Oral Insulin

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Oral Insulin

Type 1 Diabetes Prevention• Focus has been on 1 st degree relatives, at 10-fold higher risk for T1DM than general population– Overall risk for siblings is ~4%– Screened > 100,000 first degree relatives inDPT-1• Ultimately, will need to find means to apply togeneral population, not just first degree relatives– 90% of new onset T1DM occurs in families withoutproband


Oral Tolerance: Mode of ActionOral AntigenProtective CytokinesRegulatory (Th2 / Th3)Lymphocytes ProducingProtective CytokinesInhibition of β-CellAutoimmunity andPrevention of DMInsulin Producingβ-cellsAutoimmuneLymphocytes


Effect Of Oral Insulin On Progression ToT1DMSkyler et al, Diabetes Care 2005, 28: 1068


Effect Of Oral Insulin On Progression To T1DMOnly subjects with IAA > 80Oral insulin may delay DM onset ~ 4.5 yrsSkyler et al, Diabetes Care 2005, 28: 1068


TRIGR:NIP:POINT:BabyDiet:GeneticPredisposition%Beta CellMassOngoing Or PlannedPrimary Prevention Trials For Type 1 DM100avoidance of cow’s milkomega 3 fatty acidsinsulin antigenglutenVitamin D75AutoAbs501 oAbnormal Glucose Tolerance Test25Clinical DxYears0


Secondary Prevention Trials For Type 1 DM25-50% risk for DM in next 5 yrs100%Beta CellMass75Insulin: oral, intranasalGAD alum50AutoAbs2 o25Years0


Tertiary Prevention Trials For Type 1 DM> 50% chance of developing DM in next 5 yrs100%Beta CellMass7550Anti-CD3 mAbAutoAbsImpaired Glucose Tolerance25Years0


Natural History Of Type 1 DMGeneticPredisposition100EnvironmentalInsult%Beta CellMass755025Clinical DxHoneymoonYears0


‘New Onset’ Vs ‘At Risk’ Trials• Easier to find subjects, may be more motivated for recruitment• By the time of diagnosis, there may be > 15-40% of beta cellfunction remaining• Maintenance of beta cell function over time, even if onsupplemental insulin, is valuable– Decrease risk of hypoglycemia, lower HbA1C, lower risk forcomplications– Metabolic memory: early control can have long term effects• May be valuable lessons learned regarding safety and efficacy– Past experience with cyclosporine– Can prolong honeymoon• Not all respond; toxicities; effect wanes over time or whenoff drug– Some Rxs may accelerate disease process• Interventions at this stage may guide us for prevention studies

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