Characterization of residual β cell function in long-standing type 1 diabetes
ABSTRACT Some patients with long-standing type 1 diabetes (T1D) maintain detectable levels of C-peptide. The quantitative and qualitative aspects of insulin secretion in these subjects has not been assessed, but may shed light on the basis for maintained β cell function. Our objective was to characterize insulin secretion in subjects with varying duration of T1D.
Data from mixed meal tolerance tests (MMTT) were collected in this cross-sectional study. We screened 58 subjects with T1D <1 year and 34 subjects with T1D >2 years, twenty of whom had previously participated in trials of anti-CD3 monoclonal antibody. Data from 38 historical non-diabetic controls was utilized. Insulin secretory rates were calculated from C-peptide levels from MMTTs. Patterns and rates of insulin secretion (ISR) were characterized along with relationships between ISR and clinical parameters.
Detectable C-peptide was present in 68% of subjects with T1D duration >2 years. ISR was negatively correlated with HgbA1c and insulin use. A decline in total insulin secretion was seen with increasing disease duration (p < 0.0001). More subjects with long duration of T1D had a delayed time to peak secretion compared to those with new onset T1D or non-diabetics. Insulin and glucagon secretory responses appeared unrelated.
Meal stimulated insulin secretory responses are seen in those with long standing T1D and detectable C-peptide. Delayed insulin secretory responses are more common in individuals with longer disease duration. Residual insulin secretory responses are associated with improved clinical parameters. This article is protected by copyright. All rights reserved.
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ABSTRACT: Clinical onset of type 1 diabetes (T1D) is thought to result from a combination of overt beta cell loss and beta cell dysfunction. However, our understanding of how beta cell metabolic abnormalities arise during the pathogenesis of disease remains incomplete. Despite extensive research on the autoimmune nature of T1D, questions remain regarding the time frame and nature of beta cell destruction and dysfunction. This review focuses on the characterizations of beta cell dysfunction in the prediabetic and T1D human and mouse model. Studies have shown evidence supporting progressive loss of beta cell mass and function prior to T1D onset, while other scientists argue beta cell destruction occurs later in the disease process. Determining the time frame of beta cell destruction and identifying metabolic mechanisms that drive beta cell dysfunction has high potential for successful interventions to maintain insulin secretion for individuals with established T1D as well as those with prediabetes.Current Diabetes Reports 09/2014; 14(9):519. DOI:10.1007/s11892-014-0519-8 · 3.38 Impact Factor
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ABSTRACT: Background: No previous reports have clarified the relationship between glycated albumin (GA) and BMI in patients with acute-onset type 1 diabetes. Methods: We conducted a cross-sectional study evaluating the correlation between GA and BMI in 209 patients with acute-onset type 1 diabetes and in 159 patients with type 2 diabetes who were designated as the control group. The correlation between fasting serum C-peptide immunoreactivity (CPR) and GA or BMI was also evaluated to clarify the impact of insulin secretion capacity on the relationship between GA and BMI. Results: GA was significantly inversely correlated with BMI in patients with type 2 diabetes (r = -0.317, p < 0.001) but not in patients with type I diabetes (r = 0.031, p = NS). In patients with type 2-diabetes, GA was significantly inversely correlated with fasting CPR, and BMI was significantly correlated with fasting CPR. In patients with type 1 diabetes, GA was significantly inversely correlated with fasting CPR (r = -0.291, p < 0.001), but BMI was not correlated with fasting CPR (r = -0.010, p = NS). Conclusions: Unlike in patients with type 2 diabetes, GA was not significantly correlated with BMI in patients with acute-onset type 1 diabetes.Clinica Chimica Acta 09/2014; 438. DOI:10.1016/j.cca.2014.08.038 · 2.82 Impact Factor