Targeting Abdominal Obesity in Diabetology What can we do about it?

Source: www.myhealthywaist.org

TARGETING ABDOMINAL OBESITY IN DIABETOLOGY

WHAT CAN WE DO ABOUT IT?

Luc Van Gaal, MD, PhD

Department of Endocrinology, Diabetology & Metabolism Antwerp University Hospital

Antwerp, Belgium

Source: www.myhealthywaist.orgSource: www.myhealthywaist.org

Key Challenges of Type 2 Diabetes

Diabetes is a progressive disease characterized by:

Declining β-cell function

Insulin resistance

Deterioration of glycemic control

Obesity, mainly abdominal fat accumulation

Increased prevalence of cardiovascular disease

Hypoglycemia risk

Complex treatment regimens


Weight Increase With Conventional Approach

Adapted from Lancet 1998;352:854-65 and Kahn SE et al. N Engl J Med 2006;355:2427-43

Glibenclamide (n=277)

Years from randomization

Insulin (n=409)

Metformin (n=342)

Conventional treatment (n=411); diet initially then sulphonylureas, insulin and/or metformin if fasting plasma glucose >15 mmol/l.

Wei

gh

t (k

g)

Ch

ang

e in

wei

gh

t (k

g)

0

1

5

0 3 6 9 12

8

7

6

4

3

2

Years0 1 2 3 4 5

96

92

88

0

100

Rosiglitazone

Metformin

Glibenclamide

UKPDS: up to 8 kg in 12 years ADOPT: up to 4.8 kg in 5 years

UKPDS: United Kingdom Prospective Diabetes Study ADOPT: A Diabetes Outcome Progression Trial


Nurses’ Health Study: Risk for Type 2 Diabetes

Adapted from Carey VJ et al. Am J Epidemiol 1997;145:614-9

* Controlled for age, family history of diabetes, exercise, smoking, saturated fat intake, calcium, potassium, magnesium and glycemic index.

Re

lati

ve

ris

k*

of

typ

e 2

dia

be

tes

Waist circumference (inches)Waist circumference (inches)


Not all Fat Is the Same…

Adapted from Van Gaal LF Eur Neuropsychopharmacol 2006;16:S142-8

Intra-abdominal(visceral) adiposity

Subcutaneousfat Maria's metabolic cardiovascular profile:

Cholesterol 188 mg/dl (4.87 mmol/l) LDL cholesterol 106 mg/dl (2.75 mmol/l) HDL cholesterol 56 mg/dl (1.45 mmol/l) Glucose 84 mg/dl (4.7 mmol/l) Blood pressure 125/78 mm Hg

Maria Age: 58 yearsWeight: 92 kg BMI: 35.4 kg/m2


Not all Fat Is the Same…

Adapted from Van Gaal LF Eur Neuropsychopharmacol 2006;16:S142-8

Intra-abdominal (visceral) adiposity

Subcutaneousfat Claudine's metabolic cardiovascular profile:

Cholesterol 241 mg/dl (6.24 mmol/l) LDL cholesterol 185 mg/dl (4.79 mmol/l) HDL cholesterol 38 mg/dl (0.98 mmol/l) Glucose 132 mg/dl (7.3 mmol/l) Blood pressure 140/85 mm Hg

Claudine Age: 58 yearsWeight: 92 kg BMI: 35.4 kg/m2


Intra-Abdominal (Visceral) Adiposity Promotes Insulin Resistance and β-Cell Dysfunction

Adapted from Lam TK et al. Am J Physiol Endocrinol Metab 2003;284:E281-90: Carr MC et al. J Clin Endocrinol Metab 2004;89:2601-7:

Eckel RH et al. Lancet 2005;365:1415-28.

CETP: cholesteryl ester transfer protein

FFA: free fatty acids

TG: triglycerides

Intra-abdominaladiposity

Portal circulation

Hepatic glucose output

Hepatic insulin resistance Hepatic insulin resistance

Systemic circulation

TG-rich VLDL cholesterol

Small, dense LDL

Lipolysis

Low HDL cholesterol

CETP,Lipolysis

Glucose utilization Insulin resistance Insulin resistance

Long-term damageto -cells by FFA Insulin secretion Insulin secretionSplanchnic

& systemic circulation

FFA


Intra-Abdominal (Visceral) Fat or Just Ectopic Tissue Fat?

Reproduced with permission from Van Gaal LF et al. Nature 2006;444:875-80


Intra-Abdominal (Visceral) Fat Excess – What Can We Do?

Assessment of problem and risk

Reduction of total and visceral fat by:

Lifestyle intervention

Pharmacotherapy

Bariatric surgery

Prevention

Other approaches


Vascular Disease and Hypertension According to Fat Distribution in Type 2 Diabetes

Adapted from Van Gaal LF et al. Diabetes Care 1988;11:103-6.

Su

bje

cts

wit

h d

ise

ase

(%

)

NonobeseWHR<1

NonobeseWHR>1

ObeseWHR>1

CHID: coronary heart ischemic disease

WHR: waist-to-hip ratio

Vascular disease

CIHD

Hypertension


Intra-Abdominal (Visceral) Fat in Obese Diabetic Patients

From Van Gaal LF et al. unpublished data

WomenWomen

*p≤0.01


Abdominal Obesity – What to do About it?

Adapted from Van Gaal LF et al. Nature 2006;444:875-80

Visceral obesity

Insulin resistance

Glucose intolerance Dyslipidemia Hypertension Microalbuminuria

Low-grade inflammation Disturbed adipokine secretion Disturbances in hemostasis

and fibrinolysis (PAI-1)

Cardiovascular diseaseType 2 diabetes

Cardiovascular diseaseType 2 diabetes

Additional risk factors

Metabolic syndromeMetabolic syndrome


Intra-Abdominal (Visceral) Fat and the Risk of Mortality

Reproduced with permission from Kuk JL et al. Obesity (Silver Spring) 2006;14:336-41






Pharmacotherapy

Bariatric surgery

Prevention

Other approaches


Effect of Aerobic Exercise on Total and Intra-Abdominal (Visceral) Fat

Adapted from Després JP et al. Am J Physiol 1991;261:E159-67

Ch

ang

es i

n v

isce

ral

fat

area

(cm

2 ) 60

40

20

0

-40

-20

-15 -10 -5 0 5 10

Changes in fat mass (kg)

r=0.70p<0.01


Health Effects: Reduction in Subcutaneous and Intra-Abdominal (Visceral) Fat During a 3-Month Treatment Period

Adapted from Ross R et al. Ann Intern Med 2000;133:92-103

Adipose tissue (kg)

Exercise without weight loss

Exercise-induced weight loss

Diet-induced weight loss

Control

Subcutaneous adipose tissue

Visceral adipose tissue


Adapted from Christiansen T et al. Eur J Endocrinol 2009;160:759-67

EXO DIO DEX

Changes in Intra-Abdominal (Visceral) Fat and Fat Mass After a Diet-Induced Weight Loss With or Without Aerobic Exercise in Obese Subjects: a 12-Week Randomized Intervention Study

DIO: VLED-hypocaloric diet

DEX: VLED-hypocaloric diet and exercise

EXO: exercise only

VLED: very low energy diet

*

*

*

* p<0.01 – the relative reduction in visceral adipose tissue as compared with the relative reduction in fat mass.

Δ v

isce

ral

adip

ose

tis

sue/

Δ f

at m

ass


Predictors of Intra-Abdominal (Visceral) Fat Loss With Lifestyle

Adapted from Christiansen T et al. Eur J Endocrinol 2009;160:759-67

Δvi

scer

al a

dip

ose

tis

sue/

Δ f

at m

ass

0.7

0.2

0.3

0.0

Baseline visceral adipose tissue/fat mass

0.0

0.1

0.1 0.2 0.3 0.4 0.5

DIO: VLED-hypocaloric diet

DEX: VLED-hypocaloric diet and exercise

EXO: exercise only

VLED: very low energy diet

0.6

0.5

0.4

R2=0.72p<0.01

EXODIODEX


Correlations Between Changes in Anthropometric Measurements and Changes in Metabolic Variables Related to the Metabolic Syndrome

Adapted from Park HS and Lee K Diabet Med 2005;22:266-72

HOMA: homeostasis model of assessmentDBP: diastolic blood pressureFPG: fasting plasma glucoseSAT: subcutaneous adipose tissueSBP: systolic blood pressureTG: triglyceridesVAT: visceral adipose tissue

* p<0.05 by Pearson’s correlation coefficient


Twice-Weekly Progressive Resistance Training Decreases Abdominal Fat and Improves Insulin Sensitivity in Older Men With Type 2 Diabetes

Adapted from Ibañez J et al. Diabetes Care 2005;28:662-7

To

tal

abo

min

al f

at (

cm3 )

400

600

0300

Pretraining

1200

1000

800

1100

900

700

500

16-week Pretraining 16-week

1.5

2.5

0.0

1.0

5.5

4.5

3.5

5.0

4.0

3.0

2.0

0.5

*

** Insu

lin sen

sitivity ind

ex (10

-4xmin

-1xμU

xml -1)

* p<0.001vs. the pretraining value

** p<0.01 vs. the pretraining value


Ectopic Fat Change vs. Metabolic Indices

Adapted from Durheim MT et al. Am J Physiol Endocrinol Metab;295:E407-12

HD

L p

arti

cle

size

ch

ang

e (n

m)

0.6

0.4

0.2

0.0

-5 -4 -3 -2 -1 0

Intermuscular adipose tissue changes (cm2)

-6

-0.2

-0.4

r=-0.423p=0.0065

1 2 LD

L p

arti

cle

size

ch

ang

e (n

m)

1.25

0.75

0.25

-0.25

Intermuscular adipose tissue changes (cm2)

-0.75

-1.25-6

r=-0.521p=0.0006

-5 -4 -3 -2 -1 0 1 2






Pharmacotherapy

Bariatric surgery

Prevention

Other approaches


Recent Experience on Weight and Abdominal Fat With Anti-Obesity Drugs

Central active drugs Sibutramine

Topiramate/phentermin combo

Pre-absorptive nutrient partitioning Orlistat

Blockade of endocannabinoid system Rimonabant


SCOUT: Trial Population

Adapted from James WPT Eur Heart J; 2005;7:L44-8

Type 2 diabetes with cardiovascular risk:

Controlled hypertension (≤160/≤90 mmHg) Dyslipidemia Current smoker Diabetic nephropathy

Previous cardiovascular event:

Myocardial infarction Coronary artery bypass graft Percutaneous transluminal coronary angioplasty Coronary artery disease


GI lipase + Xenical

GI lipase + Xenical

TG

Intestinal lumen Mucosal cell Lymphatics

MicelleBile acidsMG

FA

MG

30%30%

Lipase Inhibition: Mechanism of Action

FFA

GI: gastrointestinal

FA: fatty acids

FFA: free fatty acids

MG: monoglyceride

TG: triglycerides


8

7

6

5

4

3

2

1

0

Time (minutes)

-60 -30 0 30 60 90 120 150 180 210 240

Intervention + placebo baseline

Δ1.20

Improvement in Glucose Utilization With Orlistat Compared With Placebo at 6 Months

Adapted from Kelley DE et al. Diabetes Care 2004;27:33-40

Δ 2.15*

Glu

cose

uti

lizat

ion

(m

g·m

in-1·k

g-1 f

at f

ree

mas

s) Intervention + placebo 6 months

Intervention + orlistat baseline

Intervention + orlistat 6 months

* p<0.05 vs. intervention + placebo


Effect of Lipase Inhibition on Fat Distribution

Adapted from Tiikkainen et al. Am J Clin Nutr 2004;79:22-30

Intr

a-a

bd

om

inal

(v

isce

ral)

fat

(cm

3)

Orlistat Placebo

Su

bc

uta

neo

us

fat

(cm

3)

Orlistat Placebo

Intr

a-a

bd

om

inal

(v

isce

ral)

fat

/to

tal

fat

(%)

Orlistat Placebo

**

†

* p<0.0001

** p<0.001† p<0.01‡ p<0.05

‡

** **

Before After Before After Before After Before After

Before After Before After


Recent Experience on Weight and Abdominal Fat With Anti-Obesity Drugs

Central active drugs Sibutramine

Pre-absorptive nutrient partitioning Orlistat

Blockade of endocannabinoid system Rimonabant


Changes in Intra-Abdominal (Visceral) and Ectopic Fat in ADAGIO-Lipids

Adapted from Després JP et al. Arterioscler Thromb Vasc Biol 2009;29:416-23

Ch

an

ge

fro

m b

as

eli

ne

in

v

isc

era

l a

dip

os

e t

iss

ue

(%

) Placebo

n=87Rimonabant 20 mg

n=92

p=0.0003 Ch

ha

ng

e f

rom

ba

se

lin

e i

n

su

bc

uta

ne

ou

s a

dip

os

e t

iss

ue

(%

) Placebon=72

Rimonabant 20 mgn=68

p=0.0043

Ch

an

ge

fro

m b

as

eli

ne

in

fa

tty

liv

er

ind

ex

*

Placebon=59

Rimonabant 20 mgn=51

p=0.0017* Fatty liver index: liver/spleen attenuation ratio


Endocannabinoids vs. Changes in Intra-Abdominal (Visceral) Adipose Tissue

Adapted from Di Marzo V. et al. Diabetologia 2009;51:1356-67

Baseline After 1 year intervention

An

and

am

ide

con

cen

trat

ion

s (p

mo

l/m

l)

Baseline After 1 year intervention

2-A

G c

on

cen

trat

ion

s (p

mo

l/m

l)

**

(1) (2) (3)

Tertiles of changes in visceral adipose tissue

Tertiles of changes in 2-AG

Vis

cera

l ad

ipo

se

tiss

ue

vari

ati

on

(cm

2)

Tri

gly

cer

ide

vari

ati

on

(m

mo

l/l)

†

*Different from tertile 1, p<0.05†Different from tertile 1 and 2, p<0.05

(1) (2) (3)

AG: arachidonoylglycerol


Future – What Is Lacking?

Long-term trial with anti-obesity drugs in patients with early onset diabetes.

Maintenance studies in patients with metabolic syndrome and type 2 diabetes.

Safe combination studies.

Outcome trials with hard cardiovascular endpoints.


Future Drug Options: A Search to Break the 10% Weight Loss Target

Second generation peripheral CB1 antagonists

11 β-hydroxysteroid dehydrogenase inhibitor

Growth hormone in lipodystrophy?

GLP-1 analogues/mimetics

Leptin – Pramlintide combination


Effect of Inhibition of 11 -Hydroxysteroid Dehydrogenase Type 1

Adapted from Berthiaume M et al. Endocrinology 2007;148:2391-7

mR

NA

(c

prx

10

-3)

SCD1

*m

RN

A (

cp

rx1

0-3)

FAS

* mR

NA

(c

prx

10

-3)

DGAT1

*

mR

NA

(c

prx

10

-3)

ATGL

*

mR

NA

(c

prx

10-3

)

PEPCK

*

Ac

tiv

ity

(n

ka

t/g

)

CPT1

*

Control

Compound A

* p<0.05 vs. control

ATGL: adipose triglyceride lipase CPT1: carnitine palmitoyltransferase 1DGAT1: diacylglycerol acyltransferase 1FAS: fatty acid synthasemRNA: messenger of ribonucleic acid PEPCK: phosphoenolpyruvate carboxykinaseSCD1: stearoyl-CoA desaturase

Mesenteric adipose depot


Effect of Growth Hormone on Intra-Abdominal (Visceral) Fat

Adapted from Beauregard C et al. J Clin Endocrinol Metab 2008;93:2063-71

Ch

ang

e i

n b

od

y fa

t (%

)

PlaceboGrowth hormone

* Ch

ang

e i

n v

isc

era

l ad

ipo

se t

issu

e (%

)


*

Ch

ang

e i

n w

ais

t-to

-hip

rat

io

(%)


*

Ch

ang

e i

n r

esti

ng

en

erg

y ex

pen

dit

ure

(%

)


*

* p<0.05


Human Glucagon-Like Peptide-1 (GLP-1) Effects: the Glucoregulatory Role of Incretins

Adapted from Nauck MA et al. Diabetologia 1996;39:1546-53 and Drucker DJ Diabetes1998;47:159-69

Promotes satiety and reduces appetite

-cells:Enhances glucose-dependent insulin

secretion

Liver: ↓ Glucagon reduces

hepatic glucose output

ɑ-cells:↓ Postprandial

glucagon secretion

Stomach: Helps regulate

gastric emptying

GLP-1 secreted upon the ingestion of food

↑ -cell response

↓ -cell workload


Liraglutide Lowers Weight in Subjects With Type 2 Diabetes

Adapted from Vilsbøll et al. Diabet Med 2008;25:152-6

Wei

gh

t ch

ang

e fr

om

bas

elin

e (k

g)

PlaceboLiraglutide

0.65 mg/dayLiraglutide

1.25 mg/dayLiraglutide1.9 mg/day

Data are mean ±SEM


Liraglutide Reduces Intra-Abdominal (Visceral) Body Fat: Results From the LEAD-2 Substudy

Adapted from Jendle J et al. Diabetes Obes Metab 2009;11:1163-72

Change in body fat DEXA scan

Ch

ang

e in

bo

dy

fat

(kg

, (%

))

Glimepiride + metformin

Liraglutide 1.2 mg + metformin

Liraglutide 1.8 mg + metformin

Visceral vs. subcutaneous fat CT scan

Visceral Subcutaneous

Ch

ang

e in

per

cen

tag

e fa

t (%

)-4

-3

-2

-1

0

1

2

3

-1.6*(-1.1%*) -2.4*

(-1.2%*)

+1.1 kg(+0.4%)

-25

-20

-15

5

0

5

10

-10

-17.1 -16.4

-4.8 -7.8* -8.5*

+3.4

Two thirds of weight lost was fat tissue (liraglutide 1.8 mg).* p<0.05 vs. glimepiride + metformin.






Pharmacotherapy

Bariatric surgery

Prevention

Other approaches


Diabetes 2006;55:2025-31

Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery.

Guidone C, Manco M, Valera-Mora E, laconelli, A Gniuli D, Mari A, Nanni G, Castagneto M, Calvani M, Mingrone G

Reproduced with permission from DeMaria EJ N Engl J Med 2007;356:2176-83


Reproduced with permission from Klein S et al. N Engl J Med 2004;350:2549-57

Intra-Abdominal Obesity or Fat Mass?

Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease

Photographs and abdominal magnetic resonance images obtained before and after liposuction.

The photographs of one study subject and images of another show the large amount of subcutaneous abdominal fat removed by liposuction.

Before liposuction

After liposuction


Reduction of Subcutaneous Fat Mass Does not Improve Inflammatory Status

Adapted from Klein S et al. N Engl J Med 2004;350:2549-57

* Plus–minus values are means ±SD. The measurements were made within 9 days before liposuction and again 10 to 12 weeks

after liposuction.

† Values were obtained from six subjects in each group.

Effects of liposuction on mediators of inflammation in obese women with normal glucose tolerance or type 2 diabetes*


Effect of Additional Omentectomy on Metabolic Features

Adapted from Thörne A et al. Int J Obes Relat Metab Disord 2002;26:193-9

Bo

dy

mas

s in

dex

(kg

/m2)

5

0

-5

-10

5 10 15 20 25Time (months)

0-15

Control

p=0.18

Glu

cose

(m

mo

l/l) 0.5

-0.5

-1.5

5 10 15 20 25Time (months)

0-2.5

0.0

-1.0

-2.0 p=0.03In

suli

n (

mU

/l)

5

-5

5 10 15 20 25Time (months)

0-20

0

-10

-15p=0.04

Omentectomy


Surgical Removal of Omental Fat Does Not Improve Insulin Sensitivityand Cardiovascular Risk Factors in Obese Adults

Fabbrini E, Tamboli RA, Magkos F, Marks-Shulman PA,Eckhauser AW, Richards WO, Klein S, Abumrad NN

Potential Additional Effect of Omentectomy on Metabolic Syndrome, Acute-Phase Reactants, and Inflammatory Mediators in Grade III Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass: A Randomized Trial

Herrera MF, Pantoja JP, Velázquez-Fernández D, Cabiedes J, Aguilar-Salinas C, García-García E, Rivas A, Villeda C, Hernández-Ramírez DF, Dávila A, Zaraín A

Adapted from Fabbrini E et al. Gastroenterology 2010;139:448-55 and Herrera MF et al. Diabetes Care 2010;33:1413-8


Effect of Additional Omentectomy on Metabolic Features(1 of 2)

Adapted from Herrera MF et al. Diabetes Care 2010;33:1413-8

Data after surgery are means ± SD or percent of change from basal (95% CI). Minus signs denote decreases and plus signs increases. All comparisons p=ns.

LRYGB: laparoscopic Roux-en-Y gastric bypass


Effect of Additional Omentectomy on Metabolic Features(2 of 2)

Adapted from Herrera MF et al. Diabetes Care 2010;33:1413-8


Data after surgery are means ± SD or percent of change from basal (95% CI). Minus signs denote decreases and plus signs increases. All comparisons p=ns.


Effect of Additional Omentectomy on Metabolic Features

Adapted from Fabbrini E et al. Gastroenterology 2010;139:448-55

Insu

lin

-me

dia

ted

in

crea

se

in g

luco

se d

isp

osa

l (%

ab

ov

e b

asal

)

0

300

900

600

LRYGB alone

LRYGB + omentectomy

1200

* * **

Hep

ati

c in

su

lin

se

nsi

tivi

ty i

nd

ex

(103

·min

·l/m

g·m

U)

0

1

3

2 **

**

Before surgery

6 months after surgery



Before surgery



* p<0.00002 vs. value before surgery


Type of Surgery vs. Effect on Intra-Abdominal (Visceral) Adipose Tissue

Adapted from Korner J et al. Int J Body Compos Res 2008;6:93-9

Vis

cera

l ad

ipo

se

tiss

ue

(kg

)

3

2

25 30 35 40 45Total adipose tissue (kg)

20

1

0

r=0.36p=0.43

Band Bypass

Vis

cera

l ad

ipo

se

tiss

ue

(kg

)

3

2

Total adipose tissue (kg)

1

0

Vis

cera

l ad

ipo

se

tiss

ue

(kg

)

3

2

20 30 40 50Weight loss (%)

10

1

0

r=-0.28p=0.53

30 40 50 6020

r=0.81p=0.005

Vis

cera

l ad

ipo

se

tiss

ue

(kg

)

3

2

20 30 40 50

Weight loss (%)

1

-1

0

r=-0.73p=0.016


Percentage of Patients With Resolution or Improvement of Major Comorbidities*

Adapted from Kral JG and Näslund E Nat Clin Pract Endocrinol Metab 2007;3:574-83

* The table shows the mean percentage of patients (with number of studies; and 95% CI). Data were compiled by Buchwald et al. JAMA 2004;292:1724-37 from separate studies.






Pharmacotherapy

Bariatric surgery

Prevention

Other approaches


Intra-Abdominal (Visceral) Fat Excess – Preventive Measures

Special lifestyle approaches (smoking).

Avoidance trans fats & fructose beverages.

Avoidance selective, atypical neuroleptics.

Selection safe medication.


Body Fat Responses to Consumption of Glucose- and Fructose-Sweetened Beverages

Adapted from Stanhope KL et al. J Clin Invest 2009;119:1322-34

(A) Changes of body weight during the 2-week inpatient baseline, 8-week outpatient intervention, and 2-week inpatient intervention periods. **p<0.01; ****p<0.0001, day 56 outpatient:intervention vs. day 1 outpatient:intervention; paired Student’s t test. Glucose, n=15;

fructose, n=17.

(B) Changes of total abdominal adipose tissue, SAT, and VAT volume in subjects after consuming glucose- or fructose-sweetened beverages for 10 weeks. *p<0.05; **p<0.01, 10 weeks vs. 0 weeks; paired Student’s t test. Glucose, n=14; fructose, n=17. Data represent mean ±

SEM.

Δ i

n b

od

y w

eig

ht

(kg

)

0.81.2

2.01.6

2.4

-0.40.00.4

Inpat

ient:

basel

ine

Outpat

ient:

inte

rven

tion

Inpat

ient:

inte

rven

tion

Inpat

ient:

basel

ine

Outpat

ient:

inte

rven

tion

Inpat

ient:

inte

rven

tion C

han

ge

fro

m b

asel

ine

(cm

3 )

3040

6050

70

01020

******

*

*

**

Glucose

Total

SAT VAT

Fructose

Total SAT VAT

SAT: subcutaneous adipose tissueVAT: visceral adipose tissue

Glucose

Fructose

A B


Intra-Abdominal (Visceral) Fat Excess – Other Approaches

Dehydroepiandrosterone (DHEA) supplements.

Nicotinic acid & receptor pathway.

Continuous positive airway pressure.


Niacin Acts Through Nicotinic Acid Receptors on Multiple Tissues

Adapted from Pike NB. J Clin Invest 2005;115:3400-3

AdipocytesAdipocytesImmune cells

(spleen, lymphoid cells, lung)

Immune cells (spleen, lymphoid

cells, lung)

Epidermal Langerhans

cells

Epidermal Langerhans

cells

Niacin

Antilipolytic effects

Probableanti-inflammatory

effect

PLA2

Arachidonic acid

PGD2

GPR109A

Flushing

Niacin Niacin

GPR109A: G protein-coupled receptor 109A

PLA2: phospholipase A2

PGD2: prostaglandin D2

Source: www.myhealthywaist.org

Targeting Abdominal Obesity in Diabetology What can we do about it?

Documents

Transcript of Targeting Abdominal Obesity in Diabetology What can we do about it?