168 research outputs found
Effect of Prior Intensive Insulin Treatment During the Diabetes Control and Complications Trial (DCCT) on Peripheral Neuropathy in Type 1 Diabetes During the Epidemiology of Diabetes Interventions and Complications (EDIC) Study
A1C Variability as an Independent Risk Factor for Microalbuminuria in Young People With Type 1 Diabetes
A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes: Data from the Diabetes Control and Complications Trial
OBJECTIVE—Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes
The Question Is, My Dear Watson, Why Did the Dog Not Bark?: The Joslin 50-Year Medalist Study
Effect of Prior Intensive Therapy in Type 1 Diabetes on 10-Year Progression of Retinopathy in the DCCT/EDIC: Comparison of Adults and Adolescents
Timing Is Everything: Age of Onset Influences Long-Term Retinopathy Risk in Type 2 Diabetes, Independent of Traditional Risk Factors
OBJECTIVE—To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia
Insulin-Based Versus Triple Oral Therapy for Newly Diagnosed Type 2 Diabetes: Which is better?
Feasibility, Acceptability, and Predictive Validity of a Psychosocial Screening Program for Children and Youth Newly Diagnosed With Type 1 Diabetes
Hyperglycemia Induces a Dynamic Cooperativity of Histone Methylase and Demethylase Enzymes Associated With Gene-Activating Epigenetic Marks That Coexist on the Lysine Tail
OBJECTIVE: Results from the Diabetes Control Complications Trial (DCCT) and the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) Study and more recently from the U.K. Prospective Diabetes Study (UKPDS) have revealed that the deleterious end-organ effects that occurred in both conventional and more aggressively treated subjects continued to operate >5 years after the patients had returned to usual glycemic control and is interpreted as a legacy of past glycemia known as "hyperglycemic memory." We have hypothesized that transient hyperglycemia mediates persistent gene-activating events attributed to changes in epigenetic information. RESEARCH DESIGN AND METHODS: Models of transient hyperglycemia were used to link NFkappaB-p65 gene expression with H3K4 and H3K9 modifications mediated by the histone methyltransferases (Set7 and SuV39h1) and the lysine-specific demethylase (LSD1) by the immunopurification of soluble NFkappaB-p65 chromatin. RESULTS: The sustained upregulation of the NFkappaB-p65 gene as a result of ambient or prior hyperglycemia was associated with increased H3K4m1 but not H3K4m2 or H3K4m3. Furthermore, glucose was shown to have other epigenetic effects, including the suppression of H3K9m2 and H3K9m3 methylation on the p65 promoter. Finally, there was increased recruitment of the recently identified histone demethylase LSD1 to the p65 promoter as a result of prior hyperglycemia. CONCLUSIONS: These studies indicate that the active transcriptional state of the NFkappaB-p65 gene is linked with persisting epigenetic marks such as enhanced H3K4 and reduced H3K9 methylation, which appear to occur as a result of effects of the methyl-writing and methyl-erasing histone enzymes
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