Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Pancreatitis, Chronic Clinical Trial

— INSPPIRE 2  

Official title:

Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) CPDPC16-03 Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03672422
• Other study ID #: 201705709
• Secondary ID: 3U01DK108334
• Status: Completed
• Start date: June 30, 2017
• Est. completion date: August 31, 2020

Study information

• Verified date: November 2020
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The investigators will enroll a total of 628 patients under 18 years of age with ARP or CP. Included in the total are the 357patients in the INSPPIRE 1 database who are planned to be reenrolled under this protocol over the next 4 years. Patient questionnaires and physician surveys will be applied at the time of enrollment and annually thereafter as long as possible. At the first study visit after turning 18 years of age, the patient will sign the informed consent to continue in the study. Specifically, the investigators will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

Description:

Disease Burden Pain. The pattern of the pain (constant versus episodic), its frequency, duration, visits to the emergency room or hospitalizations for pain, impact of pain on quality of life will be recorded in questionnaires. The intensity of the pain will be measured at enrollment, during an attack and annually using FACES Pain Scale-Revised, a self-report questionnaire validated for children >4 y/o. The names, dosing and frequency of medications taken for pain will also be queried.

Health-Related Quality of Life (HRQOL). An age-specific instrument validated for United States children will be used to measure HRQOL at enrollment and annually thereafter. Parents of children 5-18 years old will complete Child Health Questionnaire Parent Form 50 questions (CHQ PF-50). Children >10 years old will answer Child Health Questionnaire Child Form 87 questions (CHQ-87). Adults >18 years old will not complete a health-related questionnaire. These questionnaires capture physical functioning, social, emotional, physical and behavioral limitations, bodily pain, general behavior, mental health, self-esteem, general health perceptions, change in health and parental emotional impact.

Depression and anxiety. Depression and anxiety are strong predictors of chronic pain and pain-related disability in children, but it is not known whether this applies to children with ARP or CP. The investigators will assess for depression and anxiety in the INSPPIRE cohort at the time of enrollment and annually thereafter. The investigators will utilize the Child Behavioral Checklist (CBCL), one of the most widely-used standardized measures in child psychology for evaluating maladaptive behavioral and emotional problems in preschool subjects aged 1½ to 5 years and in school-age subjects between the ages of 6 and 18. For preschool-age children, the CBCL/1½-5 (completed by parents or surrogates) will be used. For school-age children 6-18 y/o, the investigators will utilize CBCL/6-18 y/o (completed by parents or surrogates). Children who are 11-18 y/o will answer a self-report questionnaire (Youth-Self Report Form or YSR/11-18). CBCL assesses internalizing (i.e., anxious, depressive, and over controlled) and externalizing (i.e., aggressive, hyperactive, noncompliant, and undercontrolled) behaviors. Adults >18 years old will not complete a behavioral checklist.

Patients/parents will spend approximately 2 hours answering questionnaires; their time will be compensated at $50 per visit. Patients will be enrolled during clinic visit as outpatient or as an inpatient. Alternatively, questionnaires can be applied over the phone or completed at home and returned via mail if the patient is unable to travel. Self-addressed stamped envelopes will be given to the patient/parent as needed for returning the questionnaires.

Disease Sequelae

The presence of exocrine pancreatic insufficiency and glucose intolerance/diabetes will be monitored at the time of enrollment and annually thereafter. Monitoring will include specifically:

1. Exocrine pancreatic insufficiency: defined as the presence of abnormal fecal elastase (< 100 ug/ g stool on 2 separate samples ≥ 1 month apart) or abnormal serum trypsin or serum trypsinogen.

2. Diabetes or prediabetes: Monitoring for diabetes in our cohort will include once yearly assessments with fasting glucose (diabetes range if ≥ 126 mg/dL), HbA1c (abnormal if >6; diabetic if >6.5%) and oral glucose tolerance test (OGTT). For OGTT, 1.75 grams/kg of standard glucose beverage (glucola, maximum 75 grams) will be consumed within 10 minutes at time 0. Glucose will be drawn prior to the beverage and at time 120 minutes. From this test, glycemic status will be defined as: (1) normal glucose tolerance (NGT, fasting glucose <100 mg/dL, 2 hour <140 mg/dL); (2) pre-diabetic based on impaired fasting glucose (IFG, fasting glucose 100-125 mg/dL) and/or impaired glucose tolerance (IGT, 2 hour glucose 140-199 mg/dL); or (3) diabetic (DM, fasting glucose >126 mg/dL or 2 hour glucose >200 mg/dL).

3. Nutritional status including micronutrient deficiency: To determine the nutritional sequelae of ARP or CP in children, the investigators will assess for malnutrition/obesity (weight, height, BMI, z scores; body fat mass and lean mass as measured by DXA scan), fat soluble vitamin deficiencies (serum vitamin levels for A, D, and E and bone density (DXA scan) in children with ARP or CP at the time of enrollment and annually thereafter.

The investigators will identify subjects within our cohort that presented with acute recurrent pancreatitis episodes, normal exocrine and endocrine pancreas function and normal pancreas imaging without any signs of chronicity (ARP cohort). The investigators will identify the development of CP on an annual basis as long as possible, as well as development of sequelae and disease burden as listed above.

Prospective Registry

The investigators will develop a database of children with ARP and CP. This will provide a cohort of well-phenotyped subjects for future studies targeting pathogenesis and novel therapies. The investigators will establish a process by which investigators outside of the consortium may have access to the data and biospecimens.

At enrollment, via the informed consent, subjects will choose whether or not to allow use of their biological samples for this study, future research, genetic analysis, genetic analysis for future research, and any type of future research. They will also choose whether or not we may keep their name and personal information in a registry to allow us to contact them for other future research.

BIOSPECIMEN COLLECTION

Sample collection for deoxyribonucleic acid (DNA): The subject will be able to give either blood or saliva. Six ml of blood will be collected from subjects in an ethylenediaminetetraacetic acid tube or 2 ml saliva samples in Oragene DNA collection kits then labeled with the barcoded specimen labels provided by the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) Coordinating Center. The specimen labels provided by CPDPC include a specimen identification (ID) number and barcode. Subject identifiers (for example names or initials) are not included on the labels. Before shipping the specimens to the central repository the specimen ID number from the label will be connected to the patient information in the CPDPC's secure IIMS Specimen Manager system. After the specimen ID number is linked to the subject in the CPDPC system the samples will be submitted to the central repository for the study via overnight courier. The central repository for DNA will be at the University of Iowa. The central repository at Iowa will not have access to the link that connects to the patient's personal identifiers in the Integrated Information Management System (IIMS). The central repository will log receipt of the specimens into the CPDPC IIMS Specimen Manager system using the specimen ID from the labeled vials. The central repository will process the specimens into aliquots for the extraction of genomic DNA following the CPDPC specimen processing described in the appendices. The aliquots will be labeled with CPDPC supplied labels and stored in a freezer at -80 degree Centigrade. The CPDPC aliquots labels contain barcodes and specimen ID numbers that do not link the aliquots to each other. The only link to the subject information resides in the secured database at the CPDPC coordinating and data management center. The central repository laboratory staff and the study researchers do not have access to this link. At the end of the study the specimens stored in the central repository at Iowa will be transferred to a central repository at National Institute of Diabetes and Digestive and Kidney Diseases.

Urine collection for bio-markers: To be completed only at sites identified by the lead site to collect urine samples. Not all sites will be collecting urine. See Appendix 14.27 for collection and processing instructions. The subject will be instructed to collect a minimum of 50 mL clean-catch urine sample. A dipstick urine analysis will be performed immediately after urine collection. Urine samples will then be kept on wet ice or refrigerated until processed. Samples will be processed within 4 hours of collection. Samples will be labeled with the barcoded specimen labels provided by the CPDPC Coordinating Center. The specimen labels provided by CPDPC include a specimen ID number and barcode. Subject identifiers (for example names or initials) are not included on the labels. Before shipping the specimens to the central repository the specimen ID number from the label will be connected to the subject information in the CPDPC's secure IIMS Specimen Manager system. After processing, samples will be frozen at -80ºC. The urine processing log sheet will be completed. Samples will be stored and batch shipped to the Central repository at University of Iowa annually. The central repository will log receipt of the specimens into the CPDPC IIMs Specimen Manager system using the specimen ID from the labeled vials. The central repository at University of Iowa will not have access to the link that connects the subject's personal identifiers in the IIMS system. The central repository will log receipt of the specimens into the CPDPC IIMS Specimen Manager system using the specimen ID from the labeled vials. The CPDPC aliquots labels contain barcodes and specimen ID numbers that do not link the aliquots to each other. The only link to the subject information resides in the secured database at the CPDPC coordinating and data management center. The central repository laboratory staff and the study researchers do not have access to this link. At the end of the study the specimens stored in the central repository at Iowa will be transferred to a central repository at NIDDK.

Other known NCT identifiers

• NCT03081182

Recruitment information / eligibility

• Status: Completed
• Enrollment: 623
• Est. completion date: August 31, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

1. All patients/parents must sign an informed consent and/or assent indicating that they are aware of the investigational nature of this study.

2 Patients/parents must have signed an authorization for the release of their or their child's protected health information.

3 All children providing samples should fit the ARP or CP inclusion criteria defined below.

4 All children must be under 18 years of age at the time of enrollment.

Acute pancreatitis (AP): AP is defined as requiring 2 of the following:

1. Abdominal pain compatible with AP,

2. Serum amylase and/or lipase values =3 times upper limits of normal,

3. Imaging findings of AP, such as gland enlargement, acute inflammatory changes, and fluid collections.

ARP is defined as:

At least 2 episodes of acute pancreatitis with complete resolution of pain and a >1 month pain-free interval between episodes.

Chronic Pancreatitis:

Children with at least:

1. One irreversible structural change* in the pancreas with or without abdominal pain +/- exocrine pancreatic insufficiency +/- diabetes.

*irreversible structural changes:

• Ductal calculi, dilated side branches, parenchymal calcifications found in any imaging (abdominal ultrasound (abd US), magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP), computerized tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic US (EUS).

• Ductal obstruction or stricture/dilatation/irregularities that are persistent (for >2 months) on any imaging.

• Parenchymal atrophy, irregular contour, accentuated lobular architecture, cavities alone are not diagnostic findings for CP.

• Surgical or pancreatic biopsy specimen demonstrating histopathologic features compatible with CP (acinar atrophy, fibrosis, protein plugs, infiltration with lymphocytes, plasma cells, macrophages).

Exclusion Criteria:

• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate study interventions.

Related Conditions & MeSH terms

• Pancreatitis
• Pancreatitis, Acute
• Pancreatitis, Chronic

Intervention

Diagnostic Test:
• Blood sample
Six ml of blood will be collected from patients in an EDTA tube. 2 ml saliva samples in Oragene DNA collection kits

Behavioral:
• Patient questionnaires
Questionnaires will be completed at the baseline and annual follow-up visits to collect data that will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

Diagnostic Test:
• Saliva sample
2 ml saliva samples in Oragene DNA collection kits collected if no blood sample being collected.
• Urine sample
50 ml of urine in collection container.

Locations

Country	Name	City	State
Australia	Sydney Children's Hospital Randwick	Randwick	New South Wales
Canada	Montreal Children's Hospital	Montréal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
Israel	Hadassah University Hospital Mt. Scopus	Jerusalem
United States	Cedars-Sinai Medical Center	Beverly Hills	California
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Health University of Texas Southwestern Medical Center	Dallas	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children Indiana University	Indianapolis	Indiana
United States	University of Iowa Stead Family Children's Hospital	Iowa City	Iowa
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Children's Hospital of Philadelphia	Philipsburg	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Stanford University	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Aliye Uc	National Cancer Institute (NCI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel, 

References & Publications (18)

Abu-El-Haija M, Kumar S, Quiros JA, Balakrishnan K, Barth B, Bitton S, Eisses JF, Foglio EJ, Fox V, Francis D, Freeman AJ, Gonska T, Grover AS, Husain SZ, Kumar R, Lapsia S, Lin T, Liu QY, Maqbool A, Sellers ZM, Szabo F, Uc A, Werlin SL, Morinville VD. Management of Acute Pancreatitis in the Pediatric Population: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas Committee. J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):159-176. doi: 10.1097/MPG.0000000000001715. — View Citation

Abu-El-Haija M, Uc A, Werlin SL, Freeman AJ, Georgieva M, Jojkic-Pavkov D, Kalnins D, Kochavi B, Koot BGP, Van Biervliet S, Walkowiak J, Wilschanski M, Morinville VD. Nutritional Considerations in Pediatric Pancreatitis: A Position Paper from the NASPGHAN Pancreas Committee and ESPGHAN Cystic Fibrosis/Pancreas Working Group. J Pediatr Gastroenterol Nutr. 2018 Jul;67(1):131-143. doi: 10.1097/MPG.0000000000002023. — View Citation

Gariepy CE, Heyman MB, Lowe ME, Pohl JF, Werlin SL, Wilschanski M, Barth B, Fishman DS, Freedman SD, Giefer MJ, Gonska T, Himes R, Husain SZ, Morinville VD, Ooi CY, Schwarzenberg SJ, Troendle DM, Yen E, Uc A. Causal Evaluation of Acute Recurrent and Chron — View Citation

Giefer MJ, Lowe ME, Werlin SL, Zimmerman B, Wilschanski M, Troendle D, Schwarzenberg SJ, Pohl JF, Palermo J, Ooi CY, Morinville VD, Lin TK, Husain SZ, Himes R, Heyman MB, Gonska T, Gariepy CE, Freedman SD, Fishman DS, Bellin MD, Barth B, Abu-El-Haija M, U — View Citation

Husain SZ, Morinville V, Pohl J, Abu-El-Haija M, Bellin MD, Freedman S, Hegyi P, Heyman MB, Himes R, Ooi CY, Schwarzenberg SJ, Usatin D, Uc A. Toxic-metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management, and Future Re — View Citation

Kumar S, Ooi CY, Werlin S, Abu-El-Haija M, Barth B, Bellin MD, Durie PR, Fishman DS, Freedman SD, Gariepy C, Giefer MJ, Gonska T, Heyman MB, Himes R, Husain SZ, Lin TK, Lowe ME, Morinville V, Palermo JJ, Pohl JF, Schwarzenberg SJ, Troendle D, Wilschanski — View Citation

Lin TK, Abu-El-Haija M, Nathan JD, Palermo JP, Barth B, Bellin M, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Heyman MB, Himes R, Husain SZ, Liu Q, Maqbool A, Mascarenhas M, McFerron B, Morinville VD, Ooi CY, Perito E, Pohl JF, Rhee S, Schwa — View Citation

Morinville VD, Husain SZ, Bai H, Barth B, Alhosh R, Durie PR, Freedman SD, Himes R, Lowe ME, Pohl J, Werlin S, Wilschanski M, Uc A; INSPPIRE Group. Definitions of pediatric pancreatitis and survey of present clinical practices. J Pediatr Gastroenterol Nutr. 2012 Sep;55(3):261-5. Erratum in: J Pediatr Gastroenterol Nutr. 2013 Apr;56(4):459. Abu-Al-Haija, Maisam [corrected to Abu-El-Haija, Maisam]. — View Citation

Morinville VD, Lowe ME, Ahuja M, Barth B, Bellin MD, Davis H, Durie PR, Finley B, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Heyman MB, Himes R, Husain S, Kumar S, Ooi CY, Pohl JF, Schwarzenberg SJ, Troendle D, Werlin SL, Wilschanski M, Yen E, Uc A. Design and implementation of INSPPIRE. J Pediatr Gastroenterol Nutr. 2014 Sep;59(3):360-4. doi: 10.1097/MPG.0000000000000417. — View Citation

Perito ER, Rhee S. Relief for Young Children With Severe Chronic Pancreatitis. J Pediatr Gastroenterol Nutr. 2017 Mar;64(3):338-339. doi: 10.1097/MPG.0000000000001509. — View Citation

Pohl J, Morinville V, Husain SZ, Uc A. Toxic-Metabolic Risk Factors Are Uncommon in Pediatric Chronic Pancreatitis. J Pediatr Gastroenterol Nutr. 2016 Jun;62(6):e66-7. doi: 10.1097/MPG.0000000000001156. — View Citation

Scheers I, Palermo JJ, Freedman S, Wilschanski M, Shah U, Abu-El-Haija M, Barth B, Fishman DS, Gariepy C, Giefer MJ, Heyman MB, Himes RW, Husain SZ, Lin TK, Liu Q, Lowe M, Mascarenhas M, Morinville V, Ooi CY, Perito ER, Piccoli DA, Pohl JF, Schwarzenberg — View Citation

Scheers I, Palermo JJ, Freedman S, Wilschanski M, Shah U, Abu-El-Haija M, Barth B, Fishman DS, Gariepy C, Giefer MJ, Heyman MB, Himes RW, Husain SZ, Lin TK, Liu Q, Lowe M, Mascarenhas M, Morinville V, Ooi CY, Perito ER, Piccoli DA, Pohl JF, Schwarzenberg — View Citation

Schwarzenberg SJ, Bellin M, Husain SZ, Ahuja M, Barth B, Davis H, Durie PR, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Heyman MB, Himes R, Kumar S, Morinville VD, Lowe ME, Nuehring NE, Ooi CY, Pohl JF, Troendle D, Werlin SL, Wilschanski M, — View Citation

Ting J, Wilson L, Schwarzenberg SJ, Himes R, Barth B, Bellin MD, Durie PR, Fishman DS, Freedman SD, Gariepy CE, Giefer MJ, Gonska T, Husain SZ, Kumar S, Morinville VD, Lowe ME, Ooi CY, Pohl JF, Troendle D, Usatin D, Werlin SL, Wilschanski M, Heyman MB, Uc — View Citation

Troendle DM, Fishman DS, Barth BA, Giefer MJ, Lin TK, Liu QY, Abu-El-Haija M, Bellin MD, Durie PR, Freedman SD, Gariepy C, Gonska T, Heyman MB, Himes R, Husain SZ, Kumar S, Lowe ME, Morinville VD, Ooi CY, Palermo J, Pohl JF, Schwarzenberg SJ, Werlin S, Wi — View Citation

Uc A, Andersen DK, Bellin MD, Bruce JI, Drewes AM, Engelhardt JF, Forsmark CE, Lerch MM, Lowe ME, Neuschwander-Tetri BA, O'Keefe SJ, Palermo TM, Pasricha P, Saluja AK, Singh VK, Szigethy EM, Whitcomb DC, Yadav D, Conwell DL. Chronic Pancreatitis in the 21st Century - Research Challenges and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas. 2016 Nov;45(10):1365-1375. — View Citation

Uc A, Fishman DS. Pancreatic Disorders. Pediatr Clin North Am. 2017 Jun;64(3):685-706. doi: 10.1016/j.pcl.2017.01.010. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of time from progression from Acute Recurrent Pancreatitis to Chronic Pancreatitis	Date of diagnosis of first acute pancreatitis to date of diagnosis of chronic pancreatitis presented as minimum, maximum, median number of days and no progression to chronic pancreatitis.	3 years
Secondary	Number of subjects with abdominal pain	Presence of abdominal pain in the past year presented as number with "Yes", "No", "I don't know" and missing responses.	1 year
Secondary	Number of subjects with constant abdominal pain	Presence of constant abdominal pain described as number of subjects with "Yes", "No", "I don't know" and missing responses.	1 year
Secondary	Number of subjects with episodic abdominal pain	Number of subjects who are usually pain free with episodes of abdominal pain described as number with "Yes", "No", "I don't know" and missing responses..	1 year
Secondary	Number of emergency room visits subject had in the past 12 months	Number of emergency room visits subjects experienced in the past 12 months presented as minimum, maximum, and median number of emergency room visits and number of missing responses.	1 year
Secondary	Number of emergency room visits subject had in whole life	Number of emergency room visits the subject experienced in their whole life presented as minimum, maximum, and median number of visits and number of missing responses..	18 years
Secondary	Number of hospitalizations subject had in past 12 months	Number of hospitalizations subject experienced in the past 12 months presented as minimum, maximum, and median number and number of missing responses..	1 year
Secondary	Number of hospitalizations subject had in whole life	Number of hospitalizations subject had in their whole life presented as minimum, maximum, and median number and number of missing responses..	18 years
Secondary	Number of school days subject missed in the last month	Number of school days subject missed in the last month presented as minimum, maximum, and median number and number of missing responses..	30 days
Secondary	Number of subjects with Exocrine Pancreatic Insufficiency	Number of subjects with abnormal fecal elastase (< 100 micrograms/ gram of stool on 2 separate samples = 1 month apart) presented as number of subjects with abnormal and normal lab values and number of subjects who did not have test done.	3 years
Secondary	Number of subjects with abnormal fasting glucose	Number of subjects with fasting glucose =126 milligrams per deciliter presented as number of subjects with abnormal and normal lab value and number of subjects who did not have test done.	3 years
Secondary	Number of subjects with abnormal hemoglobin A1c (HbA1c)	Number of subjects with HbA1c (abnormal if >6; diabetic if >6.5%) results that were normal, abnormal, and diabetic and number who did not have test done.	3 years
Secondary	Number of subjects with abnormal oral glucose tolerance test (OGTT)	Number of subjects with abnormal OGTT test results. OGTT performed with 1.75 grams/kilogram of standard glucose beverage (glucola, maximum 75 grams) consumed within 10 minutes at time 0. Glucose drawn prior to the beverage and at time 120 minutes. Glycemic status will be defined as: (1) normal glucose tolerance (NGT, fasting glucose <100 mg/dL, 2 hour <140 mg/dL); (2) pre-diabetic based on impaired fasting glucose (IFG, fasting glucose 100-125 mg/dL) and/or impaired glucose tolerance (IGT, 2 hour glucose 140-199 mg/dL); or (3) diabetic (DM, fasting glucose >126 mg/dL or 2 hour glucose >200 mg/dL). Findings presented as number of subjects with normal, pre-diabetic, impaired, and diabetic results and number that did not have test done.	3 years