Should you be Gluten Free? Gluten Sensitivity: Today s Most Under Recognized Medical Condition. Disclosures. Gluten Confusion 2/10/2014

Transcription

1 Disclosures Gluten Sensitivity: Today s Most Under Recognized Medical Condition Author: South Beach Diet Gluten Solution Arthur Agatston Should you be Gluten Free? Gluten Confusion What is gluten? What are gluten related disorders? Are gluten related disorders increasing? Why is gluten a big deal now? 1

2 Gluten Molecule Bran (Fiber) A Wheat Seed Endosperm (Starch) Gluten (Protein) Germ (Nutrients) BMC Medicine 2012, 10:13 Wheat Processing-Whole Grain to Gluten Rich White Flour Gluten Molecule Pathophysiology of Gluten Related Disorders 2

3 Gluten vs. Other Proteins Gluten Molecule AA-Tight Junctions BMC Medicine 2012, 10:13 Gluten Digestion Colon Individual Amino Acids Peptides-Gliadin 3

4 Calcium B12 Iron Autoimmune Thyroiditis Molecular Mimicry Inflammation Malabsorption Gluten Confusion What is gluten? What are gluten related disorders? Are gluten related disorders increasing? Why is gluten a big deal now? What Are They? Celiac Disease Gluten Sensitivity Wheat Allergy Baker s Asthma Wheat-dependent exerciseinduced anaphylaxis Dermatitis Herpetiformis Gluten Ataxia Consensus Conference CBMC Medicine 2012, 10:13 4

5 Celiac Disease Time line Celiac Disease Time line (continued) Antiquity 1890s 1940s 1950s Aretaeus of Cappadocia describes well fed, but undernourished children Samuel Gee describe digestive disorder in children, possibly diet related Willem-Karel Dicke, Dutch pediatrician recognized in WWII celiac children better without wheat Gluten identified as culprit in wheat; small bowel pathology described 1970s Flexible endoscopy makes small bowel bx and Celiac disease more easily diagnosed: Celiac prevalence thought to be 1/10,000 Genetic and antibody tests makes screening feasible; Fasano finds Celiac Prevalence 1/133 Discovery of Atypical Celiac Disease Gluten related disorder consensus conference establishes Non Celiac Gluten Sensitivity as an entity Gluten Related Symptoms/Conditions GRD The New Great Imitator Typical Diarrhea Bloating Abdominal Cramps Flatulence Common Atypical Migraine headaches Joint Pains Fatigue Brain Fog Reflux Esophagitis Type 1 Diabetes Other Autoimmune Diseases Skin rashes, psoriasis Consensus Conference CBMC Medicine 2012, 10:13 5

6 Symptoms of Gluten Sensitivity Volta, U. & De Giorgio, R. Nat. Rev. Gastroenterol. Hepatol. 9, (2012 Dx of Celiac Disease-need 4 of 5 1. Typical symptoms of CD 2. Positivity of serum CD IgA class autoantibodies at high titer -anti-ttg, anti-ema 3. HLA-DQ2 and/or HLA-DQ8 genotypes (40% of controls) 4. Celiac enteropathy found on small bowel biopsy 5. Response to a gluten free diet Consensus Conference CBMC Medicine 2012, 10:13 Diagnosis of Gluten Sensitivity Gluten ingestion elicits symptoms Symptoms disappear quickly after gluten withdrawal Reintroduction of gluten causes symptoms Neg celiac disease serology (IgA tissue transglutaminiase and IgA endomysial ab) Antigliadin ab present in 50% Normal intestinal mucosa or mild increase in intraepidthelial lymphocytes HLA-DQ2/DQ8 positive in 40% Consensus Conference CBMC Medicine 2012, 10:13 The Spectrum of Gluten Sensitiviy 6

7 The Gluten Free Athlete PS 70 yo WF Irritable Bowel, arthralgias, anxiety, brain fog Intermittently Positive ANA, RF, CRP- Complement, followed by rhematologist Osteopenia, low B12, low vitamin D Negative workup for celiac disease Resolution of symptoms, ANA, RF, CRP on gluten free diet-1 yr f/u Gluten Confusion What is gluten? What are gluten related disorders? Are gluten related disorders increasing? Why is gluten a big deal now? Prevalence of Celiac Disease in At-Risk and Not-At-Risk Groups in the United States = 100x more than previous estimates Fasano A. Arch Intern Med. 2003;163:

8 Increased Prevalence of Celiac Disease over past 50 Years- 4 fold increase The Incidence and Risk of Celiac Disease in a Healthy US Adult Population from Rubio-Tapia, A GASTROENTEROLOGY 2009;137:88 93 Riddle, MS. Am J Gastroenterol 2012; 107: Increase Celiac in Finland + autoimmune type 1 diabetes Gluten Confusion DM1 Celiac What is gluten? What are gluten related disorders? Are gluten related disorders increasing? Why is gluten a big deal now? Aliment Pharmacol Ther 2009; 26:

9 2/10/2014 Wheat Processing-Whole Grain to Gluten Rich White Flour to Starch and Gluten? Gluten Overload Ubiquitous Gluten Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment Total Carbs % Carbs From Fiber Gross LS, Am J Clin Nutr 2004;79:

10 2/10/2014 The Modern Gluten Trifecta Traditional v. Industrial Bread Making 1960s NSAIDS Bread Chemistry (Royal Society of Chemistry) The no time dough Sourdough Bread Made from Wheat and Nontoxic Flours and Started with Selected Lactobacilli is Tolerated in Celiac Sprue Patients A Gluten is digested B The traditional bread making process has a serious drawback. After mixing, the dough must be left to prove for at least three hours for the bubble expansion to develop the gluten. The dough is then knocked back to remove most of the CO2... before being allowed to prove a second time before it goes into the oven. Although this long fermentation develops flavor, it is costly in time, with bakers having to rise early in the morning to produce fresh bread for the day Research efforts were therefore directed to developing a no time dough: by increasing the amount of yeast; by mixing vigorously to increase the rate of bubble formation; and by adding oxidizing agents to promote disulfide bond formation. FIG. 3. Agglutination test with K 562(S) cells. (A) Cells treated with the PT digest of the chemically acidified dough at a concentration of g/liter. (B) Cells treated with the PT digest of the sourdough started with selected lactobacilli, incubated for 24 h at 37 C, at a concentration of 3.5 g/liter. Di Cagno R. APPLIED AND ENVIRONMENTAL MICROBIOLOGY 2004;70:

11 Celiac Disease and Gut Flora What About Bacteria in our Gut? Kids and adults with celiac disease have different gut flora than controls Many of the symptoms of celiac disease are associated with changes in gut flora Gut flora changes with age and may explain the variable presentations of celiac disease and gluten sensitivity over time Gut Flora and Digestive Enzymes JFK had Celiac Disease (Irish Connection?) In addition, the incidence of celiac disease is much higher in patients with autoimmune adrenal and thyroid disease (35), an interesting fact given that Kennedy had gastrointestinal symptoms (cramping, diarrhea, inability to gain weight) for most of his life Nature April 2010;464 :87-88 Mandel LR Ann Intern Med. 2009;151: Robert Caro, Passage of Power. 11

12 Bacteria: Friend or Foe? H. Pylori H. Pylori: Friend or Foe? Blaser MJ Nature Reviews-Microbiology 2009;7: 887 Blaser MJ EMBO 2006;7:957 Helicobacter pylori Colonization Is Inversely Associated with Childhood Asthma and Rhinitis, Dermatitis, Eczema and Rash Decreased Risk ofceliac Disease in PatientsWith Helicobacter pylori Colonization Men H Pylori Celiac Disease Women Chen Y. J Infectious Disease 2008;198: 553 Benjamin Lebwohl, Martin J. Blaser, Am J Epidemiol. 2013;178(12):

13 The Human Microbiome at Interface of Health and Disease Irritable Bowel Symptoms Response to a Gluten Free Diet-(double blind placebo controlled) Blaser, MJ Nature Reviews: 2012;13:260 Am J Gastroenterol 2011; 106: ? Antibiotics and Obesity Fighting Obesity with Bacteria Human Twins Mice Walker AW Science 2013;341:

14 NSAID and Small Bowel NSAID Use Fortun PJ Curr Opin Gastroenterol 2005 Mar;21(2): The Perfect Storm: Over past 30 years We grow wheat differently We process wheat more and differently We use more preservatives We bake bread differently We fortify wheat and non wheat foods with gluten We consume more processed carbs We abuse antibiotics We abuse NSAIDs Gluten Related Disorders What are they? How Common are they? Is the incidence GRDs Changing? Why now? What is Gluten Free? Should you be gluten free or gluten aware? Consensus Conference CBMC Medicine 2012, 10:13 14

15 Gluten Related Disorders What are they? How Common are they? Is the incidence GRDs Changing? Why now? What is Gluten Free? Should you be gluten free or gluten aware? Safe Threshold of Gluten < 10 mg, <20 PPM ~ 1/48 th slice of bread Consensus Conference CBMC Medicine 2012, 10:13 MK 46 Dermatolgist Long history of severe GI symptoms Family history of GI problems-mother Weight gain, inc glucose SBD GI symptoms resolved 1 st time in 30 yrs Celiac disease dxed Put on gluten free diet No symptoms but small bowel progression Strategy for Gluten Related Disorders If suspicion of gluten problem, first R/O Celiac Disease with anti ttg, anti EMA and HLA DQ2, DQ8, duodenal bx if needed If Celiac Disease->Gluten Free If no celiac disease-gluten free for 1 month, then gluten aware 15

16 72 yo WM: Celiac Disease Recent Onset Angina with TC= yo WM Recent Onset Angina with TC=114 Long Course of Antibiotics Celiac Disease Thank You 16

17 Alllessio Fasano Scientific American August 2009;