|SUN, JENNIFER K. - Joslin Diabetes Center|
|STRAUCH, CHRISTOPHER M. - Case Western Reserve University (CWRU)|
|KEENAN, HILLARY A. - Joslin Diabetes Center|
|MONNIER, VINCENT M. - Case Western Reserve University (CWRU)|
|CAVALLERANO, JERRY D. - Joslin Diabetes Center|
|DORIA, ALESSANDRO - Joslin Diabetes Center|
|ASZTALOS, BELA F. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|AIELLO, LLOYD PAUL - Joslin Diabetes Center|
|SCHAEFER, ERNST J. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|KING, GEORGE L. - Joslin Diabetes Center|
|SELL, DAVID R. - Case Western Reserve University (CWRU)|
Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2010
Publication Date: 4/1/2011
Citation: Sun, J., Strauch, C., Keenan, H., Monnier, V., Cavallerano, J., Doria, A., Asztalos, B., Aiello, L., Schaefer, E., King, G., Sell, D. 2011. Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration. Diabetes Care. 34(4):968-974.
Interpretive Summary: This study was designed to assess complication prevalence and identify protective factors in patients who have had diabetes for a duration greater than or equal to 50 years (Medalists). Characterization of a complication-free subgroup in this cohort would suggest that some individuals are protected from diabetes complications and allow identification of internally originating protective factors. Retinopathy, nephropathy, neuropathy, and cardiovascular disease were assessed in relation to HbA1c, lipids, and advanced glycation end products (AGEs) in the Medalist population. Retrospective chart review provided long-term ophthalmic data for a subgroup. A large portion of Medalists remained free from proliferative diabetic retinopathy (PDR), nephropathy, neuropathy, or cardiovascular disease. Our analysis found that current and long-term (the past 15 years) blood-sugar control were unrelated to complications. However, subjects with high plasma carboxyethyl-lysine and pentosidine were more likely to have complications. Also, the great majority of Medalists without PDR and with no retinopathy progression over the first 17 years did not experience worsening retinopathy thereafter. Specific AGE combinations were strongly associated with complications. In conclusion, the Medalist population is likely to have more protective factors against complications. These factors might prove useful to the general population with diabetes if they can be used to induce protection against long-term complications.
Technical Abstract: We performed a cross-sectional, observational study of 351 U.S. residents with at least 50 years of insulin-dependent diabetes. Longitudinal data on retinopathy progression was obtained via chart review in patients followed at the Joslin Diabetes Center eye clinic (Boston, MA). HbA1c was determined by high-performance liquid chromatography; C-reactive protein measured by particle-enhanced; lipid profiles determined by standard methods; total plasma apolipoprotein A-I concentrations measured by turbidimetric immunoassay; and apolipoprotein A-I containing HDL subpopulations determined two-dimensional gel electrophoresis. C-peptide was measured by radioimmunoassay. Standard quantitative real-time PCR (qPCR) was performed to assess oxidative stress marker mRNA levels. Fructose-lysine (measured as furosine), carboxymethyl-lysine (CML), and carboxyethyl-lysine (CEL) were determined by gas chromatography mass spectrometry using isotope dilution technique. Renal status was based on the average of urinary albumin-to-creatinine ratios (ACRs) from two spot urine samples. Scores greater than 2 on the Michigan Neuropathy Screening Instrument were considered positive for neuropathy. Medalists reporting a history of coronary artery disease, angina, heart attack, or with a prior cardiac/leg angioplasty or bypass graft surgery were deemed positive for cardiovascular disease. Our analysis showed that current and longitudinal (the past 15 years) glycemic control were unrelated to complications. Subjects with high plasma carboxyethyl-lysine and pentosidine were 7.2-fold more likely to have any complication. Also, Medalists without PDR, 96% with no retinopathy progression over the first 17 years of follow-up did not experience retinopathy worsening thereafter. Specific AGE combinations were strongly associated with complications, indicating a link between AGE formation or processing with development of diabetic vasculopathy.