Ignite Creation Date:
2025-12-24 @ 3:06 PM
Ignite Modification Date:
2025-12-26 @ 6:11 AM
Study NCT ID:
NCT00837759
Status:
TERMINATED
Last Update Posted:
2013-01-03
First Post:
2009-02-04
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Novel Therapy to Preserve Beta Cell Function in New Onset Type 1 Diabetes
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}, {'id': 'D003920', 'term': 'Diabetes Mellitus'}], 'ancestors': [{'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D007328', 'term': 'Insulin'}, {'id': 'D064747', 'term': 'Lansoprazole'}, {'id': 'D000068900', 'term': 'Sitagliptin Phosphate'}], 'ancestors': [{'id': 'D011384', 'term': 'Proinsulin'}, {'id': 'D061385', 'term': 'Insulins'}, {'id': 'D010187', 'term': 'Pancreatic Hormones'}, {'id': 'D036361', 'term': 'Peptide Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D053799', 'term': '2-Pyridinylmethylsulfinylbenzimidazoles'}, {'id': 'D013454', 'term': 'Sulfoxides'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D001562', 'term': 'Benzimidazoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D011719', 'term': 'Pyrazines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'malekr@mail.nih.gov', 'phone': '3015945288', 'title': 'Dr. Rana Malek', 'organization': 'NIDDK, National Institutes of Health'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.', 'otherNumAtRisk': 7, 'otherNumAffected': 3, 'seriousNumAtRisk': 7, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Hypoglycemic events', 'notes': 'According to the protocol, hypoglycemia adverse events are described as follows:\n\nMild= BG \\< 65 mg/dL Moderate = BG \\< 54 mg/dL \\& symptomatic Severe = patient required assistance to obtain treatment for the event.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 104, 'numAffected': 3}], 'organSystem': 'Metabolism and nutrition disorders'}, {'term': 'Rhinitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Eczema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Warts', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Thrombocytopenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'General disorders'}, {'term': 'Anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in C-peptide', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.51', 'spread': '0.53', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation", 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Only 3 subjects completed study'}, {'type': 'SECONDARY', 'title': 'Glycemia Control (Change in HbA1c Level)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.17', 'spread': '0.45', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation", 'unitOfMeasure': 'Percentage', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Only 3 subjects completed study'}, {'type': 'SECONDARY', 'title': 'Change in Insulin Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.02', 'spread': '0.32', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation", 'unitOfMeasure': 'U/kg/day', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Anti-GAD Autoantibody Titers', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'classes': [{'categories': [{'measurements': [{'value': '119278', 'spread': '174649', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation", 'unitOfMeasure': 'Titers', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Anti-IA2 Titer', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'classes': [{'categories': [{'measurements': [{'value': '-29212', 'spread': '49956', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation", 'unitOfMeasure': 'Titers', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in ZnT8 Autoantibody Titer', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.11', 'spread': '0.19', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation", 'unitOfMeasure': 'Titers', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}]}], 'dropWithdraws': [{'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'T1D Group', 'description': 'Subjects between the ages of 16 and 30 years, with T1D diagnosed within the preceding 6 month period, and with measurable circulating C-peptide levels.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age Continuous', 'classes': [{'categories': [{'measurements': [{'value': '21.9', 'spread': '3.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 7}}, 'statusModule': {'whyStopped': 'Changes to study personnel.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2009-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2012-12', 'completionDateStruct': {'date': '2011-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2012-12-31', 'studyFirstSubmitDate': '2009-02-04', 'resultsFirstSubmitDate': '2012-03-24', 'studyFirstSubmitQcDate': '2009-02-04', 'lastUpdatePostDateStruct': {'date': '2013-01-03', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2012-09-24', 'studyFirstPostDateStruct': {'date': '2009-02-05', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2012-10-24', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-03', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in C-peptide', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation"}], 'secondaryOutcomes': [{'measure': 'Glycemia Control (Change in HbA1c Level)', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation"}, {'measure': 'Change in Insulin Dose', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation"}, {'measure': 'Change in Anti-GAD Autoantibody Titers', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation"}, {'measure': 'Change in Anti-IA2 Titer', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation"}, {'measure': 'Change in ZnT8 Autoantibody Titer', 'timeFrame': "6 months following the protocol subject's randomization/treatment initiation"}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Type I Diabetes', 'Preserve Beta Cell Function', 'Sitagliptin', 'Lansoprazole', 'GAD65 (Diamyd)', 'Diabetes', 'Type 1 Diabetes', 'T1DM'], 'conditions': ['Diabetes Mellitus Type 1', 'Autoimmune Diabetes']}, 'referencesModule': {'references': [{'pmid': '11244033', 'type': 'BACKGROUND', 'citation': 'Bach JF, Chatenoud L. Tolerance to islet autoantigens in type 1 diabetes. Annu Rev Immunol. 2001;19:131-61. doi: 10.1146/annurev.immunol.19.1.131.'}, {'pmid': '1935920', 'type': 'BACKGROUND', 'citation': 'Lernmark A, Barmeier H, Dube S, Hagopian W, Karlsen A, Wassmuth R. Autoimmunity of diabetes. Endocrinol Metab Clin North Am. 1991 Sep;20(3):589-617.'}, {'pmid': '11742411', 'type': 'BACKGROUND', 'citation': 'Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature. 2001 Dec 13;414(6865):792-8. doi: 10.1038/414792a.'}]}, 'descriptionModule': {'briefSummary': 'Background:\n\n* Type 1 diabetes (T1D) occurs when the immune system attacks insulin-producing cells (beta cells) in the pancreas, resulting in their death.\n* Insulin injections currently are the best method for controlling blood sugar in individuals with T1D. However, animal studies have shown that the drugs sitagliptin and lansoprazole can help reverse beta cell damage or develop new beta cells. In addition, Diamyd has been shown to weaken the immune process that attacks pancreatic beta cells.\n\nObjectives:\n\n* To find out whether a combination treatment of sitagliptin, lansoprazole, and Diamyd will help maintain functioning beta cells and/or cause new beta cells to form.\n* To determine how the drug combination affects insulin doses and blood sugar control.\n* To determine whether the drug combination affects the immune response involved in T1D.', 'detailedDescription': 'Type 1 diabetes (T1D) is the end result of immune mediated beta-cell destruction. It is generally accepted that at the time of T1D is diagnosed, an individual has lost most (60-80%) of his/her beta cell function. The loss of insulin-producing beta cells is believed to occur over a period of months to years and individuals can retain some endogenous insulin production even years after clinical diagnosis of diabetes. The presence of residual beta cell mass may signify a complex interplay between the auto-destructive immune response and the capacity for limited beta cell regeneration. When initiated at T1D onset, immunosuppression has been shown to preserve beta cell function, but with significant and limiting toxicities. Selectively targeting the pathogenic T-cells involved in T1D development and progression could achieve the same objective with less toxicity. Various studies of the non-obese diabetic (NOD) mouse model of spontaneous autoimmune diabetes have demonstrated that administering glutamic acid decarboxylase (GAD65), a beta cell autoantigen, can prevent the immune destruction and delay or prevent diabetes onset. Preclinical studies have also identified several growth factors, including epidermal growth factor (EGF), glucagon-like peptide 1 (GLP-1), and gastrin, that appear to promote beta cell proliferation. We seek to test the potential for preserving beta cell function early in the disease course of T1D by combining antigen-specific immunomodulation with regenerative stimuli.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '30 Years', 'minimumAge': '16 Years', 'healthyVolunteers': False, 'eligibilityCriteria': '* INCLUSION CRITERIA:\n\n 1. Recently diagnosed (within the preceding 4 months of screening) diabetes clinically consistent with T1D:\n\n A. Positive for anti-GAD antibody.\n\n B. BMI between 19 and 28 kg/m2; for those between the ages of 16 to 18, the BMI must be within 10th to 90th percentile for the age.\n 2. Ages between 16 and 30 years, inclusive\n 3. Random plasma C-peptide level of equal to or greater than 0.20 nmol/L\n 4. Willingness and ability to institute intensive insulin-based glucose management.\n\nEXCLUSION CRITERIA:\n\n1. Diabetic nephropathy with a creatinine clearance less than 60 cc/min or 24 hour urine albumin greater than 300 mg\n2. Insulin requirements greater than 0.8 units/kg/day at the end of the run-in period\n3. Regular use of a proton pump inhibitor within 3 months of enrollment\n4. Use of GLP-1R agonist or DPP-4 inhibitor within 6 months prior to enrollment\n5. Use of immunosuppressive therapy in the preceding 12 months\n6. Evidence of chronic infection, for example, known human immunodeficiency virus (HIV) or hepatitis\n7. History of any malignancy other than a treated basal or squamous skin cancer\n8. Any chronic medical condition to unduly increase risk for the potential enrollee as judged by study investigators\n9. Pregnancy, breastfeeding or planned pregnancy within two years, women of reproductive age not using an effective mode of contraception and unwilling to continue adequate contraception until 1 year after the last study drug administration\n10. Any other co-existing condition/circumstances that would make patient unsuitable to participate in the study, as deemed by the investigators. For example, study investigators would exclude any potential candidate with any of the following (but the list is not inclusive):\n\nA. Clinically significant past history of an acute reaction to vaccines or other drugs\n\nB. Recent participation in other clinical trials with a new chemical entity\n\nC. A history of alcohol or drug abuse\n\nD. Significant neurological conditions like epilepsy, head trauma, or cerebrovascular accidents\n\nE. Individuals with significant gastrointestinal disorders determined by the study investigators to influence either study safety or data interpretation. Such conditions include but are not limited to gastroparesis and gastric bypass surgery\n\nF. Individuals with conditions prone to hypergastrinemia (Zollinger-Ellison syndrome, use of histamine-2 receptor blockers) or hypogastrinemia (gastric surgery).'}, 'identificationModule': {'nctId': 'NCT00837759', 'briefTitle': 'Novel Therapy to Preserve Beta Cell Function in New Onset Type 1 Diabetes', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'Novel Therapy Combining Regenerative Stimuli Immunomodulation to Preserve Beta Cell Function in New Onset Type 1 Diabetes', 'orgStudyIdInfo': {'id': '090056'}, 'secondaryIdInfos': [{'id': '09-DK-0056', 'type': 'OTHER', 'domain': 'National Institutes of Health Clinical Center'}, {'id': '09-DK-0056', 'type': 'OTHER', 'domain': 'NIHCC'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'T1D group', 'description': 'This study was terminated prior to full subject accrual because of changes to study personnel. The original study design was changed from a double-blind, placebo-controlled study to an open-label pilot study in order to collect safety data on enrolled subjects prior to study termination.', 'interventionNames': ['Drug: Insulin', 'Drug: Lansoprazole', 'Drug: Sitagliptin', 'Biological: Diamyd', 'Drug: GAD65 (Diamyd)']}], 'interventions': [{'name': 'Insulin', 'type': 'DRUG', 'armGroupLabels': ['T1D group']}, {'name': 'Lansoprazole', 'type': 'DRUG', 'armGroupLabels': ['T1D group']}, {'name': 'Sitagliptin', 'type': 'DRUG', 'armGroupLabels': ['T1D group']}, {'name': 'Diamyd', 'type': 'BIOLOGICAL', 'armGroupLabels': ['T1D group']}, {'name': 'GAD65 (Diamyd)', 'type': 'DRUG', 'armGroupLabels': ['T1D group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'National Institutes of Health Clinical Center, 9000 Rockville Pike', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}], 'overallOfficials': [{'name': 'Balow James, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)', 'class': 'NIH'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Clinical Director Intramural NIDDK', 'investigatorFullName': 'James Balow', 'investigatorAffiliation': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)'}}}}