DIABETES THE NEW EPIDEMIC 3rd June 2014 Professor Paolo Pozzilli In collaboration with Rocky Strollo...
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- DIABETES THE NEW EPIDEMIC 3rd June 2014 Professor Paolo
Pozzilli In collaboration with Rocky Strollo and Valentina
Greto
- Slide 2
- Number of people with diabetes (20-79 years), 2013 IDF Diabetes
Atlas, 6th Edition, 2013 Tot: 382,000,000 in 2013 Tot: 471,000,000
in 2035
- Slide 3
- Trends in age-standardized diabetes prevalence by regions in
MALES (1980-2008) Danaei et al. Lancet 2011 High income regions
Europe/North America Central/Eastern EuropeSub-Saharan
AfricaOceania Central Asia, North Africa, Middle-East South
AsiaEast Asia and SE Asia World Southern America Central/Andean
America High income Asia Diabetes Prevalence (%) 20 16 12 8 4 20 16
12 8 4 20 16 12 8 4 1985 1995 2005
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- Trends in age-standardized diabetes prevalence by regions in
FEMALES (1980-2008) Danaei et al. Lancet 2011 High income regions
Europe/North America Central/Eastern EuropeSub-Saharan Africa
Oceania Central Asia, North Africa, Middle-East South Asia East
Asia and SE Asia World Southern America Central/Andean America High
income Asia Diabetes Prevalence (%) 20 16 12 8 4 20 16 12 8 4 20 16
12 8 4 1985 1995 2005
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- Overall prevalence of antidiabetic drug use in children and
adolescents by age on IMS, 1998-2005 inclusive girls boys and
overall Hsia Y et al., British Journal of Clinical Pharmacology,
2008 Increased prevalence of diabetes in children and adolescents
Results from prescription data from a UK general practice
database
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- Prevalence of insulin, oral antidiabetic and oral antidiabetic
drugs with a diabetes indication amongst children and adolescents
aged 0-18 (with 95% CIs), insulin oral antidiabetic drugs oral
antidiabetic drugs with diabetes indication ; * a significant trend
for increasing use (p< 0.001). * * * Increasing use of
antidiabetic drugs among children and adolescents Hsia Y et al.,
British Journal of Clinical Pharmacology, 2008
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- Type 1 diabetes (15%) It is caused by an autoimmune reaction,
where the bodys defence system attacks the insulin- producing beta
cells in the pancreas. The body can no longer produce the insulin
that it needs. Type 2 diabetes (85%) It is the most common type of
diabetes. It usually occurs in adults, but it is increasingly seen
in children and adolescents. The body is able to produce insulin
but either this is not sufficient or the body is unable to respond
to its effects.
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- Projections of the number of individuals aged
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- Projections of the number of individuals aged
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- Prevalence of type 2 diabetes in urban and rural areas in the
Arabic-speaking countries, 2011 Badran M and Laher I, International
Journal of Endocrinology, 2012
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- Type 2 diabetes prevalence in South Africa, 2009 Betram MY et
al., Global Health Action 2013
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- Prevalence of type 2 diabetes in Asian countries in 2013 data
source: http://www.idf.org/diabetesatlas/data-visualisations
Abdullah N et al., International Journal of Endocrinology,
2014
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- Worldwide prevalence of obesity Source: World Health
Organization (WHO), 2012
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- Obesity prevalence is high in developing countries Prevalence
of obesity in Arabian countries in adult males and females aged
between 15 and 100 years, WHO estimates, 2010. Badran M et al.,
Journal of Obesity, 2011
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- Obesity prevalence in adults (Italy), 2011 Valle dAosta 8,3%
Piemonte 9.1% Umbria 11.2% Liguria 8.3% Toscana 8.7% Lazio 9.2%
Calabria 11.4% Lombardia 8.9% Trentino 7.5% Friuli-V.G. 11.8%
Basilicata 13.1% Puglia 12.6% Abruzzo 8.7% E.Romagna 12.0% Molise
13.5% Campania 10.9% Sardegna 10.2% Marche 9.6% Veneto 9.9% Sicilia
9.8% Source: ISTAT 2013
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- Percentage of US adults who were obese or diagnosed with
diabetes Centre for Disease Control and Prevention: National
Diabetes Surveillance System
http://apps.nccf.cdc.gov/DDTSTRS/default.aspx. Accessed March 2013
Diabetes Obesity (BMI 30 KG/m 2 )
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- Obesity prevalence remains high altough no significant changes
between 2003-2012 9120 participants in the 2011-2012 nationally
representative National Health and Nutrition Examination Survey
Ogden et al. JAMA 2014 Childhood obesity (2-19 years) Adult obesity
(>20 years)
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- the prevention window
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- Natural history of type 2 diabetes Progression of disease
Impaired Glucose Tolerance Insulin level Insulin resistance Hepatic
glucose production Diabetes Diagnosis Post-prandial glucose Fasting
glucose -cell function Frank Diabetes 47 years
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- Combined impaired fasting glucose (IFG) + impaired glucose
tolerance (IGT) confers the highest risk of diabetes progression
Metanalysis of total risk of pre-diabetes and diabetes progression,
based on 21 cohort studies and 9 RCT (follow-up: 1-17 years)
Gerstein HC et al. Diabetes Research and Clinical Practice 2007
Isolated IGT Isolated IFG Relative Risk (95% CI)
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- Prediabetes increases the risk for cardiovascular events and
death DECODE study group. Lancet 1999 Relative risk of death is
linear by 2h-PG DECODE study
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- Pathophysiological defects in type 2 diabetes -Cell dysfunction
Insulin resistance Kahn CR et al. Joslins Diabetes Mellitus. 14th
ed. Lippincott Williams & Wilkins; 2005 Increased glucose
production by liver
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- Loss of first phase insulin secretion in type 2 diabetes
Polonsky KS et al. N Engl J Med, 1988 time 0 200 400 600 800
6.0010.0014.0018.0022.002.006.00 breakfastlunchdinner normal Type 2
diabetes Insulin secretion (pmol/min)
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- - cell mass: decline over diabetes continuum Holman RR et al.
Diabetes Res Clin Pract 1998 100 80 60 40 P < 0.0001 Timing to
diagnosis (years) Beta cell function (%) 20 0 10987654321123456 0 1
2 Insulin resistance The United Kingdom Prospective Diabetes Study
(UKPDS) -cell function Insulin resistance HOMA model, diet-treated
n = 376
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- Obese Lean -cell mass (%) -50% -63% - cell mass is already
impaired at the diagnosis of type 2 diabetes Butler AE et al.
Diabetes 2003; Leslie RD e Pozzilli P, J Clin Endocrinol Metab 2006
Type 2 diabetes
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- Oral hypoglycemic agents targeting the pathophysiologic defects
in type 2 diabetes Glucose absorption Hepatic glucose
overproduction Impaired insulin secretion Insulin resistance
Pancreas Glucose level Muscle and fat Liver Metformin TZDs DPP-4
inhibitors GLP1 analogues Sulfonylureas Meglitinides DPP-4
inhibitors GLP1 analogues TZDs Metformin -Glucosidase inhibitors
Metformin Gut
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- Lifestyle intervention can prevent type 2 diabetes development
TrialnPopulation Follow-up (years) Interventions RR (95% CI) Da
Qing 577 IGT (China) 6 1. Diet 2. Exercise 3. Diet & Exercise
0.66 (0.53-0.81) 0.56 (0.44-0.70) 0.49 (0.33-0.73) DPS 522 IGT
overweight (Finland) 3.2 Diet & Exercise 0.42 (0.3-0.7)
DPP3,234 IGT (USA) 2 1. Diet & Exercise 2. Metformin 0.42
(0.34-0.52) 0.69 (0.57-0.83) IDPP531 IGT (India) 2.5 1. Diet &
Exercise 2. Metformin 3. Metformin + Diet & Exercise 0.72
(0.62-0.80) 0.74 (0.65-0.81) 0.72 (0.62-0.80) DPS, Finnish Diabetes
Prevention Study; DPP, Diabetes Prevention Program; IDPP, Indian
Diabetes Prevention Program
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- Placebo (n=1082) Metformin (n=1073, p
- The STOP-NIDDM: Acarbose Acarbose reduced risk of new
Hypertension >140/90; 5.3% absolute risk reduction (P=0.006)
Myocardial infarction (P=0.02) Any CVD event: CHD, CV death or
stroke, CHF, PVD (P=0.03) Acarbose 100 mg TID n=682 Placebo n=686
25% Relative Risk Reduction P=0.0022 Chiasson JL, et al. Lancet.
2002;359(9323): 2072-2077; Chiasson JL, et al. JAMA.
2003;290(4):486-494.
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- ACT NOW: Pioglitazone Pioglitazone reduced risk of type 2
diabetes by 72% vs. placebo (HR 0.28; 95% CI 0.160.49 P