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
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
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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