Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso...

43
Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Transcript of Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso...

Page 2: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Il Prof Giorgio Sesti dichiara di

essere tifoso del PALERMO

Potenziali conflitti di interesse

Page 3: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Agenda

1. Definition of Metabolically Healthy Obese (MHO) and Insulin Resistance

Obese (IRO or Metabolically Abnormal Obese [MAO]);

2. Phenotypic differences between Metabolically Healthy Obese (MHO) and

Insulin Resistance Obese (IRO or Metabolically Abnormal Obese [MAO]);

3. Are MHO protected from the development of T2D, CVD and mortality?

4. Treatment options for MHO and IRO.

Page 4: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Definition of “Metabolically Healthy Obesity”

“Metabolically healthy obese” phenotypes in NHANES III if < 1 metabolic

syndrome components:

1) triglycerides >150 mg/dL or medications;

2) systolic blood pressure >130 mmHg, diastolic blood pressure >85

mmHg, or medications;

3) Glucose >100 mg/dl or medications;

4) HDL cholesterol <40 mg/dL for men and <50 mg/dL for women;

Plus additional criteria

5) HOMA-IR

6) hsCRP level

Iacobellis S et al. Obes Res 13:1116-1122, 2005 Wildman RP et al. Arch Intern Med 168:1617–1624, 2008

Karelis AD et al. Diabetes Metab 34:183-184, 2008 Kuk Jl et al. Diabetes Care 32:2297–2299, 2009

Page 5: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Definition of “Metabolically Healthy Obesity”

In the obese group (BMI ≥ 30 kg/m2), subjects were divided into quartiles

according to their insulin sensitivity estimated from hyperinsulinemic-

euglycemic clamp studies, OGTT-derived index or HOMA-IR.

Subjects with insulin sensitivity values in the upper quartile were classified

as having MHO, while subjects in the lowest quartiles were classified as

Metabolically Abnormal Obese (MAO).

Karelis AD et al. J Clin Endocrinol Metab 90: 4145–4150, 2005 Marini et al. Diabetes Care 30: 2145-2147, 2007

Stephan N et al. Arch Intern Med 168:1609-1616, 2008 Succurro E. et al. Obesity 16: 1881–1886, 2008

Page 6: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Subjects were defined as Metabolically Healthy Obese if their glucose disposal rate was in the upper quartile

Marini et al. Diabetes Care 30: 2145-2147, 2007

6,4

15,1 14,3

0

4

8

12

16

Insu

lin

-sti

mu

late

d g

luco

se

dis

po

sa

l (

mg

/m

in x

Kg

FFM

)

P<0.0001

Metabolically Abnormal Obese (MAO)

Metabolically healthy

obese (MHO)

Nonobese Subjects

(BMI <27 kg/m2)

Page 7: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Agenda

1. Definition of Metabolically Healthy Obese (MHO) and Insulin Resistance

Obese (IRO or Metabolically Abnormal Obese [MAO]);

2. Phenotypic differences between Metabolically Healthy Obese (MHO) and

Insulin Resistance Obese (IRO or Metabolically Abnormal Obese [MAO]):

a) Cardio-metabolic risk factors

b) Organ damage

3. Are MHO protected from the development of T2D, CVD and mortality?

4. Treatment options for MHO and IRO.

Page 8: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

BMI in MHO, insulin resistant obese subjects, and nonobese subiects

23,8

37,7 39

0

5

10

15

20

25

30

35

40

BM

I (K

g/m

2) P<0.0001

Metabolically healthy obese

(MHO)

Nonobese subjects

P=0.56

Marini et al. Diabetes Care 30: 2145-2147, 2007

Insulin resistant obese subjects

(IRO)

Page 9: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Waist circumference is lower in MHO as compared with IRO, but it is higher as compared with nonobese subjects

76

98

106

40

60

80

100

120

Wa

ist

cir

cu

mfe

ren

ce

(c

m)

P<0.0001

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Nonobese subjects

P=0.04

Succurro E. et al. Obesity 16: 1881–1886, 2008

Page 10: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Klöting eN t al. Am J Physiol Endocrinol Metab 299:E506-E515, 2010

Macrophage infiltration was significantly higher in omental fat of IRO subjects

Insulin resistant obese

subjects (IRO)

Metabolically healthy,

but obese (MHO)

Page 11: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Marini et al. Diabetes Care 30: 2145-2147, 2007

113

122

132

70

80

90

100

110

120

130

140

Systo

lic b

loo

d p

ressu

re

(mm

Hg

) P=0.002

Nonobese subjects

P=0.05

Systolic blood pressure is higher in MHO as compared with nonobese subjects, but lower as compared with IRO

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 12: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Marini et al. Diabetes Care 30: 2145-2147, 2007

73

77

84

40

45

50

55

60

65

70

75

80

85

Dia

sto

lic b

loo

d p

ressu

re

(mm

Hg

) P=0.02

Nonobese subjects

P=0.02

Diastolic blood pressure is higher in MHO as compared with nonobese subjects, but lower as compared with IRO

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 13: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Marini et al. Diabetes Care 30: 2145-2147, 2007

77

98

152

0

20

40

60

80

100

120

140

160

Tri

gly

red

ide

s

(mg

/d

l) P=0.06

Nonobese subjects

P=0.008

Triglyceride levels are higher in MHO as compared with nonobese subjects, but lower as compared with IRO

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 14: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

0,51

0,59

0,94

0

0,2

0,4

0,6

0,8

1

FFA

(m

Eq

/l)

Nonobese subjects

Free fatty acid levels are higher in IRO as compared with nonobese subjects, and MHO

P=0.24 P=0.04

P=0.001

Succurro E. et al. Obesity 16: 1881–1886, 2008

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 15: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Marini et al. Diabetes Care 30: 2145-2147, 2007

64

49 52

0

10

20

30

40

50

60

70

HD

L

(mg

/d

l) P<0.0001

Nonobese subjects

P=0.28

HDL levels are lower in MHO as compared with nonobese subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 16: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Marini et al. Acta Diabetol l51:257–261, 2014

87 89 92

0

20

40

60

80

100

Fa

sti

ng

pla

sm

a g

luco

se

(m

g/d

l) P=0.57

Nonobese subjects

P=0.58

Fasting plasma glucose levels do not differ between MHO and IRO subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 17: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

103

114

127

0

20

40

60

80

100

120

140

2-h

glu

co

se

(m

g/d

l) P=0.08

Nonobese subjects

P=0.02

2-h glucose levels are lower in MHO as compared with IRO subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Marini et al. Acta Diabetol l51:257–261, 2014

Page 18: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

597

560

461

0

100

200

300

400

500

600

P=0.39

P=0.04

Nonobese subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Marini et al. Acta Diabetol l51:257–261, 2014

Insulin clearance during euglycemic hyper-insulinemic clamp is lower in IRO as compared with MHO subjects

Insu

lin

cle

rea

nce

(

ml/

min

x m

2)

Page 19: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

7

10

18

0

2

4

6

8

10

12

14

16

18

20

In

su

lin

U/m

l)

Nonobese Subjects

without MetS

Obese with Mets (MAO)

Obese without MetS (MHO)

42

56

120

0

20

40

60

80

100

120

140

Fasting insulin 2-h Insulin

Nonobese subjects

Insulin resistant obese (IRO)

Metabolically healthy obese

(MHO)

Fasting and 2-h insulin levels are lower in MHO as compared with IRO subjects

Marini et al. Acta Diabetol l51:257–261, 2014

P<0.0001 P<0.0001

P<0.0001

P=0.01 P<0.0001

P<0.0001

Page 20: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Agenda

1. Definition of Metabolically Healthy Obese (MHO) and Insulin Resistance

Obese (IRO or Metabolically Abnormal Obese [MAO]);

2. Phenotypic differences between Metabolically Healthy Obese (MHO) and

Insulin Resistance Obese (IRO or Metabolically Abnormal Obese [MAO]):

a) Cardio-metabolic risk factors

b) Organ damage

3. Are MHO protected from the development of T2D, CVD and mortality?

4. Treatment options for MHO and IRO.

Page 21: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Marini et al. Diabetes Care 30: 2145-2147, 2007

0,68

0,79

0,89

0

0,2

0,4

0,6

0,8

1

IMT

(m

m)

P<0.0001

Nonobese subjects

P=0.03

IMT is higher in MHO as compared with nonobese subjects, but lower as compared with IRO

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 22: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Sesti G. et al. Nutr Metab Cardiovasc Dis 21: 933-940, 2011

eGFR is significantly lower in IRO subjects as compared to MHO subjects after adjusting for age, gender, and BMI

102 101

94

50

60

70

80

90

100

110

P=0.18

Nonobese subjects

P<0.0001 e

GFR

(m

l/m

in/1

.73

m2)

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 23: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

19

23

32

0

10

20

30

40

ALT

le

ve

ls

(U/l)

P<0.0001

Nonobese subjects

P=0.007

ALT levels are lower in MHO as compared IRO with subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

P adjusted for age and gender

Marini et al. Acta Diabetol l51:257–261, 2014

Page 24: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

19 20

24

0

10

20

30

AS

T l

eve

ls

(U/l)

P=0.02

Nonobese subjects

P<0.0001

AST levels are lower in MHO as compared IRO with subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

P adjusted for age and gender

Marini et al. Acta Diabetol l51:257–261, 2014

Page 25: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Stephan N et al. Arch Intern Med 168:1609-1616, 2008

Liver fat in MHO is lower as compared with IRO, but higher as compared with nonobese

Insulin-resistant obese subjects

Insulin-sensitive obese subjects

overweight subjects

Normal weight subjects

Page 26: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Agenda

1. Definition of Metabolically Healthy Obese (MHO) and Insulin Resistance

Obese (IRO or Metabolically Abnormal Obese [MAO]);

2. Phenotypic differences between Metabolically Healthy Obese (MHO) and

Insulin Resistance Obese (IRO or Metabolically Abnormal Obese [MAO]):

a) Cardio-metabolic risk factors

b) Organ damage

3. Are MHO protected from the development of T2D, CVD and mortality?

4. Treatment options for MHO and IRO.

Page 27: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

MHO have a lower RR for incident type 2 diabetes as compared with IRO subjects - Framingham Offspring Study 6.8 yr follow-up (IS definition)

Meigs JB et al. J Clin Endocrinol Metab 91: 2906–2912, 2006

1

3,79

15,1

0

4

8

12

16 A

dju

ste

d R

Rs f

or

incid

en

t ty

pe

2 d

iab

ete

s

CI 7.8-29.3

CI 1.6-8.6

Nonobese subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 28: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

MHO have similar OR for incident type 2 diabetes compared with MAO subjects - Uppsala Longitudinal Study 20 yr follow-up (MetS definition)

Arnlov J al. Diabetes Care 34:61–65, 2011

1

12,2

11,0

0

2

4

6

8

10

12

14 A

dju

ste

d R

Rs f

or

incid

en

t ty

pe

2 d

iab

ete

s

CI 5.71-21.18

CI 5.10-28.96)

Nonobese Subjects without

MetS

Obese with Mets (MAO)

Obese without MetS (MHO)

Page 29: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

MHO have a lower RR for incident CVD as compared with IRO subjects - Framingham Offspring Study 11.4 yr follow-up (IS definition)

Meigs JB et al. J Clin Endocrinol Metab 91: 2906–2912, 2006

1

1,49

2,14

0

0,5

1

1,5

2

2,5

Ad

juste

d R

Rs f

or

incid

en

t C

VD

(n

ew

on

se

t a

ng

ina

, fa

tal

an

d n

on

fata

l M

I o

r str

ok

e,

tra

nsie

nt

isch

em

ic a

tta

ck

, h

ea

rt f

ail

ure

, o

r in

term

itte

nt

cla

ud

ica

tio

n)

CI 1.4-3.2

CI 0.9-2.4

Nonobese subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Page 30: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

MHO have similar OR for incident CVD as compared with MAO subjects - San Antonio Heart Study, 7.4 yr follow-up (MetS definition)

Aung K et al. J Clin Endocrinol Metab 98, 2013

1

3,9

5,2

0

1

2

3

4

5

6

OR

fo

r in

cid

en

t C

VD

(m

yo

ca

rdia

l in

farc

tio

n,

str

ok

e,

or

co

ron

ary

re

va

scu

lari

za

tio

n p

roce

du

re

at

foll

ow

-up

or

an

y m

en

tio

n o

f ca

rdio

va

scu

lar

de

ath

on

th

e d

ea

th

ce

rtif

ica

te)

CI 2.8-9.7

CI 2.0-7.7

Nonobese Subjects without

MetS

Obese with Mets (MAO)

Obese without MetS (MHO)

Page 31: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Metabolically Healthy Obesity and Risk of Mortality Does the definition of metabolic health matter? Whitehall II study, 17.7 yr follow-up

Hinnouho G-M et al. Diabetes Care 36:2294–2300, 2013

1

2,49

2,94

0

1

2

3

HR

fo

r C

V m

ort

ali

ty

CI 1.56-5.56

CI 1.05-5.91

Nonobese Subjects

without MetS

Obese with Mets (MAO)

Obese without MetS (MHO)

1 1,04

2,63

0

1

2

3

ATP-III HOMA

CI 1.51-4.60

CI 0.41-2.66

Nonobese subjects

Insulin resistant obese (IRO)

Metabolically healthy obese

(MHO)

Page 32: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Agenda

1. Definition of Metabolically Healthy Obese (MHO) and Insulin Resistance

Obese (IRO or Metabolically Abnormal Obese [MAO]);

2. Phenotypic differences between Metabolically Healthy Obese (MHO) and

Insulin Resistance Obese (IRO or Metabolically Abnormal Obese [MAO]):

a) Cardio-metabolic risk factors

b) Organ damage

3. Are MHO protected from the development of T2D, CVD and mortality?

4. Treatment options for MHO and IRO.

Page 33: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Incidence of the metabolic syndrome among IGT participants without the syndrome at baseline in the Diabetes Prevention Program

(MHO equivalent?)

Orchard TJ et al. Ann Intern Med 142:611-61, 2005

53

47

38

0

10

20

30

40

50

60

Incid

en

ce

of

me

tab

oli

c s

yn

dro

me

(P <0.001)

Placebo group (n=490)

Metformin group (n=503)

Lifestyle group (n=530)

3 years follow-up

Page 34: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Effect of lifestyle-induced weight loss on insulin sensitivity in Metabolically Healthy Obese subjects

Follow-up (months)

MHO % change in

weight

MAO % change in

weight

MHO % change in

insulin sensitivity

MAO % change in

insulin sensitivity

Shin M-J et al. (2006) 3 3% 3% +7% (HOMA)

+8% (HOMA)

Karelis AD et al. (2008) 6 -6% -7% -13% (Clamp)

+26% (Clamp)

Janiszewski PM et al. (2010) Men Women

3-6 -4%

-3.5%

-6% -5%

+22% +19% (Clamp)

+52% +31% (Clamp)

Kantartzis K et al. (2011) 9 -2.4% -3% -6% (OGTT)

+30% (OGTT)

Shin MJ et al. Int J Obes (Lond) 30: 1529–1534, 2006 Karelis AD et al. Diabetologia 51:1752–1754, 2008

Janiszewski PM et al. Diab Care 33, 1957–1959, 2010 Kantartzis K et al. Diabetologia 54, 864–868, 2011

Page 35: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Effects of weight loss on body weight in MHO and MAO subjects after laparoscopic adjustable gastric banding and hypocaloric diet

Sesti G et al PLoS ONE 6(3): e17737, 2011

108

118

92

102

0

20

40

60

80

100

120

MHO (n=48)

Bo

dy w

eig

ht

(K

g)

Baseline 6-months follow-up

Baseline 6-months follow-up

P<0.0001

14% change

13% change

MAO (n=142)

P<0.0001

Page 36: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Effects of weight loss on insulin sensitivity in Metabolically Healthy Obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet

108

47

141

84

0

20

40

60

80

100

120

140

160

MHO (n=48)

P=0.02

Ma

tsu

da

in

de

x

Sesti G et al PLoS ONE 6(3): e17737, 2011

Baseline 6-months follow-up

Baseline 6-months follow-up

P<0.0001

31% change

96% change

MAO (n=142)

Page 37: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Conclusions

1. Metabolically Healthy Obese (MHO) subjects have an intermediate cardiovascular

risk profile between healthy nonobese subjects and Obese Insulin-Resistant (IRO)

subjects

2. Obese Insulin-Resistant (IRO) subjects exhibit defects in compensatory β-cell

function as compared with Metabolically Healthy Obese (MHO) subjects;

3. Lifestyle intervention is the more appropriate treatment for MHO;

4. If diet and exercise do not work, pharmacological treatment (metformin) or

bariatric surgery may be considered.

Page 38: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

THANK YOU !

Sesti lecture

Page 39: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Metabolically healthy, but obese

(MHO)

Insulin resistant obese subjects

(IRO)

Visceral fat

Fat liver =

Fasting glucose =

2-h Post-load glucose =

Blood pressure

Triglycerides

HDL

IGF-1 =

IMT

eGFR =

1st Phase insulin secretion

Disposition index

Risk of development of DM2

Risk for CVD =/

Page 40: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Phenotypic differences between Metabolically Healthy Obese

(MHO) and Metabolically Abnormal Obese (MAO or Insulin

Resistance Obese [IRO]) in insulin secretion.

Page 41: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

1st phase insulin secretion during OGTT is lower in Metabolically Healthy Obese (MHO) as compared with IRO subjects

Sesti G ADA 2013

1179

1597

0

400

800

1200

1600 S

tum

vo

ll 1

st

ph

ase

in

de

x P=0.001

Metabolically healthy

obese (MHO)

Insulin resistant obese subjects

(IRO)

Page 42: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

Disposition index is higher in Metabolically Healthy Obese (MHO) as compared with IRO subjects

55

Dis

po

sit

ion

in

de

x

(Stu

mvo

ll 1

st p

ha

se

in

de

x x

MFFM

)

55

18046

11159

0

5000

10000

15000

20000

P<0.0001

Metabolically healthy

obese (MHO)

Sesti G ADA 2013

Insulin resistant obese subjects

(IRO)

Page 43: Il paradosso dell’obesità metabolicamente sana - Aristea · Giorgio Sesti Il paradosso dell’obesità metabolicamente sana Università “Magna Graecia” di Catanzaro ITALY

13,8

13,0

7,9

0

2

4

6

8

10

12

14

16

P=0.50

P<0.0001

Nonobese subjects

Insulin resistant obese subjects

(IRO)

Metabolically healthy obese

(MHO)

Marini et al. Acta Diabetol 2013

Insulin hepatic extraction is lower in IRO as compared with MHO subjects

Pla

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a C

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Pla

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