We have further developed several tools required for the conduct of diabetes clinical trials. Infrastructure for inpatients and outpatients will be described separately. For Clinical Center inpatients with hyperglycemia, we continued to grow the new Blood Glucose Management Service (abbreviated BGMS). Any primary care team interested in turning over all insulin-based blood glucose management decisions to our multidisciplinary team can do so by submitting a consult. The team, consisting of 2 attending physicians who share call, 2 nurse practitioners, a pharmacist, a certified diabetes educator, and both pediatric and adult endocrine fellows, assumes 24 hour/day and 365 day/year responsibility for insulin orders and glycemia control for such patients. The team rounds daily, reviews patient status and blood glucose values, then writes insulin orders and daily notes (all in the electronic medical record) to maintain near-normal glycemia. The team has already been successful with its teaching mission, i.e. diabetes treatment objectives and strategies are being clearly communicated to patients, nursing staff, and physicians. Physician providers have demonstrated their support for the service by the number of patients referred in that the service follows approximately 4 inpatients each day. We are developing tools to capture research relevant data from the patients we follow, and management questions are uncovered as good research questions. We are attempting to develop other research tools designed to measure the services impact on inpatient morbidity and mortality, as we continue to support other NIH protocol participants with difficult to control hyperglycemia. For our outpatient clinical protocols, we focus on preserving or even promoting pancreatic beta cell function is individuals with T1DM. Data from several studies have now clearly demonstrated that in 2009, the safest and most effective way to preserve beta cell function is to maintain blood glucose concentrations within normal (or near-normal) ranges. Further, for protocols designed to assess a treatments ability to preserve beta cell function, power analyses mandate enrolling approximately 80 to 120 individuals with recent onset T1DM. Enrolling that protocol participant pool in a reasonable time means casting broadly (geographically speaking), and (sadly) diabetes care delivery in the general community is not geared to adequately support patients to promote near-normal glycemia. We can easily highlight the compromises required to date by citing our recently completed protocols: we either referred patients to their local health providers for diabetes care (and glycemia control subsequently fell below modern treatment goals), or the protocol enrolled sufficiently small patient numbers that we could provide intensive-insulin management advice using e-mail and telephone contact. For all these reasons, we have worked to develop systems allowing our NIH team to mass produce diabetes care delivery such that all protocol participants could enjoy intensive-insulin managements benefits. We have developed a system for patients to employ a web-based blood glucose reporting system that will allow all outpatients we follow with diabetes to automatically download finger-stick blood glucose values from their meters to a centralized, secure data base that both they and their health care team can access 24 hours a day, 365 days a year. Further, the system serves as a secure website allowing safe communication between the patient and the health care team via the web, allowing for the frequent dose modifications inherent in any intensive insulin management regimen. We also established a legal agreement with a blood glucose meter company (LifeScan) to facilitate data transfer from their machines to the web-based system. We have also developed assays to detect anti-GAD and anti-IA2 autoantibody titers relevant for our T1DM immunotherapeutic clinical trials. We participated in the international Diabetes AutoAntibody Standardization Program (DASP) workshop in 2006 to validate our laboratory's assays, and for one of the two assays (IA2) the NIH lab scored best in the world for sensitivity/specificity. In September 2007 we also participated and again our performance was outstanding. Our most recent DASP workshop performance was also outstanding- we again ranked as one of the best in the world for IA2 autoantibody sensitivity/specificity. Along with some extra-mural collaborators, we have put together and have initiated a protocol enrolling individuals with recent onset T1DM to test whether intensive insulin management coupled with a glucagon-like-peptide 1 (GLP1) receptor agonist plus a proton pump inhibitor and immunomodulation will prolong or even promote beta cell function. The trials central hypothesis is supported by considerable rodent data. In addition, we've recently established a diabetes clinic and a natural history protocol enrolling individuals with suspected immune mediated diabetes. The clinic and the protocol will serve mutliple purposes. An important one will be to provide a population base for clinical endocrine fellow training with regard to diabetes care delivery
