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Transcript of OBESITY: EPIDEMIOLOGY, PATHOPHISIOLOGY AND CLINICAL PICTURE Carruba.pdf · OBESITY: EPIDEMIOLOGY,...
Department of Biotechnology and Traslational
Medicine
CENTER FOR STUDY AND RESEARCH ON OBESITY
University of Milan, Italy
OBESITY:
EPIDEMIOLOGY,
PATHOPHISIOLOGY
AND CLINICAL PICTURE Michele O. Carruba
Department of Medical
Biotechnology and Traslational
Medicine
University of Milan
Via Vanvitelli, 32
20129 – Milan (Italy)
L’evoluzione della specie
IL BILANCIO ENERGETICO
Centro Studio e Ricerca sull’Obesità (C.S.R.O.)
Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,
Università degli Studi di Milano, Via Vanvitelli 32, Milano
Prof. Michele Carruba
Prevalence of Obesity and Diagnosed
Diabetes Among US Adults, 1991 and 2001
Distribuzione della popolazione italiana nelle varie
condizioni di peso
Sottopeso
Normopeso
Sovrappeso
Obeso
4.000.000
16.000.000
1.500.000
Fonte: ISTAT, 4° Rapporto sull’Obesità in Italia. Istituto Auxologico Italiano, 2002
Prevalenza dell’obesità (IMC>30) in funzione dell’età negli
UOMINI
0
2
4
6
8
10
12
14
16
18-24 25-34 35-44 45-54 55-64 65-74 >74
%
Fonte: ISTAT, 4° Rapporto sull’Obesità in Italia. Istituto Auxologico Italiano, 2002
Prevalenza dell’obesità (IMC>30) in funzione dell’età nelle
DONNE
0
2
4
6
8
10
12
14
16
18-24 25-34 35-44 45-54 55-64 65-74 >74
%
Fonte: ISTAT, 4° Rapporto sull’Obesità in Italia. Istituto Auxologico Italiano, 2002
Sovrappeso e obesità aumentano il rischio
di MCV e di mortalità per tutte le cause
Dati relativi a 1 milione di uomini e donne seguiti per 16 anni con età media di 57 anni che non hanno mai fumato e non avevano una storia di malattia all’arruolamento.
Calle et al. N Engl J Med. 1999;341:1097-1105
Ris
ch
io r
ela
tivo
di
mo
rta
lità
pe
r tu
tte
le
ca
use
Mortalità per tutte le cause
Ris
ch
io r
ela
tivo
di
mo
rta
lità
pe
r m
ala
ttia
ca
rdio
va
sco
lare
Mortalità per MCV
0.6
3.0
2.6
2.2
1.8
1.4
1.0
>18 25 30 >40 BMI (kg/m2)
Donne Uomini
Normopeso Obesi Sovrappeso
BMI (kg/m2) 0.6
3.0
2.6
2.2
1.8
1.4
1.0 Normopeso Obesi
Donne Uomini
sovrappeso
>18 25 30 >40
Peeters et al. Ann Intern Med 2003; 138: 24-32
35
40
45
50
Donne Non-fumatrici Uomini Non-fumatori
Aspettativa di vita a 40 anni di età Normali (18,5-24,9 kg/m2)
Sovrappeso (25-29,9 kg/m2)
Obesi (30 kg/m2)
46.3
43.0
39.2
43.4
40.3
37.5
7,1 anni
5,8 anni
3,1 anni
3,3 anni
Aspettativa di vita a 40 anni: impatto
dell’eccesso di peso corporeo
Years of life lost and healthy life-years lost from
diabetes and
cardiovascular disease in overweight and obese
people:
a modelling study SA Grover et al. Lancet Diabetes Endocrinol. Published online December 5, 2014
Un parametro fondamentale: la
circonferenza addominale
Unmet clinical need associated with
abdominal obesity
Patients with
abdominal obesity
(high waist
circumference) often
present with one or
more additional
CV risk factors
NHANES 1999–2000 cohort (data on file)
CV risk factors in a typical patient with abdominal obesity
Adverse cardiometabolic effects of
products of adipocytes
Adipose
tissue
↑ IL-6
↓ Adiponectin
↑ Leptin
↑ TNFα
↑ Adipsin
(Complement D)
↑ Plasminogen
activator inhibitor-1
(PAI-1)
↑ Resistin
↑ FFA
↑ Insulin
↑ Angiotensinogen
↑ Lipoprotein lipase
↑ Lactate
Inflammation
Type
2 diabetes
Hypertension
Atherogenic
dyslipidaemia
Thrombosis Atherosclerosis
Lyon 2003; Trayhurn et al 2004; Eckel et al 2005
Overweight, Obesity, and Mortality from Cancer in a
Prospectively Studied Cohort of U.S. Adults
Eugenia E. Calle, Ph.D., Carmen Rodriguez, M.D., M.P.H.,
Kimberly Walker-Thurmond, B.A., and Michael J. Thun, M.D.
The New England Journal of Medicine, 348: 1625-1638, 2003
The heaviest members of this cohort (body-mass index of at least 40) had death rates
from all cancers combined that were 52 percent higher (for men) and 62 percent
higher (for women) than the rates in men and women of normal weight.
In both men and women, body-mass index was also significantly associated with
higher rates of death due to cancer of the esophagus, colon and rectum, liver,
gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's
lymphoma and multiple myeloma. Significant trends of increasing risk with higher
body-mass-index values were observed for death from cancers of the stomach and
prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in
women.
Conclusions. Increased body weight was associated with increased death rates for all
cancers combined and for cancers at multiple specific sites.
Abdominal obesity increases the
risk of developing type 2 diabetes
<71 71–75.9 76–81 81.1–86 86.1–91 91.1–96.3 >96.3
24
20
16
12
8
4
0
Rela
tive r
isk
Waist circumference (cm)
Carey et al 1997
Intra-abdominal adiposity and
dyslipidaemia
Pouliot et al 1992
310
248
186
124
62
0
60
45
30 m
g/d
L
mg
/dL
Triglycerides
Lean
HDL-cholesterol
Visceral fat
(obese subjects)
Low High Lean
Visceral fat
(obese subjects)
Low High
Abdominal obesity and
increased risk of CHD Waist circumference was independently associated with
increased age-adjusted risk of CHD, even after adjusting for
BMI and other CV risk factors
0.0
0.5
1.0
1.5
2.0
2.5
3.0
<69.8 69.8-<74.2 74.2-<79.2 79.2-<86.3 86.3-<139.7
1.27
2.06 2.31
2.44 p for trend = 0.007
Rela
tive r
isk
Rexrode et al 1998
Quintiles of waist circumference (cm)
Abdominal obesity and increased
risk of cardiovascular events
Dagenais et al 2005
Ad
juste
d r
ela
tive r
isk
1 1 1
1.17 1.16 1.14
1.29 1.27
1.35
0.8
1
1.2
1.4
CVD death MI All-cause deaths
Tertile 1
Tertile 2 Tertile 3
Men Women <95
95–103 >103
<87
87–98 >98
Waist
circ. (cm):
Adjusted for BMI, age, smoking, sex, CVD, disease, DM, HDL-C, total-C
The HOPE Study
Elaborazione Centro Studi Ricerca Obesità (CSRO) e
Farmacoeconomia UniMI
“STUDIO SPESA” : COSTI DIRETTI
ANNUI DELL’OBESITÀ IN ITALIA
Nel 2025 costo Tot (mld) da 11 a 15,7 (+43%) con obesità infantile + 205%
Studio SPESA: composizione dei costi
dell’Obesità Tot 28,2 mld Euro/anno
Voce di costo Percentuale
Ospedalizzazioni 64%
Diagnostica 12%
Farmaci 7%
Visite 6%
Altro 11%
Centro Studio e Ricerca sull’Obesità (C.S.R.O.)
Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,
Università degli Studi di Milano, Via Vanvitelli 32, Milano
Prof. Michele Carruba
Science 299: 896-899, 2003
NA
eNOS
Other
signals
cAMP
Proteins for mitochondrial
biogenesis and function
UCP1
UCP1
UCP1
b3AR
Brown adipocyte
Heat
Cold is sensed
by the brain
Sympathetic nerves are activated
NO cGMP
PGC-1
cGMP NO
eNOS
? ?
? Nucleus
Mitochondrion
Lipid droplets
Electron microscopy analysis of WAT, BAT and muscle in
ob/ob mice
WAT
Valerio et al., J. Clin. Invest., Oct. 2006
45
5
40
35
30
25
20
15
10
0
45
5
40
35
30
25
20
15
10
0 4 8 12 16 20 24 28 32 36 40 44 48 52 4 8 12 16 20 24 28 32 36 40 44 48 52
Body w
eig
ht
(g)
Bod
y w
eig
ht
(g)
Males Females
Time (weeks) Time (weeks)
a b
Growth curves of wild-type and eNOS-/- mice
wt
eNOS -/- wt
eNOS -/-
Nisoli et al., Science 299, 896–899, 2003
Visceral fat depot in eNOS-/- vs. wild-
type mice
wt eNOS-/-
Decreased energy levels can
cause and sustain obesity
Food
Fuel
ATP = Energy
Fat
Food
Fuel
ATP = Energy
Fat
Healthy subject Obese subject
Food
Fuel
ATP = Energy
Fat
Low ATP
in cells
Brain
Leptin
Sience October 14, 2005
Centro Studio e Ricerca sull’Obesità (C.S.R.O.)
Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,
Università degli Studi di Milano, Via Vanvitelli 32, Milano
Prof. Michele Carruba
Several weeks of intense endurance
training enhances mitochondrial
biogenesis in humans.
J Appl Physiol 99: 1372–1377, 2005
Centro Studio e Ricerca sull’Obesità (C.S.R.O.)
Dipartimento di Farmacologia, Chemioterapia e Tossicologia Medica,
Università degli Studi di Milano, Via Vanvitelli 32, Milano
Prof. Michele Carruba
Integrated Laboratories Network (InLaNe)
Center for Study and Research on
Obesity, University of Milan (Italy)
Enzo Nisoli, M.D. Ph.D.
Laura Tedesco, Ph.D.
Maurizio Ragni, Ph.D.
Renata Bracale, Ph.D.
Andrea Fossati, Ph.D.
Annalisa Cardile, Ph.D.
Chiara Ruocco, Ph.D.
Michele O. Carruba, M.D. Ph.D.
Department of Medicine,
University of Padua,
Padua
(Italy) Roberto Vettor, M.D.
Elisabetta Trevellin, Ph.D.
Marnie Granzotto, Ph.D.
Massimiliano Olivieri, Ph.D.
Roberto Fabris, M.D.
Roberto Serra, M.D.
Department of Biomedical
Sciences and Biotechnology,
University of Brescia,
Brescia
(Italy)
Alessandra Valerio, M.D. Ph.D.
Fracesca Fenaroli, Ph.D.
Mattia Bicelli, Ph.D.