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IMPROVING THE PATIENT’S LIFE THROUGH

MEDICAL EDUCATION

Diabetes and thyroid disorders in clinical practice today

St Petersburg, Russia - April 25, 2015

Paolo Pozzilli Dept. Endocrinology and Diabetes, University Campus Bio-Medico of Rome, Italy Centre of Diabetes, St. Bartholomew's and The London School of Medicine Queen Mary University of London, UK

Declared receipt of grants and contracts; honoraria or consultation fees.

www.excemed.org

IMPROVING THE PATIENT’S LIFE THROUGH

MEDICAL EDUCATION

Type 2 diabetes, metabolic syndrome and thyroid diseases

St Petersburg, Russia - April 25, 2015

Highlights in

Type 2 diabetes Metabolic syndrome Thyroid diseases

Obesity Trends* Among U.S. Adults BRFSS, 1991

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1992

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1993

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1994

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1995

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. Adults BRFSS, 1996

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 1997

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 1998

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 1999

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults BRFSS, 2000

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. Adults BRFSS, 2001

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. Adults BRFSS, 2002

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. Adults BRFSS, 2003

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. Adults BRFSS, 2004

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity Trends* Among U.S. Adults BRFSS, 2005

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity Trends* Among U.S. Adults BRFSS, 2006

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity Trends* Among U.S. Adults BRFSS, 2007

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity Trends* Among U.S. Adults BRFSS, 2008

Prevalence of Self-Reported Obesity Among Non-

Hispanic White Adults,by State, BRFSS, 2011-2013

Data not reported* 15%–<20% 20%–<25% 25%–<30% 30%–<35%

≥35%

* Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Prevalence of Self-Reported Obesity Among Hispanic Adults,

by State, BRFSS, 2011-2013

Data not reported* 15%–<20% 20%–<25% 25%–<30% 30%–<35%

≥35%

* Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Prevalence of Self-Reported Obesity Among Non-Hispanic

Black Adults, by State, BRFSS, 2011-2013

Data not reported* 15%–<20% 20%–<25% 25%–<30% 30%–<35%

≥35%

* Sample size <50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30%.

Factor structure of the metabolic syndrome

Adapted from Shen et al. Am J Epidemiol, 157:701-711, 2003

Insulin

Resistance

Obesity

Lipids

Blood

pressure

Fasting Insulin

Fasting Glucose

Body Mass Index

Waist/Hip Ratio

HDL Cholesterol

Triglycerides

Systolic BP

Diastolic BP

Insulin resistance

Tessuto adiposo

sottocutaneo

FFA

TNF-

ILs

PAI-1

Visceral

adipose tissue

Gluconeogenesis VLDL syntesis

Glucose uptake

Hypertriglyceridemia

Hyperglycemia

Hyperinsulinemia

Genetic

factors

Environmental

factors

Insulin

resistance

Adipose tissue

FFA

Relationship between visceral fat and insulin sensitivity

Bonora E et al, Ital Cardiol, 2008

Visceral fat amount (cm2)

r = -0.62

p<0.01

Tota

l glu

cose

(m

mol/m

in/k

g F

FM

)

0 100 150 200 250 50

10

20

30

40

50

Waist circumference is subject to interoperator variability

and is influenced by:

1) gender;

2) race or ethnicity

Waist circumference explains only 25% to 50% of the

variation in intra-abdominal adipose tissue.

The variability of waist circumference

Fox K et al., Int J Obes Relat Metab Disord, 1993

The study findings suggest a close

relationship among wrist circumference,

its bone component, and insulin resistance

in overweight/obese children and

adolescents, opening new perspectives in

the prediction of cardiovascular disease.

Buzzetti R. et al., Circulation, 2011

Wrist circumference as a predictor of T2DM

Incidence of diabetes during 8.8 years of follow-up

( Noudeh et al. JCEM 2013)

Type 2 diabetes

and personalized therapy

T2DM is a COMPLEX disease with a COMPLEX therapy!

• Detemir

• Glargine

• Degludec

• U 300

• Lispro

• Aspart

• Glulisine

• Regular human

• Biosimilar insulin INSULIN

• Glicazide

• Glibenclamide

• Glimepiride

• Glyburide

SULFONYLUREAS

• Nateglinide

• Repaglinide

GLINIDES

• Metformin

BIGUANIDES • Pioglitazone

TZDs

• Sitagliptin

• Saxagliptin

• Vildagliptin

• Linagliptin

• Alogliptin DPP-IV INHIBITORS

• Exenatide

• Exenatide LAR

• Liraglutide

• Lixisenatide

• Dulaglutide LAR

• Albiglutide LAR

• Senaglutide

INCRETINS

• Acarbose

• Miglitol

ALPHA GLUCOSIDASES INHIBITORS

• Dapagliflozin

• Ertugliflozin

• Canagliflozin

• Empagliflozin

• Sotagliflozin

SGLT2 INHIBITORS

DPP-4I and cardiovascular outcomes

Clinicaltrials.gov

2009 2010 2011 2012 2013 2014 2015 2018

TECOS (n=14.000)

SAVOR TIMI 53 (n=18.206)

CAROLINA (n estimated=6.000)

EXAMINE (n= 5.380)

CARMELINA (n estimated=8.300)

NCT02290301 (n= 5.000)

GLP-1A and cardiovascular outcomes

2010 2011 2012 2013 2014 2015 2016 2018

LEADER (n=9.340)

SUSTAIN 6 (n=3.297)

ELIXA (n=6.075)

EXSCEL (n estimated= 14.000)

REWIND (n estimated=9.622)

Clinicaltrials.gov

SGLT-2 and cardiovascular outcomes

Clinicaltrials.gov

2009 2010 2011 2012 2013 2014 2015 2018

CANVAS (n estimated= 4.365)

DECLARE TIMI (n estimated=17.150)

EMPA REG (n= 7.000)

MK-8835-004 (n estimated=3.900)

METFORMIN

The A1C and ABCD(E)* of glycaemia management in

type 2 diabetes: a physician's personalized approach

AGE (years)

COMPLICATIONS DURATION>10yrs

HbA1c (%)

HbA1c≥ 9%

HbA1c< 9%

Insulin treatment

15-40 40-70 >70

- - - + + +

<6 <6.5 <7 <6.5 6.5-7 7-8

Physician should choose drug according to pa t ient 's riskof we ight ga in, hypoglycaemia , cardio-rena l complica t ions

Pozzilli P, Leslie RD, Chan J, De Fronzo R, Monnier L, Raz I, Del Prato S. Diabetes Metab Res Rev. 2010

May;26(4):239-44. *Khazrai YM, Buzzetti R, Del Prato S, Cahn A, Raz I, Pozzilli P. J Diabetes Complications. 2015 Mar 11. pii: S1056-

8727(15)00100-2.

AD

A/E

AS

D p

osit

ion

sta

tem

en

t 2015

To

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ts

Diabetes Care, Volume 38, supplement 1, January 2015

“Primum non nocere” The challenge for diabetologist is to choose the best safe approach with concerns to potential adverse effects and benefits of intensive glucose control.

afety

ultifactorial

pproach

In diabetic patients relevant cardiovascular risk factors other than hyperglycaemia always coexist. There is a universal agreement that anti-hyperglycaemic therapy should be pursued within a multifactorial risk reduction framework

isk

A careful evaluation of the risk reduction that could really be achieved should always be performed. However the risk of macrovascular complications starts to increase very early, even in the pre-diabetic stages, claiming for precocious management strategies.

herapy

Therapy of diabetes is becoming increasingly complex, due to the complexity of pathophysiology and to the wide therapeutic options. A non univocal, but just a smart approach could be the key to turn therapeutic complexity from a problem into an opportunity.

Maddaloni E .& Pozzilli P. Endocrine, January 2014

The «SMART» diabetologist

Healthcare professionals should aim to encourage and increase patients’

perception about their ability to take informed decisions about disease

management and to improve patient self-esteem and feeling of self-efficacy

to become agents of their own health.

It is important that patients learn to manage and cope with their disease and

gain greater control over actions and decisions affecting their health.

Khazrai YM et al., JDC 2015

complEx human behaviour

uration of disease

ody weight

omplications

ge A C D

B

mpowerment / economics E

Patient perspective Physician perspective

“Normal glycaemia” Easy to use

Safe and tolerable Immediate benefit

Inexpensive

Durability Easy to prescribe

Reduce complications Long-term benefit Preserve beta-cells

Considerations for personalizing

medicine in T2DM therapy

Personalized Therapy

Cost Age

Occupation

Body Weight

Concomitant

Diseases Diabetes

Duration

Patient wishes

Safety and

tolerability

Efficacy

The A1C and ABCD of glycaemia management in type 2 diabetes: a physician's personalized approach. Pozzilli P, Leslie RDG, Chan

J, De Fronzo R, Monnier L, Raz I, Del Prato S: Diabetes Metab Res Rev 26:239-44, 2010

Thyroid and other diseases

associated with diabetes

T1DM (%) General population (%)

Coeliac disease 4-11 0.5-1

Hashimoto 3-8 <1

Graves’disease 1 1

Addison disease <0.5 0.005

Autoimmune gastritis 5-10 2

Pernicious anemia 2-4 0.15-1

Multiple sclerosis 0.18 0.02

Vitiligo 6 0.5

Rheumatoid Arthritis 2 0.5-1

Systemic Lupus

Erithematosus

0.02-0.03

Prevalence of autoimmune thyroid and other diseases associated with type 1 diabetes

Barker JM et al, JCEM, 2011; Hollowell JC, JCEM, 2012; Van den Driessche et al, J Med, 2009; Bowes J , Rheumat, 2008

Autoantigen T1DM (%) General population (%)

Celiac disease tTG 5-12 1.5

HashimotoTPO

TG

20-30

8-16

13

11

Graves'disease TRAb 5 1

Addison disease 21-OH 1-2 Rare

Autoimmune gastritis  APCA 15-20 1

Prevalence autoantibodies in type 1 diabetes and in general population

Barker JM et al, JCEM, 2006; Alonso N et al, Nat Rev, 2009

0

5

10

15

20

25

30

35

40

TPO 21-OH tTG APC

High titre GADA

Low titre GADA

T2DM p<0.004

p<0.001

p<0.03

p<0.01

p=0.03

Zampetti S et al., J Clin Endocrinol Metab 97:3759-3765, 2012

Prevalence of organ-specific autoantibodies

in NIRAD /LADA and T2D patients

Interaction between obesity, diabetes and

autoimmune thyroid and other diseases is more

than an association of different conditions but a

pathophysiological cluster which requires precise

characterization for the implementation of the

most suitable therapy.

Conclusions

www.excemed.org

IMPROVING THE PATIENT’S LIFE THROUGH

MEDICAL EDUCATION

Diabetes and thyroid disorders in clinical practice today

St Petersburg, Russia - April 25, 2015