univ prof. prim. dr. guntram schernthaner vorstand der 1. medizinischen abteilung rudolfstiftung...

Univ Prof. Prim. Dr. Guntram Schernthaner

Vorstand der 1. Medizinischen Abteilung Rudolfstiftung Wien

Non-Stop Revolution in der Diabetologie : Dramatischer Rückgang der Diabeteskomplikationen in den letzten 20 Jahren

• Typ 1 Diabetes: Mortalität der Patienten mit jugendlichem Diabetes betrug nach 30 Jahren Diabetesdauer 50% - Mortalität war um 600% höher als bei gleichaltrigem Patienten ohne Diabetes

• Typ 2 Diabetes: Patienten in der UKPDS-Studie, die bei Studienbeginn im Mittel nur 53 Jahre alt waren keine Komplikationen aufwiesen, waren nach 20 Jahren (Durchschnittsalter 73 Jahre) in 44% verstorben

• Diabetes war in der westlichen Welt die häufigste Erblindungsursache

• 50% aller Fussamputationen erfolgten bei Diabetespatienten

• 30-50% aller Hämodialyse-Patienten hatten Diabetes

• Herzinfarkt, Schlaganfall, PAVK und Herzinsuffizienz finden sich bei

Patienten mit Diabetes 2-3 x häufiger als bei Patienten ohne Diabetes

Schicksal der Diabetespatienten im letzten Drittel des 20. Jahrhunderts

Risk Reduction for Mortality in Diabetic versus Nondiabetic Patients the Framingham Study in comparison of Later and Earlier Period

Preis et al. Circulation 2009;119:1728-35

-60%

0

-30%

-23%

- 60%- 58%

Non-Diabetics

Diabetics

HR 0.70 HR 0.77

HR 0.40 HR 0.42

HR 0.95 HR 1.40

All-cause mortality CVD mortality Non-CVD mortality

p<0.001

p=0.05

Non-Diabetics Diabetics

earlier: 1950 - 1975 later: 1976 - 2001

Decline in Age-standardized mortality rates from 1997 to 2006 Comparison of a diabetic cohort with the UK general population

Men Women

Diabetic

Nondiabetic

Gulliford MC & Charlton J. Am J Epidemiol 2009;169:455–461

The study included a cohort of 48,556 subjects with type 2 diabetes first diagnosed between 1996 and 2006, drawn from 197 family practices in the United Kingdom General Practice Research Database (UKGPRD). There were 6,630 deaths observed

Relative mortality for patients diagnosed in 2006 was 37% lower than for those diagnosed in 1996

Explaining the Decline in Early Mortalityin Men and Women With Type 2 Diabetes

• Cohort study including 48,579 patients with type 2 diabetes first diagnosed between 1996 & 2006 in 197 general practices in the U.K.

• From 1996 to 2006, incidence of type 2 diabetes increased and the mean age at diagnosis declined in women

• All-cause mortality in the first 24 months after diabetes diagnosis declined signficantly in both in men and women per 1,000 person-years ► Men from 47.9 in 1996 to 25.2 in 2006 ►Women from 37.4 in 1996 to 27.6 in 2006

• In a multiple regression model adjusting for age and comorbidity prescription of statins before or after diagnosis, renin-angiotensin system drugs before or after diagnosis, and metformin after diagnosis were associated with lower mortality

A population-based cohort study

Charlton J et al: Diab Care 2008; 31:1761-6

Age-standardised rates for mortality within two years of diabetes diagnosis by year of diagnosis (1996-2006) in UK

Women

Men37.4

27.6

25.2

47.9

0

10

20

30

40

50

1996 1998 2000 2002 2004 2006


1000

per

son

year

s

Cohort study including 48,579 patients with type 2 diabetes first diagnosed between 1996 & 2006 in 197 general practices in the U.K.

Decline of mortality from 1996-2006 in men: 47 % and in women: 26 %

Women

0

10

20

30

40

50

60

70

%

1996 20060

10

20

30

40

50

60

70

%

1996 20060

10

20

30

40

50

60

70

%

1996 2006

0

10

20

30

40

50

60

70

%

1996 20060

10

20

30

40

50

60

70

%

1996 2006

Men

RAS drugsStatins

RAS drugsMetformin Statins

36,3

34,4

13,9

13,2

70

15

36,8

31,5

2,2

1,9

80 80 80

0

10

20

30

40

50

60

70

%

1996 2006

Metformin 60

20

80 80 80

Treatment Changes in Patients with Type 2 Diabetes between 1996 - 2006


Age-specific prevalences for diabetes in Denmark (1995–2007)

Men Women

Carstensen B et al. Diabetologia 2008; 51:2187–2196

The Danish National Diabetes Register: Trends in incidence, prevalence and mortality

•

• The prevalence of diabetes increased 6% per year

• The lifetime risk of diabetes was 30%

• The mortality rate in the diabetic population decreased 4% per year, compared with only 2% per year in the non-diabetic population

• The mortality rate decreased 40% during the first 3 years after inclusion in the register

• Conclusions: The mortality rate in diabetic patients decreased faster than that of the nondiabetic population

Carstensen B et al. Diabetologia 2008; 51:2187–2196

Diabetic Retinopathy Diabetic Retinopathy, particularly in its vision-threatening stages, has a substantial, negative impact on the patient

Fenwick EK et al. Postgrad Med J. 2012; 88:167-75 Fenwick EK et al. Invest Ophthalmol Vis Sci. 2012; 53:677-84.

• Ca. 12 Millionen Amerikaner haben einen Diabetes mellitus

• 5,3 Millionen haben eine diabetische Retinopathie

• 700.000 haben eine proliferative diabetische Retinopathie

• 65.000 neue Fälle / Jahr mit proliferativer diabetischer Retinopathie

• 75.000 neue Fälle / Jahr mit diabetischer Makulopathie

Epidemiologie

Clinical Stages of Diabetic Retinopathy

Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98:823-833

BDR PPDR

PDR

(Background) (Preproliferative)

No Diabetic

RetinopathyProliferative

Diabetic Retinopathy

NPDRNonproliferative Diabetic

Retinopathy

STAGES

Biochemical changes, endothelial leukocyte adhesion, basement

membrane thickening, pericyte loss, changes

in retinal blood flow

Mild to Moderate Moderate to Severe NeovascularizationNone

Macular EdemaSEVERITY

Age-standardized prevalence of diabetic retinopathy by Diabetes duration, in diabetic subjects aged 20 to

79 years

21

54

76

0

20

40

60

80

13 4

9

13

41

32

20

0

10

20

30

40

18

Vision-threatening Diabetic Retinopathy

Any Diabetic Retinopathy

Proliferative Diabetic Retinopathy

Diabetic Macular Edema

20 years<10 years 10 to <20 years

Age

-sta

ndar

dize

d pr

eval

ence

per

100

Age

-sta

ndar

dize

d pr

eval

ence

per

100

Yau et al. Diabetes Care 2012: 35:556-564

A pooled analysis of 35 studies (1980-2008) providing data from 22896 patients with diabetes (Meta-analysis for eye disease study group)

Age-standardized prevalence of Diabetic Retinopathy in Type 1 versus Type 2 Diabetes aged 20 to 79 years

32

14

38

3

6 7

0

10

20

30

4077

25

0

20

40

60

80





Type 2Type 1

Age

-sta

ndar

dize

d pr

eval

ence

per

100

Age

-sta

ndar

dize

d pr

eval

ence

per

100



Decline of Age-standardized Prevalence of Diabetic Retinopathy (Age Range: 20-79 years) in Studies Pre-2000 vs. Post-2000

10,69,3

15,6

3,5

5,5

7,9

0

5

10

15

Age

-sta

ndar

dize

d pr

eval

ence

per

100

49,6

24,8

0

10

20

30

40

50

60






Post-2000 studiesPre-2000 studies

20

Age

-sta

ndar

dize

d pr

eval

ence

per

100- 67 %

- 41 %

- 49 %- 50 %


HbA1cAge-standardized prevalence of diabetic retinopathy by HbA1c, in diabetic subjects aged 20 to 79 years

18

33

43

51

0

20

40

60

34

5

1112

18

0

5

10

15

20

76

1110

8

14






Age

-sta

ndar

dize

d pr

eval

ence

per

100

Age

-sta

ndar

dize

d pr

eval

ence

per

100

9 %7.0 % 7.1-8.0 % 8.1-9.0 %


Incidence and Progression of Diabetic Retinopathy During 17 Years of a Population-Based Screening Program in England

20 886 Patients with Type 2 Diabetes, who had annual retinal photography, from 1990-2006

Patients with non-proliferative Diabetic Retinopathy at baseline

Patients without Diabetic Retinopathy at baseline


Preproliferative Retinopathy

Sight-threatening maculopathy

after 10 yearsafter 5 yearsafter 10 yearsafter 5 years

11 %

53 %

9,6 %

6,1 %

23 %

5,2 %

1,5 %

16,4 %

1,2 %

0,68 %

4 %

0,59 %

Jones CD et al. Diabetes Care 2012; 35:592-6

Proportion of End Stage Renal Disease in Patients with Diabetes

Yoon K et al. Lancet 2006;368:1681–1688

Mal

aysi

a

Rep

ublic

of

Kor

ea

USA

Japa

nN

ew Z

eala

nd

Taiw

an

Phili

ppin

es

Aus

tria

Aus

tral

ia

40

60

0

50

30

20

10

Pro

po

rtio

n (

%)

Paki

stan

Med

ian

Per

cent

of P

opul

atio

n

0

2

4

6

8

95 96 97 98 99 00 01 02 03 04 05 06

Year

0

100

200

300

400

500

80 84 88 92 96 00 04

Year

Crude

Age-adjusted

Inci

denc

e (p

er 1

00.0

00

Pop

ulat

ion

)

William ME. Diabetic CKD/ESRD 2010: A Progress Report? Seminars in Dialysis 2010;l 23:129–133

Changing incidence rates of diabetic ESRD related to the underlying incidence of DM

Growing Prevalence of Diabetes in the General

US Population

During 1996–2007 the rate of increase in the number of persons with diagnosed diabetes was greater than the rateof increase in the number of ESRD-D cases. Thus, among persons with diagnosed diabetes, the age-adjusted ESRD-D rate decreased during the period by 35%, from 304 to 199 per 100 000 persons with diagnosed diabetes

Significant Decline of the ESRD rate by 35% in persons with diagnosed during the period 1996-2007

All New Patients receiving Renal Replacement Therapy in Austria (2004-2010)

0

100

200

300

400362 365

321

268

20%

25%

30%

35%

2004 2006 2008 2010

30 %

31 %29 %

26 %

Absolute Number of Patients with Type 2 Diabetes

02004 2006 2008 2010

1207 11791110

1032

200

400

600

800

1000

1200

Absolute Number

% Patients with Type 2 Diabetes

Österreichisches Hämodialyseregister 2010

(2010 vs. 2004)

-26 %

Kramar, R. Oberbauer R. Austrian Dialysis and Transplantation Registry (OEDTR), Annual Report 2010, Austrian Society of Nephrology

Zahl der Hämodialyse Patienten mit Typ 2 Diabetes in Relation zur Zahl der Patienten mit diagnostiziertem Typ 2 Diabetes in Österreich (Vergleich 2004 versus 2010)

2004 2010

Zahl der Patienten mit 400.000 480.000 diagnostiziertem Typ 2 Diabetes

Zahl der Hämodialyse (HD) 362 268 Patienten mit Typ 2 Diabetes

Zahl der HD Patienten mit Typ 2 Diabetes 90 60 pro100.000 diagnostizierte Patienten mit Typ 2 Diabetes

Abnahme von 2004 auf 2010 in Österreich - 33%

Abnahme von 1996 auf 2007 in USA - 35%

Möllsten A. et al. Diabetes 2010; 59: 1803–1808

• During a median time of follow-up of 20 years, only 127 out of 11.681 (1.08%) patients had developed ESRD due to diabetic nephropathy

• The cumulative incidence at 30 years of type 1 diabetes duration was very low, 4.1% in males vs. 2.5% in females.

Cumulative incidences of developing ESRD in young patients with type 1 diabetes with age at onset at 0–9 and 10–19 years (A Nationwide Population-Based Cohort Study in Sweden)

Diabetic Foot Syndrome

First described on December 31st 1887

Definition: Diabetes Complications with an increased risk for trauma, Infection

and Gangrene.

Schematischer Verlauf von der Polyneuropathie über das Trauma und das Ulkus bis hin zur Gangrän

TTNN NNNN

TT TTUUNN NNUU

HSHS

NeuropathiePrädisposition

TT

Minimal-Traumaäußere Einwirkung

UU

UlkusVerletzung

HSHS

Heilungsstörungweitere Schädigung(Druckbelastung,

Infektion)

GG

Gangränweitere

Schädigung (Thrombose)

Diabetic Foot Syndrome: High risk for Amputation and early Mortality

Mortality in Patients after Amputation: A Comparison between Patients with and without Diabetes

Median time to death was 27.2 months with diabetes (n=119) versus 46.7 months without diabetes (n=271)

14

1.00

0.75

0.50

0.25

0.000 2 4 6 8 10 12

Years from Incident Amputation or Study end Date

Surv

ival

Dis

trib

ution

Fun

ction

75% of diabetic patients are dead 6 years after amputation

Survival rates 10 years after amputationNondiabetic patients 22.9%Diabetic patients 8.4% p=0.0007

p=0.01

Schofield CJ et al. Diabetes Care 2006;29:2252

Significant Decrease in Initial Lower Extremity Amputation (ILEA) Rates among Veterans Health Administration (VHA) Health Care System Users from 2000 to 2004

- 34 % - 33 %- 36 %

- 19 %

- 49 %

1.41

-40

-30

-20

-10

0

-50

0.72

Age-

and

sex

-sta

ndar

dize

d IL

EA ra

tes

per 1

000

Age-

and

sex

-sta

ndar

dize

d IL

EA ra

tes

per 1

000

20002005

2.491.59

4.593.06

7.084.65

1.080.87

Above-kneeILEA ratesMajor

amputationMajor amputation

Below-kneeMinor

amputation

Five Year follow-up of VHA clinic users with diabetes and without prior amputations in 2000 (n= 405.580 ) and in 2004 (n=739.377)

0 0

12

40

50

60

70

80

90

100

96 98 00 02 04 06 08

Ag

e-a

djs

ute

d r

ate

s (p

er

1,0

00

)

Year

Nu

mb

er

(in

th

ou

san

ds)

97 99 01 03 05 07

10

20

30

2

4

6

8

10

From 1996-2008, p<0.05

Age-adjusted Nontraumatic Lower-Extremity Amputation (NLEA rates) among U.S. residents aged ≥40 years by diabetes status (1996–2008)

Li Y et al. (Diab Care 2012; 35:273–277)

Although patients with diagnosed diabetes increased dramatically from 5.4 million in 1988 to 17.1 million in 2008, the number of diabetes-related NLEA decreased from 83,153 in 1996 to 38.549 in 2008

0

12

96 98 00 02 04 06 08

Ag

e-a

djs

ute

d r

ate

s (p

er

1,0

00

)

Year

97 99 01 03 05 07

2

4

6

8

10

From 1996-2008, p<0.05

Age-adjusted Nontraumatic Lower-Extremity Amputation (NLEA rates) among U.S. residents aged ≥40 years by diabetes status (1996–2008)

No DiabetesDiabetes

Despite the much greater decrease in NLEA rates in the diabetic population, the age-adjusted NLEA rate in the diabetic population was still about eight times the rate in the nondiabetic population in 2008 (3.9 vs. 0.5 per 1,000 persons)

From 1996 to 2008 the NLEA rates in diabetic patients decreased by 67% (p<0.001)

Li Y et al. (Diab Care 2012; 35:273–277)

3,9

11,3

Leading Causes of Death in Type 2 Diabetes

Cancer, 29 %

CVD, 31 %

Renal, 2 %

External, 7 %

Other, 31 %

Renal, 3 % Infection, 7 %

External, 2 %

Other, 18 %

CVD, 43 %

Cancer, 27 %

Pathways Epidemiologic Study Lin et al. Ann Fam Med 2009

Alberta Diabetes Surveillance System www.albertadiabetes.ca

Increased Risk

3.5

Reduced Risk

Summary OR: 0.9 1.0 1.3 1.6 1.9 2.1 3.00.6

0.84

1.41

1.82

1.30

1.24

2.50

2.10

1.2

Bladder (Larsson, Diabetologia, 2006); N=16

Pancreas (Huxley, Br J Cancer, 2005); N=36

Non Hodgkin`s lymphoma (Mitri et al, 2008); N=5

Colorectal (Larsson, J Natl Can Inst 2005); N=15

Prostate (Kasper, Cancer Epi); N=19

Liver (El-Serag et al, 2006); N=20

Breast (Larsson, Int J Can, 2007); N=20

Endometrial (Friberg, Diabetologia 2007); N=16

Meta-analyses, 2005-2008

Diabetes & Cancer Risk

Mortalität bei Diabetespatienten mit Krebserkrankungen signifikant höher als bei Nichtdiabetikern

• Diagnose oft verspätet gestellt – weniger Sreeeninguntersuchunten ?• Erhöhte Perioperative Mortaliät• Erhöhtes Risiko für Re-Occurence• Aufgrund der Co-Morbiditäten erhöhte Toxizität der Chemotherapie• Vermindertes Ansprechen auf Chemotherapie• Gestörte Immunologische Infektabwehr bei Hyperglykämie• Diabetes „entgleist“ relativ oft bei Chemotherapie

Increases in clinically severe Obesity in the United States (1986-2000)

Sturm R. Arch Intern Med. 2003; 163:2146-2148

400

500

600

200

100

0

300

% In

crea

se (

1986

=10

0%) BMI ≥ 35 (Obesity Grade II)

BMI ≥ 30 (Obesity Grade I)

BMI ≥ 40BMI ≥ 45BMI ≥ 50

Year19

8719

8819

8919

9119

8619

9219

9319

9519

9019

9619

9719

9919

9420

0019

98

Patients with Morbid Obesity (n=1015)

41.2

Abnormal in %

28.055.9

100

63.2

40.849.8

≥ 100 mg/dl

≥ 150 mg/dl

85 mm/Hg130 mm/Hg

≤ 50 mg≤ 40 mg

Triglyceride

Components of the Metabolic Syndrome: IDF- Criteria

Blood Glucose preprandialDiastolic

Waist circumference

Systolic

HDL

FemaleMale

Hypertension

male > 94cm, female > 80cm

Impaired Glucose

Tolerance

24.6%

(HbA1c: 5.8±0.5)

Type 2 Diabetes

19.4% (HbA1c: 7.8±1.7)

Normal Glucose Tolerance

56.0%

(HbA1c: 5.5±0.5)

Rudolfstiftung Hospital Vienna

Significant lowering of HbA1c after Bariatric Surgery in 60 Type 2 Diabetic Patients with Morbid Obesity

6,15,5

7,4

5,7

9,1

5,8

0

2

4

6

8

Hb

A1c

(%

)

<0.001

Postoperative, BMI 29.3± 7.9

10

HbA1c (%) 6.8-8.0 >8.00<6.8

Preoperative, BMI 39.8±17.5

p-Value 0.004 <0.001

Schernthaner G et al. Diabetes Care, 2011; 34; Supplement 2: S355-360

15 20863 10210 4Follow-up, years

-15

-10

-5

-0

-5

-25

-30

-35

-20

Mea

n W

eigh

t Cha

nge

%

Mean Weight Change Percentages from Baseline for Controls and the 3 Surgery Groups over 20 Years in the Swedish Obese Subjects Study

1267284

1007180

ControlsBandingVertical banded gastroplastyGastric bypass

No. Of Patients

1242284987184

17650

8213

556150489

37

1490333

1086209

2037376

1369265

Sjöström L (JAMA 2012; 307:56)

Banding Vertical banded gastroplasty Gastric bypassControls

0

5

10

15

20

Diabetes(n=345)

Non-Diabetes (n=1658)

0.84 (0.67-1.06) HR 0.63 (0.45-0.90)

Treatment EffectDiabetes vs. Non-Diabetes: p<0.001

19.9

5.7

13.4

6.7

Diabetes or Non-Diabetes: Risk Factor Treatment Interaction Analyses in the SOS-Study

Sjöström L (JAMA 2012; 307:56)

Incidence per 1000 person-years

Non-Stop Revolution in der Diabetologie: Status 2012

• Kardiovaskuläre Mortalität bei Typ 2 Diabetes wurde um 60% gesenkt

• Proliferative Retinopathie nahm um 67% ab

• Diabetisches Maculaödem wurde um 41% rdeuziert

• Die kumulative Inzidenz einer terminalen Niereninsuffizienz bei Patienten mit Typ 1 Diabetes liegt nach 30 jähriger Diabetesdauer nur mehr bei ca 3%

• Signifikanter Rückgang (ca 35%) der Patienten mit Typ 2 Diabetes an der Hämodialyse (USA, Österreich)

• Rückgang der Fussamputationen um 35-50%

• Diabetesremission bei Patienten mit morbider Adipositas nach metabolischer chirurgischer Íntervention in ca 70%

• Neue Herausforderung: Früherkennung bestimmter Krebserkrankungen, die bei Patienten mit Typ 2 Diabetes signifikant häufiger auftreten

univ prof. prim. dr. guntram schernthaner vorstand der 1. medizinischen abteilung rudolfstiftung...

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