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

Präsentation zum Thema: "Non-Stop Revolution in der Diabetologie : Dramatischer Rückgang der Diabeteskomplikationen in den letzten 20 Jahren Univ Prof."—  Präsentation transkript:

1 Non-Stop Revolution in der Diabetologie : Dramatischer Rückgang der Diabeteskomplikationen in den letzten 20 Jahren Univ Prof. Prim. Dr. Guntram Schernthaner Vorstand der 1. Medizinischen Abteilung Rudolfstiftung Wien

2 Schicksal der Diabetespatienten im letzten Drittel des 20. Jahrhunderts
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

3 1972

4 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: All-cause mortality CVD mortality Non-CVD mortality Non-Diabetics Diabetics HR 0.95 HR 1.40 -23% -30% HR 0.70 HR 0.77 Non-Diabetics Diabetics -60% - 58% p<0.001 p=0.05 - 60% earlier: later: HR 0.40 HR 0.42

5 Decline in Age-standardized mortality rates from 1997 to Comparison of a diabetic cohort with the UK general population Men Women Diabetic Nondiabetic Relative mortality for patients diagnosed in 2006 was 37% lower than for those diagnosed in 1996 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 Gulliford MC & Charlton J. Am J Epidemiol 2009;169:455–461

6 Explaining the Decline in Early Mortality in Men and Women With Type 2 Diabetes
A population-based cohort study 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 ►Women from 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 Charlton J et al: Diab Care 2008; 31:1761-6

7 Age-standardised rates for mortality within two years of diabetes diagnosis by year of diagnosis ( ) in UK 47.9 50 Men 37.4 40 Women 27.6 1000 person years 30 25.2 20 Decline of mortality from in men: 47 % and in women: 26 % 10 1996 1998 2000 2002 2004 2006 Cohort study including 48,579 patients with type 2 diabetes first diagnosed between 1996 & 2006 in 197 general practices in the U.K. Charlton J et al: Diab Care 2008; 31:1761-6

8 Treatment Changes in Patients with Type 2 Diabetes between 1996 - 2006
% Men % % 80 80 80 Metformin 70 Statins RAS drugs 70 70 70 60 60 60 50 50 50 36,8 36,3 40 40 40 30 30 30 20 20 20 15 2,2 10 10 10 13,9 1996 2006 1996 2006 1996 2006 % Women % % 80 80 Metformin 60 80 Statins RAS drugs 70 70 70 60 60 60 50 50 50 40 40 34,4 31,5 40 30 30 30 20 20 20 20 10 10 1,9 10 13,2 1996 2006 1996 2006 1996 2006 Charlton J et al: Diab Care 2008; 31:1761-6

9 Age-specific prevalences for diabetes in Denmark (1995–2007)
Men Women Carstensen B et al. Diabetologia 2008; 51:2187–2196

10 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

11 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: Fenwick EK et al. Invest Ophthalmol Vis Sci. 2012; 53:

12 Epidemiologie Ca. 12 Millionen Amerikaner haben einen Diabetes mellitus 5,3 Millionen haben eine diabetische Retinopathie haben eine proliferative diabetische Retinopathie neue Fälle / Jahr mit proliferativer diabetischer Retinopathie neue Fälle / Jahr mit diabetischer Makulopathie

13 Clinical Stages of Diabetic Retinopathy
No Diabetic Retinopathy NPDR Nonproliferative Diabetic Retinopathy PDR S T A G E S Biochemical changes, endothelial leukocyte adhesion, basement membrane thickening, pericyte loss, changes in retinal blood flow Proliferative Diabetic Retinopathy BDR PPDR (Background) (Preproliferative) Macular Edema S E V R I T Y Diabetic retinopathy can be viewed as a progression. Nonproliferative retinopathy is less severe, proliferative is more severe, and macular edema can occur during either stage. The natural history of diabetic retinopathy can be viewed as a progression. Nonproliferative diabetic retinopathy: Is not associated with visual loss (unless macula becomes involved). Includes basement membrane thickening, loss of pericytes, increased blood flow and vascular permeability. Proliferative diabetic retinopathy is a stage that includes: Retinal ischemia, neovascularization, and visual impairment.   1. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98: Mild to Moderate Moderate to Severe Neovascularization None Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98:

14 Age-standardized prevalence of diabetic retinopathy by Diabetes duration, in diabetic subjects aged 20 to 79 years 41 80 76 40 32 60 30 54 20 Age-standardized prevalence per 100 40 Age-standardized prevalence per 100 20 18 13 21 9 20 10 4 3 1 Any Diabetic Retinopathy Proliferative Diabetic Retinopathy Diabetic Macular Edema Vision-threatening Diabetic Retinopathy <10 years 10 to <20 years 20 years A pooled analysis of 35 studies ( ) providing data from patients with diabetes (Meta-analysis for eye disease study group) Yau et al. Diabetes Care 2012: 35:

15 Age-standardized prevalence of Diabetic Retinopathy in Type 1 versus Type 2 Diabetes aged 20 to 79 years 77 80 40 38 32 60 30 Age-standardized prevalence per 100 40 Age-standardized prevalence per 100 20 14 25 20 10 7 6 3 Any Diabetic Retinopathy Proliferative Diabetic Retinopathy Diabetic Macular Edema Vision-threatening Diabetic Retinopathy Type 1 Type 2 A pooled analysis of 35 studies ( ) providing data from patients with diabetes (Meta-analysis for eye disease study group) Yau et al. Diabetes Care 2012: 35:

16 Decline of Age-standardized Prevalence of Diabetic Retinopathy (Age Range: years) in Studies Pre-2000 vs. Post-2000 60 20 - 50 % 49,6 50 15,6 15 - 49 % 40 10,6 9,3 - 41 % Age-standardized prevalence per 100 30 Age-standardized prevalence per 100 10 24,8 - 67 % 7,9 20 5,5 5 3,5 10 Any Diabetic Retinopathy Proliferative Diabetic Retinopathy Diabetic Macular Edema Vision-threatening Diabetic Retinopathy Pre-2000 studies Post-2000 studies A pooled analysis of 35 studies ( ) providing data from patients with diabetes (Meta-analysis for eye disease study group) Yau et al. Diabetes Care 2012: 35:

17 HbA1c Age-standardized prevalence of diabetic retinopathy by HbA1c, in diabetic subjects aged 20 to 79 years 60 20 18 51 43 15 14 40 12 33 11 11 10 Age-standardized prevalence per 100 Age-standardized prevalence per 100 10 8 7 18 6 20 5 5 4 3 Any Diabetic Retinopathy Proliferative Diabetic Retinopathy Diabetic Macular Edema Vision-threatening Diabetic Retinopathy 7.0 % % % 9 % A pooled analysis of 35 studies ( ) providing data from patients with diabetes (Meta-analysis for eye disease study group) Yau et al. Diabetes Care 2012: 35:

18 Incidence and Progression of Diabetic Retinopathy During 17 Years of a Population-Based Screening Program in England Patients with non-proliferative Diabetic Retinopathy at baseline Patients without Diabetic Retinopathy at baseline after 5 years after 10 years after 5 years after 10 years Preproliferative Retinopathy 4 % 16,4 % 23 % 53 % Sight-threatening maculopathy 0,59 % 1,2 % 5,2 % 9,6 % Proliferative Diabetic Retinopathy 0,68 % 1,5 % 6,1 % 11 % Patients with Type 2 Diabetes, who had annual retinal photography, from Jones CD et al. Diabetes Care 2012; 35:592-6

19 Proportion of End Stage Renal Disease in Patients with Diabetes
60 50 40 Proportion (%) 30 20 10 USA Japan Pakistan Taiwan Austria Malaysia Republic of Korea Australia Philippines New Zealand Yoon K et al. Lancet 2006;368:1681–1688

20 Growing Prevalence of Diabetes in the General US Population
Significant Decline of the ESRD rate by 35% in persons with diagnosed during the period Growing Prevalence of Diabetes in the General US Population Changing incidence rates of diabetic ESRD related to the underlying incidence of DM 8 500 400 6 300 4 Incidence (per Population) Median Percent of Population 200 2 Crude 100 Age-adjusted 95 96 97 98 99 00 01 02 03 04 05 06 80 84 88 92 96 00 04 Year Year During 1996–2007 the rate of increase in the number of persons with diagnosed diabetes was greater than the rate of 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 persons with diagnosed diabetes William ME. Diabetic CKD/ESRD 2010: A Progress Report? Seminars in Dialysis 2010;l 23:129–133

21 All New Patients receiving Renal Replacement Therapy in Austria (2004-2010)
Absolute Number of Patients with Type 2 Diabetes % Patients with Type 2 Diabetes Absolute Number 35% 400 1207 362 365 1179 1200 1110 31 % 321 1032 29 % 30 % 1000 30% 26 % 300 268 26 % 800 (2010 vs ) 200 600 25% 400 100 20% 200 2004 2006 2008 2010 2004 2006 2008 2010 Kramar, R. Oberbauer R. Austrian Dialysis and Transplantation Registry (OEDTR), Annual Report 2010, Austrian Society of Nephrology Österreichisches Hämodialyseregister 2010

22 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) Zahl der Patienten mit diagnostiziertem Typ 2 Diabetes Zahl der Hämodialyse (HD) Patienten mit Typ 2 Diabetes Zahl der HD Patienten mit Typ 2 Diabetes pro diagnostizierte Patienten mit Typ 2 Diabetes Abnahme von 2004 auf 2010 in Österreich % Abnahme von 1996 auf 2007 in USA %

23 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) During a median time of follow-up of 20 years, only 127 out of (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. Möllsten A. et al. Diabetes 2010; 59: 1803–1808

24 Diabetic Foot Syndrome
First described on December 31st 1887 Definition: Diabetes Complications with an increased risk for trauma, Infection and Gangrene.

25 Schematischer Verlauf von der Polyneuropathie über das Trauma und das Ulkus bis hin zur Gangrän
weitere Schädigung (Thrombose) T Minimal-Trauma äußere Einwirkung U Ulkus Verletzung HS Heilungsstörung weitere Schädigung (Druckbelastung, Infektion) HS N N N U N U N T T T Neuropathie Prädisposition

26

27 Diabetic Foot Syndrome: High risk for Amputation and early Mortality

28 Mortality in Patients after Amputation: A Comparison between Patients with and without Diabetes
1.00 Survival rates 10 years after amputation Nondiabetic patients 22.9% Diabetic patients % 0.75 p=0.0007 Survival Distribution Function 0.50 0.25 75% of diabetic patients are dead 6 years after amputation 0.00 2 4 6 8 10 12 14 Years from Incident Amputation or Study end Date Median time to death was months with diabetes (n=119) versus months without diabetes (n=271) p=0.01 Schofield CJ et al. Diabetes Care 2006;29:2252

29 Significant Decrease in Initial Lower Extremity Amputation (ILEA) Rates among Veterans Health Administration (VHA) Health Care System Users from 2000 to 2004 Minor amputation Major amputation Major amputation ILEA rates Below-knee Above-knee -10 - 19 % -20 Age- and sex-standardized ILEA rates per 1000 - 33 % - 34 % -30 - 36 % -40 Five Year follow-up of VHA clinic users with diabetes and without prior amputations in (n= ) and in 2004 (n= ) - 49 % -50 2000 7.08 4.59 2.49 1.08 1.41 2005 4.65 3.06 1.59 0.87 0.72

30 Age-adjsuted rates (per 1,000)
Age-adjusted Nontraumatic Lower-Extremity Amputation (NLEA rates) among U.S. residents aged ≥40 years by diabetes status (1996–2008) 100 12 From , p<0.05 90 10 80 70 8 60 Number (in thousands) 50 Age-adjsuted rates (per 1,000) 6 40 4 30 Although patients with diagnosed diabetes increased dramatically from million in 1988 to 17.1 million in 2008, the number of diabetes-related NLEA decreased from 83,153 in 1996 to in 2008 20 2 10 96 97 98 99 00 01 02 03 04 05 06 07 08 Year Li Y et al. (Diab Care 2012; 35:273–277)

31 Age-adjsuted rates (per 1,000)
Age-adjusted Nontraumatic Lower-Extremity Amputation (NLEA rates) among U.S. residents aged ≥40 years by diabetes status (1996–2008) 12 3,9 11,3 10 Diabetes From 1996 to 2008 the NLEA rates in diabetic patients decreased by 67% (p<0.001) No Diabetes 8 Age-adjsuted rates (per 1,000) 6 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 (3.9 vs. 0.5 per 1,000 persons) 4 From , p<0.05 2 96 97 98 99 00 01 02 03 04 05 06 07 08 Year Li Y et al. (Diab Care 2012; 35:273–277)

32 Leading Causes of Death in Type 2 Diabetes
Renal, 3 % Infection, 7 % CVD, 31 % Renal, 2 % External, 7 % Other, 31 % External, 2 % Cancer, 29 % Cancer, 27 % Other, 18 % CVD, 43 % Alberta Diabetes Surveillance System Pathways Epidemiologic Study Lin et al. Ann Fam Med 2009

33 Diabetes & Cancer Risk Reduced Risk Increased Risk
Meta-analyses, 1.41 1.82 1.30 1.24 2.50 2.10 1.2 Pancreas (Huxley, Br J Cancer, 2005); N=36 Colorectal (Larsson, J Natl Can Inst 2005); N=15 Bladder (Larsson, Diabetologia, 2006); N=16 0.84 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 Non Hodgkin`s lymphoma (Mitri et al, 2008); N=5 Summary OR: 0.6 0.9 1.0 1.3 1.6 1.9 2.1 3.0 3.5 Reduced Risk Increased Risk

34 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

35 Increases in clinically severe Obesity in the United States ( ) Sturm R. Arch Intern Med. 2003; 163: 600 BMI ≥ 30 (Obesity Grade I) BMI ≥ 35 (Obesity Grade II) 500 BMI ≥ 40 BMI ≥ 50 BMI ≥ 45 400 % Increase (1986=100%) 300 200 100 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year

36 Patients with Morbid Obesity
Type 2 Diabetes 19.4% (HbA1c: 7.8±1.7) Rudolfstiftung Hospital Vienna Impaired Glucose Tolerance 24.6% (HbA1c: 5.8±0.5) 56.0% Normal Glucose Tolerance (HbA1c: 5.5±0.5) ≥ 100 mg/dl ≥ 150 mg/dl 85 mm/Hg 130 mm/Hg ≤ 50 mg ≤ 40 mg Triglyceride Components of the Metabolic Syndrome: IDF- Criteria Blood Glucose preprandial Diastolic Waist circumference Systolic HDL Female Male Hypertension male > 94cm, female > 80cm 41.2 Abnormal in % 28.0 55.9 100 63.2 40.8 49.8

37 Significant lowering of HbA1c after Bariatric Surgery in 60 Type 2 Diabetic Patients with Morbid Obesity 10 Preoperative, BMI 39.8±17.5 9,1 Postoperative, BMI 29.3± 7.9 8 7,4 6,1 6 5,7 5,8 5,5 HbA1c (%) 4 2 HbA1c (%) <6.8 >8.00 p-Value 0.004 <0.001 <0.001 Schernthaner G et al. Diabetes Care, 2011; 34; Supplement 2: S

38 Mean Weight Change Percentages from Baseline for Controls and the 3 Surgery Groups over 20 Years in the Swedish Obese Subjects Study Controls Banding Vertical banded gastroplasty Gastric bypass -5 -0 -5 -10 Mean Weight Change % -15 -20 -25 -30 -35 1 2 3 4 6 8 10 15 20 Follow-up, years No. Of Patients Controls 2037 1490 1242 1267 556 176 Banding 376 333 284 284 150 50 Vertical banded gastroplasty 1369 1086 987 1007 489 82 Gastric bypass 265 209 184 180 37 13 Sjöström L (JAMA 2012; 307:56)

39 Diabetes or Non-Diabetes: Risk Factor Treatment Interaction Analyses in the SOS-Study
Incidence per 1000 person-years 19.9 Treatment Effect Diabetes vs. Non-Diabetes: p<0.001 20 15 13.4 10 6.7 5.7 5 Diabetes (n=345) Non-Diabetes (n=1658) HR ( ) 0.84 ( ) Sjöström L (JAMA 2012; 307:56)

40 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