Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1
ABSTRACT There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis.
Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points.
Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up.
These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.
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ABSTRACT: Type 1 diabetes (T1D), also known as insulin-dependent diabetes mellitus, is a chronic disorder that results from autoimmune destruction of insulin-producing β cells in the islets of Langerhans within the pancreas ( Atkinson and Maclaren 1994). This disease becomes clinically apparent only after significant destruction of the β-cell mass, which reduces the ability to maintain glycemic control and metabolic function. In addition, it continues for years after clinical onset until, generally, there is complete destruction of insulin secretory capacity. Because prevention and therapy strategies are targeted to this pathologic process, it becomes imperative to have methods with which it can be monitored. This work discusses current research-based approaches to monitor the autoimmunity and metabolic function in T1D patients and their potential for widespread clinical application.Cold Spring Harbor Perspectives in Medicine 06/2012; 2(6):a007708. DOI:10.1101/cshperspect.a007708 · 7.56 Impact Factor
- Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy, 11/2011; , ISBN: 978-953-307-362-0
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ABSTRACT: Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by destruction of insulin-producing pancreatic beta cells. Many broad-based immunosuppressive and antigen-specific immunoregulatory therapies have been and are currently being evaluated for their utility in the prevention and treatment of T1D. Looking forward, this review discusses the potential therapeutic use of antigen-specific tolerance strategies, including tolerance induced by "tolerogenic" antigen-presenting cells pulsed with diabetogenic antigens and transfer of induced or expanded regulatory T cells, which have demonstrated efficacy in nonobese diabetic (NOD) mice. Depending on the time of therapeutic intervention in the T1D disease process, antigen-specific immunoregulatory strategies may be employed as monotherapies, or in combination with short-term tolerance-promoting immunoregulatory drugs and/or drugs promoting differentiation of insulin-producing beta cells from endogenous progenitors.Immunity 04/2010; 32(4):488-99. DOI:10.1016/j.immuni.2010.04.002 · 19.75 Impact Factor