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Epidemiology of the Metabolic Syndrome in the USA

Epidemiology of the Metabolic Syndrome in the USA. Epidemiology Evaluates a Disease. Incidence ? Prevalence Distribution Control ?. Epidemiology of the Metabolic Syndrome. What is It ?. Why are its Limitations ?. Why is It Important ? What is its Prevalence ?

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Epidemiology of the Metabolic Syndrome in the USA

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  1. Epidemiology of the Metabolic Syndrome in the USA Epidemiology Evaluates a Disease • Incidence ? • Prevalence • Distribution • Control ?

  2. Epidemiology of the Metabolic Syndrome What is It ? Why are its Limitations ? Why is It Important ? What is its Prevalence ? What are its Clinical Outcomes ? - Cardiac - Diabetes - Nonalcoholic Fatty Liver Disease

  3. The Metabolic Syndrome Obesity Diabetes Insulin Resistance Hypertension Hyperlipidemia

  4. Epidemiology of the Metabolic Syndrome What is It ? Why are its Limitations ? Why is It Important ? What is its Prevalence ? What are its Clinical Outcomes ? - Cardiac - Diabetes - Nonalcoholic Fatty Liver Disease

  5. Metabolic Syndrome There are 3 Definitions • World Health Organization (WHO) • International Diabetes Association (IDF) • Adult Treatment Panel (ATP III) • -National Cholesterol Education Program Expert Panel

  6. Three Different Definitions ATP IDF WHO Obesity BP Fasting Glucose Triglycerides HDL Cholesterol Micro Albumin Central Same >6.1mol/L Same Similar Not Used Central Same >5.6mol/L Same Similar Not Used BMI Similar IPG/HOMA Same Not Used Used

  7. Concerns About the Metabolic Syndrome (ADA and EASD) • Criteria are Ambiguous • Rationale for Thresholds ill defined • Inclusion of Diabetes Questionable • Importance of Insulin Resistance Unclear • Questions about CVD Risk Factors Remain • Treating MS no different than treating its parts • Medical Value of Diagnosing MS is Unclear

  8. Epidemiology of the Metabolic Syndrome What is It ? Why are its Limitations ? Why is It Important ? What is its Prevalence ? What are its Clinical Outcomes ? - Cardiac - Diabetes - Nonalcoholic Fatty Liver Disease

  9. Prevalence (%) of Metabolic Syndrome CountryATPIDFWHO South Asia 26 18 23 Australia 19 16 21 France 9 13 18 Italy 18 34

  10. Prevalence (%) of Metabolic Syndrome United States and China CountyATPIDFWHO USA National 24 40 Texas 25 25 China Hong Kong 17 21 InterAsia 14

  11. Epidemiology of the Metabolic Syndrome What is It ? Why are its Limitations ? Why is It Important ? What is its Prevalence ? What are its Clinical Outcomes ? - Cardiac - Diabetes - Nonalcoholic Fatty Liver Disease

  12. Metabolic Syndrome Predicts All Cause Mortality (13 year Follow up) Metabolic Syndrome No Yes ATP III (%) 10 21 p<0.01 WHO (%) 10 18 p<0.05

  13. Metabolic Syndrome and Cardiac Death NCEP-MetS Years Of Follow-Up

  14. Metabolic Syndrome Predicts Diabetes (8 year Follow up) Diabetes No Yes ATP III (%) 14.4 28.7 p<0.0001 WHO (%) 12.5 41.3 p<0.0001

  15. Epidemiology of the Metabolic Syndrome What is It ? Why are its Limitations ? Why is It Important ? What is its Prevalence ? What are its Clinical Outcomes ? - Cardiac - Diabetes - Nonalcoholic Fatty Liver Disease

  16. Non-Alcoholic Fatty Liver Disease • What is it? • Why is it Important? • How do you treat it?

  17. Proposed Classification for NAFLD* Primary Secondary • Conditions associated • with an insulin • resistance syndrome • - Diabetes mellitus • (type II) • - Obesity • - Hyperlipidemia • SURGICAL • PROCEDURES • - Gastroplexy • - Jejunoileal • bypass • - Extensive • small bowel • resection • - Bilio-pancreatic • Diversion • MISCELLANEOUS • - Abeta/ hypobeta • - Weber-Christian • Disease • - TPN with • glucose • - Environmental • toxins • - S. Bowel • Diverticulosis • DRUGS • - Corticosteroids • - Synthetic • Estrogens • - Amiodarone • - Perhexiline • - Nifedipine

  18. Non-Alcoholic Fatty Liver Disease STEATOSIS INFLAMMATION NASH

  19. Non-Alcoholic Fatty Liver(NAFL) Type 1 Type 2 Type 3 Type 4 - Fat alone - Fat + Inflammation - Fat + Hepatocyte Injury - Fat + Fibrosis and/ or Mallory Bodies

  20. NAFLD Activity Score (NASH CRN) Histologic Finding Grade 0 - 3 0 - 3 0 - 2 8 Steatosis Inflammation Ballooning Injury Maximum Score NASH Requires a Score of  4 with at least 1 Point from Ballooning Injury

  21. WHAT IS NON-ALCOHOLIC?

  22. Benefits of Beer • Religion • Patriot • Government 9 Patron Saints Ben Franklin NIAAA

  23. Beer Is Proof That God Loves Us And Wants Us To Be Happy - Ben Franklin

  24. Relative Mortality (All Causes) 1.6 1.4 1.2 1.0 0.8 0.6 0.4 Non Wine Drinkers Wine Drinkers 0 1-7 8-21 22-35 35

  25. Risk Factors for Fibrosis in NAFLD OR95%CIP Age, years 1.07 1.04 – 1.08 <0.0001 Diabetes, yes vs. no 2.54 1.75 – 3.69 <0.0001 Alcohol usage, not abstinent vs abstinent 0.53 0.37 – 0.75 0.0004

  26. Benefits of Alcohol in NonAlcolic Fatty Liver Disease • Improves Insulin Resistance • Decreases ALT • Less NASH in Bariatric Surgery Pts • Less Fibrosis in Nash CRN

  27. Practical Conclusions • Histologic Definition • Fat + Ballooning Degeneration • Fat + Fibrosis • Exclusion Limit for Daily Alcohol Use • 7 units per wk for women • 14 units per wk for men

  28. Non-Alcoholic Fatty Liver Disease • What is it? • Why is it Important? • How do you treat it?

  29. The Importance of Any Disease Determined by: • Natural History • Prevalence

  30. Progressive FibrosisSteatosis Alone (10 Year Follow-Up) Teli (1995) 1/40 Matteoni (1999) 2/49 Dam-Larsen (2003) 1/109

  31. Matteoni Follow-up (n = 174) NASH Steatosis Indeterminant (66) (75) (32) Mortality 16% 2% 0% (LR) Confirmed by Kaplan Meier .0043

  32. Natural History of NASH 20% 30 - 40% CIRRHOSIS Liver Related Death NASH (2%) ? (8%) Sub-Acute Failure HCC Post-OLTX Recurrence

  33. Survival in NAFLD 1.0 0.8 0.6 0.4 0.2 0 Expected Observed Survival (%) p = 0.005 0 2 4 6 810 12 14 16 Time (years) Adams, 2005

  34. Survival in NAFLD 1.0 0.8 0.6 0.4 0.2 0 NAFLD patients Reference population n=129 0 5 10 15 20 Time (years) Ekstedt, 2006

  35. Survival in Steatosis 1.0 0.8 0.6 0.4 0.2 0 Steatosis Reference population 0 5 10 15 20 Time (years) Ekstedt,2006

  36. Survival in NASH 1.0 0.8 0.6 0.4 0.2 0 NASH Reference population p<0.01 0 5 10 15 20 Time (years) Ekstedt, 2006

  37. Risk factors for mortality: Diabetes (p< 0.005) Age (p < 0.001) Cirrhosis (p< 0.02) Increased mortality:* cardiovascular disease liver disease Subjects with NAFLD have a greater than expected mortality compared to matched controls Adams et al, Gastroenterology, 2005, 129:113-121 * Ekstedt et al, Hepatology, 2006, 44:865-873 * Sanyal et al, Hepatology, 2006, 43:682-689

  38. SUMMARY • NASH is Not a Benign Disease • Cirrhosis Develops in 20-25% of Cases • -Liver Related Deaths in 10% • The Prevalence is High • and Increasing World Wide

  39. The Importance of Any Disease Determined by: • Prevalence • Natural History

  40. Metabolic Syndrome(NHANES III, 1988-1994) OVERALL PREVALENCE 24% Diagnosis Based on Elevated Serum Enzymes

  41. Dallas Heart Study Hepatic Triglyceride Content (%) * Hepatic Steatosis (%) Subjects All Black White Hispanic 3.6 (2.1 – 6.6) 3.2 (2.0 – 5.3) 3.6 (2.1 – 7.3) 4.6 (2.6 – 10.3) 31 24 33 45 * Based on NMR and presented as Median (interquartiles) Browning, 2005

  42. Prevalence of NAFLD(Updated) NASH 6-8% Steatosis 30%

  43. Epidemiology of NAFLD Country Cases (in millions) Prevalence (%) • USA • Italy • Japan • Taiwan • India • 30 • 30 • 30 • 37 • 24.5 • 90 • 17 • 78 • 8 • 240

  44. SUMMARY • NASH is Not a Benign Disease • Cirrhosis Develops in 20-25% of Cases • -Liver Related Deaths in 10% • The Prevalence is High in the United • States and Increasing World Wide

  45. The Metabolic Syndrome NAFLD Diabetes Metabolic Syndrome Cardiovascular Cancer

  46. Patient Demographicsin NAFLD Patients StudyNAgeFemaleDiabeticObese↑TGs (%)(%)(%)(%) Matteoni 132 53 53 33 70 92 (1999) Angulo 144 51 67 28 60 27 (1999) Marchesini 304 42 17 7 25 3 (2003) Angulo 733 48 47 30 60 60 (2007) NASH CRN 1,266 50 64 31 62 55 (2010)

  47. Metabolic Syndrome Fatty Liver (n=63) NASH (n=110) BMI Waist(cm) % Hypertension % Low HDL % Hyperglycemia HOMA-R % Metabolic Syndrome(%) 28 96 53 57 60 3.2 67 29 100 72 76 91 4.2 88 Marchesini, 2003

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