Abstract
Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c).Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are known vanish prior to the development of T2DM, and autopsy of overt T2DM patients have shown a 60% reduction in β-cell mass.As the decline in β-cell function and mass have been proven to be pathological traits in T2DM, methods for evaluating β-cell loss is becoming of more interest. However, evaluation of β-cell death or loss is currently invasive and unattainable for the vast majority of diabetes patients. Serological markers, reflecting β-cell loss would be advantageous to detect and monitor progression of T2DM. Biomarkers with such capacities could be neo-epitopes of proteins with high β-cell specificity containing post translational modifications. Such tools may segregate T2DM patients into more appropriate treatment groups, based on their β-cell status, which is currently not possible. Presently individuals presenting with adequately elevated levels of both insulin and glucose are classified as T2DM patients, while an important subdivision of those is pending, namely those patients with sufficient β-cell capacity and those without. This may warrant two very different treatment options and patient care paths.Serological biomarkers reflecting β-cell health status may also assist development of new drugs for T2DM and aid physicians in better characterization of individual patients and tailor individual treatments and patient care protocols.
Highlights
Type II Diabetes Mellitus (T2DM) is a heterogeneous type of disease [1], meaning that affected patients display a large variability with regards to disease characteristics
A 40% reduction in β-cell mass has been observed in obese individuals with impaired fasting glucose (IFG), and a 60% reduction has been observed in patients suffering from overt T2DM [4,6]
We will in this paper describe the pursuit of novel β-cell neo-epitope biomarkers that could improve the clinical diagnosis and management of diabetes
Summary
Type II Diabetes Mellitus (T2DM) is a heterogeneous type of disease [1], meaning that affected patients display a large variability with regards to disease characteristics. Fasting serum insulin is increased in a period leading up to the diagnosis of T2DM, after which it will decline due to β-cell dysfunction and decreased βcell mass [31] It should be noted, that high fasting insulin levels (hyperinsulinemia) often occur at the same time as reduced insulin secretion upon glucose stimulation, due to β-cell dysfunction [32]. Available treatments for T2DM include metformin, sulphonylureas, meglitinides, glitazones, glucagon-like peptide-1(GLP-1) analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors, and insulin supplementation While these in most cases are efficient in reducing fasting blood glucose and HbA1c levels, they are limited by a range of factors, such as loss of efficacy over time, intolerance, the need for injection, lack of effects on β-cells, and side effects including weight gain, hypoglycemia, fluid retention, heart failure, bone loss and others [19,36].
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