence of Diabetes (Kaplan-Meier analysis)
0
0.05
0.15
0.20
0.30
Cu
mu
lati
ve H
azar
d
10 20 400 30
Months
50
0.10
0.25
Placebo
Pioglitazone 1.5%per year
6.8%per year
HR = 0.19(95%, CI) = 0.09, 0.39P<0.00001
DeFronzo RA. ADA Scientific Sessions, Late-Breaking Clinical Studies, June 9, 2008.
NNT = 3.5 patients with IGT for 1 year to prevent the development of 1 case of T2DM
80% reduction in progression to DM
Prevention Increased with Use of Incretin
9 m, 105 pts
Outline• Epidemiology and Economics of obesity/diabetes
• Perspectives on Obesity
• Consequences of Obesity, Prediabetes, Obesity
• Obesity/ Diabetes Risk Factors,
• Obesity/ Diabetes Onset can be Prevented or Delayed – Early Risk Identification and Intervention.
• Medical Benefits to Weight Loss
• Treatment-CDC’s diabetes prevention program and other Evidence-Based Interventions- – Basics, – Next Lecture in Series
Insulin Sensitivity Improves With Weight Loss in Patients With Type 2 Diabetes
*P<0.01 vs before.Wing et al. Arch Intern Med 1987;147:1749.
Insu
lin
(pm
ol/L
)
Weight Loss at 1 Year (%)
0
50
100
150
*
**
Before 0–2.4 2.5–6.9 157.0–14.0
Relationship Between Weight Change and CHD Risk Factor Sum: Framingham Offspring Study
*P<0.002 vs baseline.Wilson et al. Arch Intern Med 1999;159:1104.
Weight Change During 16-y Follow-up
Men Women
0
20
40
60
-20
-40
-60Cha
nge
in R
isk
Fac
tor
Sum
(%
)
**
**
Loss 2.25 kg
Gain 2.25 kg
+37%
–40%–48%
+20%
Plasma Lipids Improve With Weight Loss Meta-analysis of 70 Clinical Trials
Dattilo et al. Am J Clin Nutr 1992;56:320.
-0.06
-0.04
-0.02
0.00
0.02
TotalCholesterol LDL-C TG
HDL-C(weight stable)
HDL-C (actively losing)
m
mol
/L p
er k
g of
Wei
ght L
oss
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
0.5
m
g/dL per kg of W
eight Loss
*
**
*
*
*P0.05.LDL-C=low density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; TG=triglycerides.
Relationship Between Change in Weight and Blood Pressure: Trials of Hypertension Prevention II
Stevens et al. Ann Intern Med 2001;134:1.Cha
nge
in W
eigh
t (kg
)C
hang
e in
Blo
od P
ress
ure
(mm
Hg)
1 2 3 4 5
-10
-5
0
5
10
6
4
2
0
-2
-4
-6
-8
Quintile of Weight Change
DiastolicSystolic
Effect of Weight Change on Apnea-Hypopnea Index (AHI)
Peppard et al. JAMA 2000;284:3015.
Change in Body Weight (%)
-20 to <-10(n=22)
-10 to <-5(n=39)
-5 to <+5(n=371)
+5 to <+10(n=179)
+10 to +20(n=79)
6
4
2
0
-2
-4
Mea
n C
hang
e in
AH
I (E
vent
s/h)
20-2-4-6-8-10-12-14
20
10
0
-10
Reduction in Body Weight (%)Reduction in Body Weight (%)
Ch
ange
in F
MD
of
Bra
chia
l Art
ery
(%)
Ch
ange
in F
MD
of
Bra
chia
l Art
ery
(%)
R2 = 0.468p = 0.001
7%
Relation Between %Weight Loss and Endothelial Function
Hamdy et al Diabetes Care 2003;26:2119-25Hamdy et al Diabetes Care 2003;26:2119-25
p<0.05 NS NS p<0.001 p<0.01 NS
IL-6 TNF- hCRP PAI-1 Leptin
% C
han
ge F
rom
Bas
elin
e
Monzillo LU Obes Res. 2003;11(9):1048-54 Hamdy O et al. Diabetes Care. 2003;26:2119-2125
Adiponectin
Benefits of weight reduction on Benefits of weight reduction on cytokines in type 2 DM and in pre-cytokines in type 2 DM and in pre-diabetesdiabetes
Weight Loss Can Increase Life Expectancy in Obese Patients With Type 2 Diabetes
Weight Loss in First 12 Months (kg)
Lif
e E
xpec
tanc
y (y
)
18
16
14
12
10
8
00 2 4 6 8 10 12 14 16
Lean et al. Diabet Med 1990;7:228.
Impact of Intensive Therapy in Type 2 Diabetes Summary of Major Clinical Trials:
BUT Subset Evaluations Show Reduced CV Outcomes if shorter duration of DM, without significant pre-existing
complications
Study Microvascular Macrovascular Mortality
UGDP ↔ ↔ ↔UKPDS ↓ ↓ ↔ ↓ ↔ ↓
DCCT/EDIC* ↓ ↓ ↔ ↓ ↔ ↔ACCORD ↓ ↔ ↑(unadj.), ↔ (adj.)
ADVANCE ↓ ↔ ↔VADT ↔ ↔ ↔
Initial Trial Long Term Follow-up
Meinert CL. Diabetes. 1970;19(suppl):789-830.
Goldner MG. JAMA. 1971;218(9):1400-1410.UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865. Holman RR. N Engl J Med. 2008;359(15):1577-1589.DCCT Research Group. N Engl J Med. 1993;329;977-986.Nathan DM, et al. N Engl J Med. 2005;353:2643-2653.
Gerstein HC, et al. N Engl J Med. 2008;358:2545-2559.Patel A, et al. N Engl J Med. 2008;358:2560-2572.Duckworth W, et al. N Engl J Med. 2009;360.
*T1DM study.
↑↑- - likely due to likely due to hypoglycemia hypoglycemia and weight gainand weight gain