PMID- 20699420
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20220409
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 59
IP  - 11
DP  - 2010 Nov
TI  - Residual insulin production and pancreatic ss-cell turnover after 50 years of 
      diabetes: Joslin Medalist Study.
PG  - 2846-53
LID - 10.2337/db10-0676 [doi]
AB  - OBJECTIVE: To evaluate the extent of pancreatic beta-cell function in a large number 
      of insulin-dependent diabetic patients with a disease duration of 50 years or 
      longer (Medalists). RESEARCH DESIGN AND METHODS: Characterization of clinical and 
      biochemical parameters and beta-cell function of 411 Medalists with correlation with 
      postmortem morphologic findings of 9 Medalists. RESULTS: The Medalist cohort, 
      with a mean +/- SD disease duration and age of 56.2 +/- 5.8 and 67.2 +/- 7.5 years, 
      respectively, has a clinical phenotype similar to type 1 diabetes (type 1 
      diabetes): mean +/- SD onset at 11.0 +/- 6.4 years, BMI at 26.0 +/- 5.1 kg/m(2), 
      insulin dose of 0.46 +/- 0.2 u/kg,  approximately 94% positive for DR3 and/or DR4, and 29.5% 
      positive for either IA2 or glutamic acid decarboxylase (GAD) autoantibodies. 
      Random serum C-peptide levels showed that more than 67.4% of the participants had 
      levels in the minimal (0.03-0.2 nmol/l) or sustained range (>/= 0.2 nmol/l). 
      Parameters associated with higher random C-peptide were lower hemoglobin A1C, 
      older age of onset, higher frequency of HLA DR3 genotype, and responsiveness to a 
      mixed-meal tolerance test (MMTT). Over half of the Medalists with fasting 
      C-peptide > 0.17 nmol/l responded in MMTT by a twofold or greater rise over the 
      course of the test compared to fasting. Postmortem examination of pancreases from 
      nine Medalists showed that all had insulin+ beta-cells with some positive for TUNEL 
      staining, indicating apoptosis. CONCLUSIONS: Demonstration of persistence and 
      function of insulin-producing pancreatic cells suggests the possibility of a 
      steady state of turnover in which stimuli to enhance endogenous beta cells could be 
      a viable therapeutic approach in a significant number of patients with type 1 
      diabetes, even for those with chronic duration.
FAU - Keenan, Hillary A
AU  - Keenan HA
AD  - Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
FAU - Sun, Jennifer K
AU  - Sun JK
FAU - Levine, Jared
AU  - Levine J
FAU - Doria, Alessandro
AU  - Doria A
FAU - Aiello, Lloyd P
AU  - Aiello LP
FAU - Eisenbarth, George
AU  - Eisenbarth G
FAU - Bonner-Weir, Susan
AU  - Bonner-Weir S
FAU - King, George L
AU  - King GL
LA  - eng
GR  - K12-16335/PHS HHS/United States
GR  - S10 RR025065/RR/NCRR NIH HHS/United States
GR  - R24-DK-083957 01/DK/NIDDK NIH HHS/United States
GR  - K12 EY016335/EY/NEI NIH HHS/United States
GR  - T32 DK007260/DK/NIDDK NIH HHS/United States
GR  - P30 DK036836/DK/NIDDK NIH HHS/United States
GR  - R24 DK083957/DK/NIDDK NIH HHS/United States
GR  - P30-DK-036836-23/DK/NIDDK NIH HHS/United States
GR  - T32-DK-007260/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100810
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (C-Peptide)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Insulin)
SB  - IM
CIN - Diabetes. 2010 Dec;59(12):e26; author reply e27. PMID: 21115779
MH  - Aged
MH  - *Awards and Prizes
MH  - C-Peptide/blood
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 1/drug therapy/genetics/*physiopathology
MH  - Female
MH  - HLA-DQ Antigens/genetics
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Insulin/analysis/*biosynthesis/therapeutic use
MH  - Insulin-Secreting Cells/metabolism/pathology/*physiology
MH  - Male
MH  - Middle Aged
MH  - Numismatics
MH  - Phenotype
MH  - Time Factors
MH  - Tissue and Organ Procurement
PMC - PMC2963543
EDAT- 2010/08/12 06:00
MHDA- 2010/11/17 06:00
PMCR- 2011/11/01
CRDT- 2010/08/12 06:00
PHST- 2010/08/12 06:00 [entrez]
PHST- 2010/08/12 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - db10-0676 [pii]
AID - 0676 [pii]
AID - 10.2337/db10-0676 [doi]
PST - ppublish
SO  - Diabetes. 2010 Nov;59(11):2846-53. doi: 10.2337/db10-0676. Epub 2010 Aug 10.