Minimally-invasive measurements of beta cell function in (pre)type 1 diabetes.

Student thesis: Doctoral Thesis

Abstract

Type 1 diabetes is a chronic T-cell mediated autoimmune disease leading to a major loss of the insulin-producing beta cells and is marked by circulating autoantibodies. While virtually all first-degree relatives of type 1 diabetes patients who are positive for at least two types of islet autoantibodies will develop diabetes within 20 years, those with dysglycemia and/or low stimulated C-peptide release are likely to develop the disease more rapidly (≤2-3 years). The better outcome of immunointerventions in recent-onset type 1 diabetes patients with relatively preserved functional beta cell mass has provided strong arguments for considering trials in the late preclinical stage. Such secondary immune intervention trials require the identification of individuals with impending diabetes. In this respect, we reported that a decreased beta cell function (assessed by hyperglycemic clamp, the gold standard for measuring beta cell function) could identify autoantibody positive first-degree relatives with 50-70% risk of developing type 1 diabetes within 3 years. Unfortunately, these hyperglycemic clamp tests are time consuming, labor-intensive, costly and difficult to implement on a large-scale in an active seemingly healthy population. Hence there is a need for minimally-invasive alternatives which can be easily implemented Therefore, this thesis investigated the potency of early markers of dysglycemia, such as glycemic variability, and early hormonal markers of type 1 diabetes, such as the proinsulin-to-C-peptide (PI:C) ratio, as minimally-invasive as potential alternatives to the clamp. Our findings showed that elevated glycemic variability or fasted PI:C ratios may achieve diagnostic performances similar to that of the hyperglycemic clamp. Both relatively simple tools are promising for metabolic follow-up studies aiming to avoid diabetes ketoacidosis in high risk individuals and for the selection of candidates of choice for intervention studies
Date of Award28 Mar 2017
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorFrans Gorus (Promotor), Ilse Weets (Promotor), Brigitte Velkeniers-Hoebanckx (Jury), Inge Gies (Jury), Robert Hilbrands (Jury), David Leslie (Jury) & Y Taes (Jury)

Keywords

  • beta cell
  • diabetes
  • Type 1 diabetes
  • autoimmune disease

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