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Residual insulin production and pancreatic ß-cell turnover after 50 years of diabetes: Joslin Medalist Study.

Keenan HA, Sun JK, Levine J, Doria A, Aiello LP, Eisenbarth G, Bonner-Weir S, King GL - Diabetes (2010)

Bottom Line: 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).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+ β-cells with some positive for TUNEL staining, indicating apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.

ABSTRACT

Objective: To evaluate the extent of pancreatic β-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 β-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, ∼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+ β-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 β cells could be a viable therapeutic approach in a significant number of patients with type 1 diabetes, even for those with chronic duration.

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Related in: MedlinePlus

Distribution of the first 97% of C-peptide levels among 50-year Medalists. Inset shows C-peptide values from all values. These pictures demonstrate the outlying 3% in excess of 0.17 nmol/l. (A high-quality color representation of this figure is available in the online issue.)
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Figure 1: Distribution of the first 97% of C-peptide levels among 50-year Medalists. Inset shows C-peptide values from all values. These pictures demonstrate the outlying 3% in excess of 0.17 nmol/l. (A high-quality color representation of this figure is available in the online issue.)

Mentions: There were 14 individuals who had significantly higher random C-peptide levels than the majority (in excess of 0.17 nmol/l, representing the top 3.5%) (Fig. 1). On average these individuals had an older age at diagnosis versus the rest of the cohort (17.4 ± 7.4 vs. 10.8 ± 6.3 years, P = 0.0008, respectively). Trends that did not reach statistical significance comparing this group with the rest of the cohort were higher frequency of DR3 or DR4 risk alleles (100% vs. 93.2%) and lower prevalence of autoantibodies (20.0% vs. 28.7%).


Residual insulin production and pancreatic ß-cell turnover after 50 years of diabetes: Joslin Medalist Study.

Keenan HA, Sun JK, Levine J, Doria A, Aiello LP, Eisenbarth G, Bonner-Weir S, King GL - Diabetes (2010)

Distribution of the first 97% of C-peptide levels among 50-year Medalists. Inset shows C-peptide values from all values. These pictures demonstrate the outlying 3% in excess of 0.17 nmol/l. (A high-quality color representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2963543&req=5

Figure 1: Distribution of the first 97% of C-peptide levels among 50-year Medalists. Inset shows C-peptide values from all values. These pictures demonstrate the outlying 3% in excess of 0.17 nmol/l. (A high-quality color representation of this figure is available in the online issue.)
Mentions: There were 14 individuals who had significantly higher random C-peptide levels than the majority (in excess of 0.17 nmol/l, representing the top 3.5%) (Fig. 1). On average these individuals had an older age at diagnosis versus the rest of the cohort (17.4 ± 7.4 vs. 10.8 ± 6.3 years, P = 0.0008, respectively). Trends that did not reach statistical significance comparing this group with the rest of the cohort were higher frequency of DR3 or DR4 risk alleles (100% vs. 93.2%) and lower prevalence of autoantibodies (20.0% vs. 28.7%).

Bottom Line: 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).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+ β-cells with some positive for TUNEL staining, indicating apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.

ABSTRACT

Objective: To evaluate the extent of pancreatic β-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 β-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, ∼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+ β-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 β cells could be a viable therapeutic approach in a significant number of patients with type 1 diabetes, even for those with chronic duration.

Show MeSH
Related in: MedlinePlus